Insulinoma: clinical and diagnostic features of 60 consecutive cases. Insulinoma is a rare tumor, occurring more often in women and in the older age range. Eighty percent of patients have a single benign tumor, usually less than or equal to 2 cm in diameter, located with about equal frequency in body, head, or tail of the pancreas and amenable to surgical cure. About 10% have multiple tumors; in this group there is a high incidence of multiple endocrine neoplasia type I syndrome. The remaining 10% of patients have metastatic malignant insulinoma. Symptoms are intermittent, recur at irregular intervals in the food-deprived state over a median of 1 1/2 years, and arise from varying degrees of neuroglycopenia. Symptoms often lead to misdiagnosis as a neurologic or psychiatric disorder. Transient neurologic deficits and EEG abnormalities can be observed during hypoglycemia. Diagnosis requires repeated demonstration of hypoglycemia (glucose less than or equal to 40 mg/dl) during spontaneous or provoked symptoms, relief with ingestion of carbohydrates, simultaneous hyperinsulinemia (serum insulin greater than 6 muU/ml), and absence of insulin antibodies. A useful diagnostic adjunct is the intravenous tolbutamide test, for which new diagnostic criteria are presented.


Ultrastructure of platelet aggregation in refractory anemia and myelomonocytic leukemia. II. Individual platelet abnormalities: thrombasthenia-like platelets, surface defects, and dissociation phenomena. Studies of in vitro platelet aggregation were done in five patients with refractory anemia and two with acute myelomonocytic leukemia. The macroscopic results as well as the general ultrastructural findings were reviewed in a companion paper. Electron microscopic analysis of changes in the individual platelets within aggregates revealed a striking heterogeneity, both in the degree of response of each platelet are in the ultrastructural characteristics of the platelet population. Many of the unaggregated platelets had reacted individually, resembling the platelets of patients with Glanzmann's thrombasthenia. There were other abnormalities suggesting the presence of surface defects, such as the presence of areas of obliteration of the interplatelet space (so-called tight connections). One of the most striking findings was a peculiar dissociation between the different components of the aggregation sequence.


A comparison of therapeutic modalities of glomus tumors in the temporal bone. Seventy-seven patients with glomus tumors involving the temporal bone were treated by surgery, irradiation, and combined therapy. The therapeutic success rate for the surgery group was 91 percent for glomus tympanicum and 78 percent for glomus jugulare tumors. The success rate for radiation therapy was 30% in glomus jugulare tumors. Patients with extensive lesions treated by combined therapy had a therapeutic success rate of 60 percent. The clinical response of glomus jugulare tumors to radiation therapy was 65 percent. Surgery appears to be the best method for eradication of the tumors; however, with large extensive lesions, combined therapy offers a better prognosis than either modality alone.


Tonsillectomy and infectious mononucleosis--a possible relationship. A review of 1,192 student medical records shows a prior history of tonsillectomy in 41 percent of a control group and 22 percent of an infectious mononucleosis group--a significant difference (p less than 0.01). Nine hundred eighty-nine Stanford University students (421 females, 568 males) who visited Cowell Student Health Center between April and September, 1973, comprise the control group. Two hundred three students with positive monospot tests and clinical mononucleosis diagnosed between June, 1968, and May, 1973, comprise the experimental group. The lower incidence of tonsillectomy in the infectious mononucleosis group implies that the tonsillar lymphoid tissue serves as a reservoir and possible replicating milieu for the Epstein-Barr virus. Prior tonsillectomy may reduce the possibility of contracting infectious mononucleosis.


Effects of electrical stimulation and norepinephrine on cyclic-AMP levels in the cerebral cortex of the aging rat. One to 24 month old rats were anesthetized with alpha-chloralose, their cerebral cortices exposed surgically and subjected in vivo to stimulation by norepinephrine (1.0mM for 5 minutes) or electrical pulses (100 pulses/s for 10 s). After microwave fixation, cortical samples were analyzed for cyclic-AMP by the Gilman method. In similarly prepared but unstimulated control animals, cyclic-AMP levels were found to be three to four-fold lower in older than in younger rats, a pattern previously reported for unanesthetized rats. Both norepinephrine and electrical pulses led to cyclic AMP increases. With increasing age the cyclic-AMP levels attained under both stimulus conditions declined, with the levels achieved in the two cases becoming increasingly divergent.


A morphometric and cytochemical analysis of aging changes in the flight muscle of Nasonia vitripennis (Walk) (Hymenoptera, pteromalidae). A morphometric and cytochemical analysis was carried out on the effect of age and diet on the flight muscles of Nasonia vitripennis (Walk). A significant decline in mitochondrial volume with age is revealed in pupae-fed insects, but this is not recorded in sucrose-fed insects. There is also a significant decline in the activity of cytochrome oxidase in sucrose-fed, but not in pupae-fed, insects. It is concluded that the sucrose diet caused a delay in the ultrastructural deterioration of the flight muscles.


[Current concepts of intestinal fat absorption(author's transl)]. Some details of the general physiology of intestinal fat absorption are discussed taking triglyceride absorption as an example. Special emphasis is placed upon the role of the fatty acid binding protein (FABP) just recently discovered and upon the role of apoproteins for lipid transport from the epithelial cells to the intestinal lymph. On basis of own experimental results the hypothesis is put forward, that a small part of the intestinal energy requirement during fat absorption may be provided by intestinal oxydation of plasma free fatty acids.


Effect of alimentation on human serum squalene levels. Five subjects consumed a meal containing ca. 1.5 mg squalene. Postprandial serum samples showed that in three of the subjects squalene and lipid levels reached maxima at 3 hr. Squalene levels in the low density lipoproteins of these subjects also increased. The results indicate that alimentation is a major factor in the variation in serum squalene levels.


[Oxidative phosphorylation capacity of Rhodopseudomonas palustris during growth in light and darkness]. Assimilation of oxygen by the cells of Rhodopseudomonas palustris grown in the light and in the darkness is stimulated by p-chlorocarbonylcyanidephanylhydrazone, suggesting respiration coupled to phosphorylatin. Membranes of the cells grown in the light are capable of oxidative phosphorylation in the course of electron transport from NADH and succinate to O2 with P/O being 0.03 and 0.20, respectively. Membranes of the cells grown in the darkness in aerobic conditions are capable of oxidative phosphorylation in the presence of NADH, succinate and ascorbate + phenazinemetasulphate with P/O being 0.25, 0.40 and 0.06, respectively. Phosphorylation during oxidation of ascorbate + phenazinemetasulphate in the cells grown in the darkness suggests that the third point of coupling has appeared as a result of synthesis of cytochrome a. There are only minor differences in phosphorylation in the membranes of the cells grown in the light and in the darkness, as was shown by its susceptibility to p-chlorocarbonylcyanidephenyl-hydrazone, oligomycin, antimycin A and cyanide.


[Inhibitory analysis of the respiration of bacteroids from the nodules of yellow lupine]. Oxygen uptake and reduction of C2H2 by bacteroids was found to be inhibited by low concentrations of cyanide and azide. However, oxygen uptake was not completely suppressed even by 10(-3) M KCN. Cyanide-resistant respiration was not inhibited by salicyl-hydroxamic acid, and seemed to be accomplished at the account of autoxidable flavo-proteins. A small light-reversible inhibition of respiration by carbon monoxide was found only in the bacteroids with a high rate of nitrogen fixation. Rotenone, antimycin A, and tenoyltrifluoroacetone inhibited oxygen uptake and methylene reduction. Nitrogen fixation, but not respiration, was inhibited by 2,4-dinitrophenol. An electron-transport chain coupled with phosphorylation is supposed to be built into the membranes of the bacteroids. The activity of peroxidase and cytochrome peroxidase was demonstrated in the bacteroids.


Clinical studies of 5-fluorouracil + premarin in the treatment of breast cancer. Sixty patients with metastatic or primary inoperable breast cancer not suitable for hormone alteration therapy were blindly randomized between weekly 5-fluorouracil, intravenously, and daily physiologic doses of conjugated estrogens by mouth against weekly 5-fluorouracil, intravenously, and placebo. There was no difference in the survival or the effect on the tumor in the two groups. Numerous factors were analyzed as to their effect on the course of the disease. The number of organ sites of tumor involvement, age of the host, and previous treatment for the disseminated disease were not shown to influence the survival or the results of therapy of either group. However, the duration of the clinical cancer-free period from primary treatment to recurrence, the sites of organ involvement, and the performance status of the patients at the time of entry into the study significantly did influence the survival. There is no evidence in this study that physiologic doses of conjugated estrogens deleteriously influenced the course of the disease.


[Polyphosphate biosynthesis in Rhodospirillum rubrum chromatophores]. The chromatophores of Rhodospirillum rubrum were found to synthesize in the light not only ATP and pyrophosphate but also high molecular weight polyphosphates. Biosynthesis of all studied compounds was inhibited by antimycin A, an inhibitor of the electron-transport photosynthetic chain. Synthesis of high molecular weight polyphosphates is stimulated, while that of pyrophosphate is inhibited, in the conditions providing intensive synthesis of ATP (in the presence of ADP and in the absence of oligomycin). The results obtained suggest that biosynthesis of high molecular weight polyphosphates is related to photosynthetic phosphorylation, via ATP but not pyrophosphate.


[A study of the Brownian movement of alpha-chymotrypsin molecules by the spin probe method]. The rotation of alpha-chymotripsin in water solution is studied by use of nitroxyl radical, which is adsorbed by the alpha-chymotrypsin. It has been shown that under the conditions used the probe is fixed on the rotating diffusive protein monomer. Theoretical calculations of possible rotation correlation times for alpha-chymotripsin molecule were performed taking into account hydration and non-spherical shape. Experimental data obtained are in good agreement with theoretical values.


[Formation of a complex between carbon monoxide and cytochrome C]. The conditions of structural modifications of horse heart cytochrome c (pH, salt concentration) have been studied. Under these conditions the rate of carboxycytochrome c formation greatly increases in the course of the reduction process as compared to this rate after cytochrome c reduction and relaxation to the equilibrium state. According to these results the reduced intermediate which appears in the course of reduction has a high affinity for the carbon monoxide. It has been shown that the reduced low-spin cytochrome c practically does not take part in the process of dynamic conformational equilibrium with other cytochrome c forms existing in equilibrium mixture of oxidized and reduced cytochrome c.


[The combined treatment of bronchial carcinoma (author's transl)]. A preliminary assessment of a chemotherapeutic study is presented. The polychemotherapy was given as a high dosage intermittent stosstherapy with 3 infusions at intervals of a week for 3 years. The group of randomized controls included 126 patients who were classified according to the stage classification of the TNM system and Feinstein's system, which takes into account the clinical symptoms. Comparison of the death rates with the controls shows a distinct advantage in favor of the patients treated chemotherapeutically in all TNM classes.


[Congenital enzyme deficiency in carbohydrate metabolism. Its significance for clinical pediatrics and human biochemical genetics (author's transl)]. A review of the enzyme deficiencies of carbohydrate metabolism known at the present time is given. Through prominent clinical symptoms and consideration of food as a pathological agent, it is possible to suspect the various diseases before the results of the biochemical determinations are available. On account of the sometimes striking course, therapy can consequently be started at the earliest possible moment.


Elevated plasma proglucagon-like component with a glucagon-secreting tumor. Effect of streptozotocin. To determine the character of the glucagon secretion and its modification by streptozotocin, were studied the plasma of a patient with recurrent pancreatic alpha-cell carcinoma. The plasma immunoreactive glucagon level before treatment of 4.80 ng per milliliter. Biogel column separation of the plasma immunoreactive glucagon revealed four components; the predominant component had a molecular weight of 9000 daltons and was designated as proglucagon-like. This fraction constituted 60 to 90 per cent of the total circulating immunoreactive glucagon, and had a biologic activity of 32 percent of that of an immunoequivalent amount of normal (porcine) pancreatic glucagon. After treatment with streptozocin (1.5 g per square meter) the plasma immunoreactive glucagon level decreased to 0.24 ng per milliliter. Treatment was accompanied by a marked reduction in the proglucagon-like component and the appearance of pancreatic glucagon (molecular weight of 3500 daltons) as the major post-therapy fraction. These findings support the use of streptozotocin in the management of unresectable glucagon-secreting tumors.


Menopausal estrogens and breast cancer.

Menopausal estrogens and breast cancer. 1891 women given conjugated estrogens for the menopause were followed for 12 years (mean) for incidence of breast cancer. Overall, 49 cases were observed; 39.1 were expected on the basis of rates in the general population (relative risk = 1.3, P = 0.06). The relative risk increased with follow-up duration, progressing to 2.0 after 15 years (13/6.6, P = 0.01). The excess risk after 10 years was not due simply to prolonged estrogen use, since there was no clear dose-response relation to accumulated years of use. However, higher risk accrued to women using higher-dose tablets and those taking the medication on an other than daily basis. In addition, after 10 years of follow-up observation, two factors related to low risk of breast cancer, multiparity and oophorectomy, were no longer so related. Finally, estrogen use was related to an especially high risk of breast cancer among women in whom benign disease developed after they had started the drug.


Translation in vitro of vesicular stomatitis virus mRNA lacking 5'-terminal 7-methylguanosine. The 5'-terminus 7-methylguanosine of vesicular stomatitis virus mRNA is not essential for translation of the mRNA. The 7-methylguanosine seems to have a mediating rather than an obligatory role in ribosome binding by the mRNA and in mRNA translation.


Relationship between receptor and mammary tumour virus production after stimulation by glucocorticoid. A short exposure of primary cultures of mouse mammary tumour cells to glucocorticoids results in at least a three-fold stimulation of mammary tumour virus (MTV) production. Specific interaction of glucocorticoids with the cytoplasmic and nuclear receptors can also be demonstrated. The biological potency of various steroids to stimulate MTV is related directly to the retention of the steroid-receptor complex in the nuclei. Progesterone has a high affinity for the cytoplasmic receptor, is not retained by the nuclei and does not stimulate or block the basal level of MTV production. It is, however, quite effective in abolishing the glucocorticoid-mediated stimulation of MTV and thus behaves as an antagonist of glucocorticoid.


Initiation sites of Rous sarcoma virus RNA-directed DNA synthesis in vitro. Rous sarcoma virus DNA synthesis in disrupted virions is initiated mainly at a site about 200 nucleotides or less from the 5' terminus, but other initiation sites throughtout the RNA seem to be used as well. No AUG triplet occurs within a 5' terminal segment of about 25 nucleotides.


Proviral sequences of baboon endogenous type C RNA virus in DNA of human leukaemic tissues. Hybridisation of RNA from a baboon endogenous type C RNA virus to DNA from tissues of leukaemic patients indicates that a virus of this type is horizontally transmitted among humans. DNA from several patients with leukaemia hybridised 70% of the hybridisable RNA from baboon endogenous type C RNA virus (BaEV) and yielded hybrids of high tm, whereas DNA from normal human tissues hybridised only 23% of the BaEV RNA, and the tm of these hybrids was lower.


Stepwise transition of aggregate structure of high-molecular-weight avian myeloblastosis virus RNA. Mode of releasing of associated 4S RNA. Mode of releasing of associated 4S RNA species was studied during a controlled transition of aggregate structure of high-molecular-weight AMV-RNA. It has been found that associated 4S RNA constitutes 2.5% of 60S AMV-RNA complex. Approximately 60% of associated 4S RNA is successively released during treatment of viral RNA with increasing formamide concentration, concomitantly with the transition of 60S RNA aggregate through 50--55S RNA intermediate into the final 30--40S RNA subunits. 40% of 4S RNA remains associated with 30--40S RNA subunits prepared by formamide treatment and can be released from them by heating. A procedure is thus provided both for the isolation of oncornaviral RNA subunit structures deprived of various partions of associated 4S RNA and for the fractionation of 4S RNA species according to their binding affinity to the genome oncornaviral RNA.


Influence of BCG vaccination on the primary and transplantable hamster tumors induced by SV40 and on the specific SV40 virus-induced antitumor immunity. The main purpose of the study was the estimation of the effect of BCG vaccination and BCG in the combination with the specific immunization with SV40 on the incidence of primary and growth of transplantable SV40-induced tumors in Syrian hamsters. Different BCG vaccine preparations containing 60--100 millions of viable Mycobacteries per 1 mg were used. It has been demonstrated that one and two intradermal injections of BCG (0.25 mg per animal) during the latent period in Syrian hamsters inoculated with SV40 when newborn had no influence on the incidence of primary SV40-induced tumors. Repeated six injections of BCG during the latent period increased the frequency of tumors in one of two experiments. The subsequent was concern with investigation of the effect of BCG vaccination and its different combinations with specific immunization with SV40 on the growth of transplantable SV40-induced tumors in adult Syrian hamsters. Experimental data have shown that different preparations of BCG were varying in the capacity to increase nonspecific antitumor resistance; some preparations were nonimmunogeneic. Injections of a mixture of BCG and SV40 as well as BCG followed with SV40 14 and 20 days later did not lead to summation of effects of immunization, even when immunogenic preparations of BCG were used. Moreover inoculation of SV40 followed with BCG injection 4, 14 or 20 days later completely or partly declined the effect of SV40 specific immunization. Possible mechanisms of the negative effect of BCG on specific antitumor resistance are discussed.


Effect of nucleosides on the synthesis of nucleic acids and proteins in Ehrlich ascites carcinoma cells. The synthesis of nucleic acids and proteins in whole cells of Ehrlich ascites carcinoma was inhibited by adenosine and by several natural-adenosine-related compounds. The inhibitory effect of adenosine was more pronounced than that of other nucleosides tested (guanosine, inosine, cytidine, uridine and thymidine). The synthetic processes examined were only moderately inhibited by adenine nucleotides (ATP, ADP, AMP, NAD, cyclic 3',5'-AMP and its dibutyryl derivative). Respiration and aerobic glycolysis were not affected significantly by the nucleoside tested.


Induction of estrous cycles in old non-cyclic rats by progesterone, ACTH, ether stress or L-dopa. Cycling was induced in old non-cyclic, constant estrous rats by daily injections of progesterone, ACTH or L-dopa or by subjection to ether stress. Progesterone and ACTH were the most effective agents used for re-establishing estrous cycles in these rats. Most of the progesterone- and ACTH-treated rats showed regular cycles, and their ovaries had many corpora lutea; they also showed proestrous serum LH surges. Ether stress and L-dopa mostly induced irregular cycles and fewer corpora lutea in the ovaries; a smaller  number of these rats showed proestrous LH surges. After treatment with each of these agents was discontinued, most of the rats returned to constant estrus or irregular cycling.


Dissociation between LH release and pituitary cyclic nucleotide accumulation in response to synthetic LH-releasing hormone in vivo. In order to clarify the role of cyclic nucleotides in the mediation of LH-releasing hormone (LH-RH) action on LH release, the effect of LH-RH on LH release and pituitary cyclic AMP and cyclic GMP accumulation was studied in vivo. Pituitary cyclic AMP levels were increased 10 min after the intraveneous injection of 2 mg dibutyryl cyclic AMP (db-cyclic AMP) or 25 mg aminophylline. However, serum LH levels were not altered at 10, 30 or 60 min after the administration of either agent. Synthetic LH-RH (100 ng/rat) increased serum LH levels as measured 10 min after injection, but no effect on either pituitary cyclic AMP or cyclic GMP was seen 1, 5 or 10 min after LH-RH administration. These in vivo results are contradictory to the second messenger hypothesis for either cyclic AMP or cyclic GMP in the mediation of LH-RH-induced LH released and suggest that further work must be done in order to confirm or reject this hypothesis.


Effects of drugs that modify brain biogenic amine concentrations on thyroid activation induced by exposure to cold. L-Dihydroxphenylalanine (L-DOPA) significantly inhibited intrathyroidal colloid droplet formation induced by exposure to cold in the rat. Diethyldithiocarbamate (DDC) also inhibited colloid droplet formation in response to cold. The combined administration of L-DOPA and DDC produced an additive inhibition of the thyroidal endocytotic response to exposure to cold. Pretreatment with chlorpromazine (CPZ) ameliorated the inhibitory effect of L-DOPA. DL-alpha-methyl-p-tyrosine (alpha-MT) also signficantly depressed the thyroidal response. Inhibition of colloid droplet formation induced by alpha-MT was not altered by the administration of DL-dihydroxyphenylserine (DL-DOPS). On the other hand, treatment of the alpha-MT-treated rats with L-DOPA to normalize dopamine synthesis resulted in a dramatic recovery from the inhibition. Blockade of serotonin biosynthesis with p-chlorophenylalanine (p-CPA) failed to produce a significant inhibition of colloid droplet formation. However, 5-hydroxytryptophan (5-HTP) markedly inhibited the thyroidal response to cold. Brocresine phosphate (BP) was another inhibitor of the thyroidal endocytotic response to exposure to cold. Oxotremorine also markedly depressed the thyroidal response to cold. Since these drugs did not interfere with pituitary thyroid responsiveness to exogenous thyrotropin-releasing hormone (TRH), it seems that the throidal endocytotic response to exposure to cold as a reflection of TSH secretion was directly influenced by alterations of brain biogenic amine concentrations or turnover rates.


In vitro release of ACTH from dispersed rat pars intermedia cells. I. Effect of secretagogues. Studies were made to test the responsiveness of dispersed pars intermedia (PI) cells to a number of secretagogues, that are known to alter ACTH release from the pars distalis (PD) in vitro. In summary, (a) incubation in high (K+), which will increase ACTH release from the PD, did not alter ACTH release from the PI; (b) a crude extract of rat hypothalamus (HE) increased ACTH release from PD and PI; (c) the effect of HE was not due to its vasopression content, since pretreatment of the extract with thioglycolic acid did not modify its ACTH-releasing activity and neither lysine nor arginine vasopressin stimulated ACTH release from the PI; and (d) a partially purified CRF preparation, which will stimulate ACTH release from the PD, did not alter ACTH release from the PI. We conclude that the hypothalamus contains a substance(s) that will stimulate ACTH release from the PI and that the 'secretagogue' is neither vasopressin nor the same CRF that will stimulate ACTH release from the PD.


Effect of corticosteroids on the phrenic nerve-diaphragm of preparation treated with hemicholinium. A possible model of myasthenia gravis. A marked protective action of the corticosteroids prednisolone, hydrocortisone, and dexamethasone has been shown on a hypothetical model of myasthenia gravis, using the rat phrenic nerve-diaphragm preparation treated with hemicholinium-3. Dexamethasone is much more effective than prednisolone, and hydrocortisone is the least effective. Prednisolone has no effect on a neuromuscular block caused by choline, decamethonium, physostigmine, d-tubocurarine, and a high or low calcium ion concentration. The possible implications of the present study for myasthenic disease are discussed. It is tentatively concluded that the site of action of corticosteroids in myasthenia gravis is located presynaptically.


Alexander's disease: a report and reappraisal. A boy with juvenile onset of symptoms of Alexander's disease had a clinical picture of pseudobulbar palsy, ataxia, and spastic paraparesis. Pathologic examination of the central nervous system revealed the diffuse presence of Rosenthal fibers and patchy demyelination. This may be the first report of a case with significant neuronal changes and inflammation within the brain stem in this disease. The clinical picture of this entity is varied and age-dependent. Alexander's disease may be a motor system specific entity secondary to astrocytic dysfunction.


A possible mechanism for selective cerebellar damage in partial pyruvate dehydrogenase deficiency. In patients with partial deficiencies of pyruvate dehydrogenase, cerebellar ataxia has been the most prominent and sometimes the only neurologic abnormality. It is not clear how this generalized enzyme deficiency (with activity 15 to 30 percent of normal in several tissues) might lead to clinical signs referable to a limited part of the nervous system. We therefore compared the normal activity of pyruvate dehydrogenase with the normal rate of pyruvate oxidation in different parts of animal brains and then calculated the effect on pyruvate oxidation of partial deficiencies of the enzyme. The data indicate that pyruvate oxidation could be impaired in an area of anterior cerebellar vermis by deficiencies of pyruvate dehydrogenase too mild to affect pyruvate oxidation in the other areas of the brain we examined.


Melanosis of the choroid plexua.

Melanosis of the choroid plexua. A unique case of melanosis of the choroid plexus in a 74-year-old man who died of hypertensive cardiovascular disease is described. The cerebral lesion did not cause symptoms. The proposed pathogenesis is the conversion of choroidal epithelial lipofuscin into melanin. Our findings also may explain the origin of a previously reported primary malignant melanoma of the choroid plexus and of black cortical adenomas of the adrenal gland.


Experimental alterations in cyclic adenosine monophosphate concentrations in the cat basilar artery. Levels of cyclic adenosine monophosphate (AMP) in the basilar artery and in circulating blood of cats were determined after the production of spasm by topical application of blood to the vessel and following treatment with agents known to alter cyclic AMP. Isoproterenol, known to stimulate adenyl cyclase, and aminophylline, a phosphodiesterase inhibitor, were studied alone and in combination. Cyclic AMP of the basilar artery fell from a mean control value of 43 to 26 pmoles per milligram of protein following the production of vasospasm. Intravenous administration of isoproterenol alone and in combination with aminophylline produced dilatation of the basilar artery, which was associated with a marked rise in the cyclic AMP concentration in the vessel. The finding that cerebral vasospasm is associated with a fall and vasodilation with a rise in cyclic AMP concentration supports the hypothesis of an active role for cyclic nucleotides in the regulation of cerebrovascular smooth muscle tone.


[The central or peripheral nature of pain in essential headaches]. As an alternative to the conventional peripheral (vascular or chemical) thesis, the possibility of the central origin of pain in essential headaches is illustrated. In fact, observations carried out on animal and man reveal that, central pain, besides being organic, may be of a functional nature. It may be correlated to the lack of those biochemical mechanisms, which take place in the assimilation of those painful inputs at a cerebral level. Particularly pain may be caused by a lack of the 5HT turn-over. As a result of experiments carried out on animals, this takes the role of mediating pain inhibition, being present in the modulation stage of those multi-integrated processes which permit the central perception of pain. Some biochemical and pharmacological clinical observations suggest a serotonin lack in patients affected by essential headaches. A special interest is established by the reciprocal involvement of ancestral functions in essential headaches, such as: emotion, sleep, appetite, vomit, thermoregulation and sex, which are functions directly or undirectly controlled by serotonin. In the therapeutic field, the apparent contradiction between the benefit achieved by anti-serotonin drugs (such as: ergotamine, methisergide, org. G.C. 94 and LSD-25 at non-hallucinogen doses) and the substances with pro-serotonin activity (L-triptophane and L-5 hydroxy-triptophane) supports the hypothesis of a central lack of 5HT, due to the fact that the recent experiments on animal and man have shown a serotonin compatibility by "antiserotonin" drugs, when they are administered at therapeutic doses. If this initial thesis finds further confirmations, we could define essential headaches as a peculiar "pain disease", thus allowing them a well defined nosologic classification.


[Morphological substrate of antalgia and analgesia in the odontostomatological and facial area]. Prior personal work is further extended by a description of the way in which odontostomatological and facial pain is sedated by acupuncture: via peripheral receptors, whose stimulations are intercepted and modulated by various filters lying between the periphery and the cortex: cord (gelatinous substance of Rolando, gate control system), reticular formation and thalamocortical pathways.


[Acupuncture and relaxation].

[Acupuncture and relaxation]. Relaxation and tranquility are commonly induced by acupuncture. Techniques are presented and neurophysiological theories underlying the therapeutic effect are discussed. Emphasis is laid on the importance of this effect in psychiatric management.


Serum testosterone and dihydrotestosterone in patients with trophoblastic disease. Serum testosterone (T) and dihydrotestosterone (DHT) were measured by radioimmunoassay in 14 patients with unaborted hydatidiform mole and in 16 patients with normal pregnancy of similar gestational age. Serum human chorionic gonadotropin (hCG) was measured by the radioreceptor assay in patients with hydatidiform mole. Serum T ranged from 0.27 to 5.39 ng/ml with a mean +/- SE of 2.21 +/- 0.45 ng/ml in patients with hydatidiform mole mole and from 0.20 to 2.40 ng/ml with a mean +/- SE of 0.80 +/- 0.14 ng/ml in patients with normal pregnancy, the difference being statistically significant (P = less than 0.005). Similarly, patients with molar pregnancies had a significantly higher (P = less than 0.005) serum DHT (range: 0.09 to 0.62 ng/ml; mean +/- SE: 0.29 +/- 0.05 ng/ml) than patients with normal pregnancies (range: 0.04 to 0.28 ng/ml; mean +/- SE 0.12 +/- 0.02 ng/ml). There was no significant correlation between uterine size or serum hCG and serum T or DHT. The possible sources of the elevated serum T and DHT and the lack of hirsutism or virilization in patients with trophoblastic disease are discussed.


Association of liver tumors with oral contraceptives. Benign hepatocellular neoplasia occurring in 22 women receiving oral contraceptive steroids but no other known hepatotoxins is reported for the first time from a registry for liver tumors associated with oral contraceptives. A review of recent literature has yielded 45 cases including 3 previously reported by the authors. This striking increase in what were formerly rare primary liver tumors in young women strongly suggests a cause and effect of relationship. Eighteen patients presented with intrahepatic or extrahepatic rupture and hemoperitoneum with hemorrhagic shock due to vascular changes within their liver tumors. Five died as a direct or indirect result of preoperative or postoperative blood loss. The predominant lesions were focal nodular hyperplasia, hepatic adenoma, and hamartoma. Multiple synonymous nomenclature used to describe the histopathology of these tumors is disquieting and requires clarification. For diagnosis, enzyme determinations are not helpful. However, radionucleide liver scans, sonography, and celiac arteriography may be of value. Clinical surveillance must be the primary means for identification of this potentially lethal adverse phenomenon among 50,000,000 oral contraceptive users.


Boron neutron capture therapy of cerebral gliomas. II. Utilization of the blood-brain barrier and tumor-specific antigens for the selective concentration of boron in gliomas. The use of the blood-brain barrier and of tumor-specific antibodies to concentrate boron selectivity in gliomas for neutron capture therapy is considered experimentally and theoretically. The time-dependent concentration of two anionic  boranes, B12 H11 SH2- and B12 H11 SOSB12 H114-, in the blood, brain, and tumor of rats bearing a tumor of gliomatous origin is reported. The rate of clearance of each anionic borane from the blood is correlated with the fraction of non-protein bound anion in the plasma. The use of antibodies to carry therapeutical useful amounts of boron to tumor-specific or tumor-associated antigens on the tumor cell surface will require different numbers of boron atoms bound per antibody depending on several immunological and physical parameters. Calculations using published values of antibody-antigen association constants and of cell surface antigen densities predict that in order to obtain 10mug 10B/g tumor from 10 to over 10,000 boron-10 atoms will have to be bound per tumor antigenic site.


Methotrexate with leucovorin rescue in the treatment of gynecologic malignancies. Preliminary report. Experience with chemotherapy in advanced gynecologic malignancies is limited. In 6 patients, 2 of 4 with carcinoma of the cervix, and 1 patient with carcinoma of the ovary achieved partial remission when treated with a regimen of high dose methotrexate (240 mg/m2) followed by leucovorin rescue. On patient with metastatic trophoblastic disease achieved complete response (greater than 24 months). The number of doses of leucovorin 'rescue' was based on creatinine clearance. The advantage of rapid response and moderate toxicity indicate the need for further study of this regimen in the treatment of gynecologic malignancies.


[Burkitt's lymphoma (author's transl)].

[Burkitt's lymphoma (author's transl)]. Burkitt's lymphoma occurs endemically in Central Africa, but is also found sporadically in areas with temperate climate. A case of Burkitt's lymphoma found in our area is described. The literature in regard to the clinical symptoms, etiology and treatment of Burkitt's lymphoma is reviewed. At the present time cyclophosphamide is considered to be the drug of choice; it leads to a remission rate of about 90%.


Experimental regeneration in peripheral nerves and the spinal cord in laboratory animals exposed to a pulsed electromagnetic field. Peripheral nerve section and suture was performed in 132 rats. Postoperatively half the animals were exposed to a pulsed electromagnetic field each day and half were kept as controls. Nerve conduction studies, histology and nerve fibre counts all indicated an increased rate of regeneration in the treated animals. A similar controlled study of spinal cord regeneration following hemicordotomy in cats has been started, and preliminary results indicate that when the animals are sacrificed three months after the hemicordotomy, the pulsed electromagnetic therapy has induced nerve fibre regeneration across the region of the scar.


[Permissivity of mouse-man hybrid cell clones to three enteroviruses: poliovirus II, coxsackie B3 and echovirus 11. Role of human chromosome F. 19 (author's transl)]. The permissivity of human cells to enteroviruses is linked to the presence of specific cell receptors. Owing to the chance elimination of human chromosomes, the man-mouse hybrid cells may be permissive or not depending on the genome responsible for synthesis of the receptors, and whether it has been conserved or not. By comparison of the cytopathogenic effects and virus production after inoculation of the viruses Polio II, Echo 11 and Coxsachie B3 to various hybrid strains, we observed an identity of the spectrum of permissivity to these three viruses. The enzyme study revealed a very high correlation between this permissivity and expression by the clones of the human glucose phosphate isomerase enzyme, of which the structural gene was localised on chromosome F 19. These results suggest the presence on this chromosome of a gene or syntenic genes, governing the synthesis of specific cell receptors to the viruses studied.


[Tubular inclusions in the lymphocytes in a case of "hairy cells leukemia" (author's transl)]. A tubular inclusion (Hovig type) was found in the cytoplasm of the blood lymphocytes of a case of hairy cells leukemia. Its cytochemical and ultrastructural features are described ; its signification remains unknown.


Submicroscopic response of articular chondrocytes to a cholesterol-containing diet. 10 days' to 3 months' consumption of a diet containing 4% cholesterol causes a minor and transitory stimulation of articular chondrocytes of mice. The transitory disturbance is accompanied by a more permanent increase in glycogen, by abnormal deposition of cytoplasmic lipid and by an increase in the fibrillarity of the pericellular matrix. The changes are consistent with the failure of the cholesterol diet to influence the course of osteoarthrosis if fed to mice from an early age through life.


Histogenesis of hyperplasia and carcinomas of the liver arising around central veins in mice ingesting chlorinated hydrocarbons. The development of hyperplastic and neoplastic lesions of parenchymal cells of the liver adjacent to central veins was observed in C3H mice ingesting the chlorinated hydrocarbons, dieldrin or aldrin, in the diet. Lesions could be followed from pericentral hyperplasia to areas of hyperplasia, nodules of hyperplasia, small hepatocellular carcinomas, and large well-developed carcinomas, occasionally with metastases. Sometimes pericentral hyperplasia was diffuse throughout most or all of one lobe of the liver. These hyperplastic cells collided to become one large nodule and also one large carcinoma. The carcinomas were well-differentiated or moderately well-differentiated and grew on transplantation to isologous hosts. Histologically, the hyperplastic cells adjacent to central veins were increased in size, frequently with double nuclei. Carcinoma cells varied in size and shape and were huge with large nuclei, prominent nucleoli, and eosinophilic cytoplasm. Similar hepatocellular carcinomas were seen previously with carbon tetrachloride, another organochlorine chemical.


Genetics and the etiology of childhood cancer. A consideration of the world-wide incidences of childhood cancer and of hereditary subgroups leads to the conclusion that two successive mutations can initiate cancer cells and that such cells usually proceed to develop into detectable cancers in a period of time which is short compared with the time required for most adult cancers. Environmental carcinogens could hypothetically increase the rates at which these mutations occur, but they probably, in fact, contribute little to the incidences. Certain exceptions, notably leukemia and lymphoma, are noteworthy, and a viral origin for them has been widely hypothesized. If most solid tumors of childhood are indeed correctly attributable to mutations in germ and/or somatic cells, then the prospect for the prevention of childhood cancer becomes very dim. In fact, the incidence of the germinal forms may increase as treatment improves (18). In theory, one might be able to identify individuals harboring cancer genes germinally and even to identify them prenatally. But even if the burden of cancer attributable to the hereditary subgroups were elimanted, there would still remain the larger nonhereditary group resulting from somatic mutations. If this hypothesis is correct, then childhood cancer cannot be prevented. With this conclusion goes the admonition, however, that environmental mutagens might significantly increase the burden of childhood cancer. One such mutagen, therapeutic radiation, is known to increase the prospect that second tumors will occur in patients who carry a germinal cancer mutation. The major effort to reduce the incidence of childhood cancer by prevention should be spent in examining the possibility that leukemia and lymphoma are viral in origin. If the arguments presented are correct, then the main effort against childhood cancer must be that of early diagnosis and treatment. I realize that many have already argued for that strategy in the approach to cancer generally, but I now believe that it is particularly relevant to any program against cancer in children.


Growth and growth velocity of lean body mass and fat in adolescent boys. Beginning at age 10 years, height, weight, body density, and bone age of 40 normal boys were measured yearly over a period of 8 years. From body density, lean body mass and body content of fat were calculated. Values for all measurements are included in the Appendix and mean values, including those for lean body mass and percentage of body fat, are presented for each year in Table 1. Coefficients of correlation between measurements made during the first and eighth years of study were high for height (0.68), weight (0.50), and lean body mass (0.60), but relatively low for body fat (0.25). Correlation coefficients between the various parameters in a given year are presented in Table 2. The maximum yearly increment in height, weight, and lean body mass of individual subjects coincided in time. The respective mean values for the year of maximum growth were 9.4 cm, 8.1 kg, and 7.5 kg. Throughout the growth spurt, the contribution of fat to increase in body weight was small. It may be concluded that, next to height, the absolute amount of lean body mass demonstrates the most constant trend of development during adolescence.


Intestinal phosphate transport in familial hypophosphatemic rickets. The present report outlines an attempt to characterize inorganic phosphate uptake by human jejunal mucosa using biopsy material obtained from six patients affected by the X-linked form of vitamin D-resistant rickets and six control subjects. The tissue from control subjects accumulated 32P actively in a linear fashion against time. The incorporation of inorganic phosphate into organophosphate derivatives is rapid and equilibrates after 10 min at an inorganic over total phosphate ratio of 0.45. Concentrative uptake and incorporation were both suppressed by anaerobiosis or cyanide. Rates of phosphate uptake and incorporation into the organic derivatives by the tissue of hypophosphatemic patients are comparable with normal values. Saturation kinetics observed over a wide range of substrate concentrations (0.003 to 3 mM) elicits only one transport system with an apparent Michaelis constant of 0.2 mM and a maximum velocity of 0.7 mmol/liter/40 min. The kinetic data obtained from the patients do not strikingly differ from the control values. The chemical analysis of the phosphate content of intestinal mucosa from two patients and two control subjects indicates that the tissue is not specifically phosphate-depleted in the mutant individuals. These results are in accordance with the positive results obtained with the oral replacement therapy in familial hypophosphatemia.


Chemoreceptor function and sleep state in apnea. Resting ventilation and ventilatory responses to 100% oxygen and to 5% carbon dioxide in air were measured in REM and non-REM sleep in post-neonatal infants. Normal controls were compared to infants with prolonged apnea and to siblings of sudden infant death victims. No significant differences in ventilatory responses were found between the groups. We conclude that apnea may occur in infants whose central and peripheral chemoreceptor activity is normal while they are breathing.


Computerized tomography in the detection of intracranial metastases in children. Computerized tomography brain scans produce sectional tomograms of the brain substance which demonstrate intracranial lesions. The procedure is safe and painless, and can be done on an outpatient basis. Three children with malignant disease had intracranial metastases demonstrated using this technique during a recent six-month period at the Cleveland Clinic.


A transovarian transmission study of Marek's disease in Japanese quail. Experiments were conducted to determine if transovarian transmission of the JM strain of Marek's disease virus (MDV) occurs in Japanese quail. In one experiment, parent quail were infected with MDV when one-day-old; in another experiment, parent quail were infected when seven weeks old. No precipitating antigen or cytopathic or infective agent was isolated from the egg yolks, embryos, newly hatched quail, or progeny quail of the infected parents. During the eight weeks observation period, the progeny of infected parents showed no clinical symptoms, mortality, gross or microscopic lesions, MD viremia, or antibody. However, an MD-specific fluorescent antigen was observed in fibroblast and kidney cell cultures from embryos of parents infected at one day of age. Approximately 10% of the embryos contained this fluorescent antigen. Fluorescent antigen was not observed in cultures from embryos of quail infected at the age of seven weeks or control quail.


Efficacy of turkey herpesvirus vaccine when administered simultaneously with fowl pox vaccine. The efficacy of the turkey herpesvirus (HVT) vaccine in protecting chickens challenged with virulent Marek's disease (MD) virus was unaffected by the presence of either the chick embryo fowl pox vaccine or fowl pox vaccine derived from cell culture. Conversely the HVT vaccine did not affect the efficacy of the fowl pox vaccine in chickens challenged with pathogenic fowl pox virus. A combination of spectinomycin dihydrochloride pentahydrate and lincomycin hydrochloride monohydrate as well as spectinomycin sulfate tetrahydrate were found to be compatible with the HVT and fowl pox vaccines as demonstrated by resistance after challenge with virulent MD virus or fowl pox virus.


[Specific rabbit abtiserum against human chylomicrons and very low density lipoproteins]. Rabbits were immunized by repeated intravenous injections of large amounts of chylomicrons plus VLDL isolated from human lipemic plasmas. The antisera were absorbed usccessively with lipoprotein free serum, HDL and LDL2. The absorbed antisera still precipitate chylomicrons and VLDL from sera of normal and hyperlipemic subjects (post-absorptive donors and fasting patients with type IV and type V hyperlipoproteinemia). By gel diffusion methods (immunoelectrophoresis and double diffusion in two dimensions), the antisera reveal a single precipitin line which stains better for lipid than for protein. This line is pronounced in VLDL-rich sera and absent in VLDL-free sera. The antisera react with chylomicrons plus VLDL delipidated by extraction with ethanol/diethyl ether; this shows that the antigenic site is an apoprotein; in contrast to apoprotein C, this apoprotein appears to be unique to the triglyceride-rich lipoproteins.


Marek's disease in Japanese quail -- a pathological, virological and serological study. Experimental studies were performed to see whether Japanese quail (Coturnix coturnix japonica) are susceptible to JM strain  of Marek's disease virus (MDV). In three identical trials, a total of 120, one-day-old quail were inoculated intra-abdominally with 0.2 ml. of chicken blood infected with MDV (JM strain) and raised in FAPP isolators. Uninfected controls were inoculated with normal saline only and raised separately. During the 18-week post infection observation period, 65-80% of the infected quail died within six weeks, while the highest mortality in control groups was only 0-5%. In each trial, ocular lesions with or without unilateral or bilateral blindness and signs of torticollis were evident in a few quail after 10-14 weeks. Gross and microscopic lesions suggestive of MD were observed 14 days on. The most pronounced lesions were observed in lungs. Neural tissues were least affected. In general, females were more susceptible than males. MD-specific fluorescent and precipitating antigens were detected in different visceral tissues, buffy coat and cultured macrophages of infected quail. Fluorescent antigen appeared at 6-7 days after infection, whereas precipitating antigen appeared after 12-15 days. Viral (MDV) infectivity tests in cell cultures and bioassay in one-day-old chicks and quail demonstrated that infected quail become viremic around the seventh day post infection. A cytopathic agent similar to MDV was also isolated from quail. Neither Newcastle disease virus nor a bacterial agent was isolated from the quail. MD-specific fluorescent precipitating antibodies were present in the egg yolk and plasma of both infected sick and infected symptomless quail. The earliest detectable plasma MD antibody appeared in 14-21 days. Such findings were not observed in quail from parent stock and controls. Our studies demonstrated that Japanese quail are susceptible to JM strain of MDV.


Effects of stress on the corticosterone content of the blood plasma and adrenal gland of intact and bursectomized Gallus domesticus. The response of intact and bursectomized chicks to stressful stimuli has been examined. The stressors imposed were: a. fast-acting ACTH adminstration; b. immersion in cold water; c. starvation. In Bursa-intact chicks the results were as follows: 1. Plasma corticosterone was increased by all stimuli. 2. Adrenal corticosterone was decreased by ACTH treatment while it was increased by immersion in cold water and by starvation. 3. Plasma glucose was increased by ACTH administration and cold water immersion and decreased by starvation of the birds. 4. Adrenal ascorbic acid concentration was not influenced by all stimuli. 5. Adrenal weights were found to be increased by ACTH and starvation treatments only. 6. Bursa weights were increased by ACTH administration. 7. A very low concentration of corticosterone was found in the Bursa of Fabricius. Bursectomized chicks differed from the intact ones in the following: 1. Plasma and adrenal corticosterone concentrations were not increased by starvation. 2. Plasma glucose increased moderately with ACTH administration. 3. Adrenal ascorbic acid was depleted by all stimuli but was not related to the corticosterone level in the adrenals and blood plasma.


Specific and non-specific immunosuppression in chickens. Specific immunosuppression, caused by the passive transfer of immune sera, and non-specific immunosuppression, caused by ACTH, were investigated for possible interactions. The data confirm earlier studies which show that both types of suppression when administered independently cause reductions in humoral immune responsiveness. However, when both suppressive methods were administered simultaneously a level of suppression occurred which was not greater than that caused by either method alone. Additionally, when ACTH-induced non-specific immunosuppression was established in donors, passive transfers of sera from these donors did not cause suppression in the recipients.


The effect of grain component of the diet on the response of turkey poults to vitamin D3 and penicillin. Three experiments were conducted with turkey poults to study the effects of the grain component of the diet (corn or rye), added fat, penicillin or extra vitamin D on growth and bone ash. In the first trial, where rye replaced corn in the diet, growth was depressed and the pults were rachitic before two weeks of age. Adding fat or penicillin to the rye containing diets significantly improved growth and increased bone ash. In the second trial, adding extra vitamin D3 or penicillin to a diet with rye increased both growth and bone ash. Diets containing either corn or rye were used in the third trial and the results again showed that extra vitamin D or penicillin markedly improved growth and bone ash when added to the diets with rye but did not significantly increase growth of poults on the diets with corn. Bone ash of turkeys fed the corn diets was significantly increased by a combination of extra vitamin D3 and penicillin.


A comparative study of iodine and potassium perchlorate metabolism in the laying hen. 2. Uptake, distribution, and excretion of potassium perchlorate. The concentrations of 36Cl-labeled potassium perchlorate (K36CiO4) and previously reported iodide (131I) in the ova, thyroid gland, and blood of the laying hen were compared in this investigation. Radioperchlorate concentration and deposition properties showed a remarkable resemblance to those of iodide (131I). The topographic distribution of radioperchlorate in ova followed a peripheral and concentric ring deposition identical to that observed in the 131I investigation. The studies of the distribution of radioperchlorate showed that about 10.3, 2.0, and 1.4% of a single intramuscular injection of K36CiO4 was retained in the body at 3, 24, and 48 hours, respectively. The largest total concentration in the 3-hour group was found in the blood (2.9%), followed by muscles (2.4%), internal organs (1.1%), and the 10 largest ova (1.0%). The 24 and 48-hour hens' ova showed the largest concentrations with values of 1.5 and 1.2% of the dose, respectively. This represented 76.9 and 81.3% of the total activity retained in the body at these times. The excreta in the 3 and 24-hour experiments accounted for most of the radioperchlorate dose.


Calcium-binding protein and calcium absorption in the laying quail (Coturnix coturnix japonica). A vitamin D3-dependent calcium-binding protein (CaBP) has been found in the intestinal mucosa of Japanese quail (Coturnix coturnix japonica). This protein is similar, if not identical to that of the chick (Gallus domesticus). A similar protein fraction appears also in uterine mucosa of laying quail. Both intestinal and uterine CaBP levels are higher in laying than in non-laying quails. Uterine CaBP was higher during egg shell formation than during uterine inactivity. The slight corresponding difference in the intestinal CaBP was not significant. Intestinal calcium absorption measured with 91Y as a reference substance was higher in birds during formation of egg shell than in those with inactive uteri. The possible role of CaBP in calcium translocation is discussed.


The interaction between Mycobacterium bovis (BCG) and genotype of chicken in increasing the percentage of regression of Rous sarcomas. Four breeding groups of chickens were inoculated in the wing-web with Rous sarcoma virus at 8 weeks of age. Treated birds were given a single dose of live organisms of a mile strain of Mycobacterium bovis of variety Calmette Guerin (BCG) as a subcutaneous inoculation adjacent to the emerging tumor. Control birds received no BCG. The breeding groups of chickens included a line selected for ability to  cause a high percentage of spontaneous regression of tumors, a susceptible line with a very low level of regression of tumors, and the two reciprocal crosses between these lines. Treatment with BCG greatly enhanced the percentage of regression in the line selected for regression and in the two reciprocal crosses, but was ineffective in the low regression line. Bursectomy of chicks from the low regression line did not permit BCG treatment to increase regression of Rous sarcomas.


Detection of cellular immunity to rous tumors of chickens by the leukocyte migration inhibition reaction. Peripheral blood leukocytes obtained from Rous sarcoma-bearing chickens were tested for their ability to be inhibited from migrating in vitro by soluble tumor extract. It was found that the inhibition of leukocytes from chickens with regressing Rous tumors was significantly greater than that of chickens with progressing tumors or non-tumor bearing controls.


The effect of non-protein energy sources on the ability of the chick to synthesize glucose-6-phosphatase. Two experiments were conducted to investigate the relationship of energy source, age and glucose-6-phosphatase activity in the chick. In the first experiment liver glycogen and glucose-6-phosphatase were assayed in chicks of four age groups being fed either a high-fat or high-carbohydrate diet. It was observed that the feeding of the high-fat diet resulted in higher glucose-6-phosphatase activity and lower glycogen levels than did the feeding of the carbohydrate diet. Age was found to significantly influence enzyme activity. Both glucose-6-phosphatase and liver glycogen were found to be negatively correlated in the fat fed chicks. In the second experiment chicks were fed either a high-fat or high-carbohydrate diet for 28 days. Liver glucose-6-phosphatase activity was determined in representative samples of chicks from each group to establish basal levels. The diets were then reversed for a three-day period, after which the chicks were returned to their initial diets. Glucose-6-phosphatase was analysed at each step. Variation in enzyme activity in the chicks initially fed the high-fat diet could be attributed to differences in body weight. However, those chicks originally fed the carbohydrate diet did exhibit a true metabolic adaption when fed the high-fat diet.


Vaccination of chickens against Marek's disease with the turkey herpesvirus vaccine using a pneumatic vaccinator. A pneumatic vaccinator has been successfully used to administer cell-associated turkey herpesvirus (HVT) vaccine without a loss in titer due to the pressure required to administer the vaccine. Laboratory studies have also shown that chickens vaccinated with graded doses of the HVT vaccine using doses as low as 41 PFU offered protection against Marek's disease (MD) when compared to the unvaccinated controls. The pneumatic vaccinator has also been successful in administering a combination of HVT vaccine and tissue culture fowl pox vaccine. Vaccinated birds were protected against challenge with virulent MD virus as well as fowl pox virus. Antibiotics such as spectinomycin pentahydrate or lincomycin hydrochloride monohydrate and spectinomycin sulfate tetrahydrate were used in combination with the HVT and fowl pox vaccine and none of the antibiotics appear to have an adverse effect on the efficacy of either vaccine.


[A change in interneuronal transmission of excitation in the diencephalic regions of the brain under the influence of desoxycorticosterone]. Experiments were conducted on cats with the aid of electrophysiological methods and the use of blockers of cholino- and adrenoreceptors. It was shown that desoxycorticosterone facilitated the interneuronal transmission of excitation in the diencephalic portions of the brain. This was associated with the excitation under the effect of hormone of M-cholino- and beta-adrenoreceptors of the mediodorsal nucleus of the thalamus present on the postsynaptic membrane.


[The role of adrenaline and ACTH in the process of complex heparin compound formation in the blood during imobilization stress]. Intensification in immobilization stress of the process of formation of complex heparin compounds in the blood and a corresponding increase in the nonenzymatic fibrinolytic activity was largely determined by the altered hormonal status of theorganism: by adrenaline and ACTH discharge. In the animals with the ACTH secretion blocked by DOCA administration the nonenzymatic fibrinolytic activity in stress remained at the basal level characteristic of the nonstress situation. This activity remained at the basal level also after the block of the alpha-adrenoceptors by phentolaminehydrochloride. Administration of both adrenaline and ACTH considerably intensified in stress the process of formation of heparin complexes; no summation of the action of the exogenous ACTH and adrenaline occurred.


[Autoregulation of hormonogenesis in the adrenal cortex]. Experiments were conducted on 60 rats. An attempt was made to ascertain with the aid of histochemical methods the possibility of a direct action of glucocorticoids on the adrenal glands. Incomplete coincidence of histochemical changes following hypophysectomy with the changes caused by the action of cortisone for the same period (10 days), and also a distinct depression with cortisone of histochemical shifts characteristic of the action of ACTH in hypophysectomized animals pointed to the direct (not mediated through the hypophysis) influence of cortisone on the adrenal cortex.


[Mechanisms of seasonal changes in the circadian corticosteroid function of rats]. Data are presented concerning seasonal changes in the circadian 11-OCS rhythm in the adrenal glands in the plasma of rats. For the purpose of studying the mechanisms of control of circadian 11-OCS rhythms during the spring and autumn seasons there were studied circadian corticosteroid reactions to ACTH and stress. The "Cosinor" method of study was used for analysis of the real circadian rhythm. The data obtained permit to suppose that in autumn the rhythm of the adrenal glands was associated with the circadian rhythm of the central links of the hypothalamo-hypophyseo-adrenal system, and during the spring season an important contribution in the formation of the circadian rhythm of the adrenocortical activity was brought by the adrenal mechanisms.


The influence of parathyroid hormone and calcitonin on plasma levels of adenosine 3'5' monophosphate and electrolytes in normal and anephric subjects. The purpose of this study was to estimate whether target tissues other than the kidney are responsive to parathyroid hormone (PTH) and calcitonin (CT) in anephric man. Twenty subjects were studied: 12 normal, 4 anephric, 4 anuric ('anephric') individuals. PTH infused into 6 normal subjects produced several fold increase in plasma level of cAMP, whereas CT caused minimal increase in the same number of normal individuals. In 4 anephrics PTH infusion resulted in a delayed rise of plasma cAMP. CT administration to 4 'anephrics' did not change plasma cAMP. In all subjects PTH and CT failed to modify plasma electrolytes level. The data indicate that the kidneys are the main source of cAMP after PTH administration and in anephric subjects extrarenal tissues are the source of circulating cAMP.


[Conversion of proinsulin into insulin in insulin producing tumors in man]. The enzymatic activity of tissues of insulomas and also the proinsulin and insulin content in them was studied. As revealed, insulomas contained an increased amount of proinsulin in comparison with the unaffected islands of Langerhans. The tumours under study also differed by the capacity to catalyze the splitting of hippuryl-L-arginine, synthetic substrate of carboxypeptidase B. Proinsulin content in the tumours of the islar tissue depended on the presence in them of an enzyme catalyzing the splitting of the substrate at pH 6.8--7.2, this pointing to its participation in the conversion of proinsulin into insulin.


The influence of potassium and ACTH on plasma-aldosterone regulation in anephric patients. After increasing the intracellular potassium concentration of seven anephric patients without changing the total body potassium, by administration of insulin-glucose, the plasma-aldosterone concentration increased significantly to 180 percent of the pre-infusion value despite a drop in plasma potassium. A significant correlation between the decrease in the plasma potassium and the increase in plasma aldosterone concentration was found. Plasma cortisol remained unaffected. ACTH stimulation of five anephric patients resulted in a significant simultaneous increase in plasma aldosterone as well as in plasma cortisol. These studies indicate that changes in the intracellular potassium concentration, as well as ACTH stimulation, are important regulators of the aldosterone secretion in anephric patients.


[Blood levels of ACTH and cortisol in patients with Itsenko-Cushing disease treated with chloditan]. The authors present the results of examination of the content of ACTH and cortizol in the blood of 55 patients with Itsenko-Cushing disease and of 36 healthy persons. Fifty patients were examined repeatedly after a course of chloditan treatment. Plasma ACTH content was determined by the radioimmunological method, and cortizol -- by the competitive binding method with the help of sets. Investigations carried out showed an increase in blood ACTH and cortizol which proved to be most pronounced in patients with a severe form of Itsenko-Cushing disease. A marked reduction of glucocorticoid function of the adrenal glands with an elevation of ACTH secretion occurred after chloditan therapy. At remote periods after the chloditan treatment ACTH and cortizol secretion depended on clinical manifestations of the disease. It was shown that examination of blood ACTH and cortizol content could be used as an auxiliary criterion in the diagnosis of Itsenko-Cushing disease, in ascertaining the severity of this disease and in the assessment of the efficacy of the treatment carried out.


Serum lipids and lipoproteins in acute renal failure. Forty-five patients with various forms and phases of acute renal failure without or with haemodialysis treatment were investigated. The concentration of free fatty acids, triglycerides and total cholesterol in serum were determined and separation of lipoprotein classes on agarose gel was performed. Increase in free fatty acids and triglycerides, decrease in cholesterol concentration in serum characterised the anuric phase. The increase of prebeta fraction, the decrease of alpha and beta lipoprotein fraction were found in the oligoanuric phase. Decrease in triglyceride concentration was observed as a regular effect of haemodialysis. Decrease in prebeta and increase in beta lipoprotein fraction immediately after the termination of haemodialysis occurred. In the polyuric phase of acute renal failure there was significant decrease in free fatty acids and triglycerides and increase in cholesterol concentration in serum simultaneous with improvement of clinical signs. An increase in prebeta and decrease in beta lipoprotein fraction was noted in the convalescence phase, despite and opposite trend of serum triglycerides and cholesterol concentrations.


Lipid patterns in haemodialysed and transplanted patients. The plasma lipid pattern was investigated in 103 dialysis patients and 66 renal transplant patients. Only 32 percent of dialysed patients and 30 percent of transplanted patients had a normal lipid pattern. In other patients the most frequent disorder with hypertriglyceridaemia, and less frequently combined or isolated hypercholesterolaemia. Since these lipid abnormalities are known to predispose to an accelerated atherosclerosis, a dietetic therapeutic approach was tried. Fifteen transplanted patients with severe hypertriglyceridaemia were submitted to a hypocaloric (1700 kcal) and low carbohydrate (130 g) diet. During dieting the plasma lipid pattern was normalised and maintained in a normal range for the period of observation (3-12 months).


[The effect of ACTH and chorionic gonadotropin on cyclic 3',5'-adenosine monophosphate  concentration and of a homogenate of fetal hypophysis on adrenal steroidogenesis in human embryos and fetuses from the 7th to the 12th week of embryonic development]. It was shown that homogenates of the hypophysis of human fetuses from the 8th to the 12th week of gestation stimulated in vitro formation of F and DEA-sulfate in the adrenal glands of fetuses of the same gestation period. ACTH increased the cAMP concentration in the adrenal glands of all the embryos and fetuses under study; this pointed to the presence in them of ACTH-dependent adenylcyclase, and, consequently, of the ACTH receptors. On the contrary, chorionic hormone produced no effect on the cAMP concentration in the adrenal glands. The data obtained, together with those published earlier suggested that adrenal glands of human fetuses from the 8th week of gestation were already under the controlling influence of ACTH of their hypophyses and that the action mechanism of ACTH on the adrenal glands of fetuses was analogous to its action on the adrenal glands of adult.


Poliovirus-induced inhibition of polypeptide initiation in vitro on native polyribosomes. The inhibition of HeLa cell protein synthesis by poliovirus was studied by examining initiation in vitro on endogenous host polyribosomes. At an early stage, before major viral RNA replication and protein synthesis begins, the initiation of translation on cellular mRNA is strongly inhibited. Fractionation of extracts from infected cells shows that the lesion is associated mainly with the crude polyribosome fraction. The cellular mRNA appears unchanged and is as active as mRNA from control cells in stimulating incorporation. The native ribosomal subunits and KCl-washed polyribosomes from the infected cells are also active. Only the ribosomal wash fraction prepared from the inhibited polyribosomes had reduced activity. However, the reduction in the ribosomal wash activity measured in a reconstructed system is not as large as the inhibition seen with "native" polyribosomes. The results indicate that a viral induced inhibition is probably associated with the ribosomal wash fraction, but the reconstructed system is not equivalent to the "native" inhibited system.


Structure of the prosthetic group of Klebsiella aerogenes citrate (pro-3S)-lyase. The prosthetic group of citrate (pro-3S)-lyase [citrate oxaloacetate-lyase (pro-3S-CH2COO- leads to acetate); EC 4.1.3.6] from Klebsiella aerogenes was obtained by mild alkaline hydrolysis of the enzyme and purified by DEAE-cellulose chromatography. Several chemical and enzymatic degradation products of the compound have been isolated, and analyses of these have shown the structure of the prosthetic group to be 3'(or 2') leads to 1 inch-(5 inches-phosphoribosyl) dephosphocoenzyme A. Proof as to the exact linkage between the two ribose moieties and the anomeric configuration of the glycosidic bonds has not yet been obtained. A similar analysis was obtained for a product isolated after Pronase digestion of the enzyme (without alkaline hydrolysis). The isolated prosthetic group also can serve as a substrate for a crude preparation of acetate:-SH-(acyl carrier protein) enzyme ligase (AMP) from K. aerogenes, pure pig heart citrate (si)-synthase (EC 4.1.3.7), and pure rat liver ATP citrate (pro-3S)-lyase (EC4.1.3.8). This compound is the first shown to substitute for coenzyme A in the latter reaction.


Sodium-stimulated alpha-aminoisobutyric acid transport by membrane vesicles from simian virus-transformed mouse cells. Uptake of alpha-aminoisobutyric acid, by membrane vesicles derived principally from the plasma membrane and endoplasmic reticulum of mouse 3T3 cells transformed by simian virus 40, is stimulated by sodium chloride. Both in the presence and absence of Na+ uptake is time-dependent and osmotically sensitive. The Na+-stimulated uptake is inhibited by other amino acids. The kinetics of transport of alpha-aminoisobutyric acid are shown to be biphasic both in whole cells and in the membrane vesicles. Only the high affinity system is stimulated by sodium in the membrane vesicles. These results demonstrate that observations made on living cells correlate with observations made on isolated membrane vesicles, and indicate that these membrane vesicles have retained the cellular amino acid transport system functionally intact.


Affinity label for beta-adrenergic receptor in turkey erythrocytes. The compound N-[2-hydroxy-3-(1-naphthoxy)-propyl]-N'-bromoacetylethylenediamine (NHNP-NBE) was found to label covalently the beta-adrenergic receptor in turkey erythrocytes. The compound inhibits irreversibly 1-epinephrine-dependent adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in the whole turkey erythrocyte as well as in the erythrocyte membranes possessing the beta-receptor. The affinity label blocks, also irreversibly, the specific [3H] propranolol binding, whereas other bromoacetyl compounds tested have no effect on binding, even at high concentrations, which cause enzyme inactivation. 1-Epinephrine and propranolol offer protection against the affinity label in whole turkey erythrocytes as well as in membranes prepared from these cells. The potential usefulness of an irreversible beta-antagonist is discussed.


Extracytoplasmic adenylate cyclase of Bordetella pertussis. Soluble adenylate cyclase [EC 4.6.1.1] accumulates in the culture medium of exponentially growing Bordetella pertussis (300-900 pmol of cAMP formed/min per ml of 24 hr culture supernatant). In addition, there is an extracytoplasmic adenylate cyclase which enables the intact organisms to form [32P] cAMP (adenosine 3':5'-cyclic monophosphate) from exogenous [alpha-32P] ATP (200-1200 nmol of cAMP formed/min per g wet weight of cells) and which comprises 20-45% of the total adenylate cyclase activity. In contrast, only 1.7 and 2.4% of the total cell malate dehydrogenase [EC 1.1.1.37] and alkaline phosphatase [EC 3.1.3.1], respectively, are detectable in the intact cell. Trypsin treatment of intact organisms destroys 96% of the extracytoplasmic adenylate cyclase, but does not reduce the total cell malate dehydrogenase or a small pool of intracellular adenylate cyclase. Four compartments of adenylate cyclase in B. pertussis are proposed; (A) soluble enzyme in the culture supernatant (up to 20% of the total activity); (B) enzyme associated with intact cells and measurable without cell disruption (20-45%); (C) extracytoplasmic enzyme sensitive to trypsin, but not measurable in intact cells at standard substrate concentrations (40-60%); and (D) intracellular enzyme (7-9%). In comparison with previously studied bacterial adenylate cyclases, the extracytoplasmic location appears to be unique to the B. pertussis enzyme.


Regulation of viral transciption and tumor antigen expression in cells transformed by simian virus 40. We have studied the expression of simian virus 40 (SV40) specific tumor antigen (T-antigen) and viral RNA in SV40-transformed mouse 3T3 cells that are temperature-sensitive for the expression of the transformed phenotype (ts SV3T3). Although transformed by wild-type SV40, ts SV3T3 cells at 32 degrees behave like standard transformants, while at 39 degrees they became arrested in G1 after reaching saturation density or under conditions of serum starvation. ts SV3T3 cells at 32 degrees or exponentially growing at 39 degrees are uniformly T-antigen positive. However, after G1 arrest at 39 degrees the majority of the cells becomes T-antigen negative. Induction of proliferation in the resting cultures results in the reappearance of T-antigen in most of the cells, concomitant with the induction of DNA synthesis. The reason for the disappearance of T-antigen from ts SV3T3 cells arrested in G1 seems to reside in a transcriptional control operating on the integrated viral DNA, since these cells contain no appreciable amounts of SV40 specific RNA. Viral RNA can be easily detected in cells growint at 32 degrees or at 39 degrees. The results suggest that transcription of the viral genome in SV40-transformed cells is cell-cycle-dependent.


Structure of a nicked DNA-protein complex isolated from simian virus 40: covalent attachment of the protein to DNA and nick specificity. A portion of the nicked circular DNA isolated from purified simian virus 40 contains a protein-DNA complex in which protein(s) is covalently attached to the end of a DNA single strand. (Nicked DNA is double-stranded DNA that contains at least one single-strand scission.) The protein was visualized by electron microscopy and labeled in vitro with 125I. The bond between the protein and the DNA is stable in alkali, 4 M guanidine-hydrochloride, 3.86 M hydroxylamine (pH 4,23), and in 98% formamide. Most of the molecules in the nicked circular DNA fraction contained one nick. The nick occurs on either of the two complementary strands; the specific nick sites on the two strands are staggered, but lie within a few hundred nucleotides of each other.


Acceptor proteins in rat androgenic tissue chromatin. Fractionation of chromatin into urea-soluble chromosomal nonhistone proteins (UP), histones (HP), and DNA-associated nonhistone proteins (NP) revealed that the NP fraction from testicular and prostatic chromatin contains organ-specific acceptors for complexes of 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and its receptor. This acceptor capacity of androgenic tissue chromatin could be transferred to chromatins from non-target tissues with the NP fraction of DNA-associated proteins. Phosphorylation of chromatin enhanced its hormone-receptor binding capacity.


Phenotypic transformation of clonal myogenic cells to cells resembling chondrocytes. The nicotinamide analogue 6-aminonicotinamide and dibutyryl 3':5'-cAMP inhibit myogenesis in a clonal rat cell line from skeletal muscle. Both reagents produce a similar morphological response in the cells, and stimulate collagen and glycosaminoglycan synthesis. These data suggest that 6-aminonicotinamide and dibutyryl cAMP induce a phenotypic transformation of myogenic cells to cells that share many characteristics with chondrocytes.


Affinity isolation of cultured tumor cells by means of drugs and hormones covalently bound to glass and Sepharose beads. Isoproterenol, corticotropin (ACTH), and triodothyronine immobilized on glass and Sepharose beads by diazotization procedures have been shown to interact with cultured tumor cells of "target tissue" origin. Cells used were rat glioma cells (C6), rat adrenal tumor cells (Y-1), and rat pituitary tumor cells (GH3). The rat glioma cells bound principally to immobilized isoproterenol, whereas the rat adrenal tumor cells bound to immobilized corticotropin, and rat pituitary tumor cells bound to immobilized triiodothyronine. Binding was inhibited by preincubation of the cells in soluble drug or hormone. With C6 cells there was a positive correlation between adenylate cyclase [ATP pyrophosphate-lyase (cyclizing, EC 4.6.1.1] stimulation and the degree of binding to the immobilized isoproterenol. Norepinephrine, bound through the ethanolamine side chain via an amide linkage, did not bind cells, demonstrating specific structural requirements for drug-cell interactions. HeLa cells were shown to bind tightly to diphtheria toxin coupled to Sepharose beads via an amide bond. This binding was inhibited by prior incubation of the Sepharose toxin with purified antitoxin. Toxin bound to Sepharose via an azo bond did not bind cells. These data suggest that the cell affinities are due to cell surface receptors interacting with the immobilized drugs and hormones, and that the observed affinities possibly reflect the relative receptor complement of these cells.


A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug. Purified rat liver peroxisomes contain a cyanide-insensitive fatty acyl-CoA oxidizing system that uses O2 and NAD as electron acceptors. The system was detected by the ability of added palmitoyl-CoA to elicit O2 consumption, H2O2 production, and O2-dependent NAD reduction. The activity of this system is increased approximately one order of magnitude in rats treated with clofibrate, a hypolipidemic drug known to cause peroxisomal proliferation.


Temperature-sensitive changes in surface modulating assemblies of fibroblasts transformed by mutants of Rous sarcoma virus. The hypothesis that surface modulating assemblies containing microfilaments and microtubules and altered after cellular transformation was tested on cells infected with temperature-sensitive mutants of avian sarcoma virus. Untransformed cells (mouse 3T3 and chick fibroblasts), cells transformed by simian virus 40 (SV 3T3), and chick fibroblasts infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV-A-infected cells) were first compared for differences in microfilament and microtubule patterns after treatment with fluorescein-labeled antibodies to actin and tubulin. Transformed cells showed disappearance of ordered stress microfilaments and thickened or diffuse alterations of microtubular arrays. At restrictive temperatures (41 degrees), chick fibroblasts infected with a temperature-sensitive mutant (ts 68) of Rous sarcoma virus showed normal patterns of stress fialments and radial microtubular arrays originating in 1 or 2 centrioles. At permissive temperatures (37 degrees), these patterns were disordered and resembled those of SR-RSV-A-infected cells. After a shift from 41 degrees to 37 degrees, the changes in microtubules were observed in the majority of cells within 1 hr. These changes were reversible and did not result from the inability of tubulin to polymerize. In ts 68-infected cells at permissive temperatures, concanavalin A induced much less surface modulation (inhibition of receptor mobility) than at restrictive temperatures. These results suggest that cellular transformation alters both the structure and function of surface modulating assemblies and prompt the hypothesis that products of viral transforming genes may affect these assemblies with a consequent loss of growth control.


Release by human chromosome 3 of the block at G1 of the cell cycle, in hybrids between tsAF8 hamster and human cells. A temperature-sensitive mutant of Syrian hamster cells, AF8 was fused with simian-virus-40-transformed Lesch-Nyhan fibroblasts; LNSV, in the presence of beta-propiolactone-inactivated Sendai virus. The AF8 cells grow well at 33.5 degrees but are arrested in mid G1 period when shifted to 39 degrees. The LNSV cells are deficient in hypoxanthine guanine phosphoribosyltransferase. The hybrid clones were selected in hypoxanthine-aminopterin-thymidine medium at 39 degrees. A total of 20 clones was isolated and karyotyped. All clones contained most of the hamster chromosomes and one to eight human chromosomes. The preferential retention of human chromosome 3 was observed in 100% of the metaphases of all clones. In nine of the clones, the only human chromosome present was chromosome 3. The results indicate that human chromosome 3 is responsible for conferring to the hybrid cells the ability to grow at nonpermissive temperature for AF8 cells, i.e., the ability to overcome the G1 block. These findings, together with other reports in the cell cycle may be regulated by genes located on different chromosomes.


Clonal variation in albumin messenger RNA activity in hepatoma cells. The clonal variation in rate of albumin synthesis in hepatoma cells is described as a tool for the study of epigenetic control of differentiation. Previous studies have demonstrated that, from a population of hepatome cells, variant subclones can be readily isolated that produce albumin at different rates. Each clonal variant had a characteristic rate of albumin production, and the clones clustered around discrete values that formed a geometric progression. The present experiments, using a cell-free protein-synthesizing system from wheat germ; show that albumin messenger RNA activity is directly proportional to the rate of albumin synthesis in three different hepatoma clones, thus suggesting a pretranslational control of albumin production. Possible hypotheses to explain the geometric pattern of clonal variation are discussed with respect to the organization and control of the transcriptional unit.


Heredity of the GIX thymocyte antigen associated with murine leukemia virus: segregation data simulating genetic linkage. The GIX antigen is a feature of the gp70 envelope glycoprotein of murine luekemia virus (MuLV). This GIX-gp70 molecule is found on the thymocytes of some (GIX+) strains of mice, where its expression is controlled by two mendelian genes, Gv-1 and Gv-2. Previous recombination data involving the prototype GIX+ strain 129 indicated that the H-2 (chromosome 17) and Gv-1 loci are linked, at a distance of 36 units from one another. New data indicate that the association of H-2 and GIX phenotypes is an example of quasi-linkage, evidently dependent in this instance on heterozygosity at a locus or loci in the vicinity of H-2. Other previous recombination data, involving the GIX+ strain AKR, had indicated that the Gpd-1 (chromosome 4) and Gv-1 loci are linked at a distance of 19 units from one another. New data from other crosses show that this association of Gpd-1 (glucose-6-phosphate dehydrogenase 1) and GIX phenotypes also constitutes quasi-linkage, evidently due to heterozygosity at the Fv-1 locus. An important theoretical consequence of quasi-linkage in general is that it should enhance the heritability of particular constellations of unlinked genes, and so influence population structure. Our new data are discussed from the viewpoint that MuLV genomes are apparently concerned in quasi-linkage, and therefore by the same arguments may influence the genetic structure of populations. This in turn may strengthen the view that integrated MuLV genomes are not simply intruded into a self-sufficient cellular genome, but are themselves elements of the cellular genome with primary functions, perhaps in reproduction or embryogenesis.


Ammonium sulfate activation of phosphodiesterase in homogenates of larvae of the european corn borer. European corn borer phosphodiesterase is highly activated by (NH4)2SO4 and moderately activated by NH4C1 (pH 7.6, 33 degrees). Vertebrate and crayfish diesterases, on the other hand, are inhibited by (NH4)2SO4. It is likely that (NH4)2SO4 causes some configurational change in the European corn borer phosphodiesterase molecule which results in the exposure of more active sites and hence greater enzyme activity. In in vitro tests caffeine (0.008 M) and theophylline (0.008 M) inhibit phosphodiesterase more effectively in European corn borer larvae than in crayfish, ovine, bovine, or rat tissue.


Effect of adenosine 3',5'-monophosphate on serine metabolism in chick tissues. The effect of cyclic 3',5'-AMP and supplemental dietary glycine upon de novo synthesis of serine metabolic enzymes in chick livers were examined. Chicks fed crystalline amino acid diets containing 2% glycine had approximately twofold the activity in liver for 3-phosphoglycerate dehydrogenase and phosphoserine phosphatase compared to liver tissue from chicks fed diets lacking in dietary glycine. Chicks subjected to daily intraperitoneal injections of cyclic 3',5'-AMP and fed diets containing no dietary glycine contained biosynthetic enzyme activity similar to glycine-fed chicks suggesting a correlation between glycine and cyclic AMP for serine enzyme induction. The elevated enzyme activity in liver of chicks fed dietary glycine or injected with cyclic AMP was inhibited when chicks were also injected with actinomycin D indicating de novo synthesis of 3-phosphoglycerate dehydrogenase and phosphoserine phosphatase. Dietary glycine or cyclic AMP, however, did not change serine dehydratase and glycerate dehydrogenase activities in chick liver.


Studies on rats with islet beta cell tumors induced by nicotinamide and streptozotocin. Islet beta cell adenomata were induced in rats by combined treatment with nicotinamide and streptozotocin. Three weeks after treatment marked alterations in glucose tolerance were noted in animals which later exhibited large beta cell tumors. Eight months after treatment, the rats known to have beta cell tumors on the basis of marked hypoglycemia and later confirmed by autopsy showed variable response to a glucose load. Some tumor-bearing rats showed fast response to glucose load, their blood sugar levels were elevated moderately and returned to normal or below normal levels rapidly; these animals are described as having "fast-acting tumors". Rats with "slow-acting tumors" responded sluggishly to a glucose load; their blood glucose pattern was similar to that of subdiabetic animals. Animals with beta cell tumors exhibited elevated serum insulin levels 30 min after glucose administration. Insulin biosynthesis by beta cell adenomata was demonstrated by in vitro incorporation of [14C]leucine into proinsulin and insulin. In the small number of tumor samples studied, a stimulatory effect of glucose on insulin biosynthesis was observed.


Brain amines and spontaneous epileptic seizures in the Mongolian gerbil. The seizure sensitive (WJL)UC) strain of Mongolian gerbils has been used to investigate the effects of drugs that modify central monoamine activity on spontaneous epileptiform seizures. Increasing central norepinephrine and dopamine levels significantly reduced the severity of the seizures and the importance of dopamine was further demonstrated by the protection from seizures after administration of the dopaminergic agonist apomorphine. These data indicate that a search for differences in regional levels, or turnover rates, of these amines between seizure sensitive and seizure resistant strains of gerbils might be profitable in determining the genetic deficit underlying the seizure phenomenon in these animals.


The effect of ACTH-analogues on motor behavior and visual evoked responses in rats. Averaged visual evoked responses (VER) in cortical area 17 were recorded one hour after the administration of 7-l-phe ACTH4-10 or 7-d-phe ACTH4-10 to artificially ventilated rats, paralysed with gallamine. In addition, the effects of these peptides on spontaneous motor behavior were analysed. The results show that the latencies of all VER components remain unchanged and the amplitudes of the primary VER were unaffected. Measured at a wide variety of light intensities, however, the amplitudes of the VER afterdischarge were significantly and very similarly diminished by both peptides, the effect of 7-l-phe ACTH4-10 being somewhat stronger than that of 7-d-phe ACTH4-10. These results support the notion, advanced by others, that these peptides have an effect on a CNS vigilance regulating system, yet do not explain the reported opposite effects on active avoidance behavior of the two related peptides. The effects appear specific since spontaneous motor behavior, as index of changes in generalised arousal, is unaffected by these two peptides.


Effects of REMS deprivation on striatal dopamine and acetylcholine in rats. Changes in the concentration of striatal dopamine (DA) and acetylcholine (ACh) in rats deprived of REM sleep for 10 days were compared with those obtained after a 4 day deprivation procedure. Animals placed on small (7 cm dia.) islands surrounded by water were completely deprived of REM sleep but able to obtain some slow-wave sleep. Concentration of striatal DA was significantly increased after 4 days and 10 days of REM sleep deprivation by 73 and 133%, respectively when compared to controls. Levels of ACh in the striatum were significantly enhanced (by 28%) after 10 day, but failed to show significant change after 4 day REM sleep deprivation procedure. The short term locomotor activity was significantly higher in REM sleep-deprived animals. Our data indicate that REM sleep deprivation results in marked alterations of both cholinergic and dopaminergic mechanisms in the rat striatum.


Somatostatin and thyrotropin releasing hormone: central effect on sleep and motor system. The hypothalamic hormones, somatostatin (SRIF or GH-RIH) and thyrotropin releasing hormone (TRH) applied intraventricularly into rat brain had a considerable effect on motor function and resulted in profound alterations in the sleep-waking pattern. While TRH induced primarily an increase in exploratory and motor stereotyped behavior, the effect of somatostatin was striking and prolonged: stereotyped circular running in many instances evolved into catatonia, paraplegia-in extension and/or tonic-clonic seizures.


Office evaluation of breast problems.

Office evaluation of breast problems. The primary physician's best and most dependable aid to diagnosis of breast problems is a thorough and careful physical examination. A methodical approach is described.


Age and parasuicide ('attempted suicide'). A one-year cohort of parasuicide patients (n = 882) was divided into three age groups, subdivided by sex where indicated. Systematic comparisons of the groups were made, and significant discrepancies validated using a second cohort of patients. A number of social, demographic and clinical differences were found, as well as some unexpected similarities. The rates for subsequent (completed) suicide were conspicuously different in the six age-sex subgroups.


The vascular tree in the juvenile nasopharyngeal angiofibroma: a report of 10 cases. Nasopharyngeal angiofibromas have a characteristic angiographic appearance that will allow operative diagnosis without the dangers of biopsy. Angiography shows the vascularization of the tumour and is of great value to determine the extact extension of the tumour. Subtraction technique is essential. The routine skull-base view is imperative to determine if it is necessary to perform a bilateral angiography.


Angiography and histopathology of nephroblastomatosis. A case of nephroblastomatosis (diffuse bilateral Wilms' tumor) in association with congenital hemihypertrophy is reported and the angiographic findings presented. Serial angiograms and tissue biopsies documented the transition from nodular renal blastema to Wilms' tumor.


Angiography of nonfunctioning islet cell tumors of the pancreas. Two cases of nonfunctioning islet cell tumors were documented angiographically and histologically. The manifestations of islet cell tumors, with emphasis on the nonfunctioning type, are discussed, as are the differences between the functioning and nonfunctioning types.


[Binding to chicken liver lactatedehydrogenase (author's transl)]. Some information about the lactate dehydrogenase NAD binding site has been obtained by working with coenzymes analogs of incomplete molecules. 5'AMP, 5'-ADP, ATP, 5'-c-AMP and 3'(2)-AMP inhibit chicken liver LDH activity competitively with NADH. 5"-AMP and 5'-ADP show a stronger inhibition power than ATP, suggesting that the presence of one or two phosphate groups at the 5' position of adenosine, is essential for the binding of the coenzyme analogs at the enzyme binding site. Ribose and ribose-5'-P do not appear to inhibit the LDH activity, proving that purine base lacking mononucleotides do not bind to the enzyme. 5"-ADPG inhibits LDH activity in the exactly as 5'-ADP, showing that ribose moiety may be replaced by glucose, without considerable effects on the coenzyme analog binding. 2'-desoxidenosin-5'-phosphate proves to be a poorer inhibitor of the LDH activity than 5'-AMP, indicating that an interaction between the--OH groups and the amino-acids of the LDH active center takes place. Nicotinamide does not produce any inhibition effect, while NMN and CMP induce a much weaker inhibition than the adenine analogues, thus indicating a lesser binding capacity to the enzyme. Therefore, the LDH binding site seems to show some definite specificity towards the adenina groups of the coenzyme.


Nuclear protein kinase of brain: effect of S-100 protein. The non-histone chromosomal protein fraction isolated from purified brain nuclei possesses protein kinase activity. 93% of this activity is lost by heating at 80 degrees C for 5 min. cAMP does not affect the reaction, but cGMP is inhibitory. In the presence of S-100, an acidic brain-specific protein, phosphate incorporation is enhanced 3 to 4 fold. Bovine serum albumin has no effect whereas histone inhibits activity.


The growth characteristics of metastases from experimental renal tumors. Wistar-Furth rats and BALB/c mice were implanted with tumor cells from metastases or primaries of an experimental Wilms' tumor or an experimental renal cell adenocarcinoma. The survival time, metastasis formation and growth of the primary tumor after implantation of metastatic tumor cells did not exceed those found after implantation of tumor cells from the tumor primaries. It is concluded that the higher growth rate usually found in metastases is not necessarily due to a selection of metastatic cells with a short cell growth cycle but that there are other environmental factors enhancing the growth of metastases.


Enhanced pulmonary absorption of drugs in rats with experimental silicosis. To investigate the effect of pulmonary silicosis on absorption of drugs from the lung, rats were given an intratracheal injection of 50 mg quartz dust, and rates of drug absorption from silicotic and control lungs were compared at 60 and 120 days after treatment. The pulmonary absorption of procaine amide ethobromide and p-aminohippuric acid was increased by 33-41% in animals with silicosis, whereas absorption of procaine amide in silicotic animals was not significantly different from control. The results suggest that silicosis results in an increased porosity of the pulmonary epithelium.