Murine Type C viral envelope glycoprotein gp69/71 and lupus-like glomerulonephritis of New Zealand mice. An immunoperoxidase study. The location of murine Type C viral envelope glycoprotein antigen in the glomerulonephritic kidneys of NZB and NZB/NZW F1 hybrid mice was analyzed by the indirect immunoperoxidase technique at light and electron microscopic levels. Immune complex deposits of the glycoprotein antigen were present in the glomeruli in mesangial and subepithelial sites. In addition to the glomerular depositions, viral envelope antigen was also present at the brush border of proximal tubular epithelial cells and in lymphoid cells infiltrating the kidneys of these mice.


Virus-induced animal model of osteosarcoma in the rat: Morphologic and biochemical studies. Osteosarcomas were produced by the intratibial inoculation of New Zealand black rats with Moloney sarcoma virus (MSV) at 1 day and 4 days of age. Radiographic evidence of osteosarcoma development was first demonstrated at 10 to 15 days postinoculation in both groups. Subsequent radiographic and light and electron microscopic evaluation of tumor-bearing rats demonstrated that osteosarcomas in rats inoculated at Day 4 of age were more osteoproliferative osteosarcomas than those in rats inoculated on Day 1. Rats inoculated at 4 days of age lived longer, had more slowly growing osteosarcomas, and developed a consistent tumor-associated cachexia compared to tumor-bearing rats inoculated at Day 1. Both groups of rats had a 93% metastasis rate involving either sublumbar lymph nodes, lungs, or both. Tumor-bearing rats inoculated at 4 days of age had consistent elevations in both urinary hydroxyproline excretion (HOP/CR) and serum alkaline phosphatase levels, and in serum calcium levels at some time points. The high tumor incidence after a short latent period and the morphologic and biochemical similarities between the MSV-induced murine osteosarcoma and the osteosarcoma in human beings makes this discrete tumor and a valuable animal model for the evaluation of new therapeutic regimens.


Differential analyses of EMG findings in motor neuron lesions. The principle in electromyography that positive sharp waves (PSW) and fibrillation potentials (FP) are pathognomonic of lower motor neuron (LMN) pathology is challenged by recent reports that the same potentials are observed in upper motor neuron (UMN) lesions. We have also observed positive sharp waves and fibrillation potentials in patients with UMN lesions, without conditions that involve the LMN. This study was undertaken to ascertain if there are differences in the potentials between the LMN and  UMN lesions. Twenty-five UMN and 25 LMN patients were electromyographed. Manual and computer analyses were used to compare parameters from positive sharp wave and fibrillation potentials. Our findings indicate that there are interlesion differences in the mean frequency of occurrence ratio of PSW to FP and in some of the durational wave parameters.


Control of intracellular Ca2+ activity in rat myometrium. Four fractions enriched, respectively, in plasma membrane (PM), smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER), and mitochondria were isolated from estrogen-dominated rat myometrium. Ca2+ uptake by these fractions was studied in order to estimate the relative potential of the corresponding organelles for controlling intracellular Ca2+ activity. Ca2+ uptake properties of the PM, SER, and RER fractions were similar except that potentiation by oxalate was in the order RER greater than or equal SER greater than PM. However, studies with the ionophores X-537A and A23187 suggested that Ca2+ was transported into the lumen of membrane vesicles of all these fractions. Unlike that of skeletal muscle sarcoplasmic reticulum, Ca2+ uptake by the myometrial fractions was not supported by high-energy compounds other than ATP. Mitochondria took up much less Ca2+ at low, and much more Ca2+ at high, free Ca2+ concentrations than did the other fractions. The amount of Ca2+ taken up in 30 s from a 1 muM free Ca2+ solution in the presence of ATP was similar for all fractions. These results suggested that mitochondria may act as an important Ca2+ control system in rat myometrium when the intracellular Ca2+ concentration is near 1 muM or higher, whereas the PM, SER, and RER may be of major importance at Ca2+ levels of 0.3 muM or lower.


Afferent discharges from venous pressoreceptors in liver. Afterent discharges were observed in dissected filaments or single nerve fibers of hepatic nerve in the guinea pig and the rabbit. Increasing the perfusion pressure of the portal vein in isolated liver preparation in the guinea pig caused an increase in afferent discharge rate. Discharge patterns were compatible with those of the slowly adapting type. Increasing the portal venous pressure by means of intravenous injection of Locke's solution into the left jugular vein in the rabbit in vivo caused an increase in afferent discharge rate. Increasing the hepatic arterial pressure was without effect. It is suggested that pressoreceptors are present in or near the venous wall of the portal venous system and that they send information about blood pressure in the portal vein to the central nervous system.


Regulation of protein kinase by vasopressin in renal medulla in situ. Results of this study demonstrate that vasopressin activates protein kinase in intact renal medullary cells as detected by measurement of the (-cyclic AMP/+cyclic AMP) protein kinase activity ratios in freshly prepared tissue extracts (40,000 X g supernates) from bovine renal medullary slices. The activation of protein kinase was specific for vasopressin since parathyroid hormone, histamine, angiotensin II, or the inactive analog of vasopressin did not activate protein kinase. There was a direct correlation between the extent of protein kinase activation and the elevation in tissue levels of cyclic AMP elicited by increasing doses of vasopressin or with an increase in incubation time. The elevation of tissue cyclic AMP level and maximum activation of protein kinase reached maximum level at a vasopressin concentration of about 2 X 10(-9) M. Incubation of slices with vasopressin caused a dose-dependent decrease in the cyclic AMP-dependent protein kinase activity in the 40,000 X g supernate of homogenate from the renal medullary slices. This effect of vasopressin was specific for protein kinase since activity of lactate dehydrogenase or a specific [3H]colchicine-binding activity was not affected, and the decrease in the protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase activity extracted from 40,000 X g pellets of homogenate prepared from slices exposed to vasopressin. Results thus provide evidence that cyclic AMP-mediated protein kinase activation in the intact cells is an integral part of cellular response of the mammalian renal medulla to vasopressin.


Influence of mannitol on contractile responses of isolated perfused arteries. The influence of hyperosmotic mannitol on vascular smooth muscle contractile responses was examined in isolated arterial preparations. Vasoconstrictor effects of norepinephrine (NE) and potassium chloride (K+) in the perfused central artery of the rabbit's ear and in perfused mesenteric arteries of cats were significantly inhibited by infusion with Krebs bicarbonate solution made hyperosmotic with mannitol (50-200 mosM increase). Similarly, the magnitude and duration of vasoconstrictor responses to transmural stimulation of the central ear artery of the rabbit were decreased by hyperosmotic mannitol (50 mosM). Mannitol (50 mosM) produced a decrease in perfusion pressure when perfusion pressure was maintained at an increased level by K+ (60 mM). Mannitol-induced vasodilatation was not affected by ethacrynic acid (1.5 X 10(-5) M), beta adrenergic blockade or by the development of tachyphylaxis to the vasodilator effects of nitroglycerin. The concentration of cyclic adenosine-monophosphate was not changed by mannitol. Isotonic mannitol also inhibited NE-induced contractile responses. These data indicate that hyperosmotic mannitol produces vasodilatation in isolated arterial smooth muscle by a mechanism(s) that appears dissimilar from that of several other vasodilator substances and suggest that hypertonicity may not be the only factor involved in the vasodilator effect of mannitol.


Physiological inhibition and facilitation of adrenocortical response to hemorrhage. In a search for physiological feedback inhibition, secretion rates of cortisol were measured in intact dogs before and after sequential hemorrhages. The sucond of two sequential hemorrhages of 10 ml/kg separated by 90 min evoked significantly less increase of secretion rate of cortisol than did the first. This result was not explained by differential hemodynamic effects. Exhaustion of pituitary or adrenal capacities was excluded, since dogs responded normally to a second, larger hemorrhage. However, no attenuation response to a second 10 ml/kg hemorrhage was seen after a larger, 20 ml/kg, first hemorrhage. This led in turn to a search for a physiological facilitatory mechanism which might offset the feedback effect. The second of two rapid sequential hemorrhages to isovolemia following preexpansion of plasma volume evoked significantly greater increase of secretion rate of cortisol than did the first. This result also was not explained by differential hemodynamic effects. The results support the hypothesis that hemorrhage elicits both physiological feedback and facilitatory effects which interact and which are (different) functions of the intensity of stimulus.


Protriptyline: an effective agent in the treatment of the narcolepsy-cataplexy syndrome and hypersomnia. The authors present five case reports illustrating that 10-20 mg of protriptyline in a single dose at bedtime can effectively control arousal dysfunction (sleep drunkenness and hypersomnia) and the narcolepsycataplexy syndrome without the apparent development of tolerance and without the side effects that are frequent complications of treatment with other agents. Although protriptyline was efficacious in controlling symptoms, it was found to have relatively poor REM sleep-suppressing properties.


An integrated approach to tuberculosis care in the Commonwealth of Pennsylvania. A significant economization of taxpayers resources (+5.5 million per year) is the result of a major restructuring of the tuberculosis control program in the Commonwealth of Pennsylvania. Concomitantly improved patient management has accelerated the decline in the incidence of tuberculosis while maintaining recommended federal performance standards. The reasons for the success in obtaining this high degree of efficiency are discussed.


Tumors of the submaxillary gland.

Tumors of the submaxillary gland. This study reviews a thirty year experience with 217 patients who had a tumor of the submaxillary gland, comprising about 9 per cent of all patients with salivary neoplasms seen during the same period. Most of the tumors were malignant (56 per cent), with adenoid cystic carcinoma predominating, but the histologic type most frequently encountered was benign mixed tumor (43 per cent). Median age was fifty-four years in patients with malignant tumors compared with forty-six years in those with benign tumors, and 58 per cent were women. Asymptomatic swelling was the usual presenting complaint, and the clinical findings are summarized using a staging system recently proposed for patients with parotid tumors. Cervical lymph node metastasis occurred in at least 50 per cent of patients who had an adenocarcinoma or epidermoid, mucoepidermoid, or anaplastic carcinoma. Treatment was surgical and complete gland excision proved adequate in those with benign tumors. Radical neck dissection was performed in conjunction with submaxillary resection in most patients with malignant lesions, but radical en bloc resection was reserved for those few who had extensive or fixed disease. Net determinate "cure" rates at five and ten years (30 and 20 per cent, respectively) are distressingly low and compare unfavorably with those previously reported in patients treated for carcinoma of the parotid. The high local recurrence rate and the greater incidence in the submaxillary gland of more aggressive tumor types which metastasize readily suggest that current treatment should be more radical. It seems reasonable to expect that results might be improved if en bloc resections were more often performed in patients with less advanced disease, possibly in conjuction with intensive postoperative irradiation in selected cases.


Parotid tumors in children.

Parotid tumors in children. Most salivary gland tumors, both benign and malignant, develop within the parotid glands. Although an overwhelming majority of tumors are reported in the adult population, the parotid glands are also the most frequently involved salivary glands in the pediatric age group. This study represents a combination of case material from the Armed Forces Institute of Pathology and our personal experiences. Of approximately 10,000 salivary gland lesions accessioned in all ages, only 124 tumors occurred in the parotid gland in children less than fifteen years old. There were ninety benign and thirty-four malignant lesions. The two most common benign masses were mixed tumors and vascular lesions. The most common malignancies were the mucoepidermoid and acinic cell carcinomas. We recommended that all solid tumors be removed by parotidectomy.


Viral-specific humoral immunity to herpes simplex-induced antigens in patients with squamous carcinoma of the head and neck. Serum antibodies to herpes simplex virus-induced antigens (HSVIA) were quantitated in 122 patients with head and neck squamous carcinoma, 93 patients tumor-free after treatment for these malignant lesions, 27 patients with nonsquamous malignant lesions, 30 heavy smokers, and 36 nonsmokers. Serum IgA anti-HSVIA antibodies were detected in a greater percentage of sera of patients with squamous carcinoma (61 per cent), patients previously treated for these malignant lesions (56 per cent), and heavy smokers (57 per cent) than in patients with nonsquamous malignant lesions (11 per cent) or nonsmokers (8 per cent). Furthermore, titers of these antibodies were higher in patients with squamous carcinoma than in smokers. In patients tumor-free more than three years after treatment, the percentage of positive sera was significantly lower than that in untreated patients and in patients three years or less after treatment. This study demonstrates for the first time a high frequency of antibodies to HSV-induced antigens confined to subjects at high risk of developing head and neck squamous carcinoma and in patients with these malignancies as well as a correlation between the levels of these antibodies and clinical course after treatment.


Adenyl cyclase and cyclic AMP (cAMP) in acute experimental pancreatitis. The level of adenosine 3':5'-cyclic monophosphate (cAMP) and the activity of adenyl cyclase were studied in the pancreas under normal conditions and during acute hemorrhagic pancreatitis induced by intraductal injection of fresh trypsin-bile-blood mixture. In addition, the adenyl cyclase was localized histochemically in the pancreas. Basal cAMP concentration and adenyl cyclase activity were 0.88 +/- 0.11 pmoles/mg wet tissue and 3.39 +/- 0.21 pmoles/mg protein/min, respectively. The acute pancreatitis drastically reduced the adenyl cyclase activity at 15 minutes to 1.66 +/- 0.54 pmoles/mg protein/min, and totally suppressed adenyl cyclase activity at 30 minutes after the onset of pancreatitis without affecting cAMP levels. The presence of sodium fluoride in the incubation medium prolonged the enzyme activity up to 45 minutes. The progressive disappearance of adenyl cyclase activity presumably resulted from the destruction of cellular integrity caused by autodigestion by the active proteolytic enzymes released during pancreatitis.


Common bile duct obstruction by hepatoma. Two cases of hepatoma are presented in which the clinical manifestations of biliary obstruction resulted from growth of hepatoma into the extrahepatic bile duct. Recognition of such a manifestation of the hepatoma may allow for surgical extirpation of the tumor combined with radiation therapy, which may result in long survival.


Effects of pharmacologic alterations of adrenergic mechanisms by cocaine, tropolone, aminophylline, and ketamine on epinephrine-induced arrhythmias during halothane-nitrous oxide anesthesia. The purpose of this study was to examine the effects of pharmacologic alterations of adrenergic terminating mechanisms by cocaine, tropolone, aminophylline, and ketamine on the ability of epinephrine to induce arrhythmias during halothane-nitrous oxide anesthesia in dogs. Because the first three drugs inhibit intraneuronal uptake of catecholamines, extraneuronal catechol-O-methyl transferase (COMT), and phosphodiesterase, respectively, they might be expected to potentiate epinephrine-induced arrhythmias. To evaluate this possibility, the authors devised a technique for determining the minimal arrhythmic dosage of epinephrine that permitted graded assessment of changes in the sensitivity of the heart to epinephrine-induced arrhythmias. When the first three drugs were administered to the same dog in the order listed at intervals of 60 minutes, they sequentially increased the ability of epinephrine to induce arrhythmias. Ketamine, according to several investigators, also appears to block reuptake of catecholamines, and when studied was also found to enhance the arrhythmogenicity of epinephrine. The extent of enhancement was comparable to that seen with cocaine. These results indicate that drugs like cocaine and ketamine that interfere with intraneuronal uptake can facilitate the development of epinephrine-induced arrhythmias and that the successive pharmacologic interference of intraneuron uptake, COMT, and phosphodiesterase leads to a stepwise increase in the arrhythmogenicity of epinephrine.


Serum triglyceride and cholesterol levels and lipid electrophoretic patterns in intrinsic and extrinsic allergic states. This study indicates that hypertriglyceridemia and associated pre-beta hyperlipidemia (Fredrickson's type IV lipid pattern) is frequently associated with intrinsic allergic disease characterized by chemical intolerant (hypersensitivity) states, particularly of the aspirin intolerant type and to a somewhat lesser extent with the butylated hydroxyanisole and butylated hydroxytoluene intolerant type, as well as the iodide intolerant state. It confirms that diabetics suffering concomitantly with extrinsic or intrinsic allergic disease still continue to demonstrate a high occurrence of this type of hypertriglyceridemia. In contrast, pure atopic, extrinsic-allergic patients demonstrated a very low incidence of type IV hyperlipoproteinemia. The interrelationships of these findings with previously reported metabolic abnormalities in intrinsic allergic hypersensitivity states is correlated.


[Analysis of lipoproteins using polyacrylamide gel electrophoresis and fractionated precipitation with polyanions and detergents. Use in the classification of hyperlipoproteinemias]. Sodium dodecylsulphate precipitates very low density lipoproteins (VLDL and chylomicrons) rich in triglyceride and a narrow correlation (r = 0.9) was found between the turbidimetric index SDS and triglyceridemia. Heparin in calcium medium acts in the same way and precipitates also low density lipoproteins (LDL) rich in cholesterol. A correlation (r = 0.875) was drawn up between the cholesterol LDL and the difference between the turbidimetric indices (heparin Ca -- SDS). In the first case, we were thus measuring by turbidimetry a VLDL + chylomicron index and, in the second case, an LDL index which permits one to obtain simplified typing of the hyperlipoproteinemias. A nomogram linking the two indices of hyperlipoproteinemia type was drawn up experimentally. This orientation analysis may be completed by electrophoresis on polyacrylamide gel used in concentration gradient and pH. In the system proposed, the lipoproteins were previously stained with tetrazolium nitroblue and clearly shown up. The chylomicrons in particular, become separated from the VLDL, the sinking pre-beta-lipoprotein or Lp (a) was identifiable and the type III hyperlipemia was easily diagnosed.


[Thyroid gland TSH receptors].

[Thyroid gland TSH receptors]. The author first considers the general conditions of reversibility, saturability, specificity and affinity which should be filled by all receptors, but emphasizes certain special difficulties on analysis of TSH receptors. TSH is a glycoprotein of molecular weight 28,000, composed of 2 alpha and beta sub-units; the role of each of these with regard to the receptor, is discussed. The TSH receptor is mainly localised in the outer part of the plasma membrane of the thyroid cells. An important point concerns the biological significance of the link between TSH and receptors and the activation of the adenylate cyclase AMPc system. One may experimentally dissociate with lecithinase these two cell events: treatment of thyroid tissue with this enzyme abolishes the biological response but does not affect the bond. The notion of hormone dependency of thyroid carcinoma is still classical but should be reconsidered in the light of new data concerning TSH receptors. Finally, the notion of variable receptivity of the thyroid tissue to TSH permits one to imagine another regulatory mechanism for which the receptors are responsible.


[Glucagon receptors].

[Glucagon receptors]. The lecturer recalls the discovery of glucagon receptors in liver cell membranes, the role of the adenylate cyclase-AMPc system, until recent attempts at purification and isolation of this receptor. He then reviews successively, the problems of estimation, specificity of the interaction, the effects of purine and pyrimidine nucleotides on glucagon receptor interaction, etc. The importance of the two nucleotides GTP and ATP in activation of adenylate cyclase is emphasized. The VIP receptors ("vasoactive intestinal peptide") and secretin receptors are also discussed. In some ways, they resemble glucagon receptors. The possible consequences of these discoveries arethen discussed.


[Variations of membrane hormonal receptors induced by their ligands]. A great deal of research has been carried out on hormonal receptors and their quantitative variations, in particular, those which may be induced by their ligands. Insulin receptors, growth hormone, TRH and catecholamine receptors are already good examples of these variations. The authors have particularly studied angiotensin receptors which also vary with the plasma concentration of the hormone. Numerous questions of molecular biology are raised by these observations and are then discussed. The possible consequences of these discoveries on the physiopathology of endocrine diseases are finally discussed.


In vitro cytotoxicity of serum and peripheral blood leukocytes for equine herpesvirus type 1-infected target cells. The immune response in horses following experimental infection with equine herpesvirus type 1 (EHV-1) was assessed by measuring cytotoxicity for EHV-1-infected target cells. A technique was developed, using [125I]5-iodo-2'-deoxyuridine ([125I]IUDR)-labeled equine fetal kidney cells infected with EHV-1 as the target cells. It was shown that peripheral blood leukocytes from a recovered horse were capable of lysing target cells, as measured by the loss of radio-active label. Following the experimental infection of specific-pathogen-free ponies with EHV-1, cytotoxicity was obtained with fresh autologous serum, peripheral blood leukocytes in autologous serum, and washed peripheral blood leukocytes. Cytotoxicity of the serum and peripheral blood leukocytes was detected as early as one day after infection. It is suggested that cytotoxic antibodies or cells could play an important part in restricting virus spread after infection of the horse with EHV-1.


Immune electron microscopy of transmissible gastroenteritis virus and rotavirus (reovirus-like agent) of swine. Immune electron microscopy (IEM) was developed as a diagnostic aid for detecting and identifying transmissible gastroenteritis virus and rotavirus (reovirus-like agent) in fecal and intestinal contents from cases of gastroenteritis in young pigs. Variables involved in use of direct IEM and its sensitivity were determined. Aggregates of virus coated with specific antibody were seen in virus samples mixed with homologous convalescent antiserum, but not in control samples containing preexposure serum or antibody directed against a heterologous virus. At least a ten fold enhancement of the sensitivity of direct IEM for virus detection was accomplished using indirect IEM employing rabbit anti-porcine IgG to further aggregate virus-antibody complexes. The technique was used to investigate the size and morphology of the porcine rotavirus. Particles ranged from 55 to 70 nm in diameter and had capsomere structures. Morphologically, the porcine rotavirus resembled the calf and human rotaviruses. By IEM, employing specific antiserums for each virus, porcine rotavirus was found to be antigenically related to these 2 viruses, but not to the reovirus type 3.


Isolation of feline leukemia virus from clinical specimens. Specimens obtained from feline leukemia virus (FeLV)-positive cats were examined for infectious FeLV. Feline leukemia virus was detected by a focus-forming assay and confirmed by florescent antibody. Techniques of sample processing were evaluated and adjusted for optimum detection of FeLV. Low levels of FeLV were detected in 2 of 10 oral samples; however, the majority of these samples (17 of 27 tested) produced cytopathic effects in tissue culture which prevented Fe LV detection. Three of 24 urine samples and 1 of 20 rectal specimens were positive for FeLV. One milk sample contained high levels of FeLV.


Cultural and biochemical criteria for the identification of haemophilus spp from swine. Twenty-two Haemophilus cultures of types prevalent in swine and of different geographic origins were subjected to biochemical and cultural examinations. Three subgroups were identified: One was unrease-positive, produced porphyrin from delta-aminolevulinic acid, and grew on infusion mediums supplemented only with V factor; the 2nd was unrease-negative, porphyrin-positive, and grew only on serum-enriched mediums with added V factor; and the 3rd was unrease-negative, porphyrin-negative, and grew only on serum-enriched mediums with added V and X factors. The groups generally corresponded to Haemophilus parahaemolyticus, Haemophilus parasuis, and Haemophilus suis, respectively. By means of the unrease and porphyrin tests, it was possible to assign, presumptively, porcine haemophilus cultures to 1 of the 3 species. Other tests, such as beta-galactosidase, hemolysis, and fermentation of carbohydrates were of secondary value in differentiating between these species.


Demonstration of an avian adenovirus as the causative agent of marble spleen disease. A purification procedure, using chloroform or fluorocarbon extraction and centrifugation on a cushion of cesium chloride (CsCL), was designed to isolate the causative virus of marble spleen disease. Virus was purified, inoculated into turkeys, and subsequently reisolated by purification from the spleen of inoculated turkeys, thus fulfilling Koch's postulates. Splenic antigen was detected by the agar gel precipitin test, and viral inclusions with viral particles were observed by light and electron microscopy. Results of further studies indicated splenic lymphoreticulum cell hyperplasia was a sensitive indicator of marble spleen disease virus (MSDV) infection. Direct fluorescent antibody staining revealed nuclear fluorescence in virus-infected splenic cells from turkeys inoculated with purified MSDV. With negative stain electron microscopy, MSDV was observed to be 90 nm across with an icosahedral capsid composed of 252 capsomeres. This morphologic feature was consistent with that of an avian adenovirus. Serologic evidence for classification of MSDV  as an adenovirus was the cross reaction of MSDV antigen with antiserum to turkey adenovirus serotypes TA-1 and TA-2 in the agar gel precipitin test.


[Tumors of the endodermal sinus (author's transl)]. Seven cases of tumors of the endodermal sinus are reviewed. This is a highly malignant germinal tumor, arisen from extraembrionary cell differentiation. It is different both biologically and pathologically from sacrocoxigeal teratoma. There are no survivors in these series. All seven patients have been surgically treated chemotherapy has been used in four, and X-ray therapy in two. It is noteworthy that alpha-phetoprotein is present in patients with this type of tumor. This fact can be used both in diagnosis of the tumor and of its recurrence.


[Virilizing adrenal carcinoma (author's transl)]. A case of virilizing adrenal carcinoma, diagnosed in the first year of age, is presented. The difficulties of differential diagnosis with congenital adrenal hyperplasia are briefly discressed. There is not evidence of metastasis 15 months after complete surgical excision of the tumor and repeated detreminations of 17-CO and 17-OH have remained within normal limits. Finally some considerations are made regarding diagnosis, prognosis and treatment.


[Testicular tumours in infancy (author's transl)]. Eleven tumours of the testis are presented. Treatment is based in: surgery (gonadectomie and paraaortical lymphadenectomie), quimiotherapy, depending of its pathological pattern and in some cases radiotherapy. In methastasis, surgery if it is possible and poliquimiotherapy. Total mortality rate is 22% (2/11). The follow up is from two to seven years.


[Nephroblastoma on a horse-shoe kidney]. A female child, 5 years 10/12 old, is presented with a nephroblastoma inserted on a horse-shoe kidney. She is in a satisfactory state 14 months after surgery. The authors emphasize the favorable outcome with a treatment of combined surgery, radiotherapy and vincristine.


Trial and study on nephroblastomas S.I.O.P. No. 1. The International Society of Paediatric Oncology (S.I.O.P.) organised a study and trial on nephroblastomas in September 1971. This first trial was stopped in October 1974. In this period, 398 patients were included in trial and study. Patients came from 42 Centres in 14 countries. Eligible for the clinical trial were 195 patients. The clinical trial consisted of 2 parts: Part 1. Radiotherapy: Pre- and post-operative radiotherapy versus post-operative radiotherapy alone. Part 2. Chemotherapy: One single course of actinomycin D versus multiple courses of actinomycin D. For the radiotherapy trial, 137 cases were suitable after randomization. Concerning the recurrence-free survival, there were no significant differences following the actuarial statistical method. The same for survival. There was a high rate of ruptures in the post-operative group. These ruptured cases caused a higher rate of metastases and asked for a heavier treatment. Especially because of these ruptured cases the conclusion is drawn that pre- and post-operative radiotherapy is a better way of treatment for nephroblastomas when they cannot be expected to be a stage I tumour on clinical grounds. For the chemotherapy trial, 160 cases were suitable. There was no difference between the group of patients receiving a single course versus multiple courses of actinomycin D. Disease-free interval and survival in both groups in all stages were the same. The conclusion is drawn that this way of treatmetn does not make any difference. In a second study, chemotherapy with two agents is considered in two groups of patients receiving 6 months chemotherapy vincristine and actinomycin D versus 15 months.


[A case of hepatocarcinoma (author's transl)]. A case of hepatocarcinoma is presented in a five year old male treated with right hemihepatectomy and chemotherapy has been followed during nine months. The rarity of this histologic variety in childhood is emphasized, and so are the clinical, biological and pathological features.


Regression and progression of early femoral atherosclerosis in treated hyperlipoproteinemic patients. Femoral angiograms were done to evaluate change in early atherosclerosis in 12 patients with type IV hyperlipoproteinemia and 13 with type II hyperlipoproteinemia. The patients' average age was 48 years; only one had claudication. Elevated blood lipids and blood pressure were treated with drugs and diet. Repeat angiograms after an interval of 13 months showed regression of atherosclerosis in nine patients, no change in three, and progression in 13. Comparison of preangiogram levels with average levels between angiograms showed significant reduction in serum cholesterol, triglyceride, and blood pressure in the group with lesion improvement but not in the group with lesion progression. Sporadic examples of human atherosclerosis regression are known, but most other studies in man indicate only atherosclerosis progression. Our different result appears due to our selection of patients and radiographic method. We have studied patients with earlier atherosclerosis than previous workers, using a radiographic procedure more sensitive to small changes in lesions.


Receptors for peptide hormones. New insights into the pathophysiology of disease states in man. The first step in the action of polypeptide hormones and many neurotransmitters is binding to receptor sites on the plasma membrane of the cell. These receptors are usually complex, high molecular weight proteins. Using a variety of receptor preparations and radioactively labeled hormones, radioreceptor assays for several hormones have been developed. These have allowed for assay of hormones for which no immunoassay exists. Such assays have shown increased levels of NSILA-s (an insulin-like peptide) in patients with nonpancreatic tumors and hypoglycemia. In disease states, the number or affinity of hormone receptors may be altered, leading to hormone resistant states such as the insulin resistance of obesity. A major factor regulating receptor concentration is the hormone itself. Several hormones seem to accelerate inactivation of their own receptors. Antibodies to membrane receptors are produced in at least three diseases and cause hormone resistance or mimic states of hormone excess.


[Subacute excitation caused by probable herpetic encephalitis. Favorable effects of lithium]. Herpetic encephalitis in a 16 year old adolescent of average intelligence up to then and having had no psychiatric disorders. 3 years later, the subacte hypomanic excitation like behaviour disorder, distrubed alimentary and sexual behaviour rendered maintenance in the family environment and professional activity difficult; and this in spite of the absence of membory disorders, and the preservation of verbal and pragmatagnosic possibilities. Use of lithium led to the progressive sedation of the behaviour disorders and enabled return to work of the patient in a protected environment. This favorable action of lithium in a state of excitation of organic origin seems to be situated in the present stream of research which is attempting to enlarge the indications for it beyond manic depressive psychosis.


Regulation of calcium metabolism.

Regulation of calcium metabolism. This paper reviews the regulation of calcium metabolism in man. The body's calcium economy is determined by the relationship between the intestinal absorption of calcium, the renal handling of calcium, and by the movements of calcium in and out of the skeleton. These processes are influenced by many factors, the most important of which are parathyroid hormone and the hormones derived from the renal metabolism of vitamin D, notably 1,24-dihydroxyvitamin D3. The role of endogenous calcitonin in man is still controversial, but there are several other hormones which have some influence on calcium metabolism, including thyroid hormone, growth hormone, and the adrenal and gonadal steroids. Clinical disorders of calcium metabolism and their treatment are discussed in terms of the disturbances in normal physiology they represent.


Hemifacial spasm associated with benign parotid tumor. A case of hemifacial spasm associated with a benign parotid tumor is reported. Excision of the tumor relieved the symptoms.


Posturally-evoked vomiting; Association with posterior fossa lesions. Posturally-evoked vomiting (PEV) dissociated from vertigo was present in two patients with proven posterior fossa mass lesions. In both instances PEV was a major aspect of the patients' symptomatology before other findings clearly indicated the presence of an infratentorial mass lesion. A distinction is drawn between benign postural vertigo, which almost always indicates a benign disorder of the peripheral vestibular apparatus, and PEV which indicates a central lesion within the posterior fossa. A possible anatomic-physiologic basis is offered for PEV, based on the dissociation of the "vestibular syndrome," in which PEV increases while vertigo and nystagmus diminish.


Effects of drugs on platelet function.

Effects of drugs on platelet function. Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.


[Infantile digital fibromatosis. Anatomo-clinical and ultrastructural study]. About one personal case, authors consider clinical, histological and ultrastructural aspects of the infantile digital fibromatosis. They insist on the caracteristic features of the large granular and fibrillar cytoplasmic inclusions observed in the proliferative fibroblasts, and on the different signs of the metabolic hyperactivity of these cells. Elastogenesis was very scarce within the swelling but showed no evidence of qualitative abnormality. The discussion provides no definitive clue as to the nature or origin of the inclusions.


[The use of synthetic beta-1-24 corticotropin as a GH stimulating factor (author's transl)]. The authors have carried out research into the GH stimulating action of 0.25 mg of synthetic beta-1-24 corticotropin (Synacthen) injected intravenously into 26 healthy normally developed children. The results obtained prove the limited and irregular action of ACTH.


[The biochemistry of psoriasis].

[The biochemistry of psoriasis]. Numerous general metabolic systems are disturbed in association with psoriasis: the frequency of diabetes mellitus and of hyperuricaemia, lipid disturbances and a decrease in folates as a result of their excessive consumption by the skin. Cutaneous metabolism is also altered. Numerous compounds are formed in excess from glucose: amino acids, fatty acids and sterols, lactic acid--the formation of which persists in the corneal layer, ribose and ribulose--synthesised as a result of glucose-6-phosphate-dehydrogenase hyperactivity (role of the increased catabolism of dehydro-epi-androsterone) and uronic acids. The accumulation of glycogen is probably due to excessive synthesis and impaired breakdown. These abnormalities may exist to a lesser extent in healthy skin. In the corneal layer there are lipid vacuoles visible under the electron microscope. Lipogenesis is increased. The same may apply to lipolysis (blood NEFA are increased). Esterification of cholesterol is decreased. The utilisation of ATP by cell membranes is probably diminished (low ATP ase activity). The absence of formation of keratohyaline is due to persistence of the repression which normally prevents it in the mucus body. Renewal of collagen appears increased. The synthesis of DNA is increased in the lesions and neighbouring areas. It is possible that these various abnormalities are dependent upon modifications in the regulator systems of cyclic AMP and GMP, variations in which are however discussed.


[Pituitary modifications in a case of Schilder disease (author's transl)]. In a case of Schilder disease with a heavy atrophy of adrenal cortex the immunocytological analysis of anterior pituitary shows a generalized hypertrophy and a severe last of granulations of the beta cells which reacted very weakly to au anti-serum anti-ACTH 17-39. These modifications agree with biological titration proving an hypersecretion of ACTH and beta MSH.


[Dissociation of results obtained with an immunofluorescence technique by using anti-ACTH antibodies in three cases of pituitary "chromophobe" adenoma without hypercorticism; ultrastructural study (author's transl)]. Morphological studies of 3 pituitary "chromophobe" adenoma in patients without hypercorticism show positive immunofluorescenct cells with anti alpha, 17-39 ACTH antibody which are not revealed with anti beta, 1-24 ACTH antibody. These cells observed at the ultrastructural level contain secretory granules of 1,000 to 1,500 A in diameter. The existence in these cells of a substance having an immunological relationship with ACTH without biological activity is discussed.


[Synthetic A.C.T.H. test. (Results obtained on aldosterone and cortisol blood level) (author's transl)]. During the beta 1-24 corticotropin stimulation test, it appears the increase of Aldosterone Blood level is more important (170,91% +/- 35,89 (S. E.)) and more significant (alpha less than 0,001) than for cortisol (+/- 54,47% +/- 9,45 (S. E.) - alpha less than 0,10). The authors suggest aldosterone assays have to be done in order to obtain a better estimation on adrenal response to synthetic A.C.T.H.


Comparison of the binding properties of two 6 beta-amidinopenicillanic acid derivatives that differ in their physiological effects on Escherichia coli. The 6-beta-amidinopenicillanic acid derivative, mecillinam, was highly specific in its action on the growth of Escherichia coli. Concentrations from the minimal inhibitory concentration (0.05 mug/ml) up to at least 200 mug/ml resulted in the conversion of E. coli rods into osmotically stable spherical cells without significantly inhibiting cell growth or causing cell lysis. A second amidinopenicillanic acid derivative [6-([4-morpholinylmethylene] amino) penicillanic acid] showed identical effects on cell growth at concentrations from its minimal inhibitory concentration (0.2 mug/ml) up to at least 5 mug/ml but, at higher concentrations, increasing amounts of lysis occurred. Neither of these compounds showed the immediate inhibition of cell division that is observed with typical beta-lactam antibiotics. We have compared the binding of these two amidinopenicillanic acids to the individual penicillin-binding proteins of E. coli. Both compounds showed a high specificity of binding to penicillin-binding protein 2 at low concentrations. At higher concentrations mecillinam still maintained its high specificity for protein 2 and very little binding of mecillinam to any of the other binding proteins was detected with concentrations up to 1 mg/ml. The morpholino compound, however, showed extensive binding to proteins 1 and 4, and slight binding to proteins 5 and 6 at high concentrations. The morpholino compound therefore combined both the physiological properties and the binding properties of mecillinam with some of those of typical penicillins and cephalosporins. Lysis probably occurs at high concentrations of morpholino compound because it binds to penicillin-binding protein 1, since this is believed to be the target with which beta-lactams interact to inhibit cell elongation.


Inactivation of lipid-containing viruses by long-chain alcohols. This report describes the inactivation of lipid-containing viruses by several long-chain alcohols. A striking peak in antiviral activity was found for saturated alcohols having chain lengths from 10 to 14 carbons. Viruses having different membrane structure showed different susceptibilities to alcohols having different chain lengths and structural features. Decanol, dodecanol, and tetradecanol readily inactivated herpes simplex virus and the enveloped bacterial virus phi6. The lipid-containing virus PM2 was susceptible to decanol and dodecanol but comparatively unsusceptible to tetradecanol. The branched-chain alcohol phytol, a naturally occurring component of chlorophyll, was active against phi6 and herpes simplex virus but not against PM2. Polyoma virus and the bacteriophage phi23-1-a, which do not contain lipids, were not susceptible to inactivation by any of the alcohols tested. Experiments were also carried out to determine the effects of these compounds on cells. At 0.5 mM, decanol lysed human embryonic lung cells, erythrocytes, and the bacterial hosts for phi6 and PM2. Dodecanol, tetradecanol, and phytol at this concentration were less damaging to cells. At 0.05 mM, none of the alcohols caused observable cytopathic effects on human embryonic lung cells, although several of the alcohols at this concentration were active against herpes simplex virus. Our findings suggest that dodecanol, tetradecanol, and phytol may warrant further studies as potential antiviral agents, particularly for topical application to virus-infected areas of the skin.


Persistence of poliovirus 1 in soil and on vegetables grown in soil previously flooded with inoculated sewage sludge or effluent. Land disposal of sewage sludge and effluent is becoming a common practice in the United States. The fertilizer content and humus value of such wastes are useful for agricultural purposes, and the recycling of sewage onto the land eliminates many of our stream pollution problems. The potential exists for crops grown in such irrigated soil to be contaminated by viruses that may be present in the sewage. Studies were initiated to determine viral persistence in soil and on crops grown under natural conditions in field plots that had been flooded to a depth of 1 inch (2.54 cm) with poliovirus 1-inoculated sewage wastes. Lettuce and radishes were planted in sludge- or effluent-flooded soil. In one study, the vegetables were planted 1 day before flooding, and in another they were planted 3 days after the plots were flooded. Survival of poliovirus 1 in soil irrigated with inoculated sewage sludge and effluent was determined during two summer growing seasons and one winter period. The longest period of survival was during the winter, when virus was detected after 96 days. During the summer, the longest survival period was 11 days. Poliovirus 1 was recovered from the mature vegetables 23 days after flooding of the plots had ceased. Lettuce and radishes are usually harvested 3 to 4 weeks after planting.


Poliovirus aggregates and their survival in water. Inactivation of aggregated poliovirus by bromine is characterized by a continuously decreasing reaction rate. Poliovirus released from infected cells in these experiments by alternate freezing and thawing in water without electrolytes has always been aggregated. The aggregates persist even on 7,000-fold dilution in ion-free water. Virus similarly released into phosphate-buffered saline solution may be well dispersed, but it aggregates when sedimented into a salt-free sucrose gradient or when it is diluted as little as 10-fold in water. Large one-step dilutions of dispersed virus in water remain dispersed. Aggregated virus was not dispersed by one-step dilution (7,000-fold) in distilled or untreated lake water but was dispersed if phosphate-buffered saline or clarified secondary sewage plant effluent was used as diluent. Dispersed virus aggregates at all dilutions in alum-treated, finished water from the city filter plant. This may be the result of complex formation with insoluble material rather than virion-virion aggregation. A simple procedure is described for rendering a very dilute suspension of mixed virion aggregates into a three-part spectrum of sizes.


Rotavirus infections in a maternity unit. Between May and August 1975, rotaviruses were detected in the stools of 76 out of 174 (44%) newborn babies in the maternity unit at this hospital. Infection occurred less frequently in breast-fed than in bottle-fed babies (P less than 0.001). However, only 7 out of 76 (8%) babies who excreted rotaviruses had symptoms and these were mild. Complement fixation tests did not show any apparent difference in the antibody titres or serological responses between mothers of rotavirus positive or negative babies. When 68 faecal extracts known to contain rotaviruses by electron microscopy were inoculated by centrifugation on to monolayers of continuous pig kidney cell cultures (IB-RS-2), rotavirus antigen was detected by immunofluorescence in 65 (95.5%) specimens, 58 being positive after centrifugation at 3000 g and a further 7 after centrifugation at 10 000 g. Antigen was first detected 6 hours after inoculation of specimens, maximum levels being detected at 24 hours.


Effects of ozone and sulfur dioxide on virus growth in mice. Inhalation of ozone and sulfur dioxide inhibited influenza virus growth in the nose of mice. Ozone inhalation caused the more pronounced inhibition of influenza virus growth: 0.6 ppm ozone for 3 hours post-virus exposure almost completely inhibited influenza virus growth in the nose, whereas sulfur dioxide (6 ppm for 7 days) causes only partial inhibition of influenza growth in the nose. Neither gas altered the propagation of influenza virus in the lungs of mice. Vesicular stomatitis virus (VSV) growth was either unaffected by exposure to ozone (0.9 ppm for 3 hours) or, when ozone exposure preceeded VSV exposure, the virus may have grown to slightly higher titer. The inhibitory effect of ozone and sulfur dioxide on influenza virus growth in nasal epithelium suggests a competitive interaction between the chemical inhalant, the virus, and host tissues, with net consequences for the pathogenesis of this disease. If the effcts of these inhalants are to be properly interpreted, they should be determined for all major regions of virus growth and inhalant deposition.


Carcinoma of the anus.

Carcinoma of the anus. Carcinoma of the anus represents about 2% of cancers of the large bowel. From 1950 to 1970, 20 patients were treated for this condition. Included were 113 patients with squamous cell carcinoma (31 perianal), 64 with basalid squamous carcinoma, 8 with Paget's disease of the anus, 7 with melanoma, 6 with basal cell carcinoma, and 6 with adenocarcinoma. Combined abdomino-perineal resection was the treatment of choice except for perianal lesions; for these, local excision was used most frequently. Inguinal node dissection was used infrequently, and it is not possible to draw meaningful conclusions from the data. Overall survival rates for patients having anal squamous cell carcinoma are similar except when lymphatic invasion is present; then basaloid lesions have a significantly better prognosis. For rare anal carcinomas, histopathologic findings dictate the end results-- the better the findings and more satisfactory the results.


Prostaglandins E and F in endocrine diarrheagenic syndromes. The role of prostaglandins in endocrine diarrheagenic syndromes was evaluated by measuring peripheral concentration of immunoreactive PGE and PGF in patients with non-endocrine diarrhea as well as those with the Zollinger-Ellison (Z-E) syndrome, MCT, carcinoid tumors and the WDHA syndrome. In 21 normals, PGE and PGF levels averaged 272 +/- 18 and 119 +/- 14 pg/ml, respectively. Twenty eight patients with diarrhea of non-endocrine origin (mainly inflammatory bowel disease) had levels indistinguishable from normal, i.e. 353 +/- 25 and 77 +/- 37 pg/ml, respectively. Among 29 patients with the Zollinger-Ellison syndrome (mean gastrin 6127 +/- 3267 pg/ml) only 2 had significantly elevated PGE levels; mean PGE levels, 382 +/- 32 pg/ml, were not significantly different from normal and did not correlate with either diarrhea or the serum gastrin concentration. In contrast, 18 of 22 patients with carcinoid tumors (mean blood serotonin concentration 1655 +/- 604 ng/ml; mean urinary excretion of 5 HIAA 66.8 +/- 16.7 mg/day) had elevated peripheral concentrations of PGE. The mean PGE level (1367 +/- 245 pg/ml) was significantly elevated (P less than 0.001). Nonetheless PGE levels did not correlate with diarrhea, blood concentrations of serotonin, or urinary indole excretion. MCT (mean serum calcitonin 24.5 +/- 6.3 ng/ml) was similarly associated with consistent (18/19) elevation in peripheral concentrations of PGE (mean 1922 +/- 541 pg/ml; P less than 0.001). Inthis syndrome, PGE levels were higher in patients with diarrhea and in those with markedly elevated serum thyrocalcitonin levels. Finally, 8 of 21 patients with the WDHA syndrome had increased levels of PGE. Although 13 of 17 patients had high levels of VIP (mean 8133 pg/ml), 2 patients had hyperprostaglandinemia in the face of normal peripheral concentrations of VIP. In one patient the serum PGE level was elevated prior to resection of the primary pancreatic neoplasm (9939 pg/ml) as well as the subsequent extirpation of a solitary hepatic metastasis (1063 pg/ml); following each procedure the diarrhea abated and the PGE level returned to normal. In none of these syndromes were mean PGF levels elevated. The study has documented hyperprostaglandinemia in some endocrine diarrheagenic syndromes and validated the usefullness of measurements of PGE in patients with unexplained diarrhea.


Observations on the postoperative tumor growth behavior of certain islet cell tumors. Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angiogram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign.


Congenital mixed vascular deformities of the lower limb: the relevance of lymphatic abnormalities to their diagnosis and treatment. Nineteen patients with vascular deformities of the lower extremity were studied and were classified into three groups based on their clinical and angiographic findings. 1) The Klippel or Venous Dysplasia Group (n = 8) demonstrated: cutaneous nevi of metameric distribution, congenital varices (many of which were anomalous by phlebography), hypertrophy of bone and other tissues, but no evidence of arterial involvement by arteriography. 2) Congenital Arterio-Venous Fistulae Group (n = 7) showed: cutaneous angiomata, hypertrophy of bone and soft tissues, but arteriographic findings of single or multiple arterio-venous fistulae. 3) Scattered Angiomata Group (n = 4) had single or multiple angiomata involving the lower limb in particular. Arteriography was normal, while phlbography revealed venous abnormalities. Lymphography was performed on all patients. Six of 8 of the Klippel group demonstrated aplastic or hypoplastic lymphatics by lymphography. By contrast, all 7 of the patients in the Congenital Arterio-Venous Fistulae Group showed in their lymphographic findings-three of 4 of these patients had aplasia or hypoplasia. Fourteen of the 19 patients complained of painful swelling as a major symptom. Lymphatic fistulae and lymphoceles developed in several patients.Four patients underwent reduction operations for lymphedema. Lymphatic abnormalities as demonstrated by lymphography play a significant role in mixed vascular deformities of the lower extremities.


The mechanism of action of dicyclomine hydrochloride on rabbit detrusor muscle and vas deferens. Dicyclomine inhibited responses of rabbit detrusor muscle to transmural stimulation more than atropine or lidocaine, and also inhibited responses to acetylcholine and to KCl. Responses of rabbit vas deferens to noradrenaline and transmural stimulation were inhibited by dicyclomine. Dicyclomine was as potent a local anesthetic as lidocaine, as determined by the guinea-pig wheal test. 45Ca++ exchange in the rabbit detrusor, measured by the lanthanum methods, was not altered by atropine, lidocaine or dicyclomine. It is concluded that dicyclomine not only acts as an anticholinergic agent but also impairs excitation-contraction coupling and release of transmitter from autonomic nerves.


Motor disturbances produced by intrastriatal injection of cyclic AMP and cyclic GMP. Male albino rats were permanently cannulated bilaterally in the caudate/putamen nucleus and subsequently injected unilaterally with cyclic AMP or cyclic GMP. Both of these cyclic nucleotides failed to produce any obvious change in motor activity. The concomitant intrastriatal injection of carbachol and cyclic AMP resulted in enhancement of the carbachol-induced dyskinesias. Under similar conditions, cyclic GMP blocked the carbachol effects. The dibutyryl (db) derivatives of cyclic AMP and cyclic GMP both enhanced the carbachol-induced dyskinesias and both db cyclic nucleotides induced dyskinesias when injected intrastriatally alone. The concomitant intrastriatal injection of dopamine and carbachol resulted in a blockade of the carbachol-induced dyskinesias. Dopmaine had no effect on db cyclic AMP and db cyclic GMP dyskinesias. The db cyclic AMP effects characteristically involved the distal limb musculature, while the db cycle GMP effects largely involved the proximal limb and trunk muscles. The hypothesis for opposing action of cyclic AMP and cyclic GMP in the CNS and the discrepancy between the effects of intrastriatal injection of cyclic AMP and dopamine were discussed.


EEG of striate cortex in blind monkeys: effects of eye movements and sleep. After control studies, using electrodes permanently implanted in the central visual system, squirrel monkeys and macaques were in most instances blinded by acute glaucoma. This permitted subsequent observation of eye movements. Ocular nystagmus developed in all cases. Beginning immediately upon recovery from anesthesia, and persisting for at least 1 year, the EEG of the striate cortex was characterized by totally flat periods up to several seconds in duration which were ended abruptly by a sharp "spike" trailed in turn by a ragged high voltage, slow pattern for another second or two. The great majority of these "spikes" from the blind striate cortex occurred within 60-200 msec after a saccadic eye movement, made either in nystagmus or attempted fixation. They were not dependent upon proprioception from the extraocular muscles. It is suggested that they represent a "corollary discharge" for movement of the eyes. The blind striate cortex was judged to be hyperexcitable on the basis of these saccade-associated "spikes", not often observable in intact monkeys, and from the increase both in response evoked by electrical stimulation of optic radiation and amplitude of the EEG in sleep.


Electrophysiological analysis of the circuitry and of the corticonuclear relationships in the agranular cerebellum of irradiated rats. The cerebellar circuitry and the corticonuclear relationships were studied in the cerebellum of adult rats rendered agranular through 7 successive exposures to X-ray radiations during infancy. Data were obtained through examination of electrical responses induced in Purkinje cells (PC) and in neurons of the lateral vestibular nucleus (LVN) by cerebellar and spinal stimulations. In irradiated rats, PC exhibited antidromic activation with a high axonal threshold and 70% of them also presented typical climbing fiber responses (CFRs). By contrast, they exceptionnally exhibited responses via the mossy fiber (MF)-granule cell pathway, but two other classes of responses were identified: i) short latency single spike responses attributed to a direct excitatory impingement of MF onto PC; ii) atypical CFRs formed of high frequency bursts of simple spikes which were seen in 76% of PC tested. Furthermore, 53% of these cells also presented typical CFRs, strongly suggesting these PC were innervated by more than one CF, thus confirming previous data on the same type of agranular cerebellum. In the LVN neurons of control and irradiated rats, spinal and cerebellar stimulations evoked clear cut IPSPs. On the basis of their shape, latency, and occurrence in animals with or without cerebellum and with or without lesion of the CF pathway, they were interpreted as mediated through direct or synaptic activation of PC or through an extracerebellar pathway. In irradiated rats, the quantitative study of these IPSPs gave further arguments in favor of a multiinnervation of PC by CF and of an important reafferentation of MF onto PC. However, the functional efficiency of this reafferentation appeared very low, as tested by activation of MF originating in the spinal cord. Finally, the intracellular recording of LVN neurons showed that a large majority of PC axons retained normal synaptic connections with nuclear cells in treated animals, indicating that corticonuclear relationships do not markedly depend upon granule cells and normal CF input.


Myocardial scintigraphy with technetium 99m pyrophosphate. The pyrophosphate of Tc99m attaches itself to ischaemic myocardial cells, and therefore makes it possible to obtain a scintigram of necrotic or necrosing myocardium. In a series of 65 cases the scintigram was positive in every case in which there had been a recent transmural infarct (17 cases). The results showed greater variation in the other ischaemic conditions involving the myocardium (limited infarcts or simple angina). The progress as a function of time was stuided in a series of fairly recent and older infarcts. The limitations and future prospects of this investigations are discussed.


Comparative effect of methioninyl adenylate on the growth of Salmonella typhimurium and Pseudomonas aeruginosa. The bacteriostatic effect of methioninyl adenylate(MAMP)--a specific inhibitor of the enzyme methionyl-tRNA synthetase--was investigated on Salmonella typhimurium and Pseudomonas aeruginosa. 0.1 mM of this molecule added to the culture, inhibits the growth of S. typhimurium. The inhibition is specifically reversible by 0.1 mM L-methionine. In the same conditions even 1-2 mM MAMP has a very slight effect on the growth rate of P. aeruginosa and only during the first two generations. The same observation was made with the two other members of the fluorescens group P.fluorescens and P.putida. The growth rate of P. testosteroni with 1 mM MAMP in the medium is similar to the growth rate of P. aeruginosa but the other member of the acidovorans group P. acidovorans is much more affected by the smae concentration of the inhibitor. --P. multivorans is inhibited by MAMP like P. acidovorans but with a somewhat higher yield at the end of the culture. --MAMP has no effect on P. alcaligenes. The possible reasons for the weak bacteriostatic effect of MAMP on P. aeruginosa were investigated. It was established that the inhibitor enters the cells and is not used as a carbon and energy source. The intracellular methionine concentration in S. typhimurium and in P. aeruginosa is about the same and does not increase when bacteria are cultivated with MAMP. The MTS of the two microorganisms is inhibited by MAMP in vitro to about the same extent. Furthermore the tRNAmet from P. aeruginosa are fully acylated after 3 to 4 generations with this compound. Nevertheless MAMP elicits higher MTS activity in P. aeruginosa and in P. acidovorans after 1 h of incubation. The most striking difference between S. typhimurium and P. aeruginosa is that the intra and extracellular level of 5'phosphodiesterase which degrades MAMP is 10-20 fold higher in the second than in the first species.


The site for catabolite deactivation in the L-arabinose BAD operon in Escherichia coli B/r. A series of deletions beginning in the leu operon and continuing into the araC gene and also into the ara controlling site region were analyzed in reciprocal merodiploids, e.g., F' A2Cc67/B24delta719, F' B24delta719/A2Cc67, for their effects on catabolite deactivation (CD). The results of these experiments are consistent with placing the catabolite gene activator-cyclic AMP sensitive site in the controlling site region between araB and araO. With a deletion mutant, delta1109, that places araBAD under leu control when transcription begins at leuP, the araBAD operon is immune to CD even though araCGA, araP and araI are intact and functional. To focus attention on the fine structure and related functions of this region we propose that the three proteins that function therein have separate sites of action: araI (initiator-site for activator), araP (promoter-site for RNA polymerase) and ara(CGA) (catabolite gene activator-site for CGA-cAMP). None of the eighteen initiator constitutive mutants (Ic) tested have any significant effect on catabolite derepression or on the maximal level of expression of the operon supporting the view that the araI site may be distinct from araP and ARA(CGA). A series of constitutive mutants in the araC gene (Cc) also have no pronounced effect on catabolite deactivation.


Pyrimidine ribonucleoside monophosphokinase and the mode of RNA turnover in Bacillus subtilis. A protein catalyzing the phosphorylation of CMP to CDP was purified and characterized. Kinase activity for UMP copurified during ammonium sulfate fractionation, DEAE-cellulose and hydroxylapatite chromatography, and gel filtration on Sephadex G-75, the ratios of activities for the two substrates remaining constant. The purified product, possessing both activities was homogeneous as judged by the single band following polyacrylamide gel electrophoresis. The protein showed no kinase activity against purine nucleoside monophosphates or the other pyrimidine nucleoside monophosphates: dCMP, dUMP, and dTMP. Thus unlike the enteric bacteria, Escherichia coli and Salmonella typhimurium which have distinct enzymes which phosphorylate UMP and CMP, Bacillus subtilis produces a single pyrimidine ribonucleoside monophosphokinase. The Km values of this enzyme from B.subtilis are 0.04 and 0.25 mM for CMP and UMP, respectively, and 0.04 and 0.4 mM for ATP at saturating concentrations of CMP and UMP, respectively. The properties of this enzyme and the differences between enteric bacteria and B.subtilis with respect to the enzymes which phosphorylate CMP are consistent with the measurements which indicate that turnover of messenger RNA is largely hydrolytic in E.coli but largely phosphorolytic in B.subtilis.


Glycollate production and excretion by Alcaligenes eutrophus. Autotrophic cultures of the facultative chemolithotroph Alcaligenes eutrophus have been found to excrete glycollate. This excretion was greatly stimulated by the incorporation of up to 20% (v/v) oxygen in the hydrogen used for gassing. The stimulatory effect of oxygen was prevented by the addition of 10% (v/v) CO2 to the gassing mixture. Glycollate excretion only in the presence of oxygen was increased by the addition of 2-pyridyl-hydroxymethane sulphonic acid (HPMS), an inhibitor of glycollate oxidation, indicating that glycollate formation itself was stimulated by oxygen. No glycollate excretion by cultures grown heterotrophically on pyruvate was detected, either in the absence or presence of HPMS, under heterotrophic or autotrophic cells showed phosphoglycollate phosphatase and glycollate oxidoreductase activities, which were considerably lower in extracts prepared from pyruvate- or fructose-grown (heterotrophic) cells. The increase in activity of both enzymes upon cell transfer from heterotrophic to autotrophic growth was prevented by chloramphenicol and resembled the induction of D-ribulose 1,5-diphosphate carboxylase under the same conditions.


Fumarate reduction in Proteus mirabilis. 1. Proteus mirabilis formed fumarate reductase under anaerobic growth conditions. The formation of this reductase was repressed under conditions of growth during which electron transport to oxygen or to nitrate is possible. In two of three tested chlorate-resistant mutant strains of the wild type, fumarate reductase appeared to be affected. 2. Cytoplasmic membrane suspensions isolated from anaerobically grown P. mirabilis oxidized formate and NADH with oxygen and with fumarate, too. 3. Spectral investigation of the cytoplasmic membrane preparation revealed the presence of (probably at least two types of) cytochrome b, cytochrome a1 and cytochrome d. Cytochrome b was reduced by NADH as well as by formate to approximately 80%. 4. 2-n-Heptyl-4-hydroxyquinilone-N-oxide and antimycin A inhibited oxidation of both formate and NADH by oxygen and fumarate. Both inhibitors increased the level of the formate/oxygen steady state and the formate/fumarate steady state. 5. The site of inhibition of the respiratory activity by both HQNO and antimycin A was located at the oxidation side of cytochrome b. 6. The effect of ultraviolet-irradiation of cytoplasmic membrane suspensions on oxidation/reduction phenomena suggested that the role of menaquinone is more exclusive in the formate/fumarate pathway than in the electron transport route to oxygen. 7. Finally, the conclusion has been drawn that the preferential route for electron transport from formate and from NADH to fumarate (and to oxygen) includes cytochrome b as a directly involved carrier. A hypothetical scheme for the electron transport in anaerobically grown P. mirabilis is presented.


The effect of dibromothymoquinone on respiratory and photosynthetic electron transport in Rhodopseudomonas capsulata chromatophores. Dibromothymoquinone has been shown to inhibit light-induced cytochrome b reduction, and oxidation of succinate and NADH by chromatophores of Rhodopseudomonas capsulata. The half-inhibitory concentration of light-induced reactions and NADH oxidation is 2.5 muM, but of succinate oxidation is 16 muM. Hexane extraction inhibited oxidation of NADH and succinate equally. The results are interpreted to suggest that ubiquinone is concerned in all three processes described, but that the pools associated with NADH and succinate oxidation are not equally accessible to dibromothymoquinone.


Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics. I. Relapse rates after one year. In a simple remitted, nonpsychotic schizophrenics, the relapse rate within one year was significantly higher for those patients taking placebo as opposed to those taking fluphenazine hydrochloride orally or fluphenazine decanoate. There were no differences in relapse rates between the two active drugs, but there were significantly more terminations due to toxicity from fluphenazine decanoate than from pluphenazine given orally, entirely due to the fact that in 35% of patients receiving fluphenazine decanoate, severe akinesia developed.


Endogenous depression improvement and REM pressure. In the treatment of endogenous depression by rapid eye movement (REM) sleep deprivation, depression improvement, measured on Hamilton and Global scales, correlated positively and significantly (P less than .05) with REM pressure (increase of REM sleep stimulated by REM sleep deprivation). This dose-response relationship suggests that (1) REM pressure was an indicator of a process that mediated the antidepressant effects of REM sleep deprivation, and (2) since improvement varied with stimulation of REM sleep, an unknown stimulus of REM sleep is a naturally occurring, endogenous antidepressant.


[Guillain Barré- polyneuroradiculitis and Fisher-syndrome in cytomegalovirus infections (author's transl)]. In seven patients suffering from polyneuroradiculitis of the Guillain-Barré type and one case of Fisher syndrome, a cytomegalovirus infection was found. The elevation of the virus-specific IgM-antibodies was confirmed in all cases. The clinical course was severe and acute with respiratory disturbances, but complete remission occurred within 1-4 months. The complement fixing antibodies were highest during the first week of illness, so that further elevations could not be demonstrated, therefore making the IgM-antibody method of special importance. The role of cytomegalovirus infections in polyneuroradiculitis is also discussed.


Replication of cytomegalovirus in human epitheloid diploid cell line. Human diploid BAMB cells with epitheloid morphology, which had been derived from amniotic fluid cells, were capable of supporting the replication of human cytomegalovirus (CMV), without prior treatment of the cells with halogenated pyrimidines. The growth of this virus in BAMB cells and in human diploid fibroblastoid (LEP) cells was compared in parallel tests. Virus replication was slower and less efficient in the former than in the latter system. The most characteristic morphological feature of the CMV-infected BAMB cells was the formation of multinucleated giant cells which frequently contained more than a hundred nuclei; such cells were not seen in LEP cultures. The development of ultrastructural changes was slower in BAMB cells than in LEP cells. The additional most marked differences concerned the place of viral envelopment and the production of cytoplasmic dense bodies. While in LEP cells most nucleocapsids were enveloped from the inner leaflet of the nuclear membrane, in the other system a great majority of the particles acquired their envelopes by budding into vacuoles. Cytoplasmic dense bodies were rare in infected LEP cells but very frequent in BAMB cells. Budding of these structures into vacuoles was also observed.


[Morphological changes in the placenta in late pregnancy toxemias]. The article presents results of morphological, morphometric and cytochemical investigations of 100 placentae obtained in women who suffered from nephropathy of various degrees, and of placentae of mice with induced "graft versus host" reaction during pregnancy, and also of organs of two fetuses born to mothers who suffered from nephropathy of the III degree. In severe forms of late toxemia placentae, regularly showed infiltration of its structural elements with cells of the type of microlymphocytes with lytic properties. These changes occurred against the background of the placental metabolism turning into anaerobic respiration and they revealed a considerable degree of similarity to the changes in placentae of mice following the induction of the reaction "graft versus host". The morphological picture in lymphoid and other organs of the two investigated fetuses resembled very much that in "runt" disease.


[Theca-like reactions in the stroma of cilioepithelial ovarian neoplasms]. The work deals with the study of the so-called theca-like reaction in the stroma of 283 cilioepithelial tumours of the ovary (50 simple, 28 proliferating cystadenomas, and 205 cancers developed from cilioepithelial cystadenomas). The composition of the interstitial tissue of neoplasms of this type (except simple cystadenomas) included cells morphologically undistinguished from the thecal elements of the ovary. They may contain cholesterolethers and sets of redox enzymes typical of the steroidproducing tissues. Manifestation of the theca-like reaction (findings of morphometry) depended upon the degree of anaplasia of the tumour epithelium: it was most pronounced in malignant highly differentiated tumours, and least pronounced in drastically anaplasic cancer.


[Electron microscopic diagnosis of granular cell tumors]. In tumour cells organspecific ultrastructural features are retained that may be of value in differential diagnosis. For this purpose not only fresh material but also that fixed formerly in formalin may be used.


[Cyclic nucleotides].

[Cyclic nucleotides]. A survey of the available literature on the role of cyclic nucleotides (cyclic adenosine 3,5-monophosphate and cyclic guanosine 3,5-monophosphate) in the control over various aspects of cellular activity: regulation of growth and morphology of normal and tumorous cells, participation in differentiation of cells, blast-transformation, regulation of inflammatory and immunological processes governed by lymphocytes, is presented. A presumable mechanism of action of cyclic nucleotides is considered.


Myosin degeneration in a congenital myopathy. In a muscle biopsy specimen from a baby girl with hypotonia, there was the ultrastructural finding of selective myosin degeneration in some myofibers. The sarcomeres were either well aligned or completely distorted. Excessive glycogen, fiber and fibril splitting, and occasional aggregates of vesicles were the other abnormalities present.


Optic nerve decompression. A clinical pathologic study. Decompression of the perioptic meninges for intractable chronic papilledema was done in a patient with a right parietal temporal glioblastoma multiforme. The patient died 39 days postoperatively. Histologic study of the optic nerves indicated fistulas in the dura compatible with cerebrospinal fluid (CSF)  egress and maintenance of a normal subarachnoid space around the nerve. Two additional patients with unilateral optic nerve decompression producing bilateral resolution of papilledema were studied. We contend that egress of CSF was the principle mode of action in these three cases. How long the dural fistula remains patent is unknown. Reports in the literature show considerable variation in the effects of optic nerve decompression. Anatomic variation of the intracanalicular subarachnoid space together with differences in underlying pathologic condition, surgical technique, and patient response may explain discrepancies among the results reported.


Angiographic changes of head and neck chemodectomas following radiotherapy. Angiography is useful in following selected patients with chemodectoma of the head and neck treated by radiotherapy. Comparison of preradiotherapy and post radiotherapy angiograms in three patients revealed a decrease in the following: size of feeding arteries, size of tumor, intensity of tumor opacification, and degree of venous shunting. When chemodectomas are not amenable to physical examination and when the question of radiotherapy complication vs further growth of tumor arises, postradiotheraphy angiography may be of particular value.


Prognosis of nasopharyngeal carcinoma by Epstein-Barr virus antibody titer. A total of 433 samples of serum were collected from 305 patients with histopathologically proved anaplastic nasopharyngeal carcinoma (NPC). Antibodies against viral capsid antigens (VCA) of Epstein-Barr (EB) virus were titrated by means of indirect fluorescent antibody technique, using P3HR-1 cells as the target. High anti-VCA antibody titer in patients with NPC was found beginning to decline at the end of radiotherapy. Most (66.7%) of the patients were found to have a detectable reduction in antibody titer within six months after radiotherapy. Persistent high antibody titer after treatment correlates to high risk of the recurrence of the disease. This prognostic importance of anti-VCA titer becomes apparent at the end of radiotherapy, significant (P less than .05) within one year after treatment, and highly significant (P less than .0005) over one year after treatment.


[Electron microscopic examination on cytogenesis of juvenile nasopharyngeal angiofibromas (author's transl)]. After the electron miscroscopic examination of tissue samples of juvenile nasopharyngeal angiofibromas obtained from 9 male patients ranging in their age from 7-24 years the problems of cytogenesis and classification are discussed. Besides it is tried to correlate particular morphological findings to certain clinical phenomenons. The vascular component of juvenile nasopharyngeal angiofibromas shows a clear proliferation of the vascular wall cells. Particularly, proliferating pericytes, cells withous peculiar characteristics ("undifferentiated" cells) and cells in various stages of differentiation are to be emphasized. Obviously, vascular wall cells emigrate into the surrounding tissue and transform themselves into small fibroblasts. The second component of juvenil nasopharyngeal angiofibromas is represented by stromal fibroblasts with several cytological variations. Only activated "classical" fibroblasts and fibroblasts with histocyte-like features reveal the nuclear pattern unique for these growths which is characterized by the combination of protrusions of nuclear membrane with formation of nuclear "blebs" and of dense intranuclear granules. Cells with these nuclear characteristics were considered as preexisting fibroblasts. Thus juvenile nasopharyngeal angiofibromas are formed by the proliferation of two tissue components, namely by the proliferation of vascular wall cells and stromal fibroblasts, and can be conceived as reactive hyperplasias. The swelling body-like and organoid appearance, cytological pecularities, characteristic topographic relations (localization and supplying vessesl) and the sex-dependent occurrence speak for a tumor-like hyperplasia of a rudimentary organ unknown till now.


Cytotoxic T cells in the peritoneal cavity of mice infected with ectromelia virus. Peritoneal exudate cells from mice infected with ectromelia virus were cytotoxic for virus-infected target cells as measured in a 51Cr release assay. Cytotoxic activity seemed to be T cell-dependent as it was largely abolished by treatment with anti-theta serum and complement but was not impaired by macrophage depletion. The kinetics of development of cytotoxicity in the peritoneal cavity lagged behind spleen cytotoxicity by 1-2 days. Peak activity in peritoneal cells was present about 6 days after intravenous infection with virus. These studies suggest that macrophages present in the free peritoneal cell populations of ectromelia-infected mice are not cytotoxic for virus-infected target cells. The effect of macrophages in virus clearance is therefore likely to be due to phagocytic rather than cytotoxic effects.


Metastatic hepatoma in the stomach masquerading as a leiomyoma. Metastatic hepatoma in the stomach is rare. A case is described in which a gastric tumour appeared to be a leiomyoma, but after laparotomy proved to be an isolated secondary deposit from a hepatoma.


Isolation of an adenovirus from an Arab foal with a combined immunode ficiency disease. Some details of the clinical and postmortem findings of an Arab foal that died as a consequence of adenoviral pneumonia superimposed on a combined immunodeficiency disease are provided. The foal was the 17th in a series of similar deaths that occurred on a farm since 1959. An adenovirus, which by haemagglutination inhibition and serum neutralisation tests was antigenically similar to 2 other equine adenoviruses isolated in Australia, was isolated from a nasal swab taken from the foal when it was 23 days of age.


Changes in intestinal structure and function of neonatal calves infected with reovirus-like agent and Eschericia coli. Measurements of villus/crypt length ratio and mucosal beta-galactosidase activity were made on calves less than 3 weeks of age which had diarrhoea associated with reovirus-like agent and E. coli. In calves with diarrhoea, the villus/crypt length ratios at all sites examined along the small intestine were less than in normal calves of similar age. This was attributed to a reduction in length of vili in calves infected with the reovirus-like agent. The activity of mucosal beta-galactosidase in the intestine of calves with diarrhoea was less than in normal calves, at all sites examined. A relationship existed between beta-galactosidase activity in vitro and lactose hydrolysis in vivo. It was concluded that calves with diarrhoea associated with reovirus-like agent, have a reduced ability to utilize dietary lactose.


Tenosynovitis in chickens.

Tenosynovitis in chickens. An adenovirus was isolated from the tendon fluid of broilers and meat breeders with clinical tenosynovitis. The viral infection was in many cases accompanied by a staphylococcal infection. The significance of the adenovirus is not yet known, although initial transmission studies indicate that it may play a role in the tendon thickening process.


Electron microscopic study of benign hepatoma in a patient on oral contraceptives. Electron microscopic studies of a benign hepatoma in a 31-year-old women who was on contraceptive pills are presented. The electron microscopic picture showed highly differentiated liver cells with regularly developed bile canaliculi. The mitochondrial polymorphism, the formation of paracristalloids and the appearance of giant mitochondria were striking. The main change was the occurence of the numerous capillaries of varying caliber which were highly differentiated and formed an integral part of the tumor. On the basis of these finding the tumor is regarded as a benign mixed tumor. The well developed capillary system explaines the arteriographic characteristics and the frequent bleeding complications noted in the literature.


Induction of enzymes of the glycerophosphate pathway in leu-5 mutants of Neurospora crassa. The inducible cytosolic glycerokinase and mitochondrial glycerol-3-phosphate dehydrogenase have been examined during the glycerol-specific induction in Neurospora crassa. Although both the fully induced levels and the respective rates of synthesis of these two enzymes were less than observed with wild-type cells, there were no major differences in the relative rates of induction of the glycerol-3-phosphate dehydrogenase at either permissive or restrictive temperatures. These results indicate that the processes involved in the assembly of this enzyme into the mitochondrial inner membrane are normal in a mutant lacking the mitochondrial leucyl tRNA synthetase and suggest that the functions of the mitochondrial synthetase may be replaced by those of the cytosolic leucyl tRNA synthetase.


"Tonic" and "phasic" mechanisms in the regulation of myocardial contractility. Myocardial contractility can be regulated by two types of control mechanism. A "tonic control mechanism", which allows the heart to respond to sustained changes in circulatory dynamics, appears to operate through changes in the structure of various constituents of the myocardium, best understood of these being changes in the myosin molecule that cause alterations in both myosin ATPase activity and contractility. Beat-to-beat changes in myocardial contractility are affected by a "phasic control mechanism" that involves changes in at least five calcium fluxes in the myocardium. The effects of catecholamines, many of which appear to be mediated by cyclic AMP, can be understood in terms of the modification of several of the calcium fluxes involved in the phasic control of myocardial contractility.


Correlation of protein kinase activation and testosterone production after stimulation of Leydig cells with luteinizing hormone. The effect of different doses of luteinizing hormone on activation of protein kinases, cyclic AMP and testosterone production was studied in purified rat testis Leydig-cell preparations in the presence of 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). In addition, the nature of the protein kinases present in these cells and other tissues was investigated. The following results were obtained. 1. With all the amounts of luteinizing hormone used (0.1-1000 ng/ml), both activation of protein kinase and stimulation of testosterone production were demonstrated. With the lowest amount of luteinizing hormone (0.1 ng/ml), an 8.4+/-0.9% (S.E.M.,n=6) stimulation of protein kinase activation occurred, increasing to 100% with 1000 ng/ml, compared with 3.2+/-1.0%(S.E.M.,n=7) and 100% stimulation of testosterone production with 0.1 and 100 ng/ml respectively. 2. With amounts of luteinizing hormone up to 1 ng/ml (which gave half-maximal stimulation of testosterone production) no detectable increases in net cyclic AMP production were obtained. With higher amounts of luteinizing hormone, cyclic AMP production increased, but maximal production was not reached with 1000 ng/ml. 3. Two isoenzymic forms of protein kinase were present in Leydig cells and seminiferous tubules; type I was eluted with 0.075 M-and type II with 0.22-0.25 m-NaCl from DEAE-cellulose columns. 4. The protein kinase activity was not affected by the presence of erythrocytes in the Leydig-cell preparation, but varied depending on the type of histone used as substrate (histone F2b greater than mixed greater than histone F1).


Calcium metabolism and amylase release in rat parotid acinar cells. 1. A method is described for the isolation of rat parotid acinar cells by controlled digestion of the gland with trypsin followed by collagenase. As judged by Trypan Blue exclusion, electron microscopy, water, electrolyte and ATP concentrations and release of amylase and lactate dehydrogenase, the cells are morphologically and functionally intact. 2. A method was developed for perifusion of acinar cells by embedding them in Sephadex  G-10. Release of amylase was stimulated by adrenaline (0.1-10muM), isoproternol (1 or 10 MUM), phenylephrine (1 muM), carbamoylcholine (0.1 or 1 muM), dibutyryl cycle AMP (2 MM), 3-isobutyl-1-methylxanthine (1mM) and ionophore A23187. The effects of phenylephrine, carbamoylcholine and ionophore A23187 required extracellular Ca2+, whereas the effects of adrenaline and isoproterenol did not. 3. The incorporation of 45Ca into parotid cells showed a rapidly equilibrating pool (1-2 min) corresponding to 15% of total Ca2+ and a slowly equilibrating pool (greater than 3h) of probably a similar dimension. Cholinergic and alpha-adrenergic effectors and ionophore A23187 and 2,4-dinitrophenol increased the rate of incorporation of 45Ca into a slowly equilibrating pool, whereas beta-adrenergic effectors and dibutyryl cyclic AMP were inactive. 4. The efflux of 45Ca from cells into Ca2+-free medium was inhibited by phenylephrine and carbamoylcholine and accelerated by isoproterenol, adrenaline (beta-adrenergic effect), dibutyryl cyclic AMP and ionophore A23187. 5. A method was developed for the measurement of exchangeable 45Ca in mitochondria in parotid pieces. Incorporation of 45Ca into mitochondria was decreased by isoproterenol, dibutyryl cyclic AMP or 2,4-dinitrophenol, increased by adrenaline, and not changed significantly by phenylephrine or carbamoylcholine. Release of 45Ca from mitochondria in parotid pieced incubated in a Ca2+-free medium was increased by isoproterenol, adrenaline, dibutyryl cyclic AMP or 2,4-dinitrophenol and unaffected by phenylephrine or carbamoylcholine. 6. These findings are compatible with a role for Ca2+ as a mediator of amylase-secretory responses in rat parotid acinar cells, but no definite conclusions about its role can be drawn in the absence of knowledge of the molecular mechanisms involved, their location, and free Ca2+ concentration in appropriate cell compartment(s).


Studies on rat ovarian receptors for lutropin (luteinizing hormone). Applicability of radioimmunoassay to measure lutropin bound to receptors. Measurement of receptor-bound unlabelled physiologically active lutropin (luteinizing hormone, LH) was possible by a modified radioimmunoassay. The conventional radioimmunoassay conducted at 4 degrees C was inadequate, whereas the modified assay performed at 37 degrees C could measure receptor-bound lutropin. The radioimmunoassay at 37 degrees C takes only 36h for completion compared with 5-7 days at 4 degreesC. The sensitivity and range of dose-response curves are, however, unaltered. The validity of the technique was established by a number of criteria.


Studies on rat ovarian receptors for lutropin (luteinizing hormone). Factors influencing binding and response. The interaction of rat ovarian receptors with lutropin (luteinizing hormone, LH) in vitro was rapid and reversible. The degree of binding was saturable and susceptible  to changes in the concentration of lutropin in the medium. The concentration of lutropin receptors in the ovary increases during the natural pubertal period and also in immature rats given pregnant-mare-serum gonadotropin and human choriogonadotropin. In the latter case, the increase in lutropin receptor, after injection of pregnant-mare-serum gonadotropin alone, could be detected only if the ovaries are freed of the bound gonadotropin before exposure to lutropin. The concentration of lutropin receptors was higher in the luteal compartment of the ovary than in the non-luteal parts and increased slightly in aged corpora lutea. Correlation between binding of lutropin to the ovary and the ovarian response to lutropin in terms of cyclic AMP production was found only in prepubertal rat ovaries and in young corpora lutea and not in aged corpora lutea, suggesting the non-equivalence of binding in vitro and ovarian response.


Studies on rat ovarian receptors for lutropin (luteinizing hormone). Interaction with beta-subunit of sheep lutropin. By using radioimmunoassay, the interaction of sheep lutropin (luteinizing hormone, LH) beta-subunit with rat ovarian receptors was investigated. The binding of beta-subunit was specific, although of much lower order than that of lutropin. Sheep lutropin beta-subunit effectively inhibited the binding of human choriogonadotropin (chorionic gonadotropin, gCG) to the ovary, showing that both occupy the same sites. The binding of sheep lutropin beta-subunit to ovary was not followed by any detectable increase in cyclic AMP. The ovarian response to lutropin in terms of cyclic AMP production was inhibited in the presence of free beta-subunit. The alpha-subunit of lutropin, when used at concentrations where contamination with whole lutropin was negligible, enhanced the degree of binding of beta-subunit; this did not lead to increased cyclic AMP in the tissue. Surprisingly, the binding of beta-subunit in vitro was drastically decreased by the prior removal of all endogenous rat lutropin bound to receptors. The implications of these data are discussed in the light of the reported biological activity of the beta-subunit.


Vitamin D in the avian egg. Its molecular identity and mechanism of incorporation into yolk. The chemical identity of vitamin D in the egg of the domestic fowl was studied by analysing radioactivity in eggs from hens injected with [3H]cholecalciferol. Labelled molecules were found throughout the egg, but the concentration of total radioactivity in albumin was only 5-7% of that in yolk. In lipid extracts of yolk, more than 90% of the radioactivity was as unchanged cholecalciferol and 5% as 25-hydroxycholecalciferol. Only about 3% of the radioactivity in albumin was chloroform-soluble, and of this 40% was 25-hydroxycholecalciferol and 15% was cholecalciferol. Evidence is presented to support the idea that the specific transport of cholecalciferol into yolk is mediated by a cholecalciferol-binding protein in blood. This protein forms a complex with yolk proteins in transit from liver to ovary via the blood. A cholecalciferol-binding protein, chromatographically similar to that from blood, was found in egg yolk. It is postulated that cholecalciferol forms part of a complex with its specific binding protein, Ca2+ and the yolk phosphoprotein, phosvitin. This complex is then incorporated into yolk by the thecal cells of the ovarian follicle.