Plasma renin activity and in vitro synthesis of aldosterone by the adrenal glands of rats with spontaneous, renal, or pinealectomy-induced hypertension.

In the present study a comparison was made on the role of the renin-aldosterone system in rats with various forms of experimental hypertension (pinealectomy-induced, renal and spontaneous). The plasma sodium and potassium concentrations as well as renin activity were measured. The in vitro production of aldosterone by quartered adrenal glands of these rats was also determined. 5 weeks after the operations the blood pressure of the pinealectomized and renal operated rats was significantly increased. The plasma sodium concentration did not differ in various groups, but that of potassium was decreased in the renal hypertensive animals. The plasma renin activity of the pinealectomized rats was elevated while in other forms of hypertension it was at the control level. The basal aldosterone production by the adrenal quarters was equal in all the groups. ACTH, dibutyryl cyclic adenosine-3',5'-monophosphate (DBA) and 5HT stimulated the aldosterone production. The responses to ACTH and DBA were greater in the adrenals of renal hypertensive rats than in the other forms of hypertension or in the controls. We suggest that the renin-aldosterone system is of importance in the maintenance of renal hypertension, while in pinealectomy-induced hypertension elevated plasma renin activity reflects an increased sympathetic activity which probably is the main cause of hypertension in these animals.


Studies in asymptomatic primary hyperlipidaemia II. Clinical findings.

A clinical and laboratory examination of abnormalities not attributable to atherosclerosis has been performed on 188 male and 126 female adult subjects with hyperlipidaemia. The sample was recruited from 20000 subjects screened at a health control centre who had an initial serum cholesterol and/or triglyceride (TG) concentration above 350 mg/100 ml and 3.50 mmol/l. All were subjectively healthy and had no history of atherosclerotic disease. Known cases of secondary hyperlipidaemia were excluded. Lipoprotein (LP) analysis with preparative ultracentrifugation and electrophoresis was made on all subjects including control group with "nonelevated" serum lipids. Typing of hyperlipoproteinaemia (HLP) was performed according to the modified system of Fredrickson et al. Compared to controls, subjects who had elevated very low density ?LP (VLDL) (types II B, III, IV and V) were more obsese, while subjectI B and women with type IV HLP than in the control groups. Arcus corneae was seen in 29% of control groups. Arcus corneae was seen in 29% of controls and in higher frequencies in types II A and II B. A positive correlation existed between the frequency of arcus corneae and the mean low density LP cholesterol in the different types. Multiple tendon xanthomata (n equals 11) were found exclusively in type II A HLP, palmar xanthomata (n equals 3) only in the presence of floating beta-LP and eruptive xanthomata in one male with type V HLP. The mean ESR was increased in all types of HLP. The mean S-GPT and uric acid concentrations were higher in type IV HLP in both sexes than in the control groups. In men with type IV HLP S-GPT was positively correlated to tvldl tg. the uric acid level was correlated to both the VLDL TG concentration and body weight independently. Of the male subjects with HLP 1/3-1/2 had a diabetic or borderline i.v. glucose tolerance.


Effect of arginine deficiency on the reproduction of human cytomegalovirus.

In arginine-deprived human embryonic fibroblasts the reproduction cycle of human cytomegalovirus (CMV) is incomplete. Infectious virus cannot be demonstrated in cell disintergrates, and from among the CMV antigens only the diffuse cytoplasmic antigen is detectable by immunofluorescence. The antigens localized in the cell membrane and those appearing during the complete cycle as large granules or inclusion-like bodies in the nucleus do not appear in the absence of arginine. The CMV genome persists in the arginine-deprived culture; after re-feeding with arginine-containing medium, maturation of virions soon ensues. Maturation could be prevented by inhibitors of protein synthesis, but not by DNA inhibitors, added simultaneously with completion of the medium.


Post-therapeutic levels of antimicrobial drugs in faeces.

After oral administration for 3 days, furazolidone disappeared from the faeces on the first, polymyxin B and ampicillin on the fourth, and trimethoprim + sulphamethoxazole and nalidixic acid on the fifth day.


Virus-specific changes in mouse cells inoculated with a strain of human cytomegalovirus.

Cytopathic changes and virus-specific antigens developed in, then disappeared from, mouse fibroblasts infected by a strain of human cytomegalovirus (CMV), but their disappearance was delayed in cells treated with idoxuridine prior to infection. The replication of vesicular stomatitis virus and herpes simplex virus was restricted in human CMV-infected mouse cells as long as human CMV-specific antigens were present. Virus-specific antigens could be induced by treatment with idoxuridine or arginine deficiency in mouse cells which had previously turned "negative".


Interferon induction and action in transformed poikilothermic cells.

The production and effect of interferon in the virus-transformed cell line TGk1, originating from kidney cells of Testudo gracea were studied and compared to those in the primary cell culture. West Nile virus and Newcastle disease virus were used as inducers. Interferon production in TGk1 cells began 6 hr later than in the primary cell culture and reached the maximum 64 IU, 18 hr after virus inoculation. In the primary culture, interferon production increased till the 48th hr reaching a fourfold level (256 IU). A significant reduction of the antiviral effect of interferon against vesicular stomatitis virus but not against vaccinia virus was observed in the transformed cells. The decreased interferon production and effect in TGk1 cells is regarded as a consequence of the disturbance of the interferon regulatory mechanism taking place as a result of the virus-induced transformation.


Concanavalin A as a quantitative and ultrastructural probe for normal and neoplastic cell surfaces.

Concanavalin A (Con A) has been popularly used as a cell surface probe for normal and neoplastic cells. Differences between normal fibroblasts and their transformed derivatives were examined using Con A agglutination, quantitative labeling with 125I-Con A and ultrastructural labeling with fluorescent- or ferritin-Con A. Con A agglutinates confluent-SV3T3 and 3T3 cells at midpoints of 20-60 and greater than, 500-2,000 mug/ml, respectively, and sparse cells at 5-15 and 1,200-1,500 mg/ml, respectively. Quantitative binding of 125I-Con A at 4 degrees C (10 or 15 min) with saturating lectin concentrations does not indicate a difference in the number of Con A receptors on sparse or confluent 3T3 and SV3T3 cells similar to many publications, but contrary to Noonan and Burger (1973). Under these conditions of labeling, ferritin-Con A is not internalized, indicating absence of endocytosis. The lateral mobility of Con A receptors and their relative ability to be aggregated on the cell surface by Con A was investigated with fluorescent- and ferritin-Con A. The initial distribution of Con A receptors on 3T3, SV3T3 and MSV3T3 cells under conditions of labeling at low temperature (0-5 degrees C) or to fixed cells was essentially randomly dispersed, but changes quickly to aggregated on SV3T3 and MSV3T3 (but not 3T3) after shifting the temperature to 20-37 degrees C, indicating, in general, a greater relative mobility of Con A receptors on SV3T3 and MSV3T3 cells. The aggregated Con A receptors seem to be directly involved in cell agglutination because they are usually found at the sites of cell-to-cell contact during 10 min agglutination experiments with ferritin-Con A. When confluent-3T3 cells are labeled on monolayer with ferritin-Con A at 0-4 degrees C, washed and then shifted to 20-37 degrees C for 10-15 min prior to in situ embedding, two classes of Con A receptors can be identified. One class appears to have low relative mobility and is associated with the 3T3 cell's extensive subplasma membrane microfilament network, while the other is capable of being aggregated and eventually endocytosed. On confluent-SV3T3 cells, only the latter class of receptors appears to be present, indicating a possible loss of cytoplasmic control over the distribution and mobility of lectin-binding sites on transformed cell surfaces.


Cell cycle dependent agglutinability, distribution of concanavalin A binding sites and surface morphology of normal and transformed fibroblasts.

In studies on phenotypic reversion of transformed cells to normal growth patterns, we investigated the effect of dibutyryl cyclic AMP (dbc-AMP) and a protease inhibitor (TLCK) on growth of SV40-transformed mouse fibroblasts (3T3). The results did not support the hypothesis that transformed cells grown with dbc-AMP or TLCK are induced to contact-mediated growth control. The growth rate of SV-3T3 cells grown with the drugs was strongly reduced, due to accumulation of the cells in the G2 phase of the cell cycle. In addition, decreased agglutinability with concanavalin A (Con A) of those SV-3T3 cells was not caused by a direct effect of the drugs on the cell surface, but by partial synchronization of the cells in the G2 phase of the cycle. In synchronized cultures agglutinability of transformed cells reached a minimum in G2 and was maximal in mitosis and G1. Normal cells agglutinated only in mitosis. This suggested that agglutinability of cells is somehow cell cycle dependent. Cytochemical investigations on normal and transformed 3T3 cells had shown that Con A-induced redistribution of binding sites on the surface of these cells is not correlated with agglutinability. The present work on replicas confirmed this, but indicated also that normal 3T3 cells have more extended lamellipodia with less Con A binding sites than SV-3T3 cells. Preliminary scanning electron microscope data showed cell cycle dependent changes in 3T3 cells and also showed that confluent 3T3 and SV-3T3 cells suspended for agglutination tests had a different surface morphology. These results may represent additional factors important for differences in cell agglutinability by Con A.


Concanavalin A as a probe for studying the mechanism of metabolic stimulation of leukocytes.

The disruption of the molecular organization of the plasma membrane of leukocytes by phagocytosable particles, or by agents such as surfactants, antibodies, phospholipase C, fatty acids and chemotactic factors, leads to a stimulation of the phagocyte oxidative metabolism. Concanavalin A (Con A) has been used as a tool to study the mechanism of this metabolic regulation. The binding of Con A to the surface of polymorphonuclear leukocytes (PMNL) or macrophages produces a rapid enhancement of oxygen uptake and glucose oxidation through the hexose monophosphate pathway (HMP). This is explained by an activation of the granular NADPH oxidase, the key enzyme in the metabolic stimulation. The effect of Con A is not due to endocytosed lectin, since Con A covalently coupled to large sepharose beads still acts as stimulant. The metabolic changes caused by Con A are reversible. If, after the onset of stimulation, sugars with high affinity for Con A are added to the leukocyte suspension, the activity of granular NADPH oxidase and the rate of respiration and glucose oxidation return to their resting values. The metabolic burst, while partially supressed by treatment of PMNL with iodoacetate, sodium flouride and cytochalasin B, is slightly increased by colchicine. Con A induces a selective release of granular enzymes (beta-glucuronidase, peroxidase, alkaline phosphatase) from PMNL, whereas no leakage of cytoplasmic enzymes is observed. The enzyme release is inhibited by iodoacetate and by drugs known to increase cell levels of cyclic AMP. Based on a current view of the mode of interaction between Con A and cell surfaces, a model of the metabolic disruption of leukocytes is presented.


Enhanced cytotoxicity in mice of combinations of concanavalin A and selected antitumor drugs.

Concanavalin A (Con A) injected intraperitoneally at a dose of 50 mg per kg was not lethal for male BALB/c mice. Six hours after administration of 5 mg Con A/kg, the proportioy 24 hr, the proportion of granulocytes had decreased to 56%. Adiministration of 5 mg Con A/kg 24 hr before 200 mg of 5[3,3-bis(2-chloroethyl)-triazeno]-imidazole-4-carboxamide per kg, or 100 mg of 5-fluorouracil per kg resulted in a significant enhancement of lethality. Simulatenous administration of 5 mg Con A/gm and 10 mg of daunomycin per kg also resulted in enhanced lethality. Administration of 5 mg Con A/kg 24 hr before 40 mg of 1,3-bis(2-chloroethyl)-1-nitrosourea per kg, 200 mg of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea per kg, 1000 mg of cytosine arabinoside per kg, 0.1 mg of mithramycin per kg, 2 mg of pactamycin per kg or 1 mg of vincristine per kg did not result in enhanced lethality. Lipid A prepared from Escherichia coli 0127:B8 Boivin lipopolysaccharide has been complexed to Con A. The lipid A-Con A complex (5mg/kg) was no more, or less effective in enhancing the lethality of 5-fluorouracil than 2.5 mg Con A/kg. The lipid A-Con A complex (40 mg/kg), given simultaneously with drug, enhanced lethality per kg. In this regard, the lipid A-Con A complex had vincristine per kg. In this regard, the lipid A-Con A complex had activity comparable to the complex formed between lipid A and bovine serum albumin. Conceivably, Con A can be used to enhance the susceptibility of neoplastic cells to phase-specific antitumor drugs, especially those acting on deoxyribonucleic acid synthesis.


Studies on the spin state of 3-methylcholanthrene induced cytochrome P-450 from rat liver.

The time course of infuction of rat liver microsomal cytochrome P-450 by the polycyclic hydrocarbon 3-methylcholanthrene was followed by measuring the specific content of cytochrome P-450, benzpyrene hydroxylase activity, and the percent of cytochrome P-450 existing as the high-spin form (g equal to 7.9, 3.7 and 1.7) as determined by low temperature EPR spectroscopy. Significant increases in benzpyrene hydroxylase, cytochrome P-450 and high-spin ferric hemoprotein are seen twenty-four hours following 3-methylcholanthrene treatment. Administration of DL-ethionine prior to 3-methylcholanthrene treatment effectively blocks any increase in benzypyrene hydroxylase and cytochrome P-450 but not the increase in the levels of the high-spin species of the hemoprotein normally seen following 3-methylcholanthrene induction. In addition, partially purified cytochrome P-450 can be isolated from liver microsomes of 3-methylcholanthrene treated rats as low-spin ferric hemoprotein containing essentially no high-spin species (smaller than 1 per cent). This partially purified hemoprotein has the same substrate specificity as the microsomes from which it was derived. It is therefore concluded that the appearance of the high-spin form of cytochrome P-450, as quantitated by EPR, does not correlate with the induction of cytochrome P-450 and benezpyrene hydroxylase activity by 3-methylcholanthrene.


Biochemical characterization of highly purified cytochrome P-450 and other components of the mixed function oxidase system of liver microsomal membranes.

Cytochrome P-450 has been purified from liver microsomes of phenobarbital-induced rabbits in the presence of ionic and nonionic detergents to concentrations over 17 nmoles per mg of protein. The purified cytochrome P-450 LM gives a single major band on SDS-polyacrylamide gel electrophoresis representing about 90 per cent of the total protein. The polypeptide chain has a molecular weight of about 49,000 daltons. NADPH-cytochrome P-450 reductase has been purified from liver microsomes of phenobarbital-induced rats in the presence of ionic and nonionic detergents to a stage where it catalyzes the reduction of 33,000 nmoles of cytochrome c per min per mg of protein. The ratio of activities toward cytochrome P-450 and cytochrome c is constant throughout purification. The purified reductase contains equimolar amounts of FMN and FAD and gives a single major band on SDA-polyacrylamide gel electrophoresis accounting for about 70 per cent of the total protein; the molecular weight is about 80,000 daltons. The purified cytochrome P-450 is free of cytochrome b5 but contains another electron acceptor, provisionally called Factor C, which is equivalent in amount to the heme present. Two electrons are taken up per molecule of cytochrome P-450 from dithionite or from NADPH in the presence of catalytic amounts of the reductase, and both electrons are readily transferred from the reduced cytochrome P-450 to molecular oxygen or artificial electron acceptors. The reconstituted enzyme system containing purified cytochrome P-450, purified NADPH-cytochrome P-450 reductase, and phosphatidylcholine retains the ability to catalyze the hydroxylation of drugs, fatty acids, hydrocarbons, and aniline in the presence of NADPH and molecular oxygen.


The role of cytochrome b5 in mixed function oxidations: effect of microsomal binding of the hemoprotein on hepatic N-demethylations.

Incubation of rat cytochrome b5 (D-b5) with rat liver microsomes resulted in specific binding of the hemoprotein. The bound hemoprotein was rapidly reduced by NADH. The NADH cytochrome c reductase activity in these preparations increased in proportion to the amount of cytochrome. In contrast to D-b5, which inhibited N-demethylation and the NADH synergism, the binding of cytochrome b5 preparations, reconstituted from heme and apocytochrome b5 had no effect on either the NADPH-dependent N-demethylation of aminopyrine or ethylmorphine or the NADH synergism observed with rat liver microsomes. In addition, manganese protoporphyrin-apocytochrome complex, when bound to microsomes in amounts equilvalent to D-b5, showed no effect on N-demethylation activity. These results suggest that homogeneous cytochrome b5 contains contaminating amounts of tightly bound detergent which presumably is removed during the extraction of the heme from the apocytochrome.


Electroresponsive properties of dendrites in central neurons.

A brief sketch of the historic development of the concept of neuronal integration is given. Some of the properties of dendritic spikes in chromatolyzed motoneurons, alligator Purkinje cells, and fish oculomotor neurons are reviewed, as well as the various ways in which the generation of dendritic spikes has altered our basic concept of neuronal integration. The principles of dendritic inhibition are elaborated, both as a "tonic modulatory action" and as a "functional amputating system" for dendrites that generate spikes.


Some aspects of the electroanatomy of dendrites.

An understanding of the neuronal function requires the knowledge of the electroanatomy of dendrites, which comprise the major area and receive the main input in most neurons. Some simplifying assumptions are necessary to describe the electrical characteristics of the dendritic tree. The applicability of the simplified model of a combined equivalent dendritic cylinder proposed by Rall, was tested and verified by a combined analysis of anatomic and electrical data from the same spinal motoneurons. Assuming a uniform somadendritic membrane, estimates of the specific membrane resistance (RM: 2,700 +/- 920 omegacm2) were made by relating the neuronal input resistance with the combined dendritic trunk parameter (sigmaD3/2: 320 +/- 150-10(-6) CM3/2). From these combined anatomic and electrical data the dendritic electrotonic lengths (Lgeom: 1.5 +/- 0.3 times the length constant) were derived. Comparable L values (Ltrans: 1.5 +/- 0.3) resulted independently from analysis of membrane voltage transients during current steps. The linear  dendritic cable model has proved its applicability for the analysis of small voltage deflections during current step applications at the soma as well as for the analysis of the majority of minimal postsynaptic potentials (PSP's). During the transmission along the dendritic cable the PSP undergoes changes in shape. These changes often permit a determination of the distance of the dendritic input from the soma. Unfortunately, the attenuation of the dendritic signal cannot be directly assessed. Dendritic synaptic transmission can be observed in isolation in chromatolytic motoneurons because the somal synapses are peeled off from the soma by proliferating glial cells in the course of retrograde reaction. These observations support the prediction that the PSP's with relatively short rise-times and duration originate from synapses near the soma. It may be questioned as to whether the linear dendritic cable approximation also applies to the larger voltage displacements during excitatory synaptic action. Particularly interesting is an increase of the apparent membrane resistance during depolarization known as anomalous rectification. The anomalous rectification could be reversibly eliminated and turned into a normal rectification by the application of cobalt ions or other calcium antagonists. Therefore, it appears likely that this phenomenon is caused by a voltage-(and time-) dependent reaction of the membrane, consisting of a smoothly increased calcium conductance during depolarizations that are even subthreshold for eliciting action potentials. Such a process would result in a shortening of the dendritic electrotonic length and in facilitating the postsynaptic excitatory transmission.


An office technique for identifying crystal in synovial fluid.

Crystal identification is made with a polarizing, color-compensated light microscope. Most microscopes can be easily and inexpensively adapted for crystal identification. The color compensator allows differentiation between the monosodium urate crystals of gout and the crystals of pseudogout, or calcium pyrophosphate deposition disease. All synovial fluid specimens should be examined. The observation of phagocytosis of crystals establishes that they are the etiologic agent responsible for an ongoing acute attack of arthritis.


Nonbacterial thrombotic endocarditis in a Japanese autopsy sample. A review of eighty cases.

A study of nonbacterial thrombotic endocarditis has been carried out in a series of 3,404 autopsies performed upon atomic bomb survivors in Hiroshima in the period 1953-1970. The prevalence of the lesion was 2.4 per cent, with a greater frequency among the elderly and among females, and with a significant relationship to malignant neoplasms. In contrast to other reported series, there was a greater prevalence among cancers of the colon, rectum, and female genitourinary tract. No relationship was noted between the presence of NBTE and exposure to ionizing radiation. Histologic findings in the heart-valve leaflets in close proximity to the verrucae, like experimental studies reported by others, suggest that in association with severe systemic disease there appears a process consisting of degenerative changes in valve collagen and ground substance, with subsequent denudation of endothelium, localized almost entirely to the apposing leaflet surfaces of the left-heart valves. The verrucae of nonbacterial thrombotic endocarditis are then formed upon this abnormal leaflet surface. While the relationship between systemic disease and the pathologic changes observed in cardiac valve tissue is unclear, and although it is not known whether a "hypercoagulable state" may accentuate the tendency for thrombi to form upon these abnormal valves, there is no doubt that this lesion represents a clinically important complication of severe systemic disease. It also seems likely that in some cases NBTE may complicate an illness which may otherwise be curable. Increasing awareness of this pathologic entity among clinicians, coupled with appropriate laboratory techniques, most likely echocardiography, will permit more frequent diagnosis in living patients.


[Bronchial asthma and the beta adrenergic system].

The relationship between bronchial asthma and the beta adrenergic system is considered both from the physiopathologic and therapeutic point of view. A brief analysis of the sympathetic system is performed. The sympathetic nervous system is responsible for bronchodilation mediated through its beta-receptors. To evaluate this activity, beta adrenergic blockers such as propanolol are used. When this agent is administered, a descent of conductance is observed. On this condition, vagal stimulation brings about bronchoconstriction. At bronchial level, it seems that the beta-adrenergic system antagonizes vagal effect. From the physiopathologic point of view, Szentivanyi (1968) suggested a spontaneous beta block in the asthmatic. Other theories refer to a pathologic sensitivity of the peripheral bronchial receptors. The natural beta-adrenergics and the beta-adrenergic drugs enhance the synthesis of cAMP by stimulating the adenil cyclase system. This effect brings about relaxation of the bronchial smooth muscle. Considering the therapeutic effects, a comparative study of bronchodilators is performed. From all, Salbutamol has an intense broncholytic effect with little effect on heart dynamics. When sympathomimetics are bound to use in asthma, drugs such as Salbutamol and Terbutalina should be preferred because of its low cardiogenic effects. Its administration per os has rendered doubtful results.


Cyclic AMP induces ultrastructural differentiation of normal adult human adrenocortical cells cultured in vitro.

Electron microscopic studies have revealed that cyclic AMP, like ACTH, induces structural differentiation of adult human adreno-cortical cells cultured in vitro. These findings support the hypothesis that cyclic AMP can function as an intracellular mediator of the action of ACTH on the human adrenal gland.


The histogenesis of mixed cervical carcinomas. The concept of endocervical columnar-cell dysplasia.

In a case of cervical adenocarcinoma in situ, accompanied by relatively minor squamous-cell dysplasia, the neoplastic glandular cells were associated with "abnormal" but not clearly cancerous surface cells of the endocervix. Measurements of the nuclear DNA of these cells revealed an aneuploid pattern similar to that of epidermoid dysplasias. It is suggested that endocervical dysplasia is a valid entity and represents a step in the evolution of cervical adenocarcinoma from reserve cells comparable to the position of epidermoid dysplasia in the genesis of epidermoid carcinoma.


Ultrastructural analysis of the testes in male pseudohermaphrodism reductase.

Light and electron microscopic observations of the testes in male pseudohermaphrodism due to deficiency of 17-ketosteroid reductase demonstrate an increased thickness of the walls of the seminiferous tubules. Although the seminiferous tubules are filled mostly by Sertoli cells containing crystalloids of Charcot-Bottcher, clusters of spermatogonia and spermatocytes are located at infrequent intervals along their lengths. Differentiation of spermatogenetic cells beyond the spermatocyte stage was not observed. Hyperplasia of Leydig cells, which are structurally similar to those of the normal testis, was pronounced. Pigment bodies were present in Leydig cells, whereas crystals of Reinke were not observed. The decreases in plasma androstenedione, testosterone and estrone following orchiectomy and the presence of a well-developed system of organelles (smooth endoplasmic reticulum and mitochondria containing tubular cristae), typical of steroid-secreting cells, indicate that the Leydig cells were active in steroid hormone synthesis, albeit deficient in 17-ketosteroid reductase activity.


Congenital malformations. Cleft palate, congenital heart disease, absent tibiae, and polydactyly.

A girl had cleft palate, micrognathia, Wormian bones, congenital heart disease, dislocated hips, absent tibiae, bowed fibulae, preaxial polydactyly of the feet, and abnormal dermal patterns at birth. She was born after a pregnancy complicated by exposure to multiple medications. This combination of malformations may represent a distinct entity unrelated to the medication or may be a complication of the intrauterine drug exposure.


The Seattle Virus Watch. VI. Observations of infections with and illness due to parainfluenza, mumps and respiratory syncytial viruses and Mycoplasma pneumoniae.

Seattle Virus Watch families were observed, 1965-1969, for infections with paramyxoviruses and M. pneumoniae by agent isolation and antibody assay of serial sera. Infection rates, based on serology, exceeded those in Tecumseh where families contained fewer young children. Rates per 100 person-years were 44.4 for parainfluenzavirus, 21.6 for respiratory syncytial (RS) virus and 12.3 for M. pneumoniae. Preschool children experienced the highest rates for RS and parainfluenza-viruses but, for the latter, rates were also high among older children and adults. Within invaded families infection rates generally varied inversely with age, although for M. pneumoniae the rates for adults and 6-9 year old children nearly equalled the infant rate. The introducers' identity and/or the age-specific infection rates in invaded families support the role of young schoolchildren in community spread of M. pneumoniae and, together with older children and adults, of RS virus. Young schoolchildren were less important than infants, preschoolers, and adults in spreading parainfluenza-viruses and less important than preschoolers and infants for mumps. The frequent infection of exposed older children and adults suggests that reinfection with all the agents studied is common. All agents spread significantly within families and secondary attack rates for the mostly non-immune infants indicated high infectivity of parainfluenza and mumps viruses. The basic high pathogenicity of these agents and of RS virus is indicated by the high frequency of illness among virus shedders (80-90%) and among seroconverting infants (greater than or equal 68%). The less frequent illness of older persons with serologically proven infection is consistent with diminished clinical response to reinfection. Parainfluenza-associated illnesses were relatively severe and contributed up to 9.3% to total respiratory illnesses. RS virus-related illnesses also were severe but contributed less (4-5%) to total respiratory disease. Mumps-associated illness was largely respiratory, 65% overall, 77% in infected infants and 75% above age 9. Thus, mumps virus emerges as another respiratory pathogen which is spread largely by 2-5-year old children rather than by schoolchildren with "typical" parotitis.


Isolation of foamy viruses from baboon (Papio cynocephalus) tissues.

Fourty per cent of baboon kidney cell cultures were found to contain foamy virus contaminants regardless of sex of the animal, source or time of year. The older the animal, however, the higher the incidence. Fifty percent of placentas examined contained foamy virus, with first and second trimester specimens more likely to be positive. Foamy virus isolates from baboon lymphocytes were also more frequent as the age of the animal increased. Freezing and thawing these lymphocytes prevented foamy virus isolation. The foamy virus isolates were identified as types 1, 2, or 3.


Bivariate analyses of cholesterol and triglyceride levels in families in which probands have type IIb lipoprotein phenotype.

Univariate and bivariate analyses of cholesterol and triglycerides are performed after appropriate age adjustment on 247 individuals in 33 families where the probands have elevations of cholesterol, low density lipoprotein and triglycerides, and type IIb lipoprotein phenotype. Mixture of lognormal distributions are fitted by maximum likelihood to the data. Best fitting single and mixtures of lognormal distributions are compared with empirical cumulative plots, and the likelihood-ratio criterion is used to test for significance. A mixture of two lognormal distributions fits significantly better than one lognormal distribution for cholesterol but not for triglycerides. When a mixture of bivariate lognormals is fitted to the data, only one local maximum is found, suggesting action of a single genetic determinant in this sample. The best cutoff line is almost parallel to the triglyceride axis, indicating the relatively high involvement of cholesterol compared to triglycerides in separating the normal and abnormal groups. Using the best linear function, the difference in the two bivariate means is found to account for 61% of the total variation in log cholesterol and log triglycerides. To determine if the results are due to enrichment of the sample with familial hypercholesterolemia syndrome, seven families where the proband and/or any relative has tendon xanthomas are removed and the analyses repeated on the remaining 26 kindreds. The results of these analyses are virtually the same as those of the total sample. Also, a subsample of 21 families in which the proband and at least one additional kindred member are affected is analyzed in the same manner with similar results. For comparison, data from a study of families with combined hyperlipidemia [1] are analyzed in an analogous manner, bearing in mind that the populations sampled are probably different. Fitting a mixture of two bivariate distributions and finding the best cutoff to these data indicate that triglycerides are more involved in separating the two groups. Probably because of major differences in ascertainment, the distribution of lipid levels in oour patient group is practically indistinguishable from that of hypercholesterolemia, and the Seattle data [1] are more nearly similar to hypertriglyceridemia. It may be premature to consider familial combined hyperlipidemia as an entity distinct from both hypercholesterolemia and hypertriglyceridemia. We hope it will eventually be possible to analyze these data using a refined genetic model that includes both major gene and polygenic effects and to combine this form of analysis with quantitative tissue culture methods.


Leukodystrophy, skin hyperpigmentation, and adrenal atrophy: Siemerling-Creutzfeldt disease. Transmission through several generations in two families.

Two apparently unrelated families with a history of leukodystrophy associated with adrenal insufficiency are presented. Only about 20 cases of this syndrome have been reported until now. It was first described by Siemerling and Creutzfeldt; therefore we propose the designation Siemerling-Creutzfeldt disease. Our pedigrees include 15 additional cases and prove that this disease is inherited as an X-linked or as an autosomal dominant trait with male sex limitation. Within these families, the interindividual variability of clinical signs is remarkable. Patients can survive into the fifth decade, and one has reproduced. Attempts to identify heterozygotes on the basis of endocrinologic investigations were unsuccessful.


Autoimmune hyperlipidemia in a patient. Atherosclerotic course and chaning immunoglobulin pattern during 21 years of study.

A 48 year old male patient presented with xanthomatosis, hyperbeta lipoproteinemia and hyper-IgA globulinemia; these two serum components occurred as a "complex." The patient has subsequently been studied for 22 years (1952 to 1974). His serum cholesterol and triglyceride levels have been consistently and excessively high despite efforts to regulate them by means of diet or diet and drugs. Serum immunoglobulin A (IgA) concentration ranged from 1,400 to 3,400 mg/dl compared with a normal value of 156 plus or minus 92 mg/dl. The metabolism of lipoproteins, judged by vitamin A turnover studies was slow. Peripheral atherosclerosis became evident 15 years after beginning the study whereas cinecoronary arteriography concurrently demonstrated only minimum changes. Xanthomas exhibited marked regression only during the last 6 years, after 16 years of diet and the addition of clofibrate for 7 years. Beta lipoprotein and IgA globulin determined by immunofluorescent and immunoelectrophoretic technics were demonstrated in the atherosclerotic material obtained from the patient's arterial wall. They were also found in the plasma cells of the bone marrow. The IgA globulin-beta lipoprotein complex in the serum was broken with difficulty. The patient's isolated IgA globulin, free of lipoprotein, formed a firm complex when mixed with beta lipoprotein prepared from normal human serum. Initially, IgA globulin studies showed presence of both kappa and lambda light chains in normal proportion. But after 18 years, the IgA globulin has become monoclonal, type lambda. The plasma cells of the bone marrow have become progressively more atypical and immature. No clinical indications of multiple myeloma have been found. It is concluded that association of lipoproteins with IgA globulin in the serum of this patient with hyperlipidemia, hyper-IgA globulinemia did not prevent the development of atherosclerotic lesions and the deposition of lipids and lipoproteins in the plaques. It is possible that the lipoprotein-immunoglobulin association may have retarded the process, since it became manifest only after many years of known hyperlipidemia.


Low density lipoprotein cholesterol (CLDL) and lipoprotein phenotyping.

Using an estimation of CLDL, 522 sera from 311 men and 211 women were studied. Lipoprotein phenotyping was done with and without knowledge of CLDL. Two hundred sixty-four of the 522 patients were considered abnormal without knowledge of CLDL. Interpretation was changed in 70 cases when CLDL was considered. Thirty-four were reclassified from 11B to IV because CLDL was not elevated. Thirty-three were reclassified from 11A to "slightly elevated cholesterol without other evidence of hyperlipoproteinemia" because CLDL was not elevated. Three were reclassified from normal to 11A because of elevated CLDL associated with borderline normal cholesterol.


Conjugated estrogens and hypercoagulability.

A group of 11 menopausal women receiving 1.25 mg. of conjugated estrogens daily had coagulation tests to determine the development of hypercoagulability after taking 5 and 21 tablets. There was no essential change in thrombin generation or fibrinolytic activity as measured by euglobin lysis time. There was a shift toward hypercoagulability in all three parameters of the thrombelastograms. The decrease of the antithrombin III activity was not as pronounced following the administration of conjugated estrogens as had been the change associated with oral contraceptives. Fibrin monomers were observed in some women during the first week of Premarin therapy.


Cryptophthalmos syndrome with basal encephaloceles.

A 2,144-g white girl was born with absence of the right ear and eye, cleft lip and palate, two basal encephaloceles, tricuspid atresia, ventricualr and atrial septal defects, detransposition of the great vessels, right aortic arch, and aberrant right subclavian artery. Through an oval defect in the center of the sphenoid bone, soft tissue protruded into the right nasopharynx. The medial portions of the roof of both orbits and the cribriform plate were absent and soft tissue protruded through this bony defect. Basal tomography was required to demonstrate the encephaloceles, which should be suspected in any child with a median cleft syndrome, a flat broad nasal root, and hypertelorism.


Diabetic hypertriglyceridemia.

The conference opened with the clinical presentation of a 50-year-old male with fasting hyperglycemia (296 mg per cent) and hypertriglyceridemia (2736 mg per cent). The discussion began with a summary of current concepts regarding the manner in which chylomicra (intestine) and very low density lipoproteins (intestine and liver) are formed, transported into the plasma, and removed from the circulation. This was followed by a consideration of diabetic hypertriglyceridemia in which this syndrome was subdivided into two categories. The first form is seen in patients with severe fasting hyperglycemia, and is characterized by marked insulin deficiency, decreased very low density lipoprotein production, a fall in the activity of lipoprotein lipase, and hypertriglyceridemia secondary to a defect in removal of lipoproteins from the plasma. In contrast the other form of diabetic hypertriglyceridemia is seen in patients with minimal abnormalities of carbohydrate tolerance, and in this instance insulin resistance, not insulin lack, seems to play the pivotal role. In these patients, the rise in plasma triglyceride levels seems to be secondary to increased production of very low density lipoproteins, presumably as a result of the hyperinsulinemia associated with the insulin resistance. The conference ended with an attempt to relate the patient presented to the models of diabetic hypertriglyceridemia that had been defined.


Epidemic hemorrhagic keratoconjunctivitis.

A new type of acute keratoconjunctivitis developed throughout Southeast Asia, beginning in Singapore in the summer of 1970. It was highly contagious and probably was transmitted from person to person by the hand to eye route. Sixteen cases, diagnosed by viral isolation or serologic study, or both, were subjected to detailed clinical observation. The characteristic features included a short incubation period of one or two days, watery or serous discharge, subconjunctival hemorrhage, and pinpoint superficial keratopathy. The disease usually resolved rapidly within one to two weeks without sequelae.


Mammary and extramammary Paget's disease.  An immunocytochemical study.

The localization and distribution of human casein has been investigated in 20 patients with Paget's disease (16 with the mammary and 4 with the extramammary form) by means of immunofluorescence and immunoperoxidase techniques.  This milk protein has been detected in neoplastic cells in intraductal carcinomas of the nipple and in intraepidermal cells identifiable as Paget cells.  The degree of the staining varied in different cells of the same case and in different cases.  Some casein-containing intraepidermal cells, as revealed by immunofluorescence, could not be recognized after retaining of the sections as Paget cells: they could not morphologically be distinguished from other basally located epidermal cells.  This finding raises the question of the existence of "pre-Paget" cells.  The results obtained are discussed in relation to theories on the origin and nature of Paget cells.  The immunocytochemical methods for casein detection might also be find possible application in the diagnosis of Paget's disease.


Production of lymphokine-like factors (cytokines) by simian virus 40-infected and simian virus 40-transformed cells.

Macrophage migration inhibitory (MIF-like) activity was demonstrated in the supernatant fluids from primary cultures of African green monkey kidney cells infected with simian virus 40 (SV 40) virus. Kidney cell cultures not infected by virus had no MIF activity. Supernatant fluids from continuous cultures of nontransformed and SV 40-transformed human fibroblasts contained MIF-like activity. Productive infection with SV 40 virus results in the production of a lymphokine-like factor, as previously observed in other virus-cell systems, involving mumps virus and Newcast,le disease virus. However, while infection with these paramyxoviruses causes the production of macrophage and neutrophil chemotactic agents as well as an MIF, SV 40 infection does not induce chemotactic factors. The results reported here, taken in conjunction with previous observations by ourselves and others, suggest that the production of lymphokine-like factors (cytokines) may represent a general biologic phenomenon, and that many, if not all, cell types, when appropriately stimulated, may be capable of such activity.


Separation of cells with histochemically demonstrable acid phosphatase activity from suspensions of human prostatic cells in an isokinetic gradient of Ficoll in tissue culture medium.

Collagenase, trypsin, and pronase were used in separate, parallel experiments to obtain cell suspensions from human prostates obtained from surgical resections and autopsies. All of the examined prostates demonstrated benign hyperplasia. The dissociation using pronase gave both the largest number of nucleated cells and the largest proportion of viable cells from prostates. Surgically resected prostates gave a larger number of cells per gram of tissue than prostates obtained from autopsy. Cells obtained from surgically resected prostates were separated both by isopycnic sedimentation and by velocity sedimentation in a previously described isokinetic gradient. We studied fifteen prostates obtained at surgery; using pronase, we obtained 2.1 plus or minus 3.5 times 10(6) cells/g. Of these cells, 34.0 plus or minus 14.7% contained histochemically demonstrable acid phosphatase. Cells from six prostates were separated by velocity sedimentation  in the isokinetic gradients; in the purest fractions from the isokinetic gradients, 81.0 plus or minus 12.2% of nucleated cells had histochemically demonstrable acid phosphatase. The cells in the purest fractions appeared to be epithelial cells. More than 99% of these separated cells excluded trypan blue. Isopycnic sedimentation was not an effective means of purifying epithelial cells from human prostates.


Norepinephrine vascoconstrictor escape in isolated meseneric arteries.

When isolated superfused cat mesentric arterial rings were exposed to norepinephrine(NE) 10'-6 g/ml, force initially increased but subsequently declined despite continuedadministration of NE.  Phasic contractions occurred in 48% of the vessels.  Norepinephrine concentrations just above threshold induced tonic contractions without escape.  When NE was administered after brief exposure of the arterial rings to low-calcium solutions, peak force development and escape were both reduced and phasic contractions were abolished.  Escape did not occur in potassium-depolarized vessels.  The peak response was increased and escape was reduced by substituting sodium in the Krebs solution by lithium and by substituting chloride with iodide or perchlorate.  Substitution of chloride by isethionate reduced the peak NE resonse and abolished escape.  Propanolol was without effect.  It is suggested that escape from NE vasoconstriction in mesenteric arteries is due to fading of propagated activity.


Effect of intravenous infusion of corticosteroids on blood pressure, electrolytes, and water metabolism in sheep.

ACTH administration (80 IU/day for 5 days), which produces hypertension and charateristic metabolic effects in sheep (38), has been compared with the effect of intravenous infusion of cortisol (5 mg/h), corticosterone (0.5 mg/h), deoxycorticosterone (50 mug/h), and 11-deoxycortisol (1 mg/h), each given singly for 5 days.  Further, a mixture consisting of aldosterone (3 mug/h), cortisol (5 mg/h), deoxycorticosterone (25 mug/h), corticosterone (0.5 mg/h), and 11-deoxycortisol (1 mg/h), was also infused intravenously for 5 days.  In another series of experiments, 18-hydroxydeoxycorticosterone (100 mg/h) was also included in the combined-steroid solution.  With the exception of 18-hydroxydeoxycorticosterone, which was not measured, the rates of infusionproduced peripheral arterial blood levels of the steroids similiar to those seen with ACTH stimulation.  Blood pressure,water intake, urine output, and plasma and urinary electrolytes were measured: individual steroids had little effect on these, but manyof the metabolic changes produced by ATCH (hypokalemia and increased water intake andurine output) were produced by the combined-steroid infusion.  However, the combined-steroid infusion failed to induce an increase in blood pressure similiar to that seen inthe ACTH experiments.  Thus the findings are against a major role in ACTH hypertension for any steroid used, either singly or in combination.  As yet unrecgnized factor/s may be involved in the ACTH-induced hypertension.


Effect of acetazolamide on sodium and chloride transport by in vitro rabbit ileum.

Acetazolamide (8 mM) aboishes active Cl absorption and inhibits but does not abolish active Na absorption by stripped, short-circuited rabbit ileum.  These effects are not accompanied by significant changes in the transmural electrical potential difference or short-circuit current.  Studies of the undirectional influxes of Na andCl indicate that acetazolamide inhibits the neutral, coupled NaCl influx process at the mucosal membranes.  This action appears to explain the observed effect of acetazolamide on active, transepithelial Na and Cl transport.  Acetazolamide did not significantly inhibit either spontaneous or theophylline-induced Cl secretion by this preparation, suggesting that the theophylline-induced secretion may not simply be due tothe unmasking of a preexisting efflux process when the neutral influx mechanism is inhibited by theophylline.  Finally, inhibition of the neutral NaCl influx process by acetazolamide does not appear to be attributable to an inhibition of endogenous HCO3production or an elevation in intracellular cyclic-AMP levels.  Instead, it appearstheat the effect of acetazolamide is due to a direct interaction with a membrane component involved in the coupled influx process.


Insulin and epinephrine effects on heart glycogen synthase and phosphorylase activity.

The effect of intravenous epinephrine on heart glycogen synthase and phosphorylase systems in control and insulin-pretreated rats was studied.  The percent of synthase in the I form decreased rapidly after epinephrine treatment but the change was small and sometimes not significant.  In insulin-pretreated rats in which the percent synthase I was increased, epinephrine produced a definate and highly significant decrease.  There was a simultaneous increase in percent phosphorylase a in both groups.  The synthase and phosphorylase responses were statiscally significant at 2.5 mug epinephrine/kgor more.  These data are compatible with a mechanism in which protein kinase is activated by an increased cAMP concentration and affects both the synthase and phosphorylasesystems simultaneously.  Propranolol blocked the epinephrine effects on cAMP, synthase I, and phosphorylase a.  Although insulin had little effect on the response ofthe synthase and phosphorylase systems to epinephrine, it nealry completely blocked glycogen degradation.  The mechanism is unknown, but it appears to be due to an inhibition of phosphorylase a catalytic activity in vivo.  Acetylcholine had no effect on synthase I, phosphorylase a, or cAMP in control or in insulin-pretreated animals.


Glycerokinase in mammalian adipose tissue: stimulation by lipogenic substances.

A connecting link between carbohydrate and fat metabolism in adipose tissue is theconcentration of alpha-glycerophosphate derived predominantly from the glycolysis ofglucose entering the fat cell.  However, several investigators have reported the presence of a glycerol specific kinase in the epidiymal fat-pad of the rat and obob mouse. This enzyme's presence in other mammalian adipose tissue could contribute to the alpha-glycerophosphate pool and thus affect both carbohydrate and fat metabolism within the fat cell.  Glycerokinase was demonstrated in isolated fat cells obtained from the subcutaneous, perirenal, epididymal, and dorsal intrascapular brown fat depots of the adultmale rat.  It was found to be particularly sensitive to in vivo lipogenic stimuli in both the subcutaneous and the brown adipose tissue and concluded that insulin is involved in adipose glycerokinase stimulation.  Therefore, the main function of glycerokinase in normal adipose tissue may be to augment the anabolic action of insulin.  It isfurther suggested that deviation from the normal control of this lipogenic enzyme couldlead to a gradual accumulation of fat and eventual obesity.


CNS regulation of metabolic rate in the kangaroo rat Dipodomys ingens.

Water-perfused thermodes were chronically implanted around the preoptic nuclei and hypothalamus (POH) of kangaroo rats (Dipodomys ingens).  Responses in rate of metabolic heat production to manipulations of POH temperature (Thy) were measured in unanesthetized, unrestrained animals at ambient temperatures of 10, 20, 25, and 30 degreeC.  The threshold Thy and the proportionally constant (alpha) for this response consistently decreased as ambient temperature increased, but alpha was not significantly different between any two Ta's.  Average values of alpha for the three animals studied ranged between -.0024 W.g minus 1.degree C minus 1 and -.0034 W.g minus1.degree C minus 1.  No influence of extrahypothalamic core temperature on the characteristics of the central nervous system regulatory mechanism was observed.  Ahypothesis accounting for high POH and low peripheral thermosensitivities in small mammals is presented.  An additional finding was that during sleep there is a profound depression or elimination of POH thermosensitivity in this species.


Relationship between adenosine concentration and oxygen supply in rat brain.

Since adenosine is present in normal brain tissue and cerebrosipinal fluid and since it dilates the pial vessels, it is possible that adenosine, in addition to H-+, is also a mediator of the metabolic regulation of cerebral blood flow.  Evidence supporting this hypothesis was obtained under various experimental conditions characterized by achange in brain oxygen supply.  The brain was frozen in situ by means of a small bonerongeur precooled in liquid N2 and the tissue was processed for adenosine determination (nmol/g of tissue).  Electrical stimulation of the cortex at 0, 15, 30, and 45 Hz yielded adenosine levels of 5.4 plus or minus 0.7, 10.5 plus or minus 1.7, 13.0 plusor minus 1.2, and 9.0 plus or minus 2.1 nmol/g.  Arterial pressures of 87, 60, and 40mmHg gave adenosine levels of 7.5 plus or minus 0.76, 13 plus or minus 2.6, and 26.6plus or minus 3.3, respectively.  Ventilation with 29.7, 20, 10.7, and5.5% O2 significantly increased the adenosine levels to 9.4 plus or minus 3.0, 6.4 plus or minus 1.2, 30.0 plus or minus 9.3, and 63.3 plus or minus 18.2 nmol/g, respectively.  Hyperventilation significantly increased adenosine form 6.7 plus or minus 1.0 to 11.8 plus or minus 1.4 nmol/g.  This increased adenosine level was reduced by additionof CO2 to the ventilating gas mixture.  Lactate, the main H-+ donor, pyruvate, and cAMP changed in a fashion parallel to adenosine.  However, cAMP showedonly a small increase in adenosine.  These findings are in accordance with the concept that adenosine and H-+ may act synergistally to regulate cerebral blood flow and that endogenous adenosine may exert a small effect on cAMP formation.


The cost of schizophrenia.

The cost of schizophrenia has been estimated at $11.6 to $19.5 billion annually. About two-thirds of this cost is due to lack of productivity by schizophrenic patients and about one-fifth to treatment costs. The estimate might be considerably higher if better figures were available on the cost of maintaining patients in the community. In the absence of more effective treatment, the savings from the current trend toward shorter hospitalization cannot be expected to decrease-and may actually increase-the overall costs of schizophrenia to society. The authors make recommendations aimed at reducing the cost by helping schizophrenic patients to be more productive through a system of community alternative-care facilities, increased rehabilitation services, aftercare, and research.


Psychomotor activity as a correlate of Depression and sleep in acutely disturbed psychiatric inpatients.

Combining a lightweight telemetric mobility sensing system with nightly EEG-sleep recordings, the authors obtained continuous monitoring of rest-activity cycles among psychiatric patients hospitalized for primary depression or acute schizophreniform thought disorder. The patients with primary depression had a significantly higher percentage of their total 24-hour motor activity distributed during the night. Furthermore, this increased nocturnal motor activity did not correlate significantly with concurrent EEG-sleep measures of wakefulness. Indeed, the best predictors of wakefulness were measures of daytime activity. This desynchronization of sleep and nighttime motor activity in primary depression may explain the need for combined pharmacotherapy in some severely depressed patients. The authors suggest that expressing activity as a percentage distribution function, rather than in terms of absolute amplitude, provides an objective diagnostic index of depression.


Sleep-related penile tumescence as a function of age.

The authors conducted a study of nocturnal penile tumescence (NPT) in 125 healthy males aged 3 to 79 by means of EEG recordings to provide normative data on how general the phenomenon is, its range of charateristics, and how it is related to man's sexual function. The results indicate that NPT occurs consistently in a healthy male population, that its expression is significantly affected by age, that it is  related to stage of psychosexual development, and that it is worthy of further investigation. Clinical experience indicates that it is a useful, objective method of discriminating among various types of biogenic and psychogenic impotence.


Tissue culture of the sera in human ulcerative colitis.

1. Control human sera had no effect on human amnion cell culture. 2. The sera from nineteen of twenty-one patients with ulcerative colitis had a marked cytopathic effect on cell cultures, suggesting an autoimmune effect. The sera of three of these showed an additional cytopathic effect on human amnion cell culture, suggesting a viral-like quality. 3. The sera from patients after total colectomy and protectomy for ulcerative colitis had no effect on cell cultures. 4. Rabbit antisera did not produce demonstrable antibodies or protect against the cytopathic effect in cell culture.


The case against tylectomy for carcinoma of the breast. The factor of multicentricity.

Five hundred consecutive cases of breast carcinoma were studied to determine the incidence of multicentric lesions in the resected specimens. When residual tumor in juxtaposition to the primary tumor or biopsy cavity is excluded, 41.6 per cent of specimens exhibited multicentric foci of tumor; 31 per cent of such foci were in sectors or quadrants remote from the primary tumor. In more than half of these cases the lymph nodes were uninvolved and cure rate would have been maximal had these multicentric tumor foci been removed. These findings confirm previous similar studies and we consider tylectomy an inappropriate mode of therapy for breast cancer.


Regeneration of single skeletal muscle fibers in vitro.

A culture system utilizing single skeletal muscle fibers from adult rats was developed to study the origin and behavior of mononucleated myoblasts during muscle regeneration. The single fibers are removed manually from the leg and thigh muscles at 300-400 gm rats and maintained in vitro embedded in a fibrin clot overlain with culture medium. Regenerative events were monitored by continuous observations of the cultured fibers. During the first few hours in vitro the fibers undergo degenerative changes including the formation of myofibrillar contraction clots and pyknosis of myonuclei. The endomysial tube (basement lamina) remains intact along the entire length of the fiber and forms transparent chambers bridging the contraction clots. Single fibers are free of endomysial cells and display no cellular outgrowth in cultures, except at the cut ends. In contrast, a rich outgrowth of endomysial connective tissue cells is found with bundles consisting of two or more fibers. Isolated mononucleated cells, presumed to be muscle satellite cells, are present within the endomysial tube of single fibers at the onset of the culture period. There is no evidence that myonuclei contribute to the formation of mononucleated cells. The satellite cells enlarge and begin to proliferate during the second day in vitro to form clones of presumptive myoblasts within the endomysial tube. The early clones have a cell doubling time of about 22 hours and exhibit mitotic synchrony. After 5-7 days in vitro the satellite cell progeny begin to fuse to form multinucleated myotubes within the endomysial tube of the original fiber. The myotubes display spontaneous contractile activity and may extend throughout the length of the endomysial tube.


Clinical and immunologic responses of calves with colostrally acquired maternal antibody against parainfluenza-3 virus to homologous viral infection.

Exposure of colostrum-deprived calves and calves with colostrally acquired maternal antibody to aerosols of parainfluenza-3 (PI-3) virus resulted in signs of infection, leukopenia, and shedding of virus from the nasal passages. However, infection was not as severe in calves with colostrally acquired maternal antibody as it was in colostrum-deprived calves which did not have antibody to PI-3 virus before they were exposed. All calves responded immunologically to PI-3 virus, as indicated by resistance to challenge exposure and subsequent development of virus-neutralizing antibody. However, levels of serum and nasal secretion (NS) antibody at 30 days after viral exposure were lower in calves with colostrally acquired maternal antibody than in colostrum-deprived calves, and a serum antibody response in the former was primarily indicated by an anamnestic response after challenge exposure. After calves were challenge exposed to PI-3 virus, serum and NS antibodies were increased in all calves, but antibody titers were generally lower for calves that had colostrally acquired maternal antibody before their exposure than for those that acquired antibody only after PI-3 viral infection.


Lesions and pathogenesis of disease in young calves experimentally induced by a bovine adenovirus type 5 isolated from a calf with weak calf syndrome.

Lesions induced in each of 9 young colostrum-deprived calves closely resembled lesions seen in naturally occurring "weak calf syndrome" of eastern Idaho and southwestern Montana. The disease was experimentally induced by intravenous injection of bovine adenovirus type 5 that had been isolated from a calf with weak calf syndrome...


Canine adenovirus type 2-induced immunity to two canine adenoviruses in pups with maternal antibody.

Twenty-four Beagle pups with high levels of maternal antibody to canine adenovirus type 1 (CAV-1) and canine adenovirus type 2 (CAV-2) were oronasally inoculated with CAV-2 at 4 weeks of age. The CAV-2 was isolated from pharyngeal swabs on postinoculation days 2 through 6. In spite of the infection, maternal antibody continued to decrease for 4 to 8 postinoculation weeks, and then homologous CAV-2 neutralizing antibody and, to a lesser extent, CAV-1 neutralizing antibody began to increase. When these pups were challenge inoculated with CAV-1 and CAV-2 at a time when maternal antibody to CAV-1 would normally have disappeared, they were immune. In addition, 3 pups with maternal antibody to CAV-1 and CAV-2 were intramuscularly inoculated with CAV-2 at 3 weeks of age. Virus was not isolated from these pups, and maternal antibody decreased at a normal rate. These pups were not immune to challenge inoculation with CAV-1 and CAV-2.


A herpesvirus-type agent associated with skin lesions of green sea turtles in aquaculture.

Nine successive groups of green sea turtles (Chelonia mydas) were observed in aquaculture during the posthatchling period. During the first 6 months of growth, each group underwent an epizootic of skin lesions, named gray-patch disease. Two types of skin lesions are associated with gray-patch disease: papules and, more characteristically, spreading gray patches which appear 7 to 8 weeks after hatching. In both types of lesions, intranuclear inclusions are found in keratinocytes in the malpighian layer of the epidermis. Electron microscopic examination of scrapings from lesions and biopsies revealed many viral particles, with features characteristic of the herpesvirus group. Transmission of gray-patch disease is possible with bacteria-free preparations of viral particles.


Influence of vaccination with avirulent herpesvirus on subsequent infection of chickens with virulent Marek's disease herpesvirus.

Vaccination of chickens with turkey herpesvirus (HVT) or attenuated Marek's disease herpesvirus (aMDHV) blocked infection with virulent MDHV (VMDHV) for approximately 5 weeks after contact exposure. However, there was no apparent blockage of infection when challenge virus was administered intraabdominally (IA). Evidence for infection with VMDHV was based on viral isolation by in vivo assay or by detecting precipitins to "A" antigen associated with virulent virus. The HVT stimulated production of neutralizing antibody against VMDHV in a high percentage of chickens, whereas the aMDHV was a comparatively poor inducer of such antibody. Despite this difference, both of the vaccinal viruses conferred protection against development of Marek's disease.


Fluorescent antibody test for rapid diagnosis of coronaviral enteritis of turkeys (bluecomb).

Intestinal tissues obtained from coronavirus-infected embryos and turkeys were examined by fluorescent antibody tissue section technique (FAT). Evidence of viral antigen was demonstrated in the cytoplasm of the intestinal epithelial cells covering the villi. Embryo intestines that were examined from 24 to 96 hours after inoculation were positive for immunofluorescence (IF), whereas bursa of Fabricius was negative. Poults hatched from infected embryos were examined at 2 days of age and were positive for IF. Coronaviral antigen was detected by FAT in the cytoplasm of intestinal epithelial cells of the jejunum, ileum, duodenum, and cecum in all turkeys that were examined from 24 hours to 28 days.


Cellular proliferation induced in the lung by cadmium aerosol.

Rats were exposed to a polydispersed aerosol of 0.1 per cent cadmium chloride in physiologic saline for a single period of 2 hours, and the evolution of damage was followed for a 10-day period.  Control animals were unexposed rats and rats exposed to an aerosol of physiologic saline.  Wet lung weight doubled by the fourth day in animals exposed to cadmium chloride, but not in the control groups.  Apart from a transient increase in fluid content at 1 day, there was no evidence that the lung weight gain was due to inflammatory edema.  Uptake of [3H]thymidine markedly increased during the first four days after exposure to cadmium chloride.  Light autoradiography showed that [3H]thymidine labeling occurred almost exclusively in Type II alveolar cells at 1 day: later, the label appeared in interstitial cells and cells lying free within alveoli.  These changes correlated well (r=0.70) with the increase in deoxyribonucleic acid on the fourth day after exposure.  Uptake of [3H]thymidine and deoxyribonucleic acid content in rats exposed to cadmium chloride showed a significant difference from the control groups (P less than 0.001).  These experiments demonstrate that exposure to cadmium chloride aerosol evokes a wave of cellular proliferation in rat lung.  This finding is of interest, because heavy industrial exposure to cadmium in humans is known to be associated with severe physiologic impairment and anatomic damage.


Colour television, an imitation of the human visual system.

Colour television is examined as an attempt to imitate the human visual system in image formation, spectral sensitivities, adaptation, contrast effects, signal processing, signal modulation, signal transmission, and interpretation. Many similarities are found, but where differences occur they are discussed in relation to the differences between visual and television technologies.


Ulcer simulating gastric carcinoma. II. Histopathology and survival.

Forty eight benign-ulcer-simulating gastric carcinomas treated at the Second Departmxamined histologically. Twenty two cases (46%) were classified as adenocarcinomas, 15 (31%) were mucocellular and 11 (23%) were anaplastic poorly differentiated forms. Invasion was limited in the histological specimens to the mucosa or submucosa in 20 cases (43%) which also fulfilled the criterias for early gastric carcinoma. The five year survival rate, by the actuarial method, was 63%, which is good if compared with that of all gastric carcinomas. The good prognosis can mainly be explained by the high percentage of early carcinoma for which the 5 year survival rate was 77%.


A case of malignant arrhenoblastoma.

The patient was a 72-year-old married woman from whom a recurrent arrhenoblastoma had been removed three time in the course of six years. She was clearly virilized and her voice had become deep. Endocrine studies before removal of the recurrences showed pronounced elevation of the serum testosterone values. The 17-KS values did not as clearly parallel growth of the tumour. Histochemical examination showed moderate 3beta-steroid dehydrogenase activity in limited areas. The histological features were those of so-called intermediate type of arrhenoblastoma with a very scanty tubular component. Histologically the tumour was malignant, but with a relatively low degree of malignancy. Regardless of the treatment there was twice a recurrence of the tumour. The increase of the serum testosterone values during the follow-up period reflected recurrence on of the tumour.


Idiopathic facial paralysis, pregnancy, and the menstrual cycle.

The records of 42 women with Bell's palsy during pregnancy, and of 91 nonpregnant women, whose dats of onset of Bell's palsy and of the preceding menstrual cycle were precisely known, were studied for factors that might show relation between pregnancy or the menstrual cycle and Bell's palsy. Of the 42 cases in pregnancy, 31 occurred in the third trimester, five in the first two weeks postpartum, and six in the first two trimesters combined. Our calculated frequency of Bell's palsy in pregnant women is 45.1/100,000 births; for nonpregnant women of the same age group the calculated incidence is 17.4/100,000 per year. No causative relation was found between toxemia, hypertension or primigravidity, and Bell's palsy. Over 60% of the cases in nonpregnant women occurred in the first 14 days of the menstrual cycle with peaks on the first and seventh days and near ovulation. No clear evidence for an etiologic relationship was seen with edema or hormonal changes in either pregnancy or the menstrual cycle. A number of factors in pregnancy and the menstrual cycle suggested an etiologic role for herpes simplex virus reactivation in Bell's palsy. There was no evidence that prednisone treatment is contraindicated during pregnancy.


Inhibition of Coccidioides immitis in vitro and enhancement of antiococcidiodial effects of amphotericin B by polymyxin B.

Growth of the spherule phase of Coccidioides immitis in liquid glucose-mineral salts medium was suppressed for 13 days by 5 to 10 mug of polymyxin B per ml. Inhibition of growth was also noted when filter paper disks containing polymyxin B were placed on the surface of arthrospore-seeded defined medium solidified with refined agar. The antibiotic evidently damaged the cytoplasmic membrane inasmuch as spherules suspended in distilled water containing 10 mug of polymyxin B per ml rapidly lost nucleotides. Leakage of nucleotides was prevented by 0.1 M Ca(2+). The anticoccidioidal activity of amphotericin B (0.02 to 0.08 mug/ml) was enhanced by 2.5 mug of polymyxin B per ml. Colistin (polymyxin E) methanesulfonate did not inhibit spherule growth at concentrations as high as 50 mug/ml. This may be because colistin, though structurally similar to polymyxin B, is not cationic because its gamma-amino groups are masked by methanesulfonate radicals.


In vitro additive effect of polymxin B and rifampin against Serratia marcesen.

The combination of polymyxin B and rifampin resulted in an additive effect against all 12 clinical isolates of Serratia marcescens examined, including multiple-drug-resistant isolates.


Regulation of aspartokinase and homoserine dehydrogenase in acetic acid bacteria.

The regulation of aspartokinase and homoserine dehydrogenase has been studied in three Acetobacter and two Gluconobacter species. Both enzymes were regulated by feedback inhibition. Aspartokinase was inhibited by L-threonine and concertedly inhibited by L-threonine plus L-lysine. The homoserine dehydrogenase was NADP-specific and was inhibited by L-threonine. Separation of the two enzymes by ammonium sulphate fractionation was possible in Acetobacter peroxydans, A. rancens and Gluconobacter melanogenus but not in A. liquefaciens or G. oxydans.


Demonstration of virus in groundwater after effluent discharge onto soil.

The survival of virus present in secondary effluents discharged into a cypress dome was studied. Isolations were made from concentrates of water drawn from 10-foot (304.80 cm) deep wells. Data presented show vertical and lateral virus movement as well as survival within the dome for 28 days during a period of heavy rains when no effluent was being applied. Due to the inefficiency of virus concentration procedures, it is proposed that much of the virus present was probably not demonstrated. A rapid, relatively inexpensive concentration technique for sewage influents and effluents is discussed.


Radiation resistance of spores of some Clostridium perfringens strains.

Clostridium perfringens spores (eight strains) were irradiated in a model system with 60Co gamma rays at -30 C. The quantal response data obtained were analyzed with extreme value statistics. It was found (at the 95% confidence level) that all eight strains followed the same rate of death and that this rate was probably (at the 95% level) not exponential. The statistics did not exclude, however, a normal, lognormal, Weibull, or related rate of spore kill. A more definitive study would be required to distinguish between the latter distributions.


Familial chondrocalcinosis in the Chiloe Islands, Chile.

Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group.


Fine structural changes at Entamoeba histolytica rabbit kidney cell (RK 13) interface.

When bacteria-free trophozoites of Entamoeba histolytica were added to a monolayer of rabbit kidney cells, cellular injury occurred at the sites of contact. Changes appeared within the cell cytoplasm before there was any generalized cell membrane damage. At some points of contact there was apparent fusion of amoebic and cell cytoplasm. Electron-dense bodies, here interpreted as liposomes, were present in the amoebic cytoplasm and beneath the surface membrane. No surface lysosomes were seen. Various modes of cell damage and enzyme transfer from amoeba to cell are suggested, together with the possibility that cytopathic amoebae are infected with virus particles.


Experimental transmission of Japanese encephalitis virus by Culex tritaeniorhynchus and C. fuscocephalus.

Experimental transmission of Japanese encephalitis virus from swine to baby chicks was accomplished using Culex tritaeniorhynchus and Culex fuscocephalus, two of three mosquito species in Taiwan from which the virus has been recovered in nature. Whereas neither species had become infective by the twelfth day, one of ten C. fuscocephalus and 11 of 51 C. tritaeniorhynchus were infective by the seventeenth day of extrinsic incubation as verified by viraemia in chicks fed upon by potentially infective mosquitoes. The highest transmission rate obtained was 81% for C. tritaeniorhynchus on the twenty-first day of extrinsic incubation.


Inhibition of lipolysis and cyclic AMP accumulation in white fat cells by tetracycline.

The effects of tetracycline on the metabolism of isolated rat white fat cells were examined. Tetracycline at a concentration of 0.05 mg/ml inhibited lipolysis due to 0.075 or 0.15 muM norepinephrine, but not that due to adenosine deaminase, theophylline, dibutyryl cyclic AMP or 1.5 muM norepinephrine. Higher concentrations of tetracycline (1 mg/ml) inhibited lipolysis due to all added agents except dibutyryl cyclic AMP. The accumulation of cyclic AMP after 5 minutes incubation with 0.15 muM norepinephrine plus adenosine deaminase was inhibited by 0.05 mg/ml of tetracycline. The large rise in cyclic AMP accumulation at 5 minutes due to 1.5 muM norepinephrine in the presence of 100 muM theophylline was only slightly inhibited by 0.05 or 0.1 mg/ml of tetracycline. Tetracycline at 1 mg/ml did markedly inhibit cyclic AMP accumulation due to all added agents. The stimulation of adenylate cyclase activity of fat cell ghosts by norepinephrine or fluoride was inhibited by 0.05 mg/ml or greater concentration of tetracycline. Insulin-stimulated glucose oxidation by fat cells was inhibited by 1 mg/ml of tetracycline. These results suggest that the anti-lipolytic action of tetracycline on rat fat cells is secondary to inhibition of cyclic AMP accumulation.


Familial hyperalphalipoproteinemia.

A 26-member kindred had the newly recognized heritable hyperlipoproteinemia, familial hyperalphalipoproteinemia. In affected family members, hyperalphalipoproteinemia was not secondary to any diseases, drugs, or industrial exposures known to elevate alpha-lipoprotein (high-density) cholesterol (C-HDL) levels. Hyperalphalipoproteinemia was transmitted vertically through three generations. There were five matings of hyperalphalipoproteinemic to normal individuals, with 25 offspring. The ratio of offspring with elevated C-HDL levels to those with normal C-HDL levels was 12:13 (0.923), a ratio not significantly different from 1 (x2 equals 0.04), the ratio predicted for an autosomal dominant trait. In affected kindred members, levels of total plasma cholesterol were slightly elevated, those of low density lipoprotein cholesterol were normal to low, those of triglyceride were normal, and those of C-HDL were consistently elevated. Affected subjects were healthy, without xanthomata, and had no unique physical or neurological features.


Plasmalipoproteins and atherosclerosis.

The author describes and classifies the different types of lipo-proteins and their connection with the various types of hyperlipoproteinemias and he discusses their possible role in producing atherosclerosis.


Partial deficiency of hepatic glucose-6-phosphatase in an adult patient.

Patients with hepatic glucose-6-phosphatase deficiency usually have a striking clinical syndrome during childhood and are readily diagnosed by the pediatrician. An adult patient had childhood manifestations of glucose-6-phosphatase deficiency that were mild and unrecognized; symptoms of tophaceous gout, urate nephropathy and characteristic blood chemical studies suggested the diagnosis at age 39. Subsequent epinephrine and galactose tolerance tests were characteristic of hepatic glucose-6-phosphatase deficiency and direct assay of hepatic glucose-6-phosphatase confirmed a partial deficiency of the enzyme. The case emphasized that patients with this deficiency may escape diagnosis during childhood and that internists should consider the diagnosis in adolescents or young adults with acute gouty arthritis or tophaceous gout.


Noradrenaline-secreting glomus jugulare tumor with cyclic change of blood pressure.

A glomus jugulare tumor secreted a large quantity of noradrenaline (NA) and produced symptoms of tinnitus, palpitation, sweating, and labile hypertension. The NA content of the tumor was 0.75 mg/gm of tissue. Electron microscopical study of the tumor demonstrated many membrane-limited osmiophilic granules. This indicates the capacity of the tumor not only to synthesize but also to store NA in the tumor. Continuous blood pressure recording showed a cyclic change of blood pressure with a cycle length of 10 to 17 minutes that terminated after intravenous doses of phentolamine (0.1 mg/kg) or diazoxide (4.5 mg/kg) and surgical removal of the tumor.


The respiratory electron transport system of heterotrophically-grown Rhodopseudomonas palustris.

The enzymatic activities and the cytochrome components of the respiratory chain were investigated with membrane fractions from chemoheterotrophically growth Rhodopseudomonas palustris. Whereas the level of electron transfer carriers was not distinctly affected by a change of the culture conditions, the potential activities of the enzymes were clearly increased when the cells were grown aerobically. Reduced-minus oxidized difference spectra of the membrane fractions prepared from dark aerobically grown cells revealed the presence of three beta-types cytochromes b561, b560 and b558, and at least two c-type cytochromes c556 and c2 as electron carriers in the electron transfer chain. Cytochrome of a-type could not be detected in these membranes. Reduced plus CO minus reduced difference spectra of the membrane fractions were indicative of cytochrome o, which may be equivalent to cytochrome b560, appearing in substrate-reduced minus oxidized difference spectra. Cytochrome o was found to be the functional terminal oxidase. CO difference spectra of the high speed supernatant fraction indicated the presence of cytochrome c'. Succinate and NADH reduced the same types of cytochromes. However, a considerable amount of cytochrome b561 with associated beta and gamma bands at 531 and 429 nm, respectively, was reducible by succinate, but not by NADH. A substantial fraction of the membrane-bound b-type cytochrome was non-substrate reducible and was found in dithionite-reduced minus substrate-reduced spectra. Cytochrome c2 may be localized in a branch of the electron transport system, with the branch-point at the level of ubiquinone. The separate pathways rejoined at a common terminal oxidase. Two terminal oxidases with different KCN sensitivity were present in the respiratory chain, one of which was sensitive to low concentrations of KCN and was connected with the cytochrome chain. The other terminal oxidase which was inhibited only by high concentrations of cyanide was located in a branched pathway, through which the electrons could flow from ubiquinone to oxygen bypassing the cytochrome chain.


The electron transport system of the anaerobic Propionibacterium shermanii: cytochrome and inhibitor studies.

1. Electron transport particles obtained from cell-free extracts of Propionibacterium shermanii by centrifugation at 105000 times g for 3 hrs oxidized NADH, D,L-lactate, L-glycerol-3-phosphate and succinate with oxygen and, except for succinate, with fumarate, too. 2. Spectral investigation of the electron transport particles revealed the presence of cytochromes b, d and o, and traces of cytochrome alpha1 and a c-type cytochrome. Cytochrome b was reduced by succinate to about 50%, and by NADH, lactate or glycerol-3-phosphate to 80--90%. 3. The inhibitory effects of amytal and rotenone on NADH oxidation, but not on the oxidation of the other substrates, indicated the presence of the NADH dehydrogenase complex, or "site I region", in the electron transport system of P. shermanii. 4. NQNO inhibited substrate oxidations by oxygen and fumarate, as well as equilibration of the flavoproteins of the substrate dehydrogenases by way of menaquinone. The inhibition occurred at low concentrations of the inhibitor and reached 80--100%, depending on the substrate tested. The site of inhibition of the respiratory activity was located between menaquinone and cytochrome b. In addition, inhibition of flavoprotein equilibration suggested that NQNO acted upon the electron transfer directed from menaquinol towards the acceptor to be reduced, either cytochrome b or the flavoproteins, which would include fumarate reductase. 5. In NQNO-inhibited particles, cytochrome b was not oxidized by oxygen-free fumarate, but readily oxidized by oxygen. It was concluded from this and the above evidence that the branching-point of the electron transport chain towards fumarate reductase was located at the menaquinone in P. shermanii. It was further concluded that all cytochromes were situated in the oxygen-linked branch of the chain, which formed a dead end of the system under anaerobic conditions. 6. Antimycin A inhibited only oxygen-linked reactions of the particles to about 50% at high concentrations of the inhibitor. Inhibitors of terminal oxidases were inactive, except for carbon monoxide.


Physiological role for the membrane bound ascorbate-TMPD oxidase in pseudomonas putida.

The activity of the membrane-bound ascorbate-TMPD oxidase in Pseudomonas putida varies with growth conditions and age of the culture. A comparison of the effects of cyanide and azide on the oxidation of various substrates suggests that ascorbate-TMPD oxidase is not the terminal oxidase for NADH or succinate oxidation. However, it does have a role in the oxidation of nicotinate, and may act as an additional terminal oxidase under certain other growth conditions.


Kinetics and morphology of glucose-limited cultures of moulds grown in a chemostat and on solid media.

The affinity (KS value) of Geotrichum candidum for glucose determined from chemostate cultures was ca. 1 mg/1. KS values for glucose was also estimated from the radial growth rates of colonies of G. candidum and Neurospora crassa grown on media solidified with agar or silica gel. An assessment is made of the use of colony radial growth rate to determine substrate affinities. The length of apical and intercalary hyphal comparte ments, internode length and the diameter of leading hyphaat the margin of colonies grown on solid media were all reduced at low glucose concentrations.


Lactate dehydrogenases in cyanobacteria.

NAD-linked lactate dehydrogenases specific for the D- and L-lactate have been demonstrated in a number of strains of unicellular cyanobacteria.  The D-lactate dehydrogenase of one strain (Synechococcus 6716) was partially purified and its properties were studied.  The enzyme has a molecular weight of ca. 115000-120000, is highly specific, autooxidizable, and susceptible to inhibition by iodoacetamide, oxamate and ATP.  The possible physiological functions of the enzyme in the metabolism of the organism were investigated.  D-lactate carbon was incorporated in cell material during photosynthetic growth with CO2, but lactate was not used as sole source for carbon for photosynthetic or chemosynthetic development.  D-lactate and pyruvate were oxidized aerobically in the dark by resting cell suspensions with the assimilation mainly of the C2 and the C3 carbon atoms.  In the oxidation of lactate, acetate was excreted into the medium.  No fermentation of glucose was found, but a small amount of D-lactate was detected as a product of endogenous dark metabolism of the cell.  All enzymes required for the production of lactate from glucose and from glycogen were found in exponentially growing cells, but the activity of some key enzymes was low or undetectable in old cultures.


Enzymes of glycollate formation and oxidation in two members of the rhodospirillacae (purple non-sulphur bacteria).

1. Phototrophic cultures of Rhodomicrobium vanielii do not excrete glycollate when gassed anaerobically with nitrogen plus carbon dioxide, although the addition of alpha-hydroxy-2-pyridine methanesulphonate (HPMS) results in the excretion of a trace amount of glycollate. The inclucion of low amounts of oxygen in this gas mixture results in marked glycollate excretion, higher rates occurring in the presence of HPMS. 2. Cell extracts of Rhodomicrobium vannielii, and also of Rhodospirillum rubrum, which excretes glycollate only under aerobic conditions in the light, catalyze the formation of glycollate from phosphoglycollate and also the oxidation of glycollate to glyoxylate.


Mutants of Serratia marcescens lacking cyclic nucleotide phosphodiesterase activity and requiring cyclic 3',5'-AMP for the utilization of various carbohydrates.

Adenine requiring mutants of Serratia marcescens SM-6-F'lac+ have been found to grow well in minimal-glucose medium solely supplemented with cAMP. From one of these ade strains double mutants (called ade cpd) were isolated which could no longer utilize cAMP but which still grew on 5'AMP. Dialyzed cell extracts (soluble fraction) of the double mutants, assayed for cAMP phosphodiesterase, were unable to hydrolyze cAMP whereas cell extracts of the parental strains yielded 5'AMP at a rate of 1.6-2.0 mumoles min-1 mg-1 protein. The loss of the phosphodiesterase activity in S. marcescens cpd W 1181 did not cause an accumulation of large amounts of cAMP as was found for the diesterase-negative mutant AB257pc-1 of Escherichia coli. The induced synthesis of beta-galactosidase in mutant cpd W 1181 showed about the same sensitivity to transient and permanent catabolite (glucose) repression as the corresponding cpd+ strain. Starting from S. marcescens cpd W 1182 three independent double mutants (called cpd cya) were isolated which required exogenous cAMP for utilizing various carbohydrates as carbon source, for motility and for the formation of extracellular lipase and the red pigment prodigiosine. The intracellular concentration of cAMP in these mutants, grown in nutrient broth, was 40-60% of that of the parental strain which is about 4 x 10(-4) M. However, the adenylate cyclase in cell extracts of the mutants W 1237 and W 1270 was like that of the corresponding cya+ strain (about 2 x 10(-2) mumoles min-1 mg-1 protein).


[Exerimental study on cancerogenic activity of Propanol-1, 2-Methylpropanol-1 and 3-Methylbutanol-1 (author's transl)].

By using Propanol-1, 2-Methylpropanol-1 cancerogenic, hepatotoxic and haematotoxic effects could pointed out by an experimental study with rats. These high alcoholics are frequently used in the chemical industry but they are also essential parts of most of the alcoholic beverages. It is recommended to define safety limit.


[The tumor-tetanus assay--experimental studies on the biological differentiation between carcinogenesis and organ regeneration of the rat (author's transl)].

The characteristic clostridial growth which is testable, after systemic administration of tetanus spores, as a positive tumour tetanus - correlation, was manifested by a highly selective tetanus lethality of rats with progressive hepatomas following induction with dimethylaminoazobenzene and diethylnitrosamine, respectively, as well as with methylcholanthren-induced fibrosarcomas of the rat. Control tumours with transplantable Walker carcinoma cells anYoshida sarcoma cells also developed tetanus most frequently whereas healthy tumour-free rats did not show any signs of tetanus for the period of observation. There was strict time-dose-relationship of tetanus after partial hepatectomy, using the same injection technique of the spores, in sofar as the spores injected 24 hours postoperatively caused tetanus as opposed to the completely negative results following spore administration 4 days postoperatively. The mean tetanus survival time of the rats with regeneration of the liver roughly corresponded to that of the wound regeneration assay using pregant rats post partum. The interpretation of these results allows for demonstrating a fairly good agreement between the growth capacity of tumour cells on the one hand and the permanently strong tetanus reactivity on the other, as compared with the time-limited "take" and course of tetanus following regeneration of the liver.


Neurological abnormalities in the leg(s) after use of intraaortic balloon pump: report of six cases.

Six patients from a group of 39 who survived after treatment with the intraaortic balloon pump (lABP) had significant neurological deficits in one or both legs associated with the use of the lABP. The device was used in a group of 89 patients initially for cardiogenic shock but its use has been expanded for patients having the following conditions: preshock; severe congestive heart failure; refractory angina; and for those undergoing open-heart surgery. The six patients who had neurological sequelae had eight lABP insertions into the thoracic aorta through the femoral artery and had neurological abnormalities and/or electromyographic abnormalities in nine lower extremities ranging from a foot drop to almost total paralysis of the lower extremity. The pathophysiology of the neurological deficit is postulated to be an obstruction to blood flow, or thromboemboli, in the femoral artery.


Long thoracic nerve palsy: a follow-up study.

Twelve patients who had previously been treated for palsy of the long thoracic nerve of Bell and resultant serratus anterior paralysis were examined in a follow-up study designed to determine their extent of recovery and/or residual disability. The patients' histories were reviewed, following which they were recalled for updating of the history and reexamination. It was found that those patients whose lesions were due to acute trauma had only partial or no recovery of serratus function, while those with infectious, toxic, allergic or idiopathic etiologies had partial or complete recovery. The occurrence of a prolonged interval between onset of symptoms and institution of therapy was found to adversely affect prognosis. Among those patients with no recovery of serratus anterior function, some were able to maintain relatively good active motion in the affected shoulder by substituting with the trapezius.


Implications of suspicious findings in breast cancer screening.

Breast cancer screening, performed on asymptomatic women over 35 years of age, has identified 32 breast cancers in 30 of 4,500 women screened. Screening included a physical examination by trained technologists, thermography, and xeromammography. This represents 26 percent of the biopsies performed (116). Results of xerommammography were suspicious in 24 cases (80 percent), and results of physical examination were suspicious in 11 (37 percent). Only six were suspicious by both methods, with one other having changes that were considered benign. Fourteen (44 percent) were microinvasive or noninvasive. Only two (6 percent) had axillary metastases. Breast cancer detected by screening is in its "early" stages and is usually well localized. Operative management, including removal of the entire breast, has a significant potential for cure. Thirty patients with changes considered suspicious have not yet had biopsies. Improved overall survival depends on appropriate management of all patients screened.


In vitro evaluation of inhibitors of platelet release and aggregation.

In order to determine which drugs would be most effective as inhibitors of platelet release and aggregation, in vitro release reactions and platelet aggregometry were used to evaluate aspirin, dipyridamole, sulfinpyrazone, flurbiprofen, low molecular weight dextran (dextran 40), prostaglandin E1 (PGE1), apyrase, and adenosine. Adenosine diphosphate-induced aggregation was most effectively inhibited by PGF1, sulfinpyrazone, and dipyridamole. The latter had to be used in large doses. Collagen and epinephrine-induced release and aggregation were inhibited by the same drugs as well as by aspirin and apyrase. Antihynocyte globulin (ATG)-induced release and aggregation could only be partially blocked by these agents. In vitro studies suggest that sulfinpyrazone is one of the most effective of platelet inhibitors currently available for clinical testing.


Guanidine and neuromuscular transmission. I. Effect on transmitter release occurring spontaneously and in response to single nerve stimuli.

The effect of guanidine on neuromuscular transmission was studied in human intercostal muscle and mouse diaphragm preparations in vitro. Guanidine greatly increased the number of acetylcholine (ACh) quanta released by a single motor nerve action potential. This effect of guanidine was greater at junctions with a low quantum content. The spontaneous release of ACh quanta was not substantially changed by guanidine. No change was found in the postsynaptic sensitivity to ACh released from the motor nerve or iontophoretically applied to the muscle fiber. Effects of the drug had slow onset and were very long-lasting and resistant to wash.


Guanidine and neuromuscular transmission. II. Effect on transmitter release in response to repetitive nerve stimulation.

The effect of guanidine on the neuromuscular transmission in human intercostal and mouse diaphragm muscle in vitro during repetitive nerve stimulation was studied. The drug greatly increased the release of acetylcholine (ACh) quanta by nerve impulses at low frequencies of nerve stimulation and at the beginning of tetani at high frequencies of stimulation. The effect was shown to be produced by an increase in fractional release from an unchanged store of ACh quanta available fro immediate release. This seems to explain why guanidine has a poor therapeutic effect in myasthenia gravis but a good effect in the myasthenic syndrome.


Axonal degeneration in sodium cyanate-induced neuropathy.

Two patients with sickle cell disease who had been maintained on sodium cyanante therapy for periods of 440 and 600 days on dosages up to 44 and 41 mg/kg per day developed a motor and sensory neuropathy. In both, definite abnormalities of myelinated and unmyelinated fibers were found. In one, the predominant abnormality of myelinated fibers was segmental demyelination and remyelination; in the other, there were histological features typical of axonal degeneration. It seems unlikely that the brunt of the metabolic derangement was on Schwann cells in the first case and on the nerve cell in the second. Probably, in both cases, the primary effect was on the nerve, with Schwann cell changes being concomitant or secondary. The clustered distribution of the segmental demyelination favors the latter.


Phenytoin and membrane fluidity in myotonic dystrophy.

Electron spin resonance spectroscopy was used to substantiate the presence of a membrane defect in myotonic erythrocytes. There was increased membrane fluidity and decreased polarity in myotonic membranes. Phenytoin (formerly diphenylhydantoin) "normalizes" fluidity differences in spectra derived from myotonic erythrocytes but has no significant effect on normal spectra. These experiments demonstrate the applicability of biophysical methods to human erythrocyte membranes and support the concept of a membrane defect in myotonic dystrophy that does not have a primary myopathic, neuropathic, or vascular cause.