Follicular growth in the rat: a reevaluation of the roles of FSH and LH.

The growth of preovulatory ovarian follicles involves hormonally induced proliferation and differentiation of theca cells and granulosa cells resulting ultimately in an increased ability of follicles to produce estradiol and to respond to the pituitary gonadotropins. The increased ability of follicles to produce estradiol appears to depend on an increased ability of theca cells to produce androgen as well as an increased ability of granulosa cells to aromatize androgens to estradiol. Estradiol in turn, appears to be required for FSH or FSH and LH to stimulate the appearance of functional receptors for LH in granulosa cells. Thus, the intrafollicular hormone estradiol enhances the response of granulosa cells to the gonadotropin. Therefore production of estradiol appears to determine which follicles will gain the mechanisms, including LH receptor, necessary for ovulation and luteinization. Since LH can act to increase its own receptor in the presence of estradiol and low amounts of FSH, it is possible that LH plays a predominant role in the final stages of preovulatory follicular growth both to promote estradiol production stimulation of theca cell androgen production as well as by facilitating an increase in its receptor by acting directly on granulosa cells.


Steroidal modulation of steroid secretion in vitro: an experimental approach to intra-follicular regulatory mechanisms.

Studies in vitro and in vivo indicate that steroid secretion by granulosa cells of the developing follicle is modulated in part by steroid hormones themselves. Androgens stimulate progestin synthesis in vitro by granulosa cells of all developmental stages independently of their role as an estrogen precursor; generally, the action of estradiol results in suppression of progesterone secretion. The nature of the relationship between steroid secretion by granulosa cells and the physiological processes of follicular development or atresia remains to be investigated in greater detail. The cellular mechanism(s) of steroidal modulation of steroid secretion is unknown but apparently does not involve changes in the number of granulosa cell LH receptors per se.


The influence of sodium diethyldithiocarbamate (DDC) on serum lipids in the rabbit. Acta Physiol. Pol., 1979, 30 (2): 327--329. The level of cholesterol, phospholipids and triglycerides in blood serum of rabbits treated with sodium diethyldithiocarbamate (DDC) was determined. DDC administration in daily doses of 100, 200 and 400 mg/kg, during 4 weeks, resulted in an increase of triglyceride and phospholipid levels changes were found in the serum cholesterol concentration.


Mammalian oocyte maturation: model systems and their physiological relevance.

Maturation of mammalian oocytes is studied mainly in two dissimilar in vitro models: isolated oocytes maturing spontaneously in culture, and hormone-induced maturation of follicle-enclosed oocytes. In this discussion the following aspects of maturation in vitro in the two aforementioned models were compared: timing of germinal vesicle breakdown (GVB), involvement of cyclic nucleotides, protein synthesis and divalent cations. A third approach to the study of oocyte maturation in vitro, namely oocyte co-culture with follicular constituents was adopted in order to test the role of follicular components in the control of the resumption of meiosis. Such studies demonstrated an inhibitory action of granulosa cells, granulosa cell-conditioned medium and of follicular fluid upon the spontaneous maturation of the co-cultured oocytes. Furthermore, addition of LH to co-cultures of oocytes and granulosa cells induced resumption of meiosis. Although oocytes obtained by spontaneous or by hormone-induced maturation cannot be distinguished morphologically, the developmental potential of oocytes matured spontaneously has been questioned, at least in some species. Furthermore, analysis of the kinetics of spontaneous maturation suggests that oocytes dislodged from their follicles escape physiologic mechanisms ensuring meiotic arrest and skip some of the regulatory steps involved in the normal hormonal triggering of maturation. Oocyte co-culture with granulosa cells offers a close approximation to physiological conditions in that meiotic maturation depends on hormonal stimulation, while the system permits the application of separate treatments to the oocyte-cumulus complex and granulosa cells. As in any in vitro system, critical evaluation is required to discriminate between artifacts inherent in the model and physiological processes.


LH-induced desensitization of the adenylyl cyclase system in ovarian follicles.

Studies on the gonadotrophin-responsive adenylyl cyclase (AC) system of rabbit and porcine ovarian follicles reveal that hCG or LH-induced desensitization of the AC system can be divided into two phases: an initial, LH-specific phase and a second phase which is not specific for LH. The first phase occurs within the first hour after LH-hCG-receptor interaction, is agonist specific, and is not mediated by protein synthetic events or by cAMP. In view of our previous demonstration of the critical dependence of the LH-induced desensitizing process in cell-free membrane preparations of porcine follicles upon Mg2+ and ATP, we investigated the role of a phosphorylation reaction in the first phase of the AC desensitizing process. Porcine follicular membranes rich in LH-sensitive AC activity were found to contain the molecular requirements necessary for a phosphorylation reaction: namely, cAMP-dependent and cAMP-independent protein kinases as well as phosphoprotein phosphatases. The following lines of indirect evidence indicated that reversal or resensitization of the desenzitized AC system to LH was mediated by a dephosphorylation reaction. Activators of endogenous phosphoprotein phosphatases--Mn2+ and dithiothreitol--promoted a specific resensitization of the follicular AC system to LH. Likewise, a partially purified phosphoprotein phosphatase also resensitized the desensitized, LH unresponsive AC to LH, and boiling of the phosphatase prevented its effect. LH-induced desensitization of the AC system, on the other hand, did not appear to be mediated by a cAMP-dependent protein kinase, as evidenced both by the inability of beef heart protein to promote desensitization of AC and by the inability of an inhibitor of cAMP-dependent protein kinase to prevent LH-induced densensitization. The second phase of desensitization, which occurs after the first hour following hCG-LH-receptor interaction, is characterized by a loss of responsiveness to FSH as well as to LH and can be promoted by dibutryl cAMP (in the absence of LH). These results provide new evidence on the characteristics and molecular mechanism of LH-induced densensitization of the follicular AC system. These results indicate that the level of phosphorylation of membrane-associated components may, in part, regulate the activity of the AC system during this first phase of homologous desensitization.


Mechanisms of PGF2 alpha action in functional luteolysis.

The luteolytic action of PGF2 alpha appears to be due to loss of gonadotropin support of corpus luteum function. This "chemical hypophysectomy" produced by PGF2 alpha in the rat has several components: 1. A rapid block of gonadotropin uptake in vivo by an unexplained mechanism. 2. A rapid and direct block of adenylate cyclase activation by the LH receptor complex in isolated luteal cells. 3. An eventual loss of LH receptor binding activity produced by inhibition of prolactin action.


hCG-induced loss of LH-hCG receptor and desensitization of adenylate cyclase.

hCG-induced loss of hCG (LH) receptors and desensitization of adenylate cyclase in the pseudopregnant rat ovary have been studied. At various time intervals after hCG treatment, the decrease in hCG-stimulated adenylate cyclase activity was closely related to the reduction in available hCG receptors. The hCG-induced desensitization of adenylate cyclase and a fall in hCG binding activity were also dose-dependent and directly correlated. There were no changes in the affinity of receptors binding and in the apparent Km for adenylate cyclase activation. These findings indicate that the loss of hCG receptors is associated with desensitization of adenylate cyclase following the hCG injection.


Evidence of a greater activity of LH/HCH binding inhibitor present in aqueous extracts from old compared to young porcine corpus luteum.

As porcine corpus luteum tissue ages there is an increase in amount of LH/hCG vinding inhibitor. This inhibitor is absent in non-luteal ovarian tissue, heart and lung.


Suppression of ovarian function by LHRH and its analogues in pregnant rats.

1. LHRH and its analogues, when infused continuously at the doses that inhibit ovum implantation, reduced serum concentration of progesterone in pregnant rats. The progesterone concentration fell between Days 3 and 4 of pregnancy in rats treated with LHRH and Analogue I (Des-Gly10-LHRH-ethylamide), but fell between Days 4 and 5 in rats treated with Analogue II [Des-Gly10-(D-Ala6)-LHRH-ethylamide]. 2. Ovarian LH/hCG receptor levels were markedly reduced in rats treated with LHRH and its analogues in the first week of pregnancy. 3. Continuous infusion of LH to pregnant rats did not reduce the serum concentration of progesterone even with the highest dose that inhibited implantation. Interruption of pregnancy by LH appears to be due to excessive secretion of estrogen as indicated by uterine swellings, presence of large follicles in the ovaries, and absence of free blastocysts in the uterine lumen. Thus, the antifertility effects of LHRH and its analogues were not reproduced by LH administration.


Clinical applications in the area of contraceptive development.

The ovary is not necessarily a prime locus for regulating reproductive function but in the process of understanding various aspects of ovarian function, opportunities have arisen to test both the role of specific functions in the reproductive process and the possible use of a given function as a site for contraceptive regulation. Better understanding of corpus luteum physiology from receptor site-gonadotropin interaction to natural luteolytic processes still hold promise for contraceptive development.


Hypothermia-induced potentiation of histamine H2-receptor-mediated relaxation and cyclic AMP increase in the isolated mesenteric artery of the rabbit.

On helically cut strips of the rabbit's mesenteric artery, a temperature decrease from 42 degrees C to 25 degrees C reduced the contractile responses to histamine. Metiamide shifted the dose-response curve of the histamine-induced contraction towards higher values at 25 degrees C, but not at 42 degrees C. Furthermore, on arterial strips contracted by phenylephrine histamine evoked a dose-dependent relaxation at 25 degrees C whereas at 42 degrees C only slight relaxing responses to histamine occurred. Metiamide was capable of preventing the relaxation induced by histamine in a competitive manner. At 25 degrees C the relaxation as produced by histamine was accompanied by increases in cyclic AMP which occurred prior to the relaxing effects. Metiamide abolished the cyclic AMP increase in response to histamine. At 42 degrees C histamine was unable to elevate the cyclic AMP content. Thus, it is concluded that a cyclic AMP-mediated relaxation due to stimulation of H2-receptors counteracts the histamine-induced contraction and reduces the contractile responses to histamine at low temperatures. In addition, clear-cut evidence exists from the present study that also on artery smooth muscle the H2-receptor-mediated responses are closely associated to cyclic AMP.


Skeletal effects of megavoltage irradiation in survivors of Wilms' tumor.

The skeletal effects of megavoltage irradiation (60Co) in 25 long term survivors of Wilms' tumor are described. In general, the changes seen with megavoltage irradiation are as frequent but not as severe as those previously reported after orthovoltage irradiation. Vertebral body changes generally occur within 5 years after irradiation. Scoliosis and/or kyphosis do not usually develop until after five years postirradiation. Kyphotic curves tend to progress after the adolescent growth spurt while scoliotic curves do not. Other bony and nonosseous changes are detailed.


Radiology of epidemic adenovirus 21 infection of the lower respiratory tract in infants and young children.

The radiologic features of 18 children admitted to Princess Mary Hospital, Auckland, New Zealand, in the winter and spring of 1977 with adenovirus 21 infection are reported. Attention is drawn to the severity of the disease in the respiratory tract, manifest radiologically as widespread patchy or confluent pulmonary opacification, extensive bronchial wall thickening, or peribronchial linear opacities. No hilar adenopathy was present. Prominent residual bronchopulmonary abnormalities were present in 13 of 15 patients 6--12 months after epidemic. High kilovoltage chester radiography or bronchography demonstrated bronchiectasis in five patients. These findings emphasize the role of adenovirus as a cause of chronic pulmonary disease and bronchiectasis in children.


Size and skeletal maturation of the hand in children with hypothyroidism and hypopituitarism.

Hypothyroidism affects linear growth less than it affects skeletal maturation, while hypopituitarism linear growth is more severely affected. By determining the mean age for the length of the second metacarpal and dividing by the skeletal age, a ratio R was obtained in 15 hypothyroid children and in 33 with hypopituitarism. R was more than 1 in most hypothyroids and less than 1 in most children with hypopituitarism. Thus, a distinction between these two entities can be made simply from a hand radiograph and appropriate reference sources for determining second metacarpal length age and skeletal age.


Two dimensional echocardiographic quantification of infarct size alteration by pharmacologic agents.

In 27 closed chest dogs left ventricular wall motion abnormalities assessed quantitatively with two dimensional echocardiography were used as a measure of myocardial infarct size, and the change in extent of segmental wall motion abnormalities due to drug intervention early after infarction was evaluated. The extent of wall motion abnormalities was measured with echocardiography before and at 20 and 40 minutes and 5 1/2 hours after coronary occlusion. Three subgroups of dogs received, respectively, an infusion of nitroglycerin, phenylephrine or saline solution. Infarct size was measured with technetium pyrophosphate scintigraphy of the excised left ventricle. The infarct size correlated well with the extent of wall motion abnormalities before death. Wall motion was initially similar among the three groups but was significantly improved after treatment with nitroglycerin (P less than 0.025), remained stable with continued saline infusion and worsened significantly (P less than 0.05) after treatment with phenylephrine. Two dimensional echocardiography can be used to quantify experimental canine myocardial infarction and assess the effect of nitroglycerin.


Epicardial ischemia as delineated with epicardial S-T segment mapping andnicotinamide adenine dinucleotide (NADH) fluorescence photography.

In isolated rabbit hearts with an experimental coronary arterial occlusion, epicardial ischemia was identified by reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique that detects areas of myocardial anoxia. Epicardial S-T segment mapping was performed to evaluate the S-T segment changes across an ischemic border defined by NADH fluorescence. After S-T segment mapping and perfusion with a fluorescein dye, serial selections of the hearts revealed that the ischemic area was transmural and and the border was nearly perpendicular to the epicardial surface. As the epicardial ischemic border was approached, S-T segment elevation was first detected 3.3 mm outside the ischemic border, and increased over a transition zone 7 mm wide. S-T segment negativity was not detected immediately outside the ischemic border. It is concluded from these studies that S-T segment changes give relatively imprecise definition of an ischemic border, and that S-T segment changes across an ischemic border are not consistent with those predicted by solid angle analysis.


Immunocytochemical evidence for anti-LHRH and anti-ACTH activity in the "F" antiserum.

An antiserum which has previously been thought to be specific for LHRH-like immunoreactive material was shown to contain two populations of antibodies, one demonstrating anti-LHRH activity and the other anti-ACTH(1-24) activity. In rat and mouse, ACTH(1-24)-like immunoreactive substance is present in perikarya within the basal hypothalamus and in fibers in arcuate, periventricular and dorsomedial nuclei. LHRH-like immunoreactivity is present in fibers within the median eminence and arcuate nucleus, in a few fibers running along the ventral border of the hypothalamus, and in a small number of cell bodies within the medial basal hypothalamus.


Height, weight, and head circumference in survivors of marasmus and kwashiorkor.

The physical growth of 44 survivors of marasmus and 43 survivors of kwashiorker 7 1/2 years after their hospitalization and cure from malnutrition has been evaluated. The collected data on height, weight, and head circumference of these 87 previously malnourished children have been compared with data on height, weight, and head circumference of 559 children of the same age and sex from the same environment who have never been malnourished. The statistical analysis of the data indicate the following conclusions. 1) The survivors of marasmus are shorter and lighter and have a smaller head circumference than controls. The observed difference is statistically significant. 2) The survivors of kwashiorkor have the same physical stature as controls. 3) The survivors of marasmus are shorter and lighter and have a smaller head circumference than survivors of kwashiorkor. 4) The survivors of marasmus who were hospitalized for treatment of malnutrition when younger than 1 year have the same physical stature as the survivors of marasmus who were hospitalized for treatment of malnutrition when older than 1 year.


[Action of repeated doses of a beta-adrenergic in the response of plasma cyclic AMP in asthmatic patients].

The present work studies the behaviour of plasma cAMP after repeated doses of a beta mimetic currently used as a broncodilator in asthmatics. A group of patients repeatedly treated with Phenoterol showed increased cAMP values, particularly evident when compared with those obtained throughout the day. It is notable that this increase does not continue with treatment, but levels off and even shows some tendency to diminish. After the final dose of beta mimetic there is an abrupt fall of cAMP to initial (pre-treatment) values. It is suggested that the increase in nucleotide values is not maintained after repeated doses of beta-stimulants because asthmatics show a diminished response as a result of exhaustion or "tolerance" to the response. It is probable that, as in the case of some hormones, the receptors in the effector organs are exhausted.


Sexual precocity with hypothalamic hypopituitarism.

Two girls, one with septo-optic dysplasia and the other with posttraumatic brain damage, had the unusual combination of human growth hormone, thyrotropin, adrenocorticotrophic hormone, and vasopressin deficiencies that were associated with sexual precocity in one patient and early sexual maturation in the second patient, and of adult follicle-stimulating hormone and luteinizing hormone concentrations. At autopsy, the first patient had optic nerve aplasia, a normal pituitary gland, and some disorganization of myelinated fibers in the hypothalamus. The second patient had a normal thyrotropin and prolactin response to thyrotropin-releasing hormone, plus hyperphagia, deranged thirst mechanism, and temperature instability. These findings suggest that the lesion may be a defective hypothalamic regulation of pituitary hormone secretion. Congenital or traumatic hypothalamic-pituitary lesions may not affect all releasing factors or trophic hormones in a similar fashion.


Coxsackievirus B epidemic at a boys' camp.

An epidemic of coxsackievirus B2 infections occured at a boys summer camp. The resulting illness was characterized by malaise, headache, muscle pain, and high fever that persisted for four to six days. The boy in the index case arrived at the camp the first day of the season. The attack rate was 89% among campers and 47% among counselors. The spread of infections appeared to be on a person-to-person basis and in a disorderly fashion. Unusual features of the epidemic included the high attack rate, restriction of infection to the camp residents, and evidence of prolonged pharyngeal viral shedding. Conditions at camps are ripe for similar epidemic and the potential problem is greater than is generally realized.


Computerized tomography in infantile encephalitis.

Although computerized tomographic (CT) findings are well recognized in numerous neurologic diseases of children, CT scan abnormalities of encephalitis have only been associated with herpes simplex infection. We describe two infants, one with coxsackievirus B2 meningoencephalitis and one with clinical encephalitis, whose CT scans were similarly abnormal during the acute phase of their illness. In both infants, recovery of both neurologic and developmental deficits was accompanied by resolution of the abnormalities of the initial CT scan. Speculation is offered as to the role of the CT scan in the assistance of the physician who must evaluate both the diagnosis and prognosis of infants who have a clinical picture of encephalitis.


Greig cephalopolysyndactyly syndrome.

Based on the family presented and five others previously described, it can be concluded that the Grieg cephalopolysyndactyly syndrome is a fully penetrant autosomal dominant disease consisting of four variably expressed malformations: postaxial polydactyly (type B), preaxial polydactyly, syndactyly, and minor craniofacial abnormalities. This entity can be differentiated from other craniofacial-digital syndromes because of the absence of mental retardation, craniosynostosis, and brachydactyly.


Influenza A virus associated with acute encephalopathy.

During the period of February 1972 until February 1976, we documented six cases of influenza A-associated acute encephalopathy. The illnesses occurred during periods of influenza A activity in our community. The encephalopathy was invariably preceded by an upper respiratory tract infection, and, thereafter, patients soon became confused, vomited, and showed noticeable restlessness. Patients then followed either of two courses, some becoming comatose within 24 hours and others improving rapidly within three days or less. None of these patients exhibited the hepatic and biochemical abnormalities associated with Reye's syndrome. All patients survived but some had sequelae. The syndrome of influenza-associated acute encephalopathy deserves wider recognition.


Demonstration of specific antibodies to a coxsackie-like virus in patients of a hepatitis outbreak.

Lynchburg fecal virus (LFV), originally isolated from the stool of an infectious hepatitis patient, was passaged 15 times in WI-38 cells and partially characterized. Its properties are as follows: RNA virus; 27 nm in diameter, picornavirus-like morphology; inactivated at 56 C for 60 minutes; resistant to treatment with hydrochloric acid (pH 3.0), chloroform (33%), and diethyl ether (20%). Neutralization studies indicated that LFV is antigenically related to coxsackievirus A-24 but not to prototype hepatitis A virus (HAV). The simultaneous occurrence of infections with LFV and with HAV was indicated by the results of enzyme immunoassay (EIA) of the sera of patients of the Lynchburg outbreak. Absence of anti-LFV in patient sera was accompanied by an absence of anti-HAV and, conversely, an increased titer in anti-LFV was accompanied by an increased titer in anti-HAV. Each antibody type was shown to be elicited independently indicating simultaneous infections with LFV and HAV. The contribution, if any, of LFV to disease in the outbreak remains unknown.


Association of Herpes simplex virus (HSV) with cervical cancer by lymphocyte reactivity with HSV-1 and HSV-2 antigens.

Twenty-six women with invasive cervical cancer were examined for lymphocyte responsiveness to phytohemagglutinin (PHA) herpes simplex virus (HSV). Blood specimens were obtained from each patient before radiation therapy and separated into subpopulations by Ficoll-Hypaque centrifugation. Lymphocytes were cultured in RPMI-1640 containing autologous plasma and exposed to PHA, HSV-1, HSV-2, and control antigens. The results compared with those of women having negative Papanicolaou smears and matched to the cancer patients by age, race, and socioeconomic class revealed significant differences in blastogenic response (3H-thymidine) to HSV-2 antigens. Results from groups with known HSV-1 and HSV-2 infections indicated that differences were associated with the cancer patients having a higher frequency of HSV-2 infection. Results generally agreed with the findings of previous studies in which serologic test procedures were used.


Infant blood pressure and heart rate: relation to ethnic group (black or white), nutrition and electrolyte intake.

Blood pressure (BP) and heart rate were measured during non-rapid-eye-movement sleep in 392 full-term newborns and in 318 of these infants at age six months. Two-day records of food intake were collected at age six months for 150 infants. Black babies did not differ substantially in BP from white babies either at birth or at six months. The earliest BP tracking was from age six to 15 months (systolic (SBP): r = .29, p less than .001; diastolic:r = .45, p less than .001). No relationship was found between BP at six months and breast- or bottle-feeding, infant weight or weight change, or nutrient intake. The relationship between parental BP, on the one hand, and infant electrolyte intake and BP on the other, suggested that electrolyte intake was related to BP in the six-month-old infant, and that the relationship was different in white babies than in black babies. Among 56 white infants whose mother's mean BP was above the median for this population, infant sodium intake correlated with infant SBP (r = .31, p less than .009). Among 32 black infants, regardless of parents' BP, sodium intake was negatively correlated with SBP (r = -.36, p less than .021).


Tumorous phosphaturic osteomalacia. Report of a case associated with multiple hemangiomas of bone.

A case of osteomalacia associated with hypophosphatemia, decreased tubular reabsorption of phosphorus, hyperphosphaturia and renal glycosuria with associated bone pain and myopathy is presented. The patient was found to have multiple osteolytic lesions of bone which, on biopsy, proved to be sclerosing hemangiomas of bone. Treatment with oral phosphate and vitamin D effected a diminution in his symptoms of bone pain and muscular weakness. The literature on hypophosphatemic phosphaturic osteomalacia associated with mesenchymal tumors is reviewed. It has been suggested that certain mesenchymal tumors elaborate a yet to be identified humoral substance which decreased synthesis of 1 alpha, 25-dihydroxycholecalciferol causing decreased tubular reabsorption of phosphorus, hyperphosphaturia, hypophosphatemic osteomalacia and hypophosphatemic myopathy.


Silicosis due to intentional inhalation of abrasive scouring powder. Case report with long-term survival and vasculitic sequelae.

Silicosis due to inhalation of abrasive scouring powder is now an unusual event. We report a nonindustrial case of acute silicosis due to intentional inhalation of commercial, silica-containing scouring powder. This case is unique in that the patient had a 20 year survival (after onset of symptoms) with typical roentgenographic and histopathologic changes of silicosis, and evidence of immune complex disease in extrapulmonary tissues.


Increased platelet aggregation and decreased high-density lipoprotein cholesterol in women on oral contraceptives.

In vivo platelet function, serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and serum triglycerides (TG) were determined in 26 women starting oral contraceptives (OCA). Studies were run prior to, and after one and two months of therapy. Platelet aggregation time decreased by 50 percent or more in eight of the 26 women from a pre-experimental mean value of 387 +/- 136 seconds. TC did not vary but after the women were on medication for two months, HDL decreased from 56 +/- 14.4 mg/dl to 52 +/- 12.3 mg/dl (p less than 0.05). There was a progressive increase in TG under treatment, 74 +/- 23.3 mg/dl on the pre-experimental measurement to 93 +/- 31.0 mg/dl after two months of therapy (p less than 0.005). Women planning to use OCA might best be advised to have aggregation and serum lipid studies done before and early in usage.


Bilateral Paget's disease of the nipple: case report.

Paget's disease of the breast accounts for 1% to 4.1% of all cancers; however, bilateral Paget's disease is extremely rare. A case of bilateral Paget's disease is presented and treatment is described.


Study of secretory component in patients with metastatic breast cancer.

A radioimmunoassay was developed for secretory component, a glandular epithelial cell product secreted as an accessory protein with dimeric immunoglobulins A and M. Forty-four normal women between the ages of 40 and 70 had plasma concentrations of secretory component of 7.195 microgram/ml +/- 3.590 (+/-2 SD). Of the patients with metastic breast cancer of epithelial origin, 34 (91.9%) had plasma concentrations greater than 8.990 microgram/ml; 29 (78.1%) had plasma concentrations greater than 10.785 microgram/ml; 10 (27%) had concentrations greater than 15.000 microgram/ml; and 3 (8.1%) had concentrations greater than 22.710 microgram/ml. Serial plasma concentrations (averaging 3.48 per patient) of 35 (94.6%) of these patients reflected the clinical course of the disease. All patients had some combination of surgery, radiation therapy, and chemotherapy. No direct correlation was noted between the type of therapy and concentration of secretory component. However, plasma secretory component served as a marker in the systemic circulation of a change in the status of the metastatic breast cancer. The impact of this research may lie in its incorporation into clinical management.


Comparative pathology of silicate pneumoconiosis.

A simple pneumoconiosis with lamellar birefringent crystals was observed in animals dying in the San Diego Zoo. We studied 100 autopsies from 11 mammalian and eight avian species. In mammals, mild pulmonary lesions comprised crystal-laden macrophages in alveoli and lymphatics. Interstitial fibrosis was present in 20% of cases. There were no nodules. In birds, dust retention produced large granulomas around tertiary bronchi without fibrosis. Mineralogic analysis using scanning and transmission electron microscopy showed most of the crystals to be silicates. Ninety percent were complex silicates, with aluminum-potassium silicates comprising 70% of the analyzed particles. Electron and x-ray diffraction showed the silicates to be muscovite mica and its hydrothermal degradation product, ie, illite clay. This mica was also present on filtration membranes of atmospheric air samples obtained from the San Diego Zoo. The amount of dust retention was related to the animal's age, anatomic or ecologic variances, and length of stay in the San Diego Zoo. Its semidesert atmosphere is rich in silicates, which are inhaled and deposited in the lungs. Similar mica-induced lesions are found in humans living in this region or the Southwest of the USA. This simple pneumoconiosis is likely to be widespread in human populations living in desert or semidesert climates.


Endocrine regulation of thymic biosynthetic polyamine decarboxylases in adult rat.

The activities of ornithine and S-adenosyl-L-methionine decarboxylase were assayed in the thymuses of adult rats killed at 7-day intervals up to 6 wk after either pinealectomy or sham pinealectomy. The absence of the pineal gland markedly influenced the ornithine decarboxylase activity in the thymus, in which the level of the enzyme was decreased permanently by the 4th wk after the operation (P less than 0.05). The time course of the changes in S-adenosyl-L-methionine decarboxylase activity in the thymus during the entire period investigated was also significantly (P less than 0.05) modified by pinealectomy but did not show any stable trend. Adrenalectomy significantly raised (P less than 0.001) for ornithine decarboxylase; P less than 0.01 for S-adenosyl-L-methionine decarboxylase) the basal levels of the thymic biosynthetic polyamine decarboxylases. A pharmacological dose of corticosterone or cortisol produced a rapid and significant decrease in ornithine and S-adenosyl-L-methionine decarboxylase activities (P less than 0.02) in the thymus, whereas the injection of either D-aldosterone or ACTH was ineffective. Therefore, the thymic biosynthetic polyamine decarboxylases that in this organ are known to be located only in the lymphocytes appear to be regulated in opposing ways by the pineal gland and by the adrenal cortex.


Renal metabolism of N6,O2'-dibutyryl adenosine 3',5'-monophosphate.

Metabolism of dibutyryl cyclic AMP was studied by including the 3H- or C-labeled nucleotide (0.1 mM, 5 mumol) in the recirculating perfusate of the isolated rat kidney. Kidneys were perfused with nucleotide for 60 min. Dibutyryl cyclic AMP was almost completely cleared from the perfusate, about one-quarter as urinary excretion principally by probenecid-sensitive secretion and about one-half as metabolism beyond 3'-phosphate bond cleavage. The principal metabolite, N6-monobutyryl adenosine, accounted for one-third of added dibutyryl cyclic AMP. The remaining metabolites were ATP, ADP AMP, and N6-monobutyryl AMP. Dibutyryl cyclic AMP (0.1 or 1.0 mM) elevated renal ATP but did not alter uricogenesis. Both dibutyryl cyclic AMP and cyclic AMP at 0.2 mM produced similar activation and subcellular redistribution of renal protein kinase. N6-monobutyryl adenosine, unlike adenosine, had no effect on the renal activity of adenylate cyclase, low Km cyclic AMP phosphodiesterase, and protein kinase. Dibutyryl cyclic AMP is like exogenous cyclic AMP in that it penetrates the rat kidney, activates protein kinase, and is metabolized to ATP (R. Coulson, J. Biol. Chem. 251: 4958-4967, 1976), but is unlike cyclic AMP in its extent of secretion and metabolism to ATP and urate and in its formation of the unique metabolites N6-monobutyryl AMP and N6-monobutyryl adenosine.


Influence of hypothalamic and ambient temperatures on sleep in kangaroo rats.

Unanesthetized, unrestrained kangaroo rats (Dipodomys) were studied to examine the changes in the frequency and duration of sleep states caused by long-term manipulations of hypothalamic temperature (Thy) at a thermoneutral (30 degrees C) and a low (20 degrees C) ambient temperature (Ta). A cold stimulus present in either the hypothalamus or the skin decreased both the total sleep time (TST) and the ratio of paradoxical sleep (PS) to TST. At a low Ta, TST, but not the PS-to-TST ratio, was increased by raising Thy, indicating that a cold peripheral stimulus could differentially inhibit PS. At a thermoneutral Ta, cooling Thy decreased both TST and the PS/TST. Changes in the amount of PS were due largely to changes in the frequency, but not the duration, of individual episodes of PS, suggesting that the transition to PS is partially dependent on the thermoregulatory conditions existing during slow-wave sleep (SWS). These results are consistent with the recent findings that the thermoregulatory system is functional during SWS but is inhibited or inactivated during PS.


Receptor affinity and biological potency of thyroid hormones in thyrotropic cells.

The nuclear receptor affinity for L-triiodothyronine (L-T3), L-thyroxine (L-T4), L-triiodothyroacetic acid (triac), and D-triiodothyronine (D-T3) was compared to the potency of these thyroid hormone analogues in regulating thyrotropin (TSH) production and the number of membrane receptors for thyrotropin-releasing hormone (TRH) in mouse thyrotropic tumor cells in culture. L-T3 and triac were equally potent and D-T3 was one-sixth to one-fifth as potent in binding to the receptor and in regulating TSH production and TRH receptor number. L-T4 was the least potent analogue in each instance, but its relative receptor-binding affinity, measured after 3 h, was significantly less than its somewhat variable relative biological potency, measured after 48 h. The cells were shown to monodeiodinate L-[125I]T4 to L-[125I]T3 in a time-dependent manner, and the enhanced biological potency of L-T4 was ascribed to its conversion to L-T3. Thyroid hormones appear to regulate TSH production and the number of receptors for TRH in thyrotropic cells in culture through interaction with a nuclear receptor.


Synthesis of taurocholate by rat fetal liver in organ culture: effects of cortisol in vitro.

Taurocholate production by fetal hepatic organ cultures was measured by radioimmunoassay. Taurocholate production was maximal on day 1 of in vitro incubation, but was demonstrable in organ cultures maintained for periods up to 15 days. Explants obtained from fetuses of 18 gestational days of age produced only 82 pmol taurocholate per milligram dry weight of tissue during the first 24 h of incubation. Explants obtained from fetuses 21 gestational days of age produced 1,043 pmol taurocholate per milligram dry weight. The presence of cortisol (2.0 X 10(-6) M) in the incubation medium increased synthesis of taurocholate by rat fetal liver in which total taurocholate rose 50-fold above control after 120 h of incubation. In increasing concentrations from 2.0 X 10(-9) M to 2.0 X 10(-7) M, cortisol produced an incremental rise in taurocholate. However, additional increases in cortisol dose failed to provide further stimulation, and taurocholate production was inhibited by cortisol concentrations of 2.0 X 10(-5) M. The results provide further validation for the technique of fetal hepatic organ culture. They demonstrate that taurocholate synthesis is increasing rapidly during the final stages of gestation and show that cortisol augments taurocholate synthesis in a dose-response pattern.


Determination of Na-K-ATPase activity in single segments of the mammalian nephron.

A micromethod for the determination of Na-K-ATPase in discrete segments of nephrons from rabbit, rat, and mouse kidneys is described. To facilitate tubule microdissection, the kidneys were perfused with collagenase after it had been verified that collagenase had no effect on ATPase activity. Individual tubule segments were dissected under stereomicroscopic observation, exposed to a hypotonic environment followed by rapid freezing, and incubated in 1 microliter assay medium. Enzyme activity was determined by direct measurement of labeled inorganic phosphate release by the hydrolysis of [gamma-32P]ATP and was expressed as a function of tubule length. This method is technically simple enough to permit simultaneous measurement of the enzyme in large numbers of tubules and sufficiently sensitive to determine its activity in each region of the nephron. Correlation of Na-K-ATPase activity in single tubules with functional measurements obtained in the corresponding segment of the nephron with the perfused tubule or micropuncture techniques should help define the role of this enzyme in tubular ion transport.


Na-K-ATPase activity along the rabbit, rat, and mouse nephron.

Na-K-ATPase activity along the rabbit, rat, and mouse nephron was determined with a micromethod that measures directly labeled phosphate released by the hydrolysis of [gamma-32P]ATP. Na-K-ATPase activity was highest in the rat, intermediate in the mouse, and lowest in the rabbit nephron. With the exception of rabbit cortical thick ascending limb, the enzyme profile was similar in the three species: Na-K-ATPase activity per millimeter tubule length was highest in the distal convoluted tubule and thick ascending limb of Henle's loop, intermediate in the proximal convoluted tubule, and lowest in the pars recta and collecting tubule. The enzyme was present in the thin limbs of Henle's loop, but its activity was very low and measurements were close to the sensitivity limit of the method. Both the absolute activity and the fraction of the total enzyme represented by Na-K-ATPase were severalfold higher than in kidney homogenates. Finally, the Na-K-ATPase activity measured in certain segments of the rat and rabbit nephron in this study seems sufficient to account in theory for the active component of the net sodium transport found in the corresponding region of the nephron with either in vivo or in vitro single tubule microperfusion techniques.


Hormonal regulation of active chloride transport in the dogfish rectal gland.

Active transport of chloride is modulated by cyclic AMP in the rectal gland of Squalus acanthias. Vasoactive intestinal peptide (VIP) specifically activates the production of cyclic AMP by the gland and stimulates the secretion of chloride. Somatostatin inhibits VIP-induced secretion but has no effect alone. Both these peptides are present in the dogfish shark and may play an important role in electrolyte homeostasis.


Electroconvulsive therapy for iatrogenic hypothalamic-hypopituitarism (CRF-ACTH type).

A 41-year-old man with hypothalamic hypopituitarism (CRF-ACTH type) that persisted for 2 years after discontinuation of exogenous dexamethasone was treated with bilateral ECT for severe chronic depression. The depression improved only evanescently after 17 ECT sessions but the hypothalamic-pituitary suppression cleared completely and permanently, based on responses to four metyrapone stress tests in a 2-year follow-up period. ECT may be an effective treatment for persistent hypothalamic-pituitary suppression, even in the absence of a psychiatric disorder.


Experimental amebiasis. IV. Amebal viruses and the virulence of Entamoeba histolytica.

We have attempted to determine whether amebal viruses are capable of viral conversion of the virulence of Entamoeba histolytical. Amebae of little or no virulence for the newborn hamster liver were infected with viruses obtained from four amebal strains of different virulence. Cultures of surviving amebae were increased in virulence by viruses from amebae of high, moderate, or low virulence, but decreased in virulence by the virus of the second most pathogenic amebal strain. Sequential infection with two viruses did not produce consistent cumulative effects on virulence. The changes in virulence noted are considered to be the unpredictable result of either selection pressures exerted by the lytic virus infection or possibly viral alterations of the amebae.


Immunoperoxidase staining for detection of Colorado tick fever virus, and a study of congenital infection in the mouse.

Indirect immunoperoxidase (IP) staining was evaluated for sensitivity and specificity in detecting Colorado tick fever (CTF) virus antigen in infected cell cultures and infected mouse tissues, and then was applied to a study of congenital CTF infection in mice. The sensitivity of IP staining was comparable to that of immunofluorescence staining in detecting CTF antigen in infected cell cultures. Endogenous peroxidase activity of mouse tissues caused nonspecific reactivity in the IP system, but this could be abolished by treatment with sodium azide and hydrogen peroxide without destroying CTF antigen. Offspring of mice infected with CTF virus during the 2nd week of pregnancy showed a highly significant increase in the incidence of stillbirths and neonatal deaths as compared with offspring of uninfected controls. CTF antigen or virus was demonstrable in only a low proportion (7%) of embryos, ill newborns or stillborns examined, but a high proportion of mice examined at a time when maternal antibody would be lost (6 and 12 weeks) showed CTF antibody, indicating a higher incidence of infection. IP staining showed potential for use in studies of viral pathogenesis in the mouse model.


Dimethyl sulfoxide enhancement of phlebotomus fever virus plaque formation.

Dimethyl sulfoxide (DMSO)incorporated into an agar overlay containing DEAE-dextran enhanced plaque formation in Vero cells by Naples sandfly fever virus passaged in mouse brain or Vero cell cultures. No plaques were visible when DMSO was used without the DEAE-dextran, some plaques were rarely visible (less than 0.5mm) when DEAE-dextran was used without the DMSO, and up to 10-fold more plaques were clearly visible (0.5-1.5 mm) when both chemicals were used. The combined enhancing effect of DMSO and DEAE-dextran was also observed with mouse brain passaged, but not Vero passaged Sicilian sandfly fever virus. Other Phlebotomus group viruses produced a bit plaques (3-5 mm) and did not require DMSO for plaque formation, although an increase in plaque clarity was obtained with DMSO for some of them. Plaque reduction neutralization tests were assayed successfully under agar containing DMSO. The alphavirus Sindbis produced slightly larger plaques under agar containing DMSO, but there was no effect on clarity or size of plaques produced by the flavivirus dengue-2.


Discriminant analysis: a method of identifying foci of vector-borne diseases.

Identification of foci of vector-borne diseases does not require knowledge of exact abundances of vectors and pathogens; rather, a focus is defined by the presence, or some minimal level of abundance, of a vector and pathogen. Stepwise discriminant analysis (DA) was applied to data on free-ranging adult wood ticks (the vector) and to data on isolations of Colorado tick fever virus from small mammals. Trap stations were grouped on the basis of relative abundance of wood ticks for one set of analyses and on the presence or absence of virus for another set of analyses. Additional data consisted of easily measured environmental variables. It is concluded that DA provides a useful tool for analysis of ecosystem structure and an effective means of identifying foci of infection.


The development of functional heterogeneity in the liver parenchyma of the golden hamster.

Prenatal and postnatal stages of the development of golden hamsters were studied histochemically and biochemically. It was shown that, beginning with the 12th gestational day, the fetal liver starts to store glycogen, and that this process reaches its maximum a birth. Glycogen phosphorylase and glucose-6-phosphatase (G6Pase)-activity increased drastically in the last two days before birth, glycogen phosphorylase preceding G6Pase. As a histochemical characteristic, an even distribution of glycogen, glycogen phosphorylase and G6Pase activity is found in the liver parenchyma at birth. During the first two postnatal weeks typical heterogeneous patterns of distribution developed: glycogen depletion could be demonstrated predominantly in zone 1 of the liver acinus, this being at the same time the area of highest glycogen phosphorylase and G6Pase-activity. The periportal zone 1 thus became characterized as the primary site of glycogenolysis (glycogen phosphorylase) and gluco(neo)genesis (G6Pase). "Metabolic Zonation" is interpreted as the chemomorphological equivalent of the regulatory function of the liver as a glucostat.


Intramitochondrial rod-like inclusions in human breast tumors.

Ultrastructural screening of human breast tumor biopsies has revealed, in 43% of the carcinomas, and in 16% of the benign lesions examined. the presence of rod-like inclusions in mitochondria of epithelial cells. The inclusions are cylindrical in cross section, with a diameter of about 50 nm, and show regular striations in longitudinal sections. They are probably derived from cristae. Mitochondria with inclusions are usually enlarged and are found most frequently in epithelial cells of invasive tumors and near zones of tumor necrosis. Similar although not identical inclusions have been observed by other investigators in the liver of women with hydatidiform mole or choriocarcinoma, of pregnant women, and of women taking oral contraceptives. Identical inclusions have been found in mitochondria of HeLa cells treated with anti-HeLa serum. Although no clear-cut correlations were found between the finding of inclusions and parameters such as age of patients, nuclear grade or lymphocytic infiltration of the breast tumors, it is conceivable that the presence of mitochondrial inclusions reflects the effect of hormonal or of immunological factors.


Feline plasma cortisol (hydrocortisone) measured by radioimmunoassay.

Plasma cortisol (hydrocortisone) was measured by radioimmunoassay in 6 normal cats. Blood was collected from the cats by venipuncture at intervals of 3 hours for 3 days. Resting plasma cortisol concentrations averaged 17.0 +/- 2.8 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 82.8 ng/ml. Of 144 plasma samples, 95% contained less than 40 ng of cortisol/ml. Circadian rhythm of cortisol secretion was not detected, suggesting that adrenal function tests may be started in feline patients at any time of day. Intramuscular injection of 2.2 U of ACTH gel/kg of body weight caused detectable increase in plasma cortisol concentrations at 1 and 2 hours after injection. Maximal response to ACTH in the 6 cats ranged from 41.6 to 178.4 ng/ml. Oral administration of 0.1 mg of dexamethasone/kg suppressed plasma cortisol to nondetectable concentrations for 32 hours in 5 of the 6 cats.


Demonstration of cytotoxic lymphocytes to virus-infected target cells in pigs inoculated with transmissible gastroenteritis virus.

Lymphocytes, cytotoxic to virus-infected target cells, were induced in pigs orally exposed to transmissible gastroenteritis virus. They were studied and experiments were carried out by using autochthonous testicle cells as target cells to avoid genetic incompatibility of effector lymphocytes and target cells. Cytotoxic lymphocytes were demonstrated in Peyer's patches, mesenteric lymph nodes, spleen, and peripheral blood on postinoculation day (PID) 7. Cytotoxic activity of lymphocytes increased thereafter and reached the maximal amount at PID 21. Lymphocyte cytotoxicity was somewhat greater in lymphocytes of peripheral blood and spleen than in those of Peyer's patches and mesenteric lymph nodes after PID 14. On the contrary, lymphocyte reactivity to the viral antigen measured by lymphocyte proliferative assay was higher in Peyer's patch and mesenteric lymph node cells than in peripheral blood and splenic cells. Lymphocyte cytotoxicity was depressed by treating effector cells with anti-porcine thymocyte serum and complement. However, lymphocyte suspensions treated with anti-porcine thymocyte serum and complement were still cytotoxic to some extent against virus-infected target cells, although T lymphocytes were completely excluded by the treatment. This suggests that cytotoxic mechanism other than the direct action of cytotoxic T lymphocytes may be involved in the cytotoxicity assay systems used in the present studies. In experiments in which allogenic cells (testicle cells of siblings) were used together with autochthonous cells as targets, lymphocyte cytotoxicity was equally expressed against both autochthonous and allogenic target cells in 2 of 3 experiments. However, lymphocyte cytotoxicity was greater against autochthonous cells than against allogenic target cells in 1 of 3 experiments.


Responses of immune and nonimmune adult rhesus macaques (Macaca mulatta) to adenovirus SV-20.

Adenovirus SV-20 (ASV-20) was inoculated subcutaneously into adult rhesus macaques (Macaca mulatta), and various immunologic parameters were studied. Similar changes were observed in macaques that had anti-ASV-20 serum-neutralizing antibodies prior to inoculation and in those lacking detectable antibodies. There were absolute decreases in numbers of peripheral blood lymphocytes (PBL), erythrocyte-rosetting lymphocytes, complement-receptor lymphocytes, and Fc-receptor lymphocytes. These changes were most significant (P less than 0.05) on postinoculation days (PID) 3 and 7. Mitogenic responsiveness to concanavalin A, phytohemagglutinin, and pokeweed mitogen in cultured PBL from immune and nonimmune macaques was depressed on PID 3, 7, and 14. Ultraviolet-inactivated ASV-20 caused moderate suppression of phytohemagglutinin-induced mitogenesis when viral particles and lectin were added simultaneously to PBL cultures. Plasma cortisol (hydrocortisone) values were not significantly altered following inoculation of ASV-20. High titers of anti-ASV-20 antibody developed by PID 7 in nonimmune macaques, and previously immune macaques showed a booster effect in the same time period. Antibody titers were still increased 120 days after inoculation. There was no clinical evidence of an adverse effect of ASV-20 infection in these macaques.


Equine infectious anemia virus: development of a simple reproducible method for titrating infectivity of the cell-adapted strain.

An equine dermal cell line between the 14th and 30th subpassages was used to develop a reproducible method of titrating the infectivity of the cell-adapted strain of equine infectious anemia virus (EIAV). Cells inoculated with EIAV were subcultured or fed once each week and were monitored for the production of P26 antigen of EIAV in supernatant fluids. Ultrathin sections were prepared once each week and were examined for the detection of budding virus-like particles (VLP). The VLP could not be detected in the infected cells subcultured once each week. When the medium was changed once week and when the cells not transferred, budding VLP were detected routinely after 3 to 4 weeks, Feeding of the infected cells once each week was used to establish the infectivity assay. The reproducibility of the assay on a frozen viral stock preparation was within an endpoint of one tenfold dilution.


Multiple granular cell tumors of the bronchi: treatment with laser.

Granular cell tumors involving multiple bronchial and extrapulmonary sites were found in a young man. Carbon dioxide laser ray was applied through a specially fitted rigid bronchoscope to a lesion at the left mainstem bronchus. Serial follow-up bronchoscopies revealed a white scarred plaque without evidence of regrowth. A partially obstructing lesion at the left lower lobe bronchus did not respond to one application of laser therapy. Laser treatment of proximal benign bronchial lesions is feasible; however, peripheral lesions may require several courses of laser therapy.


Pulmonary cell-mediated cytotoxicity in hamsters with parainfluenza virus type 3 pneumonia.

A 51Cr-release cytotoxic assay in vitro was developed to permit definition of the role of local pulmonary cell-mediated immunity in the recovery phase of experimental parainfluenza virus type 3 pneumonia in the Syrian hamster. Cytotoxic effector cells were obtained by bronchalveolar lavage; virus-infected targets were syngeneic secondary hamster kidney cells. Maximal target-cell killing was mediated by lung lavage cells obtained one week after infection; the response waned rapidly thereafter. There was a close temporal correlation between the cytotoxic response and termination of virus replication in the lung. Cytotoxicity was virus specific and was restricted by a requirement for species identity between effector and target cells. Immune spleen cells mediated one-fourth the amount of 51Cr release effected by lung lavage cells, which suggests that cytotoxic effectors were concentrated in the lung. Although the identity of the cytotoxic effector cell was not established conclusively, the characteristics of the response suggested strongly that thymus-derived lymphocytes mediated lysis of target cells. Further work is required to determine the relative importance of this aspect of the host response during recovery from respiratory viral infection.


[Sleep apnea in a child with adenotonsillar hypertrophy (author's transl)].

A three year old with sleep apnea due to adenotonsillar hypertrophy is presented. The picture improved after treatment with antibiotics and corticosteroids, and disappeared after adenotonsillectomy. The symptomatology is studied in relation to primary alveolar hypoventilation and the "sudden death" syndrome in infants. The need of an early diagnosis is emphasized to avoid onset of an irreversible "cor pulmonale". It is suggested that aside from a probable predisposing "central" and constitutional factor in children with this syndrome, apparently there are heterogeneous electroencephalographic sleep patterns.


Fever: pathogenesis, pathophysiology, and purpose.

Fever appears to have evolved in vertebrate hosts as an adaptive mechanism for controlling infection. This phenomenon is produced by certain exogenous (largely microbial) stimuli that activated bone-marrow-derived phagocytes to release a fever-inducing hormone (endogenous pyrogen). Endogenous pyrogen, in turn, circulates to the thermoregulatory center of the brain (preoptic area of the anterior hypothalamus) where it causes an elevation in the "set-point" for normal body temperature. Warm blooded animals produced fever by increasing heat production (through shivering) or reducing heat loss (by peripheral vasoconstriction), whereas cold blooded animals do so only by behavioral mechanisms (seeking a warmer environment). This paper discusses current concepts that involve the mechanism of endogenous pyrogen production, the role of central transmittors, and the probable function of fever in combating disease.


High-density lipoprotein, lipid, and carbohydrate metabolism during increasing fitness.

Eleven unfit bank executives in sedentary employment exercised daily for 10 weeks according to the Canadian Air-Force 5BX Exercise Programme. Over this period no changes were observed in the glucose or insulin responses to a standard breakfast or to intravenous glucose, or in the glucose response to intravenous insulin. There was a significant reduction in high-density-lipoprotein cholesterol, but total plasma triglyceride and cholesterol levels were unaffected by exercise.


Coexisting benign mixed tumor and mucoepidermoid carcinoma of the parotid gland.

Multiple unilateral parotid gland tumors are very rare. A review of the literature shows only seven cases of coexisting unilateral parotid tumors. This patient had a benign mixed tumor and a mucoepidermoid carcinoma of the right parotid gland. This is the eighth reported case of multiple unilateral parotid tumors and the first to show such a combination of tumors.


Thermal hazard during mastoid surgery.

Torque speed characteristics of two mastoid drills were measured. Potential temperature elevations in temporal bones were calculated from these measurements. Measured temperature elevations in temporal bones drilled without irrigation agreed well with predictions. Irrigation was demonstrated to be of critical importance in minimizing thermal hazard from mastoid drills.


Paraneoplastic vasculitis of nerve: a remote effect of cancer.

The development of mononeuritis multiplex brought three men to medical attention weeks to months prior to the diagnosis of a malignancy. In each case, sural nerve biopsy exhibited active wallerian degeneration with vasculitis. Two of the men died and at autopsy were found to have clinically unrecognized oat cell carcinoma and carcinomatous sensory neuropathy with brainstem encephalitis. The third patient is still alive but was found to have a lymphoma and has subsequently developed a liposarcoma. The vasculitis in all 3 cases seems limited mainly to the peripheral nervous system. Mononeuritis multiplex due to vasculitis may represent a new remote effect of cancer on the nervous system.


Cytomegalovirus isolation from a human inner ear.

Cytomegalovirus (CMV) infection of the fetus has been associated with congenital deafness or hearing loss. This association has previously been based on clinical or pathological studies. We report an infant who died with the congenital CMV syndrome in which CMV was isolated from the perilymph of the inner ear providing additional evidence that this virus can infect the labyrinth.


Abnormal auditory evoked potentials in hereditary motor-sensory neuropathy.

From a kinship with a dominantly inherited motor-sensory neuropathy, we studied 2 brothers with brainstem auditory evoked potentials and behavioral audiometric tests. They had abnormal prolongation of I-III interpeak intervals. Wave V was poorly developed. Conventional audiometric tests did not reveal a peripheral hearing loss. It is probable that their auditory nerves and spiral ganglia are undergoing a pathophysiological process analogous to that of their peripheral nerves.


Immunohistochemical evidence for RNA virus related components in human breast cancer.

The localization of antigenic components with cross-reactivity to a 52,000 dalton group specific glycoprotein (gp52) of the mouse mammary tumor virus (MMTV) in paraffin sections of human breast carcinomas is described using an indirect immunoperoxidase method. This method was first optimized on paraffin sections of mouse mammary tumors. The specificity of the reaction observed in the human tissues was established by absorption of the specific IgG with: a) purified gp52; b) several relevant and irrelevant viral preparations; c) normal human plasma, leukocytes, breast tissue, milk, actin, collagen, and hyaluronic acid; d) sheep erythrocytes, bovine mucin and fetal calf serum. Only MMTV and purified gp52 eliminated the immunohistochemical reaction in human breast tumors. Positive reactions were seen in 171 of 376 (45.5 percent) randomly selected breast carcinomas of various histopathologic types, while negative reactions were obtained in all 137 normal and benign cases tested. In those invasive tumors with an intraductal component, a higher percentage (63.9 percent) of positive cases was seen. A positive reaction of different specificity was observed in foci of apocrine metaplasia. With one exception, 99 carcinomas from 13 organs other than breast and eight cystosarcomas were negative.


Islet cell tumors of the pancreas: clinico-biochemical correlations.

Islet cell tumors produce a spectrum of syndromes. Intensive investigations of these tumors have enhanced our understanding of cellular origin, physiology and biochemistry of the islet hormones. Biochemical studies on the hormones are helpful in the diagnosis and treatment planning of the islet tumors. For example, insulinoma and glucagonoma can be diagnosed more readily by demonstration of proinsulin and proglucagon-like components, respectively, in the blood. Similarly, measurement of vasoactive intestinal polypeptide is not only useful in the diagnosis, but also in the follow-up of patients with pancreatic cholera syndrome. This mini-review examines these and other clinico-biochemical correlates seen in islet tumors.


Ontogeny of spontaneous blinking and of habituation of the blink reflex.

Habituation of the blink reflex to glabellar percussion was examined in 164 infants and children from ages 2 days to 18 years and in 18 adults aged 18 to 50 years. Spontaneous blink rates were measured in 269 children and 179 adults. The mean number of glabellar taps required for habituation of the blink reflex increased from 2.7 (SD 1.2) at 0 to 2 months of age to a peak of 13.3 (SD 5.6) at age 3 to 4, remained at more than 10 until age 6, after which a rapid decline occurred, reaching the adult level of 2 to 5 blinks to habituation at age 12 years. The mean rate of spontaneous blinking was less than 2 per minute in early infancy and increased steadily during childhood up to age 14 or 15. The inverse relationship of spontaneous blink rate and number of blink reflexes to habituation in early childhood and in disorders of dopamine transmission suggests that spontaneous blink rate and habituation of the blink reflex reflect maturation and integrity of dopaminergic circuits in the brain.


[Synthesis of spin-labeled rubomycin and a study of its interaction with DNA].

Hydrochloride of 14-(I-oxyl-2,2,6,6-tetramethylpiperidyl-4)-acetoxyrubomycin (spin-labeled rubomycin or SL-rubomycin) was prepared by interaction of hydrochloride of 14-bromrubomycin with potassium salt of I-oxyl-2,2,6,6-tetramethylpiperidyl-4-acetic acid. Its interaction with DNA and synthetic poly A and poly U polyribonucleotides was studied. The character of the EPR spectra was indicative of DNA binding with SL-rubomycin and forming a system with a high level of regularity similar to that of liquid crystals. The results of the study of the EPR spectra correlated with the model of rubomycin intercalation between the pairs of DNA bases and were indicative of water surrounding of the nitroxyl group of SL-rubomycin bound with DNA.


[Pseudomonas aeruginosa melanin].

The EPR, IR, UV and visible absorption spectra of a melanin-like pigment from P. aeruginosa were studied. By the whole complex of the spectral characteristics the pigment may be classified as belonging to the melanin group. The study of the antibiotic properties of the pigment showed that it did not inhibit the growth of P. aeruginosa and E. coli. Still, it possessed some antistaphylococcal activity.


In vitro system for studying the efficacy of antiviral agents in preventing the reactivation of latent herpes simplex virus.

Antiviral antibody and interferon did not prevent in vitro reactivation of herpes simplex virus in latently infected sensory ganglia. Phosphonoacetic acid and 9-beta-d-arabinofuranosyladenine blocked reactivation, but this treatment did not eradicate the latent infection.


A new method for obtaining viable cells from dermal infiltrates. A study on 2,4 dinitrochlorobenzene induced contact dermatitis.

Experimental contact dermatitis has been induced in 2,4 dinitrochlorobenzene (DNCB) sensitized guinea pigs. The developing dermal infiltrate was excised and the infiltrating cells were obtained by mechanical extraction alone as well as by the combination with collagenase and elastase treatment. The most viable cells appeared in the elastase and mechanically extracted samples and the least in those subjected to mechanical treatment alone. The most cells in the enzyme-treated samples were present 24 h after re-exposure of the sensitized animals to DNCB consisting mainly of lymphocytes and of polymorphonuclear granulocytes. The optimum conditions for the action of enzymes including optimum duration of the treatment, buffer milieu, aspecific proteolytic effect on foreign substrate and action on T and B cell receptors have been elaborated. It was concluded that 80 min of collagenase treatment with gentle mechanical extraction under specified conditions does not affect any measurable immunologic properties of the liberated cells resulting in the second best yield. A comparison of these data with earlier reports and their significance is being discussed.


DNA-binding proteins in the sera of patients with malignant melanoma.

Sera of patients with various malignancies are known to contain DNA-binding proteins (DBP) which are not present in sera of normal individuals. In this paper sera of patients with malignant melanoma (MM) were examined as to whether characteristic DBP are present, too. DBP are isolated by DNA-affinity chromatography and represent 0.5-0.9% of all serum proteins. After separation of the DBP by SDS slab gel electrophoresis no typical DBP is detectable in sera of MM-patients. However, quantitative differences are found in sera of patients in the clinical stages I-III and/or tumor level 3-5: 1. All 9 sera of patients who had clinical signs of MM contain more DBP with molecular weight (mw) of 20,000-24,000 dalton than control sera. However, these DBP are only increased in 30% of the 22 sera from MM-patients who had clinical signs for 13-73 months after tumor excision. 2. All sera of the 10 MM-patients of whom sera were drawn twice after tumor excision at an interval of 7-46 months without clinical signs, showed a reduction of DBP with mw 30,000, 68,000, and 165,000.


Effect of ACTH and corticosterone on melanogenesis and cyclic nucleotide levels in the B-16 melanoma.

The acute in vitro action of ACTH and corticosterone individually and in combination were determined in the B-16 melanoma grown in vivo. ACTH elevated levels 10-fold while tyrosinase activity generally was depressed. Corticosterone depressed cAMP levels and tyrosinase activity. ACTH in the presence of corticosterone produced a coincident peak in tyrosinase activity and cAMP levels followed by a depression of enzymatic activity. The results demonstrate that cAMP is not the sole modulator of tyrosinase activity and that ACTH, corticosterone and cAMP interact in the regulation of B-16 melanoma tyrosinase activity.


Essential fatty acid deficiency in total parenteral nutrition. Detection by changes in intraocular pressure.

Essential fatty acid deficiency (EFAD) has been commonly and readily diagnosed during fat-free total parenteral nutrition (TPN), with only vague awareness of possible functional and clinical derangements secondary to essential fatty acid deficiency. Arachidonic acid is known to be a precursor for prostaglandin (PG) synthesis. Prostaglandins are known to be intermediaries between stimulus and cellular response in a variety of physiologic and pathologic processes; one would suspect therefore that EFAD would result in PG deficiency with resultant multiple derangements in functions regulated by PG. We tested this hypothesis by serially measuring intraocular pressure (IOP) in patients before and during fat-free TPN and after supplementing these patients with fat. In the eye as well as in various other organs PG are believed to act as mediators of adrenergic neurotransmission by a negative feedback mechanism. As catecholamines are potent ocular hypotensive agents, decreased levels of PG due to EFAD will cause increase in catecholamine turnover with a reduction in IOP. Two groups of patients matched as to their age, sex, nutritional status and diseases were studied. One group (control) was receiving a normal diet or fat-containing TPN while the other group was receiving fat-free TPN. IOP in the fat-free TPN group dropped from 13.7 +/- 0.4 mmHg pre-TPN to 9.3 +/- 0.5 mmHg during the first week of fat-free TPN. Within two weeks after supplementation of fat or return to normal oral diet IOP returned to 13.9 +/- 0.3 mmHg. Prostaglandin levels, which were 0.025 +/- 0.004 ng/ml pre-TPN or in control patients decreased to 0.012 +/- 0.002 ng/ml (p < 0.001) during fat-free TPN, to return to normal after fat was added to TPN regime or patients returned to normal oral diet. During fat-free TPN linoleic acid levels decreased to 40% of its initial value with a mild increase upon the addition of fat, while eicosatrienoic acid and the triene:tetraene ratio increased to 6.5 times their initial values. Arachidonic acid levels did not change during fat-free TPN or after repletion with fat. Intraocular pressure determination seem to be a simple, harmless, inexpensive, reliable and sensitive indicator of EFAD. Moreover, IOP determination represent a functional derangement which in a clinical setting lends functional credence to the biochemical changes of EFAD whose entire significance has not yet been determined. Similarly, serial IOP determinations are sensitive in detecting adequate functional repletion of EFAD. As PG are known to act as intermediaries in a variety of physiological processes it seems reasonable to assume that the change in IOP is only one of many different changes and derangements to occur as a result of PG and EFA deficiency.


Carcinoma of the hepatic hilus. Surgical management and the case for resection.

Tumor resection for treatment of carcinoma of the hepatic hilus was preferred over routine palliative decompression at the University Hospital Center, Rennes, France, in 1974. Since then, resection has been performed on 18 patients. In seven of these patients resection proved impractical because of the extension of a neoplasm into the portal vein or liver, therefore palliative decompression was performed. In 11 patients (61%) tumor resection, followed by reconstruction of the biliary tree, was performed successfully. All the resected tumors were adenocarcinomas of the proximal bile ducts. Four patients had simple hepatic duct resection. In two patients duct resection was associated with right lobectomy, in three patients with left lobectomy, in one patient with segmentectomy, and in one patient with excision of the right branch of the hepatic artery. There were two postoperative deaths. The mean survival time for the remaining nine patients is 521 days. Five patients were alive in August 1978, at intervals ranging from 175 to 1180 days after resection. These results contrast favorably with those obtained between 1968 and 1973, during which period nine patients had palliative decompression, with three postoperative deaths and a mean survival time of 164 days for the remaining six patients.


Peripheral beta-receptor responsiveness in patients with essential hypertension.

Peripheral beta-adrenergic receptor sensitivity was characterized in 24 patients with essential hypertension and in 13 age-matched normotensive subjects using an isoproterenol hydrochloride bolus dose-response technique. Decreased beta-receptor responsiveness to this exogenously administered beta-agonist was observed in hypertensive patients; for an equivalent chronotropic effect, higher doses of isoproterenol were required in hypertensive subjects than in normal subjects. Among "normal-renin" hypertensive patients, beta-receptor responsiveness was directly related to furosemide-stimulated plasma renin activity (PRA), suggesting that independently stimulated PRA may provide an indirect estimate of endogenous beta-receptor sensitivity. Hypertensive patients whose mean arterial pressure fell at least 10 mm Hg after four weeks of treatment with hydrochlorothiazide had even further depression in beta-receptor responsiveness, whereas receptor sensitivity was unchanged in patients whose blood pressure was unaffected. Thus, it is unlikely that this decreased receptor responsiveness in patients with untreated essential hypertension is a direct consequence of elevated arterial pressure.


Plasma cell neoplasia with osteosclerotic lesions. A study of five cases and a review of the literature.

Sixty-eight patients with plasmacytic neoplasia and osteosclerotic lesions were analyzed. Men predominated in this series. Mean age was 55.3 years and 26 patients were younger than 51 years at diagnosis. Early onset of disease was statistically different from multiple myeloma in general. Thirty patients had peripheral polyneuropathy and often neurological manifestations preceded other symptoms. Skeletal pain was less common, whereas hepatomegaly, splenomegaly, and lymphadenopathy were more common than in myeloma in general. Incidence of azotemia, hypercalcemia, high ESR, and anemia was lower than in myeloma. In one fourth of the patients, the number of skeletal lesions did not exceed three. Mean survival was less than 20 months from first symptom and 12 months from diagnosis. Mortality was related sometimes to polyneuropathy. Thus, in several aspects, plasmacytic neoplasia with osteosclerotic lesions is different from the classical multiple myeloma.


[Virological research in acute respiratory diseases in 1976--1977 (author's transl)].

From October 1976 to June 1977 virological researches have been carried out on 5 subjects with influenza, on 302 children hospitalized in pediatric departments for respiratory illness and 94 children hospitalized in the same departments for other (non respiratory) diseases. The incidence of influenza was moderate and restricted to small epidemic episodes in school and preschool children. The isolated viruses resulted of A type, substantially similar to the prototype strains appeared from 1972 to 1975. Among children hospitalized for respiratory diseases Adenoviruses (6.8%) and, with decreasing frequency, Enteroviruses, paraifluenza viruses and RS have been also isolated. The incidence of isolation of RS virus is significantly related to bronchopneumonia cases in infants under on year of age. The incidence of significant increases of FC antibodies against influenza (A and B) viruses, RS and Myc. pneumoniae in children with bronchitis and broncho-pneumonia is also considerable. The drawing of pharyngeal swabs at different intervals from the entry to the hospital has shown that the shedding of respiratory viruses is generally very short and that hospital cross-infections may occur.


Phosphate inhibition of secondary metabolism in Streptomyces hygroscopicus and its reversal by cyclic AMP.

Inorganic phosphate inhibited the biosynthesis of the macrolide antibiotic turimycin in different strains of Streptomyces hygroscopicus. In the wild type strain a depression was observed with increasing phosphate concentrations. A total inhibition was found at 0.1 M phosphate. In a high producing mutant a minimum of turimycin production occured when the phosphate concentration was between 5 mM and 10 mM. Above this concentration the antibiotic synthesis increased again but the production period shifted to a later period of cultivation. Addition of inorganic phosphate resulted in an initial increase of intracellular cyclic AMP content. But a second elevation characterizing the normal level of cyclic AMP throughout the growth phase was prevented by phosphate. Exogenous cyclic AMP as well as positive effectors of the adenylyl cyclase system were able to overcome the phosphate suppression. Cyclic AMP abolished the reduction of protein synthesis following phosphate addition and caused the reappearance of a protein band which may be responsible for the turimycin biosynthesis.


[Thrombocytic reactions in experimentally induced neoplasms (author's transl)].

Strain XVII mice with Graffi virus induced leukemia of various hematological types showed a pronounced thrombocytopenia which was severe in erythroblastic leukemia and weaker in lymphatic ones. The thrombocytic reactions shortly following Friend and Rauscher virus applications and occurred 3 weeks after birth in AKR mice are not found in Graffi virus system. A significant preleukemic thrombocytopenia did appear only 8 weeks after Graffi virus infection. The origin of both the preleukemic and the secondary thrombocytic reactions are discussed. (XVII X AKR) F1 hybrids, neonatally treated with N-nitroso-N-methylurea (NMU), resulted also in a decline in the number of thrombocytes after manifestation of leukemia. In contrast to the expection following NMU treatment a preleukemic thrombocytopenia appeared as in viral leukemogenesis too. The possibility of a co-operation of oncogenic viruses in chemical carcinogenesis is considered.


Electron microscope study on the bat testicular interstitial cell with special reference to the cytoplasmic crystalloid.

The testicular interstitial cell of the bat, Myotis schreibersi (Temmink), captured late in August was electron microscopically investigated. The cytoplasm of Myotis interstitial cells is packed by strikingly numerous mitochondria with many electron dense small matrix granules, endoplasmic reticulum and variable numbers of osmiophilic lipid droplets. The Myotis interstitial cell is characterized by alternate development of the SER and RER: In some Leydig cells the major part of the cytoplasm is packed by tubular SER, whereas in others this apparently is replaced by abundant free ribosomes containing sparse cisternae of the RER. These changes in the amounts of ser and RER are likely reversible and probably reflect functional alterations of Leydig cells of the bat, a hibernator. The Myotis interstitial cell possesses small cytoplasmic crystalloids composed of regularly oriented, compressed tubules, 20-28 m mu thick, which are continuous to the tubular SER (SER derived crystalloids). Type I and type II crystalloids are classified, which show, in suitable planes of section, honeycomb-like and fabric-like patterns, respectively. The Myotis Leydig cell extends cytoplasmic processes of irregular shape and long microvilli, the latter often conglomerates on the cell body or cytoplasmic processes. The entire surface of the cell including the processes is completely surrounded by a basal lamina.


Demonstration of alpha 1-antitrypsin in hepatomas.

Sixty-nine primary malignant hepatomas were examined for the presence of alpha 1-antitrypsin (alph 1-AT) in tumor cells using immunohistochemical methods. Twenty-eight tumors showed positivity for alpha 1-AT. The reaction was globular and PAS-positive in 12 hepatocellular tumors and thus simulated the pattern of alpha 1-AT accumulation in hepatocytes in subjects carrying the Z-gene for alpha 1-AT. In fact, eight of these 12 tumors presented this pattern in the nontumours liver tissue. In ten hepatocellular tumors the reaction was finely granular throughout the hepatocytic cytoplasm, but was present in only a small number of cells. Still fewer cells were positive in six cholangiocarcinomas. The globular alpha 1-AT in tumor cells may be genetically determined when associated with the Z-gene. A reappearance of fetal gene products may be assumed in three hepatocarcinomas with globules positive for alpha-fetoprotein as well as alpha 1-AT.


Intrasinusoidal bodies in the livers of thermally injured patients.

Acidophilic intrasinusoidal liver bodies appearing at autopsy in cases in which thermal injury occurred were examined by light microscopy using several special stains and by scanning and transmission electron microscopy. Morphologically, these bodies were found to be membrane-bound protein material that were usually present in the hepatic sinuses but were also identified in hepatocytes, spaces of Disse, and Kupffer's cells. Correlation of clinical data with pathologic findings failed to determine a specific cause for the intrasinusoidal bodies.


Granular cell tumors of biliary ducts. Report of two cases and review of the literature.

There were two cases of granular cell tumor of the extrahepatic biliary system; to our knowledge, 17 have previously been reported. The initial symptoms most often are those of biliary colic. The majority of the patients are black and female. The cystic duct and the common bile duct are most commonly involved. Additional biliary pathologic disorder is present in more than half of the patients.


Malakoplakia of the skin. Ultrastructure and quantitative x-ray microanalysis of Michaelis-Gutmann bodies.

The etiologic agent in a case of malakoplakia of the skin was identified as Staphylococcus aureus from culture of the lesion and from ultrastructural observations. Ultrastructurally, electron-dense inclusions were observed in addition to membranous whorls and Michaelis-Gutmann (MG) bodies. These were labeled "precalcification formations" since they possessed an organic crystalline structure. These formations may act as nucleation centers for further incorporation of organic and inorganic material. Deposition of fine crystalline material in the outer region may occur as the structure becomes saturated with inorganic elements, thus completing formation of the MG body. Quantitative x-ray microanalysis of MG bodies demonstrated the presence of phosphorus, calcium, and iron, with average concentrations of 2.1%, 2.6%, and 0.7% by weight, respectively.


Glioblastoma multiforme presenting as stroke: an electrophysiological and clinicopathological case report.

A 55-year-old man having hemiplegia after the sudden onset of a stroke was referred for rehabilitation. Cerebral angiography had demonstrated occlusion of the left middle cerebral artery and steroid therapy had been started. Attempted tapering of the steroid therapy on admission for rehabilitation resulted in the patient having severe headaches and confusion. Blink reflex evaluation, somatosensory cerebral evoked potential determinations and visual evoked responses were all consistent with a widespread process involving the parietal lobe of the patient's left cerebral hemisphere. Computerized axial tomography indicated an abnormality consistent with a space-occupying lesion. Craniotomy revealed the presence of a glioblastoma multiforme in the left cerebral hemisphere. Electrodiagnostic evaluation was entirely consistent with the operative finding of widespread involvement of the patient's left parietal lobe. Stroke patients whose conditions deteriorate over time must be serially evaluated in order to determine possible other causes of their symptoms.


Organotropic mutagenesis in tissues of Chinese hamsters induced by chemical carcinogens.

In order to investigate the relationship between mutation and carcinogenesis in vivo, a method has been developed in which somatic mutation can be studied in specific organs of Chinese hamsters after acute dosing with chemical carcinogens. In preliminary experiments an increase in mutation was detected in cultures derived from lung tissue of hamsters after intraperitoneal dosing with the direct-acting mutagen and weak carcinogen, ethyl methanesulphonate, or with diethylnitrosamine, a carcinogen which requires metabolic activation before mutagenic activity can be demonstrated in vitro. Subsequent experiments have shown the induction of mutation in cells dereived from the bladder of animals dosed with diethylnitrosamine or methyl nitrosourea and in a variety of tissues from animals dosed with methane-sulphonates, 2-acetylaminofluorene and 3-methylcholanthrene.


[Carcinoma of the ileo-cecal appendix].

A structurally impaired appendix observed during laparotomy in a woman of 62, suffering from gall stones with stenosis of the papilla, was removed. Histological examination showed carcinoma. Right hemicolectomy was performed later.


Effect of intratracheal and oral application of corticosteroids on the adrenal function test in beagle dogs after ACTH-stimulation.

The effect of synthetic corticosteroids given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test. In addition, histological and morphometrical examinations of the adrenal cortex were performed at the end of the study. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05, 0.1 and 0.5 mg/kg body weight led to a dose dependent adrenal suppression on the basis of plasma cortisol concentration and eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg body weight. Also the oral administration of 0.1 mg/kg body weight/day of beclomethasone dipropionate had a definite adrenal suppressive effect comparaable to that of 0.1 mg/kg body weight given intratracheally. However, intratracheal administration of fluocortin butylester, a local antiinflammatory drug but systemically a nearly ineffective corticosteroid (2 X 8 mg/kg body weight/day) had no suppressive effect on the adrenal gland of the beagle dog, even after a 320 times higher dose.


Unscheduled DNA synthesis in male rabbit germ cells induced by methylmethane sulfonate, cyclophosphamide and adriamycin.

Male rabbit germ cells were labelled by intratesticular injection of [3H]-thymidine (3H-T). In sperms of control animals, radioactivity was first demonstrated between the 40th and 43rd day after labelling, corresponding to preleptotene spermatocytes. In rabbits treated with 22.5 mg/kg methylmethane sulfonate (MMS), significant radioactivity was shown in sperms collected from day 19 ownwards. These cells derived from spermatocyes and early spermatids at the time of labelling. 3H-T incorporation into these cell populations represents unscheduled DNA synthesis (UDS), a repair process initiated after chemical damage of germ cell DNA. After i.v. injection of 20 mg/kg cyclophosphamide, an alkylating agent that must be activated, labelled sperms were found 28--37 days after treatment. This shows that UDS took place in spermatocytes during the pachytene and zygotene stages. Adriamycin (1.0 and 3.0 mg/kg) induced UDS during pachytene and zygotene stages of spermatogenesis. Sperm counts decreased during spermatogonial stages by a factor of about ten in cyclophosphamide and adriamycin treated rabbits. It was not changed after MMS-treatment.


Granular cell tumor (myoblastoma) of the orbit.

A 43-year-old woman had a three-month history of increasing proptosis and visual loss secondary to an inferior orbital mass. Surgical exploration revealed an encapsulated mass that was excised with good visual recovery. Light microscopy as well as electron microscopy confirmed the diagnosis of granular cell myoblastoma. The tumor's location within the orbit was unusual and its histologic origin was uncertain.


Herpetic ganglionic latency. Aciclovir and vidarabine therapy.

This study report the therapeutic efficacy of systemic antiviral drugs in reducing the incidence of trigeminal ganglionic latent herpes simplex virus (HSV) after ocular infection in mice. Aciclovir sodium, 60 mg/kg daily for five days starting three and 24 hours after inoculation, resulted in a significant decrease in recovery of latent HSV, 28% and 54% positive, respectively, in comparison to untreated controls, 100% positive. Initiation of similar therapy three weeks after inoculation for 5, 10, and 15 days resulted in progressive decrease in persistence of latent virus, being 100%, 33%, and 12% positive, respectively. Systemic vidarabine, 50 mg/kg daily for 15 days starting three weeks after inoculation, also resulted in a significant decrease of positive ganglionic cultures (60% positive) in comparison to the untreated controls. The results indicate that replication of HSV in the trigeminal ganglia in mice is probably continuous and that this reservoir of recurrent ocular herpes is amenable to therapy with systemic antiviral agents.


Herpetic eye disease in rabbits after inoculation of autonomic ganglia.

Since herpes simplex virus (HSV) can cause persistent infection of autonomic ganglia of both humans and experimentally infected animals, we followed the pattern of eye disease and viral growth after HSV inoculation of one superior cervical ganglion in rabbits. Of 27 inoculated animals, eye disease or detectable virus developed in 18. Anterior uveitis was the most common clinical manifestation (94%), but conjunctivitis and dendritic keratitis were also frequent (60%). All 12 uveal-retinal specimens tested and five of seven ipsilateral superior cervical ganglia had detectable virus. If recurrent herpetic iritis in humans is associated with persistent infection of the superior cervical ganglion, autonomic mediators might trigger episodes of virus shedding. In patients with herpetic iritis, then, the use of epinephrine and other adrenergic agonists or antagonists should be avoided.


Clinical observations on 600 cases of recurrent laryngeal nerve paralysis.

A statistical review was made on 600 cases of recurrent laryngeal nerve paralysis who visited the author's clinic during the last 16 years. The yearly incidence, the age and sex distributions and the classifications of the causes of paralysis were presented and discussed. A special attention was given to the topics of associated laryngeal paralysis, bilateral recurrent laryngeal nerve paralysis and the so-called epidemic paralysis. A brief comment was also made on diagnosis and treatment of recurrent laryngeal nerve paralysis in general.


Growth failure, somatomedin and growth hormone levels in juvenile diabetes mellitus--a pilot study.

Growth hormone (hGH) responsiveness to exercise and somatomedin C (SmC) activity were measured in ten children with insulin-deficient diabetes mellitus. Four of the ten children showed a significant degree of growth retardation. Normal SmC activity was found in association with elevated hGH levels. The hypothesis that growth-retarded diabetics have a failure of Sm production despite high hGH levels (analogous to malnutrition and Laron dwarfism) was not substantiated by this study. Chronic deficiency of insulin, itself a somatomedin, may play a major role in diabetic growth failure.


Liver disease associated with chronic arsenic ingestion.

The association of chronic liver disease with long-standing arsenic ingestion is well documented, although the spectrum and incidence of liver disease due to arsenic remain uncertain. We report two patients with chronic liver disease and arsenical skin changes that followed previous chronic arsenic ingestion. One patient developed macronodular cirrhosis and the other non-cirrhotic portal hypertension with perisinusoidal fibrosis. The latter patient developed a primary liver cell cancer. There is only one previously reported case of malignant hepatoma in a non-cirrhotic liver complicating chronic arsenicism. Lack of awareness of this uncommon but well described cause of chronic liver disease may account for a small proportion of patients with "cryptogenic" liver disease. Previous arsenic administration should be considered as a cause of chronic liver disease, especially when typical skin changes or internal neoplasia develop.


Reverse phase passive haemagglutination and single radial immunodiffusion to detect epsilon antigen of Clostridium perfringens type D.

Two in vitro immunological assays were developed for detection of the epsilon (epsilon) antigen of Cl. perfringens type D. It was found that the reverse phase passive haemagglutination assay (RPHA) was able to detect concentrations of epsilon-antigen as low as 6 x 10-7 mg/ml whereas the single radial immunodiffusion techniques (SRID) was capable of detecting concentrations of epsilon-antigen above 0.01 mg/ml. When applied to gut contents from freshly dead infected sheep the RPHA test was found to be more sensitive than mouse toxicity assay in detecting the presence of epsilon-antigen. However, very low titres were detected in gut contents from normal sheep which meant that in a diagnostic situation interpretation of RPHA titres would be difficult. No epsilon-antigen was detected by SRID in gut contents from normal sheep or in gut contents from freshly dead infected sheep. The SRID assay could detect epsilon-antigen in gut contents from infected sheep allowed to decompose for 20 h post-mortem.


Infection studies on a reticuloendotheliosis virus contaminant of a commercial Marek's disease vaccine.

Reticuloendotheliosis virus (REV) was isolated in cell cultures from commercial Marek's disease (herpesvirus of turkeys) vaccine and re-isolated from the organs of vaccinated chickens. Runting and feathering abnormalities were produced when 1-day-old specific pathogen free chickens were inoculated with REV. Histopathological lesions in infected chickens were hypoplasia of the thymus, bursa and spleen, and inflammation of the proventriculus, kidneys and liver. Serological responses to REV were detected by the indirect immunoflorescence test in chickens directly inoculated with contaminated vaccine, and spread of REV infection to in-contact chickens was demonstrated by histopathological and serological investigations.


Poxvirus infection of the skin of an eastern grey kangaroo.

A solitary cutaneous papillomatous lesion, present for 6 weeks, was surgically removed from the hind limb of an 18-month old eastern grey kangaroo (Macropus giganteus). The lesion did not recur within 6 months of excision. Poxvirus particles were demonstrated in epidermal cells of the lesion by electron microscopy.


Quantification of human plasma inorganic pyrophosphate. I. Normal values in osteoarthritis and calcium pyrophosphate dihydrate crystal deposition disease.

The methodologic variables of the UDPG pyrophosphorylase method for analysis of inorganic pyrophosphate (PPi) levels in biologic fluids are described. Use of a tourniquet in collection of blood specimens elevated plasma PPi levels from 35% to 55% above control values and may explain the differences in published normal values. The sodium pyrophosphate decahydrate used to prepare the standard solution lost 8 waters of hydration after dessication, which could result in the calculation of spuriously elevated PPi levels. Normal plasma PPi concentration was 2.18 muM with a range (95% confidence limits) of 0.58-3.78 muM. Comparison of plasma PPi in normal subjects, patients with primary osteoarthritis, and patients with calcium pyrophosphate dihydrate deposition disease revealed no significant intergroup differences.


Quantification of human plasma inorganic pyrophosphate. II. Biologic variables.

Plasma inorganic pyrophosphate (PPi) levels rose predictably (28%) after vigorous systemic exercise and returned to baseline values after 30 minutes of rest. Plasma PPi levels were greater (36%) in femoral venous blood than in femoral arterial blood. Forearm muscular exercise, however, did not result in a detectable rise in plasma PPi levels in antecubital veins. The physiologic reasons for both the systemic exercise effect and the arteriovenous differences remain unknown. Measurement of plasma PPi for 10 consecutive days in a single normal subject under basal conditions, where these and other previously identified biologic variables (fasting and diurnal variation) were controlled, showed a coefficient of variation of 12.7%. Thus biologic variability contributed less to observed variation in plasma PPi than did methodologic errors (coefficient of variation of method = 8%). The striking reproducibility of plasma PPi in this subject suggests that this important metabolite is under rather tight homeostatic control.


[The possibility of endorphins playing a role in psychic disturbances].

1. The release of endorphins appears to play a role as a reserve-mechanism in stress situations. 2. The application of high doses of the specific opiate antagonist 12-allyl-7,7a,8,9-tetrahydro-3,7a-dihydroxy-(4aH)-(8,9-c)-iminoethanophenanthro(4,5-b,c,d)furan-5(6H)-one (naloxone) to schizophrenic patients induces a partial reversal of hallucinations and actual delusional experience within 2--7 h after injection. 3. The blockade of opiate receptors by naloxone is possibly also effective against catatonic states of schizophrenia. 4. In affective psychoses no curative action of naloxone could be detected so far.