The effect of angiotensin infusion, sodium loading and sodium restriction on the renal and cardiac adrenergic nerves. The renal and cardiac adrenergic nerve patterns in rats infused with large and small amounts of angiotensin and in rats given NaCl plus DOCA, NaCl alone, and salt-free diets were examined by the histochemical fluorescence method. Infusion of small amounts of angiotensin led to a persistent blood pressure elevation whereas infusion of large amounts of angiotensin resulted in a transient rise in blood pressure, probably due to the development of tachyphylaxis. Nerve patterns were found to be normal in angiotensin-infused rats and in rats given NaCl. In rats given NaCl plus DOCA and in rats subjected to salt restriction, a partial or complete disappearance of the transmitter of the adrenergic nerve terminals were recorded. The findings suggest that angiotensin in itself is incapable of inducing visible alterations in the transmitter content of the terminals. The findings agree with the view that angiotensin potentiates a norepinephrine depletion of the terminals during sympathetic activity, since it can be assumed that increased plasma angiotensin levels as well as various degrees of increased sympathetic tonus were present in the rats subjected to salt restriction. The similar effect on the nerve terminals produced by the combined NaCl and DOCA administration is consistent with earlier reports of an increased turnover of norepinephrine in animals thus treated.


Histology of the human corpus luteum of early and late pregnancy. The aim of this investigation has been to examine which histological parameters are of value in the age determination of the corpus luteum of pregnancy. The material comprises representative ovarian biopsies from 16 women from the 10th through 42nd week of gestation. The following histological parameters have been found useful for the age determination of the corpus luteum: 1) the size of the granulosa cells; 2) the number of K-cells, vacuoles and colloid inclusions in the granulosa cell layer; 3) the size of the theca interna cells; (4) the size of the vessels in the theca interna. Futhermore, the differentiation of the corpus luteum of pregnancy from the corpus luteum of menstruation is described, and some indications for a histological age determination of the corpus luteum of pregnancy are mentioned.


Different effects on renal and submaxillary renin release after blockade of the renin system in mice. Ingibition of the angiotensin I converting enzyme with SQ 20,881 results in a rapid marked increase in plasma renin concentration in mice. The maximum effect is short-lasting, but the values are still elevated 2 hours after the injection, the time course being similar to that previously found in rats. The relative increase is the same in normal and sialo-adenectomized mice. The plasma renin concentration of nephrectomized mice with their submaxillary glands intact is, however, totally uninfluenced by injection of the blocker. This finding indicates that renin release from the submaxillary glands is not controlled by the plasma angiotensin II concentration as is that of the renin release from the kidneys.


Studies of some twitch and fatigue properties of different motor unit types in the ankle muscles of the adult cat. Contractile responses of motor units in the gastrocnemius, soleus and pretibial flexor muscles of adult cats were elicited by intracellular stimulation of motoneurones. The motor units were classified into types FF, FR and S (Burke et al. 1971) and their responses to the same stimulation patterns as those used in a previous investigation of whole muscles (Hammarberg and Kellerth 1975 a) were studied. The duration of motoneurone afterhyperpolarization was short in both the fast twitch FF and FR units; it was longer in the soleus S units than in the S units of the pale muscles. Twitch time-to-peak was less than 30 ms in the FF and FR units, but exceeded 40 ms in the S units. Soleus S units were slower than S units of the pale muscles. Potentiation was observed in the gastrocnemius units, but not in the soleus S units. A short rest allowed fatigued extensor units of the FF and FR types to regain some contractile strength. This was less evident in the S units which, on the other hand, were extremely resistant to fatigue. Differences in response patterns between corresponding motor unit types of the flexor and extensor muscles were observed. A few fast twitch units were identified in the slow soleus muscle.


Liver, lung and malignant disease in heterozygous (Pi MZ) alpha1-antitrypsin deficiency. Theoccurrence of PAS-positive, diastase-resistant, inclusion bodies in hepatocytes has been used as a marker of heterozygous (Pi MZ) alpha1-antitrypsin deficiency in order to study the frequency of lung, liver and malignant disease in a consecutive autopsy material from a well defined population. Typical PAS-positive inclusion bodies were found in the liver in 26 (3.7%) of the 700 cases studied. In these 26 subjects both liver (cirrhosis or fibrosis) and lung disease (emphysema) were significantly more prevalent (p less than 0.001) than among PAS-negative controls. The prevalence of malignant disease did not differ between the groups. The results are consistent with the concept that heterozygous (Pi MZ) alpha1-antitrypsin deficiency predisposes to both liver and lung disease but does not influence the survival rate.


Lp(alpha) lipoprotein and pre-beta1-lipoprotein in relation to lipid levels in males. Previous studies have shown that a slow-moving pre-beta-lipoprotein fraction, named the pre-beta1-lipoprotein, occurred significantly more frequently among subjects with coronary heart disease (CHD) than among healthy individuals. This lipoprotein is closely related to, and probably identical with, the Lp(a) lipoprotein. Immunological tests likewise showed that Lp(a) lipoprotein was significantly more common among patients with CHD than among controls. Mean cholesterol and triglyceride levels were higher in pre-beta1-lipoprotein positive than in pre-beta1-lipoprotein negative individuals. Lp(a+) individuals tended to have higher serum cholesterol values than did Lp(a-) persons but there was no difference in the mean triglyceride value. This apparent discrepancy seems to be due to the presence in occasional sera of lipoprotein fractions with pre-beta1-mobility, usually of a VLDL nature. These lipoproteins are not associated with the Lp(a) lipoprotein.


A rapid screening test for Cushing's syndrome. A combination test consisting of two parts, a single dose of dexamethasone and a (1-24) ACTH injection, has been used for the diagnosis of Cushing's syndrome. The test was performed by administering 1 mg dexamethasone orally at 11 p.m. on the first day and 25 IU synthetic ACTH i.v. at 8 a.m. on the second day. Plasma cortisol was determined at 8 a.m. on the first and second day and 1-1/2 and 2 hours after the ACTH injection. The test was performed in 33 patients with Cushing's syndrome and in 114 controls without adrenal disease. After dexamethasone administration alone, cortisol values frequently overlapped between patients with Cushing's syndrome and controls. The validity of the test was considerably improved by adding ACTH stimulation. The test procedure is recommended as a screening test for Cushing's syndrome in ambulatory practice.


Effects of electrical stimulation of the mesencephalon and diencephalon on the paradoxical phase of sleep. During paradoxical sleep electrical stimulation of the mesencephalic reticular formation and emotiogenic structures in the mesencephalon and diencephalon produced depression or an increase in the theta rhythm of the hippocampal and entorhinal electrical activity. However, stimulation not involving behavioral arousal did not cause a transition from paradoxical phase into slow wave sleep. The cessation of stimulation restored the normal structure of the paradoxical phase. Stimulation of the reticular formation causing the depression of the hippocampal and entorhinal theta rhythm without behavioral arousal did not affect duration of the paradoxical phase, which was shortened, however, by electrical stimulation of the emotiogenic structures evoking an increase in the hippocampal and entorhinal theta rhythms. Stimulation of ventromedial hypothalamus or septum (during wakefulness inhibiting motivational behavior and emotional stress) caused transition from the paradoxical into slow wave sleep. This is probably caused by a decrease in emotiogenic stress, which during the paradoxical phase is usually on a high level.


Coronary insufficiency in children. Coronary arteriographic studies in two siblings from a family with hyperbetalipoproteinemia. A family affected with hyperbetalipoproteinemia was studied. Two siblings, a boy 11 and a girl 9 years of age, with characteristic findings of homozygous type II hyperlipoproteinemia are described. The highly atherogenetic nature of this disorder is illustrated by the occurrence of progressive coronary atheromatosis in the boy, in whom two coronary arteriographic studies documented the development of progressive obstruction of two coronary arteries in the course of 2 years. During this interval angina pectoris developed followed by myocardial infarction, cardiomegaly and congestive heart failure. The sister has remained asymptomatic, with apparently normal coronary arteries at age 9 years. Phonocardiograms were suggestive of aortic valve involvement although no aortic valve gradient was demonstrated by cardiac catheterization.


Autonomic nervous cardiovascular regulation in borderline hypertension. Borderline hypertension attracts investigative interest since it is an early predictor of established hypertension and its sequelae. This condition offers the opportunity of studying arterial hypertension at its inception, before the development of secondary pressure-related changes. A number of abnormalities of the circulation have been described in borderline hypertension. The peripheral resistance is either elevated or inappropriately adjusted to the prevailing increased cardiac output and blood flow. Cardiac output, heart rate and stroke volume are elevated in a proportion of patients. Decreased plasma volume, enhanced pressor responsiveness and elevated plasma renin activity have also been noted. All these changes could hypothetically be explained by a neurogenic mechanism. Although the experimental evidence supporting a neurogenic origin of borderline hypertension is incomplete and often indirect, most findings point toward an abnormal autonomic control of the circulation in this disorder. It is postulated that in a subgroup of patients with borderline hypertension a neurogenic mechanism is in fact operative. There is a need for further characterization of this category of borderline hypertension and for description of its natural history, particularly in relation to the possible subsequent development of essential hypertension.


Application of adrenocorticotropin assays in a routine clinical laboratory. The radioimmunoassay of ACTH was used in a routine laboratory to localize the site of the lesion in 20 patients with Cushing's syndrome. Eight of the patients had no detectable circulating ACTH and had adrenal tumors removed, 12 had high levels and were diagnosed as having pituitary Cushing's syndrome. Very high levels of plasma ACTH were found in eight patients who had primary adrenal insufficiency, while ACTH was undetectable in ten patients with secondary hypoadrenalism. The routine use of this assay in endocrinology should reduce the hospitalization of patients under investigation for disorders of the pituitary--adrenal axis. Eight patients who had the ectopic ACTH syndrome and carcinoma of the lung were found to have very high levels of ACTH with no diurnal variation. Forty-seven patients with oat-cell carcinoma but without evidence of the ectopic ACTH syndrome had normal ACTH levels. A possible role of ACTH and other peptide hormones as tumor markers is mentioned.


Hemiatrophy and hemiparesis in a patient with congenital cytomegalovirus infection. A 3-year-old girl with congenital cytomegalovirus (CMV) infection has been followed up since birth. Hemiatrophy and hemiparesis occurred at 9 months of age. These unusual sequels of congenital CMV infection should encourage physicians to do longitudinal studies on infants with congenital CMV infection, as well as to examine children with hemiatrophy and hemiparesis for CMV infection.


Pseudohypoparathyroidism with normal serum calcium level. A mildly obese 15-year-old boy had short stature with rounded facies and short, stubby hands and toes. He had the fully expressed syndrome of pseudohypoparathyroidism but was the only member of his family who had all the somatic characteristics of this disease. The serum parathyroid hormone level was substantially elevated. Urinary excretion of cyclic adenosine monophosphate and phosphate failed to increase following intravenous infusion of parathyroid hormone. However, he did not have hypocalcemia. The present entity is probably a transient form of pseudohypoparathyroidism with partial responsiveness of skeletal adenyl cyclase to parathyroid hormone.


Joint effusions, chondrocalcinosis and other rheumatic manifestations in hypothyroidism. A clinicopathologic study. Twelve patients with severe hypothyroidism and rheumatic signs and symptoms were studied before or within four days of receiving thyroid replacement therapy. Eight patients had synovial effusions. Seven effusions were extremely viscous and six contained calcium pyrophosphate crystals. Leukocyte counts were less than 1,000/mm3, except in two patients during crystal-induced synovitis. "Bulge signs" were present but often sluggish, possibly because of the viscosity of the fluid. Flexor tendon sheath thickening, joint laxity and popliteal cysts were documented. All patients complained of generalized stiffness and two had proximal myopathy. Roentgenograms were obtained in 11 patients, and chondrocalcinosis was identified in seven. Needle synovial biopsy specimens in five patients showed only mild inflammation in the thick synovium. These findings can suggest hypothyroidism, a treatable disease, as the cause of musculoskeletal problems.


Necrotizing pneumonia and empyema due to Clostridium perfringens. Report of a case and review of the literature. Clostridia are rare causes of pleuropulmonary infections in the absence of penetrating chest injuries; only 10 previous cases have been reported from civilian practice. An additional case of a rapidly progressive, necrotizing pneumonia and empyema is reported. Clostridial pneumonia is more likely to occur in patients with underlying pleuropulmonary disease. Unlike clostridial myonecrosis, it is rarely associated with toxemia; its mortality rate is comparable to that of nonclostridial pleuropulmonary infections. Appropriate antimicrobial therapy with surgical drainage of the empyema is the treatment of choice. Among the cases reviewed, an iatrogenic cause of infection involving an invasive procedure into the pleural cavity could be identified in seven of 11 cases. Aspiration of oropharyngeal contents was the likely route of infection in three other cases. In the remaining case, bacteremic seeding of the pleural cavity was the most probable mode of infection.


Atypical adrenal insufficiency with failure of the pituitary feedback receptor. A case with associated diabetes mellitus and selective IgA deficiency with steatorrhea. A 59 year old woman with insulin-dependent diabetes mellitus and chronic diarrhea was found to have mild steatorrhea, selective plasma IgA deficiency and adrenal insufficiency. Significant adrenal secretion of corticosteroids resulted only after prolonged stimulation with large doses of exogenous ACTH. Plasma ACTH levels were not elevated during clinical adrenal insufficiency or after metyrapone administration but did respond normally to vasopressin and insulin-induced hypoglycemia. These studies were interpreted as showing both primary adrenal insufficiency and impaired pituitary reserve for ACTH secretion in response to the feedback stimulus. No deficiency was found in secretion of other pituitary tropic hormones. Jejunal biopsy showed a lack of IgA-containing plasma cells. With cortisone replacement, diarrhea subsided and a malabsorption pattern on a film of the small bowel was no longer seen. IgA deficiency has been noted frequently with steatorrhea but rarely with diabetes and only once previously with adrenal insufficiency.


Viral hepatitis: a pathologic spectrum.

Viral hepatitis: a pathologic spectrum. Acute viral hepatitis has several identifiable morphologic components but the major categories are (1) cytopathic, (2) inflammatory, and (3) regenerative. Each category has independently variable characteristics. Extreme alterations related to severity of disease, alteration of immune response, or pre-existing liver disease may result in diagnostic difficulties for the pathologist. In contrast to the usual concept, patients who survive fulminant viral hepatitis rarely, if ever, develop cirrhosis and those who have severe hepatic necrosis from hepatitis also do not usually develop serious sequelae of that disease except in the older age group where the difficulty is in impaired regeneration (IR). The usual criteria for the diagnosis of chronic active hepatitis or chronic aggressive hepatitis need a thorough review since many of the variations of acute viral hepatitis result in histologic patterns that might be considered to be chronic aggressive hepatitis using the previous definitions; yet such patients recover without developing chronic liver disease. Chronic active hepatitis, a progressive hepatic disorder, is characterized by changes in the distribution of necrosis and regeneration within the lobule from that usually observed in acute viral hepatitis. Persistent viral hepatitis, a development in 10 to 12 per cent of adult patients after icteric acute disease, is characterized by a "cobblestone" hepatocellular change that resembles continued regeneration, focal hepatocytolysis, and often portal lymphoid hyperplasia. Apparently with time, these histologic features fade and the incidence, in type B PVH, of "ground glass" HBs Ag laden cells increases. This may reflect a continued adaptation of host and virus to one another.


Persistent HB antigenemia: associated clinical manifestations and hepatic lesions. The clinical, biochemical and histological features in nine asymptomatic HBs Ag carriers, 15 patients with symptomatic HBs Ag-positive chronic active hepatitis (CAH), and 29 patients with HBs antigenemia persistent for five months or longer following a documented attack of acute viral hepatitis were compared, and contrasted with those in 67 patients with HBs Ag-negative CAH. The findings were remarkably similar in all groups. However, young males predominated in all three HBs Ag-positive groups, whereas most HBs Ag-negative cases of CAH were in middle-aged women. Moreover, in the latter group, the lesions tended to be more extensive and more commonly were accompanied by smooth muscle antibody, antinuclear antibody and LE cells, and extrahepatic manifestations, such as ulcerative colitis, arthritis, pleurisy and pericarditis.


Adult cytomegalovirus inclusion retino-uveitis. A 27-year-old male renal transplant recipient acquired cytomegalovirus (CMV) infection of both eyes. This was characterized early by a distinctive necrotic retinitis with discrete advancing edges. A large exudative retinal detachment and hypopyon developed in one eye, and cultures from the anterior chamber aspirate grew CMV. Cytomegalovirus was also isolated from the urine and throat; after serial negative base-line titers, CMV antibody titer became positive. At autopsy CMV was isolated from lung, esophagus, and kidney tissue. Light and electron microscopic studies demonstrated extensive necrosis and disruption of the sensory retina and retinal pigment epithelium with exudative retinal detachments. The diseased retinal cells contained a multiplicity of viral particles in various stages of maturity. Cytomegalic inclusion-bearing cells were demonstrated in the choroid of the more severely affected eye.


Hepatitis in marmosets.

Hepatitis in marmosets. Some species of marmosets are susceptible, not only by parenteral inoculation but also by oral exposure, to human hepatitis A virus present in sera or feces. The stools of animals inoculated parenterally or orally contained fecal antigen during certain times of the incubation period and the early, acute phase of the disease; viruslike particles were present in feces of orally infected animals and such feces were infectious when inoculated into marmosets. The fecal antigen crossreacted both with the fecal virus particles and the immune-adherence antigen (see also papers by Purcell et al and Hilleman et al). The MS-1 and CR-326 strains of hepatitis A appeared antigenically similar or identical whereas the GB strain was antigenically different and may be associated with the recently defined type of hepatitis termed hepatitis C or hepatitis non-A/non-B. On repeated challenge hyperegic responses with diffuse liver cell necrosis occurred in some immune animals and this phenomenon must be taken into account in any future vaccination studies.


Review of infectivity studies in nonhuman primates with virus-like particles associated with MS-1 hepatitis. Using the technique of immune electron microscopy we have conducted hepatitis A infectivity studies in marmoset monkeys and chimpanzees. Marmosets inoculated with human serum containing the MS-1 strain of hepatitis A virus have developed hepatitis and seroconverted to 27 nm virus-like particles isolated from stools of humans in the early acute stages of hepatitis. Similar results have been observed through several marmoset subpassages, and the virus-like particles have been recovered from the liver of animals in the acute phase of hepatitis. Chimpanzees inoculated with stool filtrates containing the virus-like particles develop hepatitis with concomitant excretion of the particles in early acute phase stools and subsequent development of serum antibody to the particles. These studies provide evidence that the above particles constitute the virus of hepatitis A of the MS-1 prototype.


Cytomegalovirus in tears from patients with normal eyes and with acute cytomegalovirus chorioretinitis. Cytomegalovirus (CMV) was recovered from the tears in eight of 41 (19.5%) children excreting CMV in their urine or saliva. Tear excretors were all immunosuppressed children with acute lymphocytic leukemia. Three had active CMV chorioretinitis and five did not develop retinal disease in nine to 15 months of observation. To our knowledge this was the first report of the recovery of CMV from tears and of acquired CMV chorioretinitis in children. One patient with active chorioretinitis presented with a disciform elevation of the macula. Therapy with adenine arabinoside (ara-A) or idoxuridine was ineffective in two patients while a third patient treated with ara-Apossibly had a more rapid recovery. However, the significance is uncertain due to the unusual disease presentation and lack of data regarding the nature of cytomegalic inclusion disease chorioretinitis. Areas of retinal calcification were present at autopsy in one patient.


Biophysical and biochemical properties of CR326 human hepatitis A virus. CR326 human hepatitis A virus purified by isopycnic banding from infected marmoset sera was shown to consist of 27 mmu spherical particles on electron microscopic examination. The particles were identified as hepatitis A virus by tests by infectivity and by specific neutralization of infectivity with convalescent human hepatitis A serum. Also, identical 27 mmu viruses in liver extracts gave specific reactions with hepatitis A antisera when tested by immune electron microscopy. The buoyant density of the virus in CsCl was 1.34 and it was heat (60 C), ether, and acid stable but was destroyed by heat (100 C), formalin (1:4000), and ultraviolet irradiation. Electron microscopic studies of sections of infected marmoset liver showed intracytoplasmic virus particles, usually in vesicles. Presumptive findings for RNA, together with the intracytoplasmic location of the virus, indicated the virus to be of RNA-type. The attributes of the virus indicate it is closely related to the enterovirus family and not to hepatitis B virus.


Neurologic complications with elevated antibody titer after acute hemorrhagic conjunctivitis. Nine patients with polyradiculomyeloneuropathy after acute hemorrhagic conjunctivitis (AHC) infection were studied serologically. All except one patient had neutralization titers larger than or equal to 1:16 against the prototype J670/71 strain of AHC virus in at least one of their serum samples. The development of a significant fourfold rise in antibody titer against AHC virus occurred in one of the patients who developed neurologic complications five days after the onset of AHC infection.


Viral hepatitis: clinical aspects.

Viral hepatitis: clinical aspects. In the majority of instances acute viral hepatitis resolves totally without sequelae. Fulminant hepatitis is a highly lethal lesion but 20 to 25 per cent of patients, principally young patients, survive. Survivors do not appear to develop chronic liver disease. Persistent viral hepatitis follows acute icteric hepatitis, both type B and non-B, in 10 to 12 per cent of patients. Six long-term HBs Ag carriers demonstrated HBs Ag clearance after 14-73 months. Chronic active viral hepatitis often progresses to cirrhosis. This progressive hepatitis appeared as a sequelae of acute icteric type B hepatitis in 3 per cent of 429 patients. In patients with chronic active type B hepatitis, low titers of HBs Ag are common.


An experimental mouse testicular teratoma as a model for neuroepithelial neoplasia and differentiation. II. Electron microscopy. The electron microscopic features of the stages of divergent neuroepithelial differentiation in the solid implants of a transplantable mouse testicular teratoma (OTT-6050) are presented and compared to the sequential stages of cytogenesis that have been described in the developing avian and mammalian central nervous system. Primitive neuroepithelial tumor cells showed the features of undifferentiated multipotential matrix (or ventricular) cells of the neural tube. They formed primitive medullary rosettes, from which various transitions were traced to more differentiated, cilia-containing ependymoblastomatous rosettes; the transitional features included increased granular endoplasmic reticulum and microvilli formation. Glial differentiation was characterized by the presence of mature ependymal rosettes and of astrocytes containing glial filaments. Neuronal differentiation included the development of synapses and the presence of dense-core vesicles in nerve cell processes. No intermediate cell forms were found that suggested multiple lines of differentiation occurring within a single cell.


Effect of Ca++ on renal handling of PO4 identical to: evidence for two reabsorptive mechanisms. The effect of hypercalcemia on renal handling of phosphorus was studied in parathyroidectomized rats during 1) extracellular volume expansion with normal saline (0.1 mg/100 g per min) and 2) parathyroid extract infusion (1 U/100 g per h). Hypercalcemia (serum calcium 12-15 mg/100 ml) blunted the phosphaturic response to volume expansion, both when serum calcium was raised acutely during volume expansion and when volume expansion was induced in rats with sustained hypercalcemia. These changes were not associated with significant variations in glomerular filtration rate and serum concentration of phosphorus. Hypercalcemia failed to alter the phosphaturic response and the increase in urinary cyclic AMP excretion following both continuous infusion and a single injection of parathyroid extract. These results are consistent with two components of tubular reabsorption of phosphorus. The first is suppressed by extracellular volume expansion and stimulated by hypercalcemia. The second is suppressed by parathyroid hormone and is not affected by hypercalcemia.


Effect of 25(OH)vitamin D3 on urinary excretion of cyclic adenosine monophosphate. To further evaluate the effect of 25(OH)vitamin D3 (25(OH)vit D3) on renal handling of phosphorus, fractional excretion of phosphorus (CP/CIn) and urinary excretion of cyclic AMP (UcAMP) were measured in the following groups of animals: 1) intact rats receiving intravenously 25(OH)vit D3. 2a) Parathyroidectomized (PTX) rats receiving a continuous infusion of parathyroid hormone (PTH). 2b) PTX rats undergoing continuous infusion of PTH and receiving intravenously 25(OH)vit D3. In group 1 a decrease in CP/CIn from a control value of 0.210 +/- 0.064 (kappa +/- SE) to 0.052 +/- 0.017 (P less than 0.001) during 25(OH)vit D3 infusion was associated with a corresponding decrease in UcAMP from 182 +/- 18 to 87 +/- 8 pmol/min (P less than 0.001). In group 2a an increase in CP/CIn from a control value of 0.031 +/- 0.014 to 0.365 +/- 0.017 during PTH infusion was associated with a corresponding increase in UcAMP from 76 +/- 17 to 330 +/- 51 pmol/min (P less than 0.001). In group 2b a decrease in CP/CIn from 0.365 +/- 0.017 to 0.256 +/- 0.011 (P less than 0.01) during 25(OH)vit D3 infusion was associated with a decrease in UcAMP from 356 +/- 63 to 191 +/- 33 pmol/min (P less than 0.01). These results indicate that the blunting of the phosphaturic response to PTH by 25(OH)vit D3 is associated with a decrease in UcAMP. This observation suggests that the mechanism underlying the enhanced tubular reabsorption of phosphorus is inhibition of the PTH-induced activation of adenylate cyclase in the kidney.


Daily living group: focus on transition from hospital to community. A group (Daily Living Group) that prepares patients for discharge from a psychiatric hospital was formulated to provide patients with information on activities essential for their integration into the outside community. The information included the use of support systems in the hospital setting to aid in bridging the gap between hospital and community, as well as emphasis on the patients' leisure interests, community resources, and environment outside the hospital. The group then gave the patients the opportunity to apply what they learned, that is, practical experience in working through their problems. Patients with an investment in making behavioral changes responded well, but those with no investment lowered the morale of the group when coerced into attending.


The fine structure of the urinary bladder epithelium in the hartebeest, Alcelaphus buselaphus cokii and the Masai giraffe, Giraffa camelopardalis tippelskirchi. The microscopic anatomy and ultrastructure of the urinary bladder epithelium are described in the giraffe and the hartebeest. Differences between the epithelial cell layers of the urinary bladder are described. Cells belonging to different layers show variations in their cell organelles and inclusions. The surface cells contain relatively few fusiform and spherical vesicles.


The isolation of epithelial cells from the rat epididymis. Epithelial cells from the epididymis were released by digesting the chopped epididymis with pronase followed by collagenase plus hyaluronidase. The epithelial cells were further separated from contaminating cell types by differential centrifugation and sedimentation at unit gravity through a gradient of sucrose in Ringer. The isolated cells remained viable as judged by the exclusion of trypan blue. The cells respired in the presence of glucose and the rate of respiration was not altered by the subsequent addition of pyruvate.


Limbic neuronal firing rates in man during administration of nitrous oxide--oxygen or sodium thiopental. Electroencephalographic activity and extracellular discharges from neurons in deep temporal lobe structures were recorded from fine wire microelectrodes chronically implanted in seven psychomotor epileptic patients for diagnostic localization of seizure foci. In four patients, inhalation of 80 per cent nitrous oxide resulted in loss of consciousness without change in firing rates of temporal lobe neurons (n = 22). In all seven patients, thiopental (400 or 200 mg, iv) decreased limbic neuronal firing rates (n = 38) until the return of wakefulness. In only three of these patients, however, did the firing rates of the neurons (n = 19) decrease significantly (P less than .05). Thiopental suppression of unit activity was not related to systemic hypoxia. This study demonstrates that anesthetic induction with nitrous oxide-oxygen does not significantly affect the firing of neurons in various regions of the human limbic system, which may explain the incidence of patient awareness reported when nitrous oxide-oxygen is administered alone. Thiopental depresses the firing of limbic neurons, and this may account in part for the temporary confusion and amnesia often manifested by patients recovering from the effects of thiopental.


Recovery of transmissible gastroenteritis virus from chronically infected experimental pigs. Transmissible gastroenteritis (TGE) virus was reisolated from pulmonary and intestinal tissues from 6 of 9 chronically infected experimental pigs (principals) necropsied 30 to 104 days after inoculation. Tissue homogenates (lung and small intestine) from the principals were prepared and inoculated into 3- to 5-day-old gnotobiotic pigs. The virus reisolated from the tissue homogenates produced a milder disease on 1st passage and a more severe disease on 2nd passage. The chronically infected experimental pigs (principals) developed serum-neutralization titers to TGE of 1:30 to 1:525. There appeared to be no relationship between serum titers and reisolation of TGE virus from the 9 principals. The persistence of virus in lung or intestine to 104 days indicates the recovered (or carrier) pig may be considered the primary source of TGE virus infection.


Comparative characteristics of three cytomegaloviruses from rodents. One cytomegalovirus isolate from the vole (Microtus arvalis) and 2 cutomegalovirus strains from mice (Apodemus sylvatious and Mus musculus) were compared. The rates of inactivation of these 3 viruses were virtually identical after each of 3 treatments: Repeated cycles of freezing and thawing, ultrasonic vibration, and exposure to trypsin and chymotrypsin. The replication of the 3 viruses was similar in each of 3 types of mouse embryo fibroblast cells tested. A number of other characteristics of the vole isolate were the same as those of the mouse strains, including buoyant density (1.20 g/cu cm), enhanced plaquing efficiency in diethylaminoethyl-dextran, and induction of an abortive replication cycle in human cells. The 3 viruses were indistinguishable with regard to their antigenic characteristics, and electron microscopic examination revealed that the nucleocapsids and enveloped virions of the 3 viruses were indistinguishable.


Methylmercury: effect on oncogenic and nononcogenic viruses in mice. Mice fed methylmercury chloride at dosages of 1 or 10 ppm for 84 days had significantly higher mortality rates when inoculated with encephalomyocarditis virus (nononcogenic) than did nonmethylmercury-treated mice. However, methylmercury fed to mice which were inoculated with Rauscher leukemia virus (oncogenic) did not alter the course of neoplasia. These results demonstrate that prolonged exposure to subclinical concentrations of methylmercury increased susceptibility of a host to a nononcogenic, but not to an oncogenic, virus.


Effects of intramedullary injection of methiodal and lidocaine on spinal cords of dogs. A solution of methiodal sodium (20%) and lidocaine HCl (0.20%) was given by intramedullary injection into the lumbar spinal cords of 12 anesthetized dogs (group I). Two control groups of 12 dogs each were subjected to needle placement only or were given 5% dextrose. The results showed that both solutions given by intramedullary injection caused severe spinal cord malacia and cavitation in 2 group I dogs and in 1 group III dog.


Cell-to-cell attachments and associations in tumors induced by CELO virus or virus-transformed cells in hamsters. Cell-to-cell attachments or associations in expermentally induced sarcoma of chicken embryo lethal orphan virus (avian adenovirus) origin were studied in hamsters by electron microscopic examination. In many instances, the neoplastic cells seemed to be held together either by desmosome-like structures or an "interlocking" of their apposing plasma membranes. Less frequently, the cells were attached by button-like projections between the cell surfaces. Only rarely, interdigitation occurred between filopodial processes of cell surface of adjoining cells.


Immunoglobulins and anti-Marek's disease virus antibody synthesis in chickens after passive immunization with immunoglobulin Y anti-Marek's disease virus antibody. The effect of passive immunization with immunoglobulin Y (IgY) antibody against Marek's disease virus (MDV) was examined in MDV-susceptible chickens. The production of IgY, immunoglobulin M, and probably also immunoglobulin A was depressed in passively immunized chickens when compared with that in MDV-exposed chickens which had not been given IgY anti-MDV antibody. In passively immunized chickens, the synthesis of immunoglobulin M and IgY anti-MDV antibodies in response to MDV infection also was delayed as determined by agar gel precipitin and indirect fluorescence antibody tests.


Thermostability of duck hepatitis virus. The comparative thermostability of 4 duck hepatitis (DH) viruses were tested at various temperatures for different times. Titer of duckling-passaged, pathogenic DH virus decreased from 10(4.50) to 10(2.33) and 10(2.20) median infective doses (ID50/0.1 ml, respectively, in 2 tests; titer of chicken embryo-passaged, nonpathogenic, but embryo-lethal, DH virus decreased from 10(6.00) to 10(0.46) and from 10(6.62) to 10(0.63) ID50/0.1 ml, respectively; duck embryo fibroblast culture-passaged and duck embryo liver cell culture-passaged, chicken ebryo-infective, but nonlethal, DH viruses were completely inactivated or nearly so after being kept at 56 C for 30 minutes. Duckling-passaged DH virus was not detected on day 21, whereas 10(0.62) ID50 of chicken embryo-passaged DH virus per 0.1 ml remained on day 32 when being kept at 37 C. Titer of chicken embryo-passaged DH virus decreased from 10(7.00) to 10(1.16) ID50/0.1 ml after being kept at room at room temperature for 150 days, to 10(5.17) ID50/0.1 ml after being kept at 4 C for 70 weeks, to 10(6.17) ID50/0.1 ml after being kept at -20 C for 70 weeks, and to 10(6.38) ID50/0.1 ml after being kept at -60 C for 1 year.


[Influence of some substances on the titration of a poliovirus aqueous suspension (author's transl)]. Important changes of virus titer are observed when low concentration of mineral salts (NaCl, MgCl2, AlCl3) or detergents (Tween 80) are added to a poliovirus suspension in distilled water. Calf serum addition to these suspensions induces new variations of virus titer. The highest titre is obtained in isotonic medium with calf serum.


[Effect of sodium salicylate on the "in vitro" development of RNA viruses (author's transl)]. Sodium salicylate 10(-3) M is able to limit the number of plaques induced by RNA viruses on monkey kidney cell cultures (Cercopithecus aethiops and Macaccus rhesus). However, the inhibition rate changes with the virus type or even the strain used. Poliovirus 2, Coxsackie B3, echovirus and reovirus 1 were the most susceptible to the inhibitory effect of the drug. Latent infection caused by SV5 decreases the antiviral activity of salicylate. The stages of the poliovirus type 2 growth affected by sodium salicylate, were studied. The drug has no direct activity on the infectivity of the virus. It decreases adsorption and penetration. In spite of heavy virus concentration (10(-5,5) to 10(-7)) ID/ml) the eclipse phase is delayed about 3 hours. After 6 hours, viral maturation proceeds and reaches the same level as the controls, and virus quantities recovered are equivalent after 12 hours. Viral infectious RNA fails to induce plaques on salicylate treated cultures. The drug seems to act during the eclipse phase.


[Isolation of "Neisseria elongata" and "Moraxella urethralis" (author's transl)]. A strain of Neisseria elongata and a strain of Moraxella urethralis have been recently isolated from pathological material in the course of a systematic search for rodshaped oxidase positive and Gram negative micro-organisms. The morphological, cultural and biochemical characters of these fewly known strains of which pathogenicity is not clearly defined, are reported in the present paper together with some comments.


Fish health--some concepts, constraints, and comparisons. This has been an overview of fish health, a comparison of some aspects of fish husbandry with other animal husbandry, and comments concerning fish health research--especially where it is going. The 1972 disease survey identified current problems; it ranked the problems according to priority. More important, research effort has been redirected. Problems of highest priority are receiving the greatest attention; those of lesser priority are receiving the appropriately lesser attention. Just as veterinary and human medical research have become more mission-oriented, fish health research has also become much more of a problem-solving activity. There are fewer dollars; they must be used wisely and they must produce. Research in fish health is expected to yield usable information that will be of significant help in producing better fishes. If destined for the table, such fishes should convert feeds rapidly and efficiently, and they should not suffer losses from diseases. If intended for stocking, such fishes should be capable of thriving in the environment and of surviving to fulfill their destiny.


The mechanism of action of 3-deazauridine in tumor cells sensitive and resistant to arabinosylcytosine. Deazauridine inhibited growth of tumor cells in culture and in culture and in vivo; this agent was significantly more effective against L1210/AraC than against the parent sensitive line. Inhibition of growth of tumor cells in culture was prevented by uridine and cytidine and was partially alleviated by deoxycytidine, but not by deoxyuridine or thymidine. DeazaUR inhibited nucleic acid synthesis but not protein synthesis in tumor cells in culture; deoxycytidine alleviated inhibition of nucleic acid synthesis. The labeling of pyrimidine ribonucleotides by 6-14C-orotic acid was inhbited by deazaUR. DeazaUR treatment of tumor cells in culture resulted in increased uptake of cytidine-3H into RNA, whereas uridine-3H uptake into RNA was inhibited. Labelling of DNA by uridine-3H/ and cytidine-H was inhibited by deazaUR. Pools of CMP, CDP, and CTP decreased markedly during deazaUR treatment of L1210 cells in culture and in vivo. These observations in growing cells pointed to deazaUR inhibition of the synthesis of cytidylic acid. Deazauridine 5'-triphosphate was found to be an inhibitor of the synthesis of CTP from UTP catalyzed by enzyme preparations from L1210 cells. This observation is in agreement with those of McPartland et al.19 that deazaUTP inhibited CTP synthetase purified from calf liver. Deazauridine treatment of L1210 cells in culture stimulated the uptake of deoxycytidine-3H into DNA while inhibiting the uptake of 3H-labeled deoxyuridine, thymidine, deoxyadenosine, and deoxyguanosine. Intracellular pools of dCTP were decreased by deazauridine treatment in L1210 cells in culture and in vivo. Deazauridine 5'-diphosphate inhibited the enzymatic reduction of pyrimidine ribonucleoside 5'-diphosphates to the corresponding deoxyribonucleotides. These results are consistent with the view that deazauridine, after its uptake and intracellular phosphorylation, strongly inhibits the formation of CTP. This is considered to be the primary metabolic effect of the analog. A secondary effect appears to be an inhibition of dCTP formation.


Unique bactericidal action of metronidazole against Bacteroides fragilis and Clostridium perfringens. The comparative bactericidal activity of penicillin G, carbenicillin, clindamycin, and metronidazole against eight susceptible strains of Bacteroides fragilis and four strains of Clostridium perfringens was determined by performing colony counts anaerobically of cultures incubated in brucella broth. With the B. fragilis strains, there was a lag phase of growth of approximately 8 h, during which time metronidazole did not reduce the colony counts. However, within 4 h of the onset of exponential growth, metronidazole caused an abrupt decrease in counts to less than 100 colonies per ml in all strains tested. Moreover, in two strains in which the bactericidal rate was followed hourly, a 3- to 6-log decrease occurred over 1 h or less. In contrast, penicillin G and carbenicillin caused a gradual decline in colony counts from the start of approximately 1 log for each 8-h interval and were bactericidal for all strains tested. Clindamycin demonstrated the slowest bactericidal activity and for 25% of the strains was only bacteriostatic. With the C. perfringens strains, after a lag phase of 4 h, an abrupt decrease in colony counts also occurred with metronidazole, whereas penicillin and clindamycin again demonstrated more gradual killing effects. These studies showed a unique, time-related bactericidal action of metronidazole as compared with the other three antimicrobial agents.


Foreign body removal: a new role for the fiberoptic bronchoscope. Artificial and animal lung models initially were used to investigate the removal of foreign bodies from the tracheobronchial tree with the flexible fiberoptic bronchoscope. Different extraction instruments (claw, basket, forceps, and balloon catheter) were passed separately through the channel of the bronchofiberscope, and tested for usefulness prior to human application. The Fogarty balloon catheter served as a valuable aid in dislodging impacted objects so that the operator could then grasp them with the claw, basket or forceps. The wire claw recovered many of the metallic and organic objects, the wire basket was successful in retrieving only the bulky objects and the forceps (ACMI) was effective in capturing all of the metallic foreign bodies. These techniques, developed in our laboratory, are now being used to augment rigid bronchoscopy in the removal of foreign bodies from adults and older children. At the present time fiberoptic foreign body removal is not recommended for pediatric cases because of the small diameter of the trachea and glottis in infants and young children.


[Juvenile hormone in diapausing Pieris brassicae and mutations. Tetrahydrofolic acid and pterins incubated in chrysalids, provoking ontogenic and mutagenic genetic information alterations in Drosophila melanogaster]. Study of AMPc phosphodiesterase shows presence of JH in diapausing chrysalids and antogonistic action of FH and pterines. Study of farnesoldeshydrogenase and farnesal deshydrogenase in Dm shows that FH4 and pterines inhibite FDH, active ADH. Conclusion is JH in diapause chrysalides is active factor with FH4 provoking genesis of pigmentary mutation, cellular proliferation or growth deficiencies. Comparison with JH+FH4+ teromes incubated in Bar (Muller 5) mutants of Dm in place of diapausing chrysalids reproduce larval deficiences, mosaics and mutations observed in precedent experiments.


Inhibition of experimental deoxyribonucleic acid virus-induced encephalitis by 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate. 9-beta-d-Arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP) significantly controlled the development of encephalitis produced by deoxyribonucleic acid viruses in mice. In most experiments the activities of ara-HxMP and 9-beta-d-arabinofuranosyladenine (ara-A) were determined simultaneously. In the intracerebral (target organ) and intravenous therapy experiments, ara-HxMP had a pronounced advantage over ara-A since the water solubility of ara-HxMP enabled it to be used in much higher concentrations. In experiments where the two drugs were administered intraperitoneally or orally they exhibited similar activity. In several intraperitoneal therapy experiments ara-HxMP was tested alone, using various treatment schedules and dosages. In these experiments, efficacy was observed in groups that had treatments initiated as late as 72 h after virus inoculation.


[Proceedings: Role of endogenous and exogenous ACTH on aldosterone secretion (author's transl)]. The role of ACTH in the control of aldosterone secretion has been investigated in volunteers under a normal sodium diet. Endogenous ACTH suppression by dexamethasone (DXM) does not alter the plasma aldosterone (PA) response to 20 mg furosemide since identical PA increases are observed in control subjects and in subjects with DXM suppressed endogenous ACTH. The sodium depletion induced by furosemide during continuous ACTH infusion increases plasma renin activity but does not change PA.


Efficacy of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate in therapy of equine abortion virus-induced hepatitis in hamsters. Equine abortion virus (EAV)-induced hepatitis in hamsters presents an interesting animal model for the evaluation of drugs possessing anti-deoxyribonucleic acid virus activity. These experiments demonstrate that 9-beta-d-arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP), a new synthetic, water-soluble, antiviral agent, effectively controls this disease in hamsters with a therapeutic index of approximately 60. Ara-HxMP prevented hepatitis-associated deaths in hamsters, reduced the titer of EAV developing in hamsters, and inhibited the increase of serum glutamic pyruvic transaminase in EAV-infected hamsters.


[Effect of furosemide and ACTH on plasma renin, aldosterone and cortisol levels in normal man]. Plasma renin activity (PRA), aldosterone and cortisol's variations are studied in normal salt repleted voluntary men (120 mEq/24 h sodium) before and after furosemide infusion and/or constant infusion of ACTH (beta 1-24 corticotrophin). PRA is determined by angiotensin I radioimmunoassay, plasma aldosterone by specific radioimmunoassay and plasma cortisol by competitive transcortine binding radioassay. 1) PRA and plasma aldosterone increase clearly after acute sodium depletion secundary to furosemide infusion; plasma cortisol increases a little. PRA and aldosterone's variations are identical after endogenous ACTH suppression by dexamethazone administration before study. 2) PRA is not influenced by constant infusion (16 ng/kg/mn) after acute infusion (0.3 mg intravenously) of ACTH (beta 1-24); plasma aldosterone and plasma cortisol increase dramatically and remain constant along the experience. 3) If acute sodium depletion is realized 120 mn after ACTH infusion, PRA still raises; on the other hand plasma aldosterone remains constant. These results confirm that acute sodium depletion stimulates aldosterone secretion by the way of renin angiotensin system then ACTH acts directly on the adrenal cortex. Nevertheless the stimulative action of acute sodium depletion on aldosterone secretion is suppressed by previous acute ACTH stimulation.


Solid-phase radioimmunoassays for quantitative antibody determination of Clostridium perfringens type D epsilon toxin. Two reversed solid-phase radioimmunoassays were developed for quantitative determination of antibodies against Clostridium perfringens type D epsilon toxin. 125I-labeled prototoxin was used in the bromoacetylcellulose-bound antibody method and in the antibody-coated tube method. The antibody values which can be detected by the assays are in the range of 0.004 IU/ml of investigated serum. The methods allow the screening investigation of large groups of vaccinated sheep in a rapid and inexpensive way, and are very suitable for measuring small amounts of C. perfringens D epsilon antibodies with a small experimental error.


Convenient non-chromatographic assays for the microbial deconjugation and 7alpha-OH bioconversion of taurocholate. We described two convenient assay methods to estimate bile acid deconjugation and bile acid bioconversion at the 7alpha-OH position by individual microorganisms grown in media containing taurocholic acid. The methods are based on (i) a selective chemical assay for taurine conjugates previously described and (ii) the use of a cell-free preparation of 7alpha-hydroxysteroid dehydrogenase from Escherichia coli to directly quantify 7alpha-OH groups. These non-chromatographic approaches have been applied to the study of three model strains of intestinal organisms, E. coli, Bacteroides fragilis, and Clostridium perfringens, grown in standard media in the presence of purified tritiated taurocholate. Assay results were confirmed by thin-layer chromatography solvent systems designed to separate conjugated from unconjugated bile acid and unmodified cholic acid nucleus from 7alpha-OH bioconversion product(s) (primarily 3alpha, 12alpha dihydroxy, 7-keto-cholanoic acid). In addition, 7alpha-hydroxysteroid dehydrogenase activity was demonstrated in cell-free extracts of all three organisms. Of the three organisms, only C. perfringens was demonstrated to (i) deconjugate taurocholic acid, (ii) contain 3alpha-hydroxysteroid dehydrogenase activity, (iii) convert cholic acid into at least five labeled metabolites visible on thin-layer chromatography, and (iv) catalyze significant tritium exchange with water in the medium.


Studies on the survival and fate of enteroviruses in an experimental model of a municipal solid waste landfill and leachate. In laboratory scale municipal solid waste lysimeters containing simulated refuse, and seeded with either laboratory or field strains of poliovirus type 1 and echovirus type 7, viruses were not detected in the lysimeter leachate produced over a 4-month period. In addition, viruses were detected in the lysimeter refuse contents after termination of lysimeter operation. These results appeared to be due to virus retention in the lysimeter caused by virus adsorption and virus inactivation. Evidence for virus inactivation was provided by the results of experiments on virus inactivation in composite leachate samples. Evidence for virus adsorption was supported by the rapid adsorption of viruses to various municipal solid waste components in the presence of a salt similar in composition to the major inorganic salts of leachates.


[Direct reaction between complement system and cell nuclei (author's transl)]. A direct in vitro reaction between complement system and cell nuclei of human leucocytes and of cryostat sections of rat liver or kidney, has been demonstrated by an indirect immunofluorescence technique. The first step of this reaction involves a fixation of C1q to the nuclear DNA as shown by the peripheral distribution of the fluorescence and by the extinction of the fluorescence when the tissue-slices are pretreated by DNase but not by RNase or trypsin. This fixation gives rise to an activation of C1 which can be demonstrated by the capacity of the fixed C1 to induce a fixation of C4 of the same distribution. Although the sequential fixation experiments have not allowed to establish directly the fixation of the following components of the complement system (C2 and C3), the positive results obtained using whole fresh normal human serum as a source of complement and a fluorescent anti-human C3 serum clearly indicate that the activation of the classical pathway by whole cells DNA can go as far as the C3 step. All these results were obtained at physiological pH and molarity: this can suggest a physiopathological meaning for this reaction.


Enzymatic transformation of morphine by hydroxysteroid dehydrogenase from Pseudomonas testosteroni. Eznyme preparations from Pseudomonas testosteroni containing alpha- and beta- hydroxysteroid dehydrogenases catalyzed the oxidation of morphine and codeine by nicotinamide adenine dinucleotide. Morphine was converted in relatively low yield into 14-hydroxymorphinone probably via morphinone as an intermediate. Codeine was converted to codeinone and 14-hydroxycodeinone. Only the conversions at the 6-position were carred out by the hydroxysteroid dehydrogenase. Hydroxylation at the 14-position did occur spontaneously (or enzymatically with a contaminating enzyme) ater oxidation at the 6-position.


Milker's nodules. Pathogenesis, tissue culture, electron microscopy, and calf inoculation. We report the occurence of milker's nodules in nine patients. In man, the disease goes through maculopapular, target, acute weeping, nodular, papillo-matous, and regressive stages. Papular and papillomatous stages were noted following vaccination of a calf with material prepared from a human lesion. A viral agent was isolated in cultures of bovine kidney cells and human skin fibroblast cells. Cytoplasmic inclusions were frequently seen in the infected bovine kidney cells. Electron microscopy revealed viroplasm, partially encapsulated viroplasm, encapsulated viroplasm, and oval particles with spires around the outside.


Ulnar neuropathy after liquid nitrogen cryotherapy. Ulnar neuropathy after liquid nitrogen cryotherapy for verruca vulgaris (common wart) overlying the ulnar nerve at the elbow resulted in much disability from sensory and motor deficits.


Cytomegalovirus-mononucleosis in a newborn infant. A 3-week-old infant with haemophilia A developed fever and mononucleosis and was found to have cytomegalovirus, infection, possibly acquired by blood transfusion. At 6 months, while still excreting cytomgalovirus, he developed transient clinical jaundice with a hepatitis-like picture.


Epidermal neoplasms with epidermolysis bullosa dystrophica with the first report of carcinoma with the acquired type. Carcinoma, usually always squamous cell carcinoma, is one of the most serious complications in epidermolysis bullosa dystrophica. It can occur on the skin, mucous membranes, the esophagus and possibly the upper part of the bronchial tree. We are reporting on four new patients; one, the youngest to be so reported, one with a definite autosomal dominant inheritance and one with a chronic acquired dystrophica epidermolysis bullosa. Most cases have an autosomal recessive inheritance, but the disorder is probably more hetereogeneous in its inheritance than has been reported. Studies of the collagen indicate a disturbance, but present studies indicate the defect to be more a cellular defect in the fibroblast yet undetermined. The carcinomas, usually multiple, appear to arise on scarred tissue and to metastasize rapidly with death.


Studies on the role of C-type viruses in the development of epithelial tumors induced with DMBA. Epithelial tumors were induced using 0.5 per cent solution of DMBA in two strains of mice--one infected with leukoviruses (Swiss mice), and the other is free of these viruses (hairless mice). Tumors from 15 mice of each strain were examined light- and electron-microscopically. Depending on the period of administration of the carcinogen, benign growths of the type of papilloma or keratoacanthoma were obtained, or malignant tumors. In the tumors in Swiss mice electron microscopy revealed a distinct increase in the numbers of viruses in comparison with surrounding skin and intact skin of healthy mice of this strain. In spite of certain histologic differences between tumors produced in Swiss and hairless mice, the results argue against a role of leukoviruses in the pathogenesis of experimentally induced epithelial tumors in mice.


Desmosome-like structures in the cytoplasm of normal human keratinocyte. Desmosome-like structures in the cytoplasm which have so far been described in tumoral and acantholytic epidermal cells were observed on two occasions in morphologically normal basal and prickle cells. It seems that under specific conditions a normal epidermal cell can lose contact with the surrounding cell during cell division and forms intracytoplasmic desmosomes.


In vitro action of quartz on alveolar macrophage lipid peroxides. The in vitro effects of quartz particles on the lipid peroxide rate were measured on guinea pig pulmonary alveolar macrophages (PAMs). As controls, either PAMs alone or exposed to inert dust were used. The amount of lipid peroxide resulting after one-hour incubation was determined by means of the thiobarbituric acid test (TBA). The results showed that quartz induced a substantial increase of lipid peroxide in PAMs compared with both samples (dust-free or exposed to corundum). The influence of pretreatment of quartz by polyvinylpyridine-N-oxide (PVPNO) and by mineral water containing carbonate and chloride ions was also studied.


Adenyl cyclase.

Adenyl cyclase. Many hormones interact with their target cells by binding to receptors located on the external surface of the target cells' plasma membrane and subsequently stimulating the enzyme, adenyl cyclase, which is located within the plasma membrane. Stimulation of adenyl cyclase results in formation of cyclic AMP which is released from the membrane into the cell and acts within the cell to regulate a wide variety of cellular processes. In this review, the characteristics of hormone receptors and the relationship between receptor occupancy and adenyl cyclase stimulation are discussed. Our current understanding of the roles of hormones, substrate, magnesium, calcium, and guanine nucleotides as regulators of adenyl cyclase activity is summarized. Because of the central importance of adenyl cyclase and cyclic AMP as mediators of the cellular response to hormones, it is to be expected that many diseases may result from defects in this enzyme system. Indeed, several adenyl cyclase related diseases have been identified and the molecular bases for these diseases are discussed in this review.


Relationship of cell type and lymph node metastasis to survival after resection of bronchial carcinoma. In the completed adjuvant chemotherapy lung trials conducted by the Veterans Administration Surgical Group, the cell type was recorded in 2,341 of 2,349 curative resections; extent of lymph node involvement was known in all cases. Nodes were normal in 1,231 patients. Five- and ten-year survival computed by the life-table method was 33.7% and 20.4%, respectively. These rates were significantly greater than the 16.2% and 8.8% recorded in 1,118 patients whose nodes showed metastases. Among patients whose cell type was known, five-year survival in 484 with hilar node involvement was 17.4% and was not significantly different from 20.1% in 364 patients in whom only lobar nodes were involved. The survival was 8.9% in 268 patients with cancer in the mediastinal nodes; this was significantly worse than either of the aforementioned groups. A five-year survival of 26.8% in 1,482 patients with squamous cell carcinoma was greater than the 24.3% in 359 with adenocarcinoma and 22.4% in 500 with undifferentiated cell types, but the differences were not significant. Variations between these groups remained nonsignificant when nodes were normal and were of only borderline significance, at the 5% level, when they showed metastasis. When a curative resection has been accomplished, cell-type as classified in this study has little bearing on long-term survival, whereas the presence of node metastasis as well as its location is of the utmost importance.


Effects of phentolamine on dibutyryl cyclic AMP and norepinephrine in rats anesthetized with amobarbital. In vitro evidence demonstrated that norepinephrine (NE) increased endogenous levels of cyclic AMP in brain tissue. In vivo findings showed that in rats anesthetized with amobarbital, NE certrally administered prolonged narcosis whereas exogenous dibutyryl cyclic AMP shortened it. Phentolamine, an alpha adrenergic receptor inhibitor, administered centrally prolonged narcosis but did block all symptomatology accompanying its administration. Phentolamine added to dibutyryl cyclic AMP dose-relatedly antagonized the shortening of the duration of narcosis. Such ovservations suggest that whereas the inhibitory action of phentolamine affects NE at the alpha adrenergic receptor site, it antagonizes cyclic AMP at other sites as well.


In vivo pulmonary metabolism of bradykinin, angiotensin I and 5-hydroxtryptamine in the rat. Involvement of the pulmonary vasculature of the rat in the in vivo metabolism of bradykinin, angiotensin I and 5-hydroxytryptamine was studied by monitoring the systemic blood pressure response of the test animal during intravenous or intraarterial administration of these substances. Observation of essentially the same blood pressure response regardless of the route of injection indicated that neither agiotensins I or II nor 5-hydroxytryptamine was metabolized by the pulmonary vasculature, while bradykinin was inactivated to the extent of 95+% on one passage through the lung. In the rat the major portion of bradykinin inactivation and angiotensin conversion apparently occur at different places in the vascular tree and therefore could not be carried out by the same enzyme. Differential inhibition by 2-mercaptoethanol and the bradykinin potentiating peptide, Pyr-Lys-Trp-Ala-Pro, support this postulate. One rat was found which had no pulmonary kininase but could convert angiotensin I to angiotensin II. In addition, infusion of large doses of known inhibitors of lung converting enzyme had no effect on either angiotensin I conversion or bradykinin inactivation in this system. These results support the idea that the pulmonary vasculature is not a major site for conversion of angiotensin I in the rat.


Lack of steroidogenic response to cyclic AMP and ACTH in adrenal cells from rats bearing the MtTF4 tumor. Adrenal cell suspensions prepared from rats bearing the MtTF4 tumor failed to increase corticosterone production when exposed to adenosine 3', 5'-cyclic monophosphate (cyclic AMP) or ACTH, placing the defect in these adrenals beyond the ACTH receptor site. Adrenal cells from normal rats responded well to these stimuli. Adrenal cyclic AMP phosphodiesterase prepared from the tumor bearing rats appeared normal both with respect to its specific activity and inhibition profile with theophylline. Exposure of the MtTF4 adrenal cells to 1,2-3H-cholesterol in the presence of either cyclic AMP or ACTH did not result in an increase in radioactively labeled corticosterone, whereas increased label could be demonstrated in adrenal cells from normal rats similarly treated.


[Suitability of immune serums from different animal species for the preparation of conjugates against Aujeszky's disease virus]. A comparison was made of immune serum from rabbits, sheeps, pigs and cattle. Pure IgG was prepared by the Rivanol sulphate method and immune electrophoresis. Optimum protein quality, conjugation time under various conditions and using two preparations of fluorescein isothiocyanate were studied. Conjugate purified by DEAE-Sephadex A-50 and concentrated to 1% protein by ultrafiltration was freeze-dried and then tested for activity and the degree of non-specific fluorescence. Evaluation by yield of immuno-electrophoretically pure IgG, conjugation time, antibody content, degree of non-specific fluorescence and the intensity of specific fluorescence before and after dilution showed that pig serum was the best, followed by cattle and sheep serum; rabbit serum was the least suitable for conjugate preparation.


The immunological response of calves after submucosal application of a live vaccine against parainfluenza-3- and adenovirus. (Brief report). Using submucosal application of live attenuated vaccine against parainfluenza-3-virus and cattle adenovirus within the nasal opening, calves reacted with the formation of secretory (local) and serum antibodies of significantly higher titers than are received using subcutaneous application. The same vaccine induces interferon activity in the serum and nasal secretion after submucosal vaccination. Adenovirus antigen is a stronger interferon inducer than para-influenza-3-virus.


[Electron microscopy studies on proliferation of foot-and-mouth disease virus in cell cultures. I. Morphologic changes in cell nucleus]. The first morphological indication of FMD infection of a cell culture was in the nucleus. Components of nucleoli became segregated and were finally present only as remnants. It was not possible to distinguish different stages of segregation, as in the case of entero-virus infections, because of the rapidity of FMD virus proliferation. Following changes in nucleoli there was margination of chromatin. Particularly striking was an increase in interchromatin granules. Changes in the nuclear membrane seemed to facilitate the transfer of nuclear material to the cytoplasm. Strongly pronounced dilatation of the peri-nuclear cleft, like that seen in aphthae and other tissues, were rarely visible in infected cell cultures.


[Electron microscopy studies on the proliferation of foot-and-mouth disease virus in cell cultures. II. Changes in nucleic acid metabolism of the cell nucleus]. BHK cells were infected with FMD virus and treated with tritium-labelled thymidine and uridine for examination by autoradiography under the electron microscope. Labelling of the DNA, examined by autoradiography under the optical microscope, showed inhibition of 3H-thymidine incorporation. For demonstrating RNA labelling of nuclei, some cells were treated with actinomycin D and others were left untreated. Under the lectron microscope there was no evidence of increased 3H-uridine incorporation in the untreated cells after virus infection, but actinomycin treatment increased RNA labelling in extranucleolar parts of the nucleus, evidently RNA synthesis independent of DNA. There was evidence of some synthesis of virus-specific RNA in the nuclei. The extent of virus-specific RNA synthesis in the cytoplasm was less extensive than in the nucleus.


[Electron microscopy studies on the proliferation of foot-and-mouth disease virus in cell cultures. III. Morphogenesis in cytoplasm]. The previous parts have been concerned with the participation of the cell nucleus in the formation of the RNA of FMD virus. However, the actual morphogenesis of the virus takes place in cytoplasm. In BHK cells, changes attributable to virus infection were visible by the second hour, with the formation of threads and large polysome complexes near the nucleus. Viral particles soon appeared between these structures. There were no pronounced foci of viroplasma, and it seemed that they were not necessary. Simultaneously new membranes formed in the cell. Clumps of viral particles were next visible in the cxtoplasma. The clumps became enveloped and were transported in this way to the periphery of the cell. Elsewhere there was uptake of particles in autophagic vacuoles, an expression of cellular defensive processes. In ultra-thin sections the virions measured 21-25 nm. Within vacuoles the inner part of the virus, the nucleoid, showed greater contrast than the periphery, the capsid. At first there were only slight changes in mitochondria. Liberation of virus by cell rupture occurred only after severe damage to the cell, particularly the lysosome membranes.


[Enzyme activity in cell cultures infected with herpesvirus suis]. The activity of succinate dehydrogenase (SDH) and lactage dehydrogenase (LDH) was studied in chick-embryo fibroblast cultures after inoculation of the virulent strain "A2" and the avirulent strain "MK" of herpesvirus suum. Strain "A2" reduced SDH activity, and so did strain MK, but here the decrease of enzyme activity was slower, and it did not become evident until the 24th hour. LDH activity fluctuated after "A2" infection but was generally increased, while there was no change in LDH activity, compared with uninfected control cells, after "MK" infection. When interaction of cell and virus took place in the presence of 5-iodo-2-desoxyuridine (IUDR), strain "A2" produced little change in the enzymes, but "MK" infection was accompanied by a definite fall in SDH and a slight increase in LDH. The presence of IUDR inhibited the proliferation of the virulent strain but had no apparent effect on proliferation of the attenuated strain "MK". Investigation of the enzyme activity of cells infected with Aujeszky's disease virus has revealed new biological properties of the virus, which might serve to distinguish between different strains of the virus.


[The mutagenic effect of methyl methanesulfonate (MMS) in vitro and in the host-mediated assay (author's transl)]. The concentration- and time-dependent genetic activity of methyl methanesulfonate (MMS) was investigated in vitro and in the host-mediated assay using four different indicator organisms. Dose/effect curves achieved with the different indicator organisms are similar.


[Histochemical study of the enzymes of glycogen metabolism in the human endometrium during the normal menstrual cycle]. The content of glycogen in the human endometrium is dependet on the activity of enzymes involved in processes of synthesis and dissociation of glicogen: glycogen-synthetase, phosphorilase and glycogen-6-phosphatase. The activation of "D" form of glycogensynthetase dependent on glucose-6-phosphate and the increase of the glycoogen quantity in the endometrium glands epithelium is observed in the period of growing gestagenic function of the ovaries. At the end of the secretory phase there occurs activation of the glycogen dissociation enzme-phosphorilase which goes in parallel with abrupt inhibition of the glycogensynthetase activity and disappearance or glycogen from the gland epithelium. The inhibition of glycogen synthetase is conditioned by a decreased level of intracellular glucose-6-phosphate which appears due to activation of glucose-6-phosphate in this period.


[Effect of physical work on the aging process in certain skeletal bones of the extremities]. The long-term investigation of the influence of physical exercise upon the structure of human skeleton revealed certain peculiar features in the process of developmental reconstruction of joints of the upper (humeral joint, hand joints) and lower (knee joint, the joints of the foot) extremities resulting from the occupation of the persons under study. Roentgen-anatomical studies performed in 433 industrial and 430 office workers established the fact of retardation and deceleration of ageing of the extremities bone system in representatives of physical labour as compared with office workers. So the significance of spectal physical exercises compensating the progressing with age hypodynamia in persons of non-physical labour gets special importance.


[Types of the secretory cells in the pancreatic islands of some vertebrates]. Three types of secretory cells -- B, A and D were found in the pancreatic islets of the frog, turtle, crucian, rat and cat by the method of electron microscopy. The fine structure of secretory granules is a basis for identification of the endocrine cell types. The structure of the insuline granules is changed more markedly in the evolution process while the granules of A and D cells have a similar structure in the vertebrates under study.


[Electrophysiology in neuropathy caused by vincristine]. Ten patients treated with vincristine were submitted for electrophysiological examination. It was investigated the number of motor units within the thenar muscle following a technique described previously (Sica et al. - 1974); motor and sensitive conduction velocities as well as motor distal latencies in the median nerve were studied following conventional techniques. The behaviour of the evoked muscle potential with repetitive supramaximal stimulation over the median nerve was also investigated. The findings were compared with control groups. The estimated number of motor units was disminished in eight of ten patients and the average number was significantly different from the control group (control 318 +/- 71 UM; patients 174 +/- 84 UM; P less than 0.001). The potential amplitudes in most of the surviving units were reduced, others remaining within the normal range. This makes apparent that the peripherical nervous system fails to compensate adequately and, furthermore, a loss of individual muscle fibres occurs within some individual units. The conduction velocities of the fastest conducting motor nerve fibres were reduced and motor distal latencies prolongued (Table 1). Maximal impulse conduction velocities were measured in sensory fibres. In 5 of 7 subjets investigated the values laied just beyond the lower limit of the normal range. The amplitude of the sensory orthodromic evoked potential in the median nerve at the wrist was disminished almost in the whole group. The decremental muscle response to repetitive nerve stimulation, can be interpreted as the result of the damage at the neural apparatus at the motor end plate; it was observed in 57% of the patients. In summary, evidences have been registered showing that the nervous supply to the muscle is affected in patients treated with vincristine; the motor unit behaviour under this conditions is discussed.


Acute ocular infection by type 2 herpes simplex virus in adults. Acute ocular infections in two adults were caused by type 2 herpes simplex virus (HSV) ("genital herpesvirus"). One patient had an acute blepharoconjunctivitis, the other an acute keratoconjunctivitis. Genital infections had preceded the eye infections, and type 2 HSV was isolated from the eyes of both patients and from the genital lesions of one patient. This strongly suggests transmission of type 2 HSV from the genital site to the eye.


Oat cell carcinoma of the bronchus and the carcinoid syndrome. A man with high urinary levels of 5-hydroxyindole acetic acid had an oat cell carcinoma of the bronchus. The patient had symptoms of the carcinoid syndrome and at autopsy was found to have evidence of carcinoid heart disease. This report supports the hypothesis that bronchial carcinoids and oat cell carcinomas are derived from argentaffin (Kulchitsky)-type cells of the lung.


Endocrine-type granules in cells of glomus tumor of the stomach. The ultrastructure of a gastric glomus tumor was studied. The tumor cells were found to possess structural features similar to those of smooth muscle cells. In addition, hitherto undescribed granules of endocrine type and cilia were identified.


Primary adenocarcinoma of the appendix. A clinicopathological study of 11 cases. Of eleven cases of adenocarcinoma of the appendix that were studied, five were examples of mucinous cystadenocarcinoma and four were examples of colonic-type adenocarcinoma. Two lesions were very distinctive, with thick, cord-like transformation of the appendix. The term linitis plastica carcinoma is proposed to describe this rare variant of appendiceal carcinoma. Justification for the separation of linitis plastica carcinoma from the other two types is based on morphological appearance and on outcome. Both our linitis plastica patients died of metastases within six months of surgery, whereas, in the other two groups, death was directly related to spread of the carcinoma in only two of nine patients.


The effect of natural and artificial breeding using bulls infected with, or semen contaminated with, infectious bovine rhinotracheitis virus. Ten cows and heifers (Group B) were inoculated into the uterus at oestrus with semen followed by IBR virus for the first insemination and semen alone if a second insemination was necessary. All animals developed infectious pustular vulvo-vaginitis (IPV), and 2 cows conceived to the first and 2 to the second insemination (pregnancy rate of 40 percent requiring 4.5 services per conception). This group was compared with 10 control animals (Group A) which were treated similarly but received tissue culture fluid instead of virus at the first insemination. Group A had a pregnancy rate of 90 percent requiring 1.7 services per conception. Natural mating of 4 bulls with preputial infections due to infectious bovine rhinotracheitis (IBR) virus with 9 susceptible cows and heifers (group D), resulted in the production of lesions of IPV. The IPV infection did not affect their fertility (pregnancy rate of 89 percent requiring 1.4 services per conception) when it was compared to a similar group of females (group C) mated to the same bulls prior to infection with IBR virus (pregnancy rate of 100 percent requiring 1.2 services per conception). The 6 animals in Group B that were not pregnant and returned to oestrus 3 times were found on slaughter to have endometritis, salpingitis and vaginitis. A high incidence, 5 out of 18 (28 percent), of shortened oestrous cycles (less than 18 days) was a feature of the breeding pattern of this group. The undesirable consequences of distributing semen contaminated with IBR virus from artificial insemination centres are apparent.


Studies on the effects of infectious bovine rhinotracheitis virus on reproduction in heifers. Natural venereal infection of heifers with IBR virus resulted in vulvovaginal lesions in 9 of 12 heifers at 3 weeks after introducttion to bulls, and virus was isolated from 5 of the 9 affected animals. The infection was not associated with any effect on conception. Experimental nasal and conjunctival infection of 18 heifers pregnant for 3, 5 or 7 months with a genital strain of IBR virus caused mild rhinitis or conjunctivitis in all inoculated animals and virus was recovered from 14 animals at 8 days after inoculation. No effects on pregnancy were recorded.


Maintenance of DNA and repair of Apurinic sites. Escherichia coli cells contain an enzyme which hydrolyzes a phosphodiester bond near each apurinic site in double-stranded DNA. This endonuclease is specific for apurinic sites; it has no effect on normal DNA, and its action on alkylated DNA is restricted to apurinic sites. In vitro incubation with the endonuclease for apurinic sites, DNA polymerase I, and ligase permits repair of DNA containing apurinic sites. The endonuclease for apurinic sites might thus play a role in cell survival after a treatment with alkylating agents; as DNA spontaneously loses purines, the enzyme might also play a role in the maintance of a normal DNA in every cell. Indeed, an endonuclease for apurinic sites has been found not only in bacteria but also in animal and plant cells; it is very active in thermophilic bacteria.


Influence of repair on the specificity of ultraviolet-induced reversion of an ochre alleles of the structural gene for iso-1-cytochrome c. The specific action of UV on the reversion of the ochre allele cycl-9, in which 21 out of 23 revertants have been shown to arise from A-T-to-G.C transitions at position one in the UAA codon, was found to depend on the function of the RAD6 gene, since cycl-9 reversion occurred by a variety of single-base-pair substitutions in a strain carrying the rad6-1 allele.


Repair of DNA strand breaks in progeric fibroblasts and aging human diploid cells. The rate of rejoining of DNA strand breaks induced by 10 krad of gamma-irradiation has been studied in normal human diploid skin fibroblasts and in skin fibroblasts from six patients with symptoms of progeria. Although slightly more rapid in very early passage, the repair rate in normal cells was similar throughout most of their life span in vitro. The appearance of cells with reduced repair capacity was evident as the cultures became senescent. The progeric fibroblasts varied greatly in their response to irradiation. The rate of repair was greatly reduced in two strains, whereas in two others extensive DNA degradation was consistently observed in unirradiated cells. Degradation was apparently related to the radiation received from the incorporated radiolabel. Normal repair was seen in progeric fibroblasts transformed by SV40 virus.


Radio-enzymic assay of oxo steroids by their reduction with the tritiated form of reduced nicotinamide--adenine dinucleotide. A method of analysis is proposed based on the enzyme-catalysed transfer of tritium from [3H]NADH to suitable substrates. Its practicability is demonstrated on the examples of oestrone and progesterone with the respective use of the 3 beta, 17 beta- and 3 alpha, 20 beta-hydroxysteroid oxidoreductase. Specificity is tested by application to the analysis of the plasma of pregnant women and measurement of the 3H/14C ratios on purification of the enzymic reduction products.


Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines. Ethylation and isopropylation of guanine in alkaline solution, or of adenine in formic acid, by alkyl methanesulphonates gave the following products: 1-, N2-, 3-, O6-, 7- and 9-alkylguanines; 1-, 3-, 7- and 9-alkyladenines. The products were identified from their characteristic u.v-absorption spectra, by comparison with either known ethyladenines or with the corresponding known methyladenines, and were also characterized by mass spectrometry. Their chromatographic properties on paper, t.l.c. and various columns were determined. DNA was alkylated in neutral solution with 14C-labelled alkyl methanesulphonates and the ratios of the alkylpurines formed were obtained, and compared for alkylation by methyl, ethyl and isopropyl methanesulphonates and by N-methyl-N-nitrosourea. The extents of alkylation at O-6 of guanine relative to those at N-7 of guanine varied with the reactivity of the methylating agents according to the predictions of Swain & Scott (1953) relating nucleophilicity of the groups alkylated with the substrate constants of the alkylating agents. The relative extents of alkylation at N-3 of adenine did not follow this correlation.


The contribution of atrial stretch receptors to salt and water homeostasis in the human. Studies carried out in both the human and experimental animals provide reasonably strong evidence that receptors contained within the atria are involved in the control of body water. When atrial pressure is increased (and the atria distended) atrial receptor discharge is increased leading to an increase in urine flow and, depending upon the experimental condition, a less consistent increase in sodium excretion. At least two mechanisms appear to contribute to the renal response; inhibition of the secretion of antidiuretic hormone and inhibition of renal nerve discharge. None of the factors presently known to alter sodium excretion have been shown to account completely for the increase in sodium excretion. The failure of patients with chronically distended atria to experience a chronic diuresis appears to be partly the result of a resetting of atrial receptor sensitivity. Recent evidence suggests that the sensitivity of atrial volume receptors has a species variation.


Molecular mechanisms in alkylation mutagenesis. Induced reversion of bacteriophage T4rII AP72 by ethyl methanesulphonate in relation to extent and mode of ethylation of purines in bacteriophage deoxyribonucleic acid. Survival and reversion to T4r+ of bacteriophage T4rII AP72 after treatment with ethyl methanesulphonate at 37 degrees or 45 degrees C were studied in relation to the extent and mode of alkylation of purines in DNA of ethylated bacteriophage. A single-burst technique was used for reversion assay. Survival was lower at 45 degrees C than at 37 degrees C at a given extent of ethylation of bacteriophage DNA, confirming that events subsequent to ethylation, probably depurinations, are the main cause of decreased survival. Reversion was positively correlated (approximately linearly except at low extents at 37 degrees C) with ethylation of bacteriophage DNA, showing that ethylation itself causes mutation. Following the concept that reversion results from G-C leads to A-T transition at a single site (Krieg, 1963a,b) and the suggestion that O6-alkylation of guanine generates the miscoding base (Loveless, 1969), it was calculated that about one-third of induced O6-ethylguanines at this site would miscode to induce mutation.


A method for investigating the effect of temperature on the 695 nm band of insoluble cytochrome c. A method is described for computer analysis of simple spectrophotometric changes in particulate systems, and this has been applied to the bleaching of the 695 nm band of insoluble ferricytochrome c by temperature. The results show that insolubilization has no effect on the standard enthalpy change but lowers the value for the standard entropy change. This effect appears to be independent of the concentration of the gel matrix to which the cytochrome c is bound, but dependent on the ionic strength of the surrounding solution.


A double-beam rapid-scanning stopped-flow spectrophotometer. A double-beam rapid-wavelength-scanning stopped-flow spectrophotometer system based on the Norcon model 501 spectrometer was construced, which enables u.v.-or visible absorbance spectra to be recorded at the rate of 800/s after the rapid mixing (within 3ms) of two reactant solutions. Each spectrum spans about 200nm in 1ms. It is possible to record difference spectra during reactions with half-lives less than 10ms involving absorbance changes of less than 0.1 absorbance unit. Analogue circuitry is used to produce spectra of absorbance against wavelength. Up to 32 such spectra can be recorded at pre-selected times during a reaction and stored in an 8Kx8-bit-word hard-wired data-capture system to be subsequently displaned individually or simultaneously. Time-courses at different wavelengths can also be displayed. By averaging up to 216 spectra it is possible to record spectra under conditions of low signal-to-noise ratios...


A sensitive radiochemical assay for angiotensin-converting enzyme (kinase II). [[125I]Tyr8]Bradykinin is degraded by angiotensin-converting enzyme to [125I]Tyr-Arg. The reaction product can be separated completely and recovered nearly quantitatively from unchanged substrate by cation-exchange chromatography. Thus it is possible to use [[125I]Tyr8]bradykinin at high specific radioactivity (about 400Ci/mmol) to measure the small quantities of angiotensin-converting enzyme encountered in small-scale cultures of pulmonary endothelial cells.


The isolation of collagen-associated proteoglycan from bovine nasal cartilage and its preferential interaction with alpha2 chains of type I collagen. A collagen complex from bovine nasal cartilage was prepared by extraction of the tissue with 3M-MgCl2 solutions, by using two different procedures. When it was compared with calf skin acid-soluble tropocollagen by polyacrylamide-gel electrophoresis, the 3M-MgCl2-soluble cartilage collagen in the complex appeared to be predominantly type I in nature, consisting of both alpha1 and alpha2 chains. The soluble cartilage collagens were digested with purified bacterial collagenase, and the soluble digests were fractionated on Sepharose 4B. Hydroxyproline-free proteoglycan was isolated in the excluded volume of the column eluate, and this was found to be an aggregate which could be dissociated to link proteins and proteoglycan subunit by equilibrium-density-gradient centrifugation in a CsCl-4M-guanidinium chloride gradient. Interaction with calf skin-soluble tropocollagen was studied by CM-cellulose chromatography. The link-protein system did not interact, but proteoglycan from the bottom of the gradient did interact. In addition, when proteoglycan subunit was allowed to interact with collagen, there was a preferential binding to the alpha2 and beta12 components, and this effect was also observed with the proteoglycan material obtained from the collagenase digests of 3M-MgCl2-soluble cartilage collagen complexes. However, specificity for alpha2 and beta12 chains was not exhibited by chondroitin sulphate glycosaminoglycan, and it is therefore concluded that preference for alpha2 and beta12 chains is a function of the intact proteoglycan structure.


Serum lipids in young female survivors of myocardial infarction. Fasting serum lipids and lipoprotein patterns were studied in 44 female survivors of acute myocardial infarction under the age of 45 years, and in 84 matched control subjects. Type II hyperlipoproteinaemia was present in 41 per cent of the myocardial infarction patients and in none of the controls. There was, however, no difference in the prevalence of the type IV abnormality, which was present in 7 per cent of the myocardial infarction patients and 8 per cent of the control subjects. Mean cholesterol and triglyceride levels were both significantly higher in the women who had survived myocardial infarction than in the controls; the difference in triglyceride was attributable to the type IIb abnormality which occurred in 11 per cent of these patients. It is suggested that ovarian hormones may protect premenopausal women from type IV hyperlipoproteinaemia and its possible atherogenic sequelae.


Wrist arthropathy in calcium pyrophosphate dihydrate deposition disease. Calcium pyrophosphate dihydrate deposition disease is associated with chondrocalcinosis and a characteristic radiographic abnormality. In the wrist this abnormality consists of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration of the carpal bones. These changes sometimes occur in the absence of chondrocalcinosis. Two investigate the significance of this occurrence, 18 patients with the radiographic abnormality of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration were examined. Six had neither local wrist nor distant chondrocalcinosis. Five of the latter had wrist arthrocentesis and 4 had calcium pyrophosphate dihydrate crystals. Calcium pyrophosphate dihydrate deposition disease can occur in the absence of chondrocalcinosis and the diagnosis is strongly suggested by a characteristic radiographic picture.


Connective tissue activation. IX. Modification by pharmacologic agents. Alpha- and beta-adrenergic blocking agents and imipramine inhibit the increased hyaluronate synthesis that may be induced in human synovial cultures by connective tissue activating peptide (CTAP). Considerations of drug concentration requirements, actions of analogues, and time studies all indicate that the adrenergic blockers do not act in this circumstance as conventional blockers of alpha or beta receptor sites. It is suggested that the membrane-stabilizing properties of these agents may be the important determinant for their limited "antiactivation" effect. Ethacrynic acid, a potent and more complete inhibitor of connective tissue activation, appears to act via a different mechanism.


Corticotrophin after corticosteroids in children with asthma and growth retardation. A study of the growth patterns of 19 children with chronic asthma, whose growth had become retarded while they were receiving regular treatment with prednisolone, showed that this trend was reversed after the substitution of corticotrophin.


ACTH content of pituitary glands of arteriosclerotic breeder vs. non-arteriosclerotic virgin rats. Acid extracts were made of the pituitary glands of non-arteriosclerotic male and female virgin rats and arteriosclerotic, male and female breeder rats. The ACTH content of these pituitary glands was determined by measuring the amount of corticosterone produced by the adrenal glands of healthy but hypophysectomized rats when challenged by the various ACTH acid extracts. The pituitary glands of the arteriosclerotic animals were significantly heavier than non-arteriosclerotic rats and contained decreased amounts of ACTH commensurate with the severity of the pituitary donor's arteriosclerosis. Similarly, arteriosclerotic donors had heavier adrenal glands but contained considerably less corticosterone than non-arteriosclerotic virgin rats. Male breeder rats developed microscopic aortic lesions involving intimal mesenchymal cell and ground substance alterations whereas the female breeder lesions progressed from intimal ground substance and connective tissue changes to medial elastolytic degeneration and eventual medial cartilaginous and osseous metaplasia. Histopathologic examination of the pituitary and adrenal glands demonstrated hyperplasia of basophil and other cytologic elements of the pituitary gland including colloid-filled cysts and lipid depletion of the zona glomerulosa as well as hemorrhage and thrombosis of the adrenal cortex of the arteriosclerotic breeder rats. The hypothesis is made that repeated breeding leads to abnormal hypothalamic regulation of pituitary gland synthesis and release of ACTH, which, in turn, contributes to abnormal adrenal glandular function conditioning the aortic wall toward abnormal changes in mesenchymal cell activity and metabolism of connective tissue ground substance.


The effects of iron deficiency on rat liver enzymes. The effect of iron deficiency on a number or iron containing enzymes in rat liver has been examined. In addition, 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase have been assayed. Of the mitochondrial electron transport reactions only succinate-cytochrome C reductase activity was decreased in iron deficient animals. Microsomal reductase enzymes associated with the NADPH-oxidase system were also markedly decreased although cytochrome P450 concentrations were unaffected. Both 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase were reduced in young iron deficient rats but the former had returned to control levels at the age of 14 weeks.


In vivo microscopic observations of the pathogenesis of acute mouse viral hepatitis. In vivo microscopy of the liver was undertaken to determine the extent of involvement of the hepatic microvascular system in mice infected with viral hepatitis (MHV-3). It was found that the major effects of the disease were produced in localized areas where parenchyma, sinusoids and blood were obliterated. However, immediately peripheral to these lesions blood flow and vessels were unaffected other than by localized hypertrophy of Küpffer cells. While each lesion produced a sinusoidal block to blood flow, portal hypertension did not occur even in the presence of extensive focal and confluent necrosis.


Effects of dextrothyroxine on hyperlipidemia and experimental atherosclerosis in beagle dogs. Beagle dogs, 24 +/- 6 months old, fed a thiouracil-free semi-synthetic diet containing hydrogenated coconut oil and cholesterol (SS diet) for 12 months, developed marked hyperlipidemia and severe atherosclerosis. SS diet produced a marked elevation of serum cholesterol, triglyceride, phospholipid, and beta-lipoprotein and severe atherosclerosis in large and small arteries. Intimal fatty lesions were always present in the abdominal aorta and many of its branches. Large and small coronary arteries showed similar lesions. The degree of atherosclerosis was directly related to circulating lipid levels. Dextrothyroxine, at dose levels of 0.1 (equivalent to normal human dose) and 0.5 mg/kg body weight, produced a significant dose related lowering of serum lipids and was associated with a markedly decreased severity of aortic and coronary artery lesions. Untreated control dogs that were maintained on purina dog meal developed neither hyperlipidemia nor atherosclerosis.