[Phosphorylation of lysine-rich histones by swine brain histokinase]. The phosphorylation of lysine-rich histones F1, F2a2 and F2b of calf thymus has been investigated using homogeneous histone kinase from pig brain. 32P-labelled phosphopeptides from tryptic digests of corresponding histones were obtained. According to N-terminal analysis and the quantitative determination of amino acid composition of the obtained radioactive peptides the sites of phosphorylation were identified in the primary structure of lysine-rich histones, namely, Ser-38 for the polypeptide chain of histone F1, Ser-19 or 18 for histone F2a2 and Ser-14 and 36 for histone F2b. Thus, the high specificity of brain histone kinase in vitro was demonstrated.


School failure and deafness after "silent" congenital cytomegalovirus infection. We found IgM antibody directed against cytomegalovirus in the umbilical-cord blood of 53 of 8644 newborns. Forty-four of the 53 had psychometric and pediatric evaluations at 3.5 to 7.0 years of age. The group's mean IQ was 102.5+/-22.4 (+/-S.D.), whereas in matched controls it was 111.7 (PC 0.025). Bilateral hearing loss was present in five of 40 children with antibody against cytomegalovirus and in one of 44 matched controls without antibody (P less than 0.1). Three of the antibody-positive children, however, had profound deafness, an abnormality that occurs once in approximately 1000 children. The predicted school failure rate, based on IQ, behavioral, neurologic and auditory test data, was 2.7 times that of matched socioeconomic controls and eight times that of randomly selected controls. We conclude that clinically inapparent congenital cytomegalovirus infection can adversely affect central-nervous-system development.


C-type virus expression in systemic lupus erythematosus. Kidneys from patients with lupus nephropathy, non-lupus immune-complex glomerulonephritis and other renal diseases were examined by indirect immunofluorescence for antigens related to a C-type virus from human cells (HEL-12 virus). All 11 specimens of lupus nephropathy contained HEL-12 virus antigens deposited in the same pattern as the immune complexes. The intensity of immunofluorescence with anti-HEL-12 virus serum correlated with the extent of immune-complex deposition. In contrast, nine renal lesions other than lupus nephropathy and seven normal tissues did not react with anti-HEL-12 virus serum. Antibody eluted from one kidney with lupus nephropathy reacted by indirect immunofluorescence with human and dog cells infected with HEL-12 virus but not with uninfected control cells. These findings demonstrate a specific association of lupus nephropathy with a C-type viral antigen that is deposited as antigen-antiviral antibody complex.


Susceptibility of chickens to avian encephalomyelitis virus. III. Behavior of the virus in growing chicks. A chick embryo-adapted strain of avian encephalomyelitis virus was inoculated subcutaneously and orally into 40-day-old (middle-aged) and 110-day-old (advanced-aged) chicks to examine the behavior of the virus in the chick body. In the middle-aged chicks, the virus appeared in the muscle at the site of inoculation, liver, spleen, pancreas, lumbar and cervical portions of the spinal cord, and brain 1 approximately 9 days after subcutaneous inoculation, and remained mostly in the central nervous system up to 17 days after the inoculation. The virus was found in large amounts in the muscle at the site of inoculation (10(3.1)), lumbar portion (10(2.5)) and cervical portion (10(2.1)) of the spinal cord, brain (10(1.9)), and in minute amounts in the other organs examined. It appeared in 11 of 21 organs examined. In the middle-aged chicks inoculated by the oral route, the virus was detected transiently in small amounts from esophagus, pancreas, and rectum 4 approximately 14 days after inoculation. In the advanced-aged chicks inoculated by the subcutaneous route, the virus was detected in titer of 10(2.1) approximately 10(3.0) from the muscle at the site of inoculation 2 approximately 7 days after inoculation. The virus was also found sporadically in several organs up to 17 days after inoculation. In the advanced-aged chicks inoculated by the oral route, no virus appeared in any organ, but these chicks turned to be weakly positive for neutralizing antibody in the 4th or later week after inoculation.


Isolation and properties of reovirus from cattle in an outbreak of acute respiratory disease. A cytopathogenic virus was isolated in the primary culture of bovine kidney cells from a nasal swab of affected calves in an outbreak of acute respiratory disease in Japan in 1971. It agglutinated human type O erythrocytes and produced cytoplasmic inclusion bodies. Viral replication was inhibited by 5-iodo-2'-deoxyuridine, indicating that the viral nucleic acid was RNA. The virus was resistant to ether, chloroform, sodium deoxycholate, and acid, and passed readily through Sartorius' membrane filter 100 nm in pore size, but not through the filter 50 nm in pore size. Electron microscopy showed many spherical particles 60 approximately 75 nm in diameter with a double-layered capsid in a sample taken at a buoyant density of 1.34 produced by CaCl equilibrium centrifugation. The virus suspended in 1M MgCl2 solution was stable against heating at 50 degrees C for 30 minutes, but not against freezing at -20 degrees C for 60 minutes. The virus was resistant to, and increased in infectivity after, treatment with 0.063 approximately 1.0% trypsin. These properties were consistent with those established for the reoviruses. Most affected cattle showed a significant rise of antibody titer against reovirus and bovine respiratory syncytial virus, whereas only a few of them presented a serological evidence for recent infection with parainfluenza virus type 3, bovine adenovirus type 7, and bovine parovirus.


Separation and properties of enterovirus and reovirus recovered from a fecal sample of calf with diarrhea. In April, 1971, a disease with pyrexia and diarrhea as main symptoms broke out collectively among calves. Fecal samples were collected from calves involved and inoculated into bovine kidney (BK) cell cultures. As a result, the diarrheal feces of one calf were suspected to contain two agents simultaneously. One agent (C-121 E strain) was isolated from the primary infected BK cell culture fluid by terminal dilution passages. It had been predominant in replication and shown a cytopathic effect which gave rise to a granular appearance in the early stage of culture. The other agent (C-121 R strain) was isolated from the primary infected BK cell culture fluid by neutralizing the C-121 E strain contained in this fluid with antiserum against this strain. It caused cytoplasmic inclusion bodies to form. On the basis of their physico-chemical properties, the C-121 E strain was identified as bovine enterovirus and the C-121 R strain as reovirus. Serological tests indicated that some of the affected calves had been infected not only with the two strains isolated, but also with bovine viral diarrhea virus, bovine adenovirus type 7, and bovine parvovirus.


Increased intestinal absorption in the rat caused by sodium lauryl sulphate, and its possible relation to the cAMP system. The increases in the absorption of ouabain, phenolsulphonphthalein and pralidoxime caused by 17 mM sodium lauryl sulphate (SLS) from jejunal loops of anaesthetized rats were significantly reduced if sodium and chloride (Briseid et al., 1974) or chloride and bicarbonate were replaced by other ions in the loop fluid. Separate substitutions of sodium, chloride of bicarbonate did not significantly alter the SLS-caused absorption, except that the substitution of choline for sodium reduced the absorption of pralidoxime, both in the presence and in the absence of SLS. The increases in the absorption of phenolsulphonphthalein and pralidoxime caused by SLS were potentiated by theophylline (25 mM) and reduced by imidazole (25 mM). The addition of dibutyryl cyclic AMP (2.5 mM) to the loop fluid increased this absorption of the test substances. This effect was reduced by imidazole, but under the experimental conditions it was not potentiated by theophylline. Determinations of cyclic AMP in the rat intestinal mucosa showed that the level of this substance was significantly higher in the presence than in the absence of SLS. The experimental conditions were as described for the absorption experiments. It is concluded that the data obtained support the idea of an increased level of cyclic AMP as the main basis for the effect of SLS on the absorption.


Catecholamine receptor agonists: effects on motor activity and rate of tyrosine hydroxylation in mouse brain. Motor activity during the first 5 min in a motility meter was measured in mice given 0.025-3.2 mg/kg of the dopamine and noradrenaline receptor agonists apomorphine and clonidine, respectively. The accumulation of Dopa, as induced by the inhibitor of aromatic amino acid decarboxylase, NSD 1015, was measured in parallel in two dopamine-rich regions, i.e. the limbic system and the corpus striatum, and in two noradrenaline-rich regions, i.e. the neocortex and the lower brain stem. Low doses (0.025-0.2 mg/kg) of apomorphine reduced locomotion in a dose-dependent manner, while the reduction after higher doses was less pronounced, indicating a biphasic dose-response relationship. Clonidine caused a dose-dependent locomotor depression. When low doses of the two drugs were combined, the inhibitory effect observed was at least additive. When clonidine was combined with a high dose of apomorphine (0.8 mg/kg), it caused a significant inhibition of locomotion in a dose of 0.1-0.2 mg/kg, but not after 0.8 mg/kg, indicating a biphasic dose-response relationship. Either drug given alone reduced Dopa accumulation after inhibition of its decarboxylation, in all regions, but smaller doses of apomorphine had a clearcut effect only in the dopamine-rich regions, whereas the lowest dose of clonidine investigated (0.05 mg/kg) had an inhibitory effect on Dopa formation only in the neocortex. The relationship between the dose of apomorphine and Dopa formation in the neocortex appeared biphasic, the highest dose (3.2 mg/kg) having no significant effect. Further, apomorphine in this dose accelerated the disappearance of noradrenaline after inhibition of synthesis by alpha-methyltyrosine. Reversal of reserpine-induced suppression of motor activity was taken to indicate postsynaptic receptor activation. The threshold dose of apomorphine causing reversal was 0.2 mg/kg. The inhibitory effect of e.g. 0.05 mg/kg on locomotion and on Dopa formation suggests a preferential activation of inhibitory autoregulatory dopamine receptors by low doses of this drug. A similar trend was observed for clonidine. The basal importance of dopamine neurones for the locomotor function studied in the present paper is illustrated by the marked inhibition by low doses of apomorphine. On the other hand, the observations with clonidine suggest a somewhat less striking and perhaps less direct influence of noradrenaline neurones on motor activity. Mice with a low motor activity, as induced e.g. by reserpine or, in another experiment, mice adapted to the motility meter, displayed an increased motor activity after higher doses of apomorphine (from 0.2 and 2 mg/kg, respectively), whereas all doses depressed the initial high motor activity. Probably, high motor activity requires active dopamine neurones, making this behaviour more susceptible to interference with autoregulatory mechanisms, whereas a low basal activity may be more affected by activation of postsynaptic dopamine receptors.


Conversion of angiotensin I in isolated perfused guinea-pig and rat lung. Increasing concentrations of angiotensin I and different perfusion rates were used to study the conversion of angiotensin I in guinea-pig and rat lungs. Even the highest concentration used (32.0 muM), which is a thousand times higher than that which occurs in vivo, was unable to saturate the converting system indicating the enormous capacity of this system. SQ 20881 proved to be a reversible inhibitor of the converting system. Its effect on the angiotensin I conversion was greater in guinea-pig lungs than in rat lungs (ID50 was 40.0 nM in guinea-pig lung and above 360.0 nM in rat lungs at a substrate concentration of 38.6 nM).


Non-specific inhibition of membrane-ATPase by amiloride: a comparative in vivo and in vitro study with ouabain. The submaxillary duct epithelium, which actively transports Na+ (rabbit) and, in addition, K+ and H+/HCO-/3 (rat), was used as a model epithelium to compare the effects of ouabain and amiloride on transport parameters. 1. Ouabain was only effective from the interstitial side, amiloride, however, only from the luminal side. Amiloride induced effects on transport of the ions were seen within less than 1 s, ouabain effects, however, only after minutes. 2. Ouabain inhibited in a parallel fashion the Na+ transport potential and the Na+-K+-ATPase activity. It had no effect on the Mg2+-ATPase and the HCO-/3-ATPase. 3. Amiloride also inhibited the Na+ transport potential and the Na+-K+-ATPase; however, the Na+ transport potential was significantly more sensitive to amiloride than the Na+-K+-ATPase. 4. Amiloride inhibited in a similar fashion the Na+-K+-ATPase, the Mg2+-ATPase and the HCO-/3-ATPase, but did not influence active HCO-/3 secretion. 5. It is concluded that the amiloride induced effects on the membrane ATPases are non-specific.


Adrenal cortex adenylate cyclase. Is Ca2+ involved in ACTH stimulation? The chelator EGTA inhibits the activation of bovine adrenal cortex adenylate cyclase by ACTH. Hormonal response is restored by addition of Ca2+, Mn2+ and other cations which are able to significantly reduce the concentration of uncomplexed EGTA in the adenylate cyclase assy medium. Time course studies reveal that the enzyme in the activated state (induced by adenylate cyclase reagents and hormone or by pretreatment with hormone) is resistant to EGTA inhibition.


Effects of stimulatory and depressant drugs on cyclic guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate levels in mouse brain. Cyclic GMP levels were dose-dependently increased by excitatory drugs such as picrotoxin, pentetrazol, oxotremorine and harmaline in mouse cerebellum and medial forebrain (parts of the cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) in vivo. Cyclic AMP levels remained unchanged under these conditions. Pretreatment with diazepam completely abolished the effect of picrotoxin and harmaline and significantly reduced the effects of pentetrazol and oxotremorine on cyclic GMP levels, but the tremor due to harmaline and oxotremorine was not blocked. Pretreatment with pentobarbital also prevented or strongly reduced changes in cyclic GMP levels elicited by excitatory drugs without abolishing the tremorigenic effects of harmaline and oxotremorine. Pretreatment with atropine was only effective in blocking cyclic GMP rise and tremor induced by oxotremorine and picrotoxin. Since pentobarbital and diazepam also decreased cyclic GMP levels in a dose-dependent manner in brains of control animals, the changes in cyclic GMP levels observed after administration of excitatory drugs appear to be related to the arousal reaction of the central nervous system.


The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum. Striatal slices were continuously superfused with L-3,5-(3)H-tyrosine (50 muCi/ml) and 4H-H2O [index of 3H-dopamine (3H-DA) synthesis] and 3H-DA estimated in 0.5 ml (2.5 min) superfusate fractions. Depolarization with 50 mM K+ for 7.5 min induced a marked increase in 3H-DA release and a biphasic effect on synthesis (slight increase in the first fraction followed by a significant decrease in the third and fourth fractions). The decrease in the rate of 4H-H2O formation induced by K+ was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. Benztropine in a concentration which produced inhibition of DA uptake (10(-6) M) increased the K+ induced overflow of 3H-DA but failed to alter the inhibition of synthesis. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked 3H-DA uptake (10(-6) M) it potentiated 3H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. A similar effect was seen following the in vivo treatment of rats with fluphenazine (2 mg/kg; 1 1/2 h before sacrifice). The addition of exogenous DA (0.6 X 10(-6) M) or NA (10(-6) M) to the superfusion medium increased 3H-DA outflow and reduced DA synthesis while isoproterenol (10(-6) M) was without effect. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10(-6) M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10(-6) M) significantly prevented the decrease in 3H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. In addition, the effect of exogenous DA on the inhibition of synthesis was still seen in the presence of 2-amino-4-hydroxy-6,7-dimethyl-5,6,-7,8-tetrahydropteridine hydrochloride (DMPH4) (to protect against end-product inhibition). The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter.


Effects of diethyldithiocarbamate on the catabolism of tyrosine in the rat brain. 500 mg/kg sodium diethyldithiocarbamate (DDC) and trace quantities of uniformly labelled 14C-tyrosine were administered simultaneously to male albino rats of Porton-Wistar strain of approximately 210 g body weight. Thirty minutes later total radioactivity, the concentration and the specific activity of free tyrosine were increased both in plasma and in the brain by 40% compared with rats untreated with DDC. The incorporation of 14C from 14C-tyrosine into the fraction corresponding to the elution of glutamine-glutamate from the amberlite resin column was 80% less in the brain 30 min after DDC. The exhalation of 14CO2 was depressed by 80% in the first hour after DDC. When 14C-tyrosine was given 3.5 h after DDC the only differences between experimental and control rats were the increased incorporation of 14C into the glutamine-glutamate and aspartate fractions and the increased exhalation of 14CO2 which became significiant in the third and fourth half hour periods after the injection of 14C-tyrosine. From the experiments it is concluded that DDC, an inhibitor of dopamine-beta-hydroxylase, also interferes with the major catabolic pathway of tyrosine.


Interaction of digitoxigenin with lecithin membranes. The binding of digitoxigenin to lecithin model membranes was investigated by application of electron spin- and nuclear magnetic resonance methods. A digitoxigenin spin-label derivative was found to bind specifically to the pseudohexagonal rigid lattice of lecithin membranes. The binding is accomplished by some of the structural features which are required for the biological activity of cardiac glycosides. Digitoxigenin has a procooperative effect on dipalmitoyl-lecithin membranes. The induction of lipid phase separation is discussed as a hypothetic molecular mechanism of action of cardiac glycosides on biological membranes.


Effects of dopaminergic stimulants on cyclic nucleotide levels in mouse brain in vivo. Dopaminergic stimulants (amantadine, amphetamine, apomorphine, nomifensine and L-dopa plus benserazide) increased cyclic GMP levels in the medial forebrain and cerebellum of mice. Cyclic AMP levels were not significantly altered under these conditions. Drug-induced stereotyped behaviour correlated in intensity and duration to the changes in cyclic GMP levels in the medial forebrain. Amantadine, apomorphine and nomifensine showed a linear dose response relationship, but differed as to the extent and time course of the increase in cyclic GMP. Amantadine and apomorphine were were more effective in elevating cyclic GMP in the medial forebrain than in the cerebellum. Amphetamine produced an exponential dose-related elevation of cyclic GMP in both parts of the brain, being more effective in the cerebellum than in the medial forebrain at high doses, thus indicating a complex mechanism of action. L-Dopa (50 mg/kg) and benserazide (40 mg/kg) alone did neither significantly increase cyclic GMP levels nor induce stereotyped behaviour. However, in animals pretreated with benserazide (15 min prior to L-odopa) L-dopa produced a significant elevation of cyclic GMP and stereotyped behaviour.


[Corticofugal influences on the reticulospinal neurons of gigantocellular nucleus in cats]. Stimulation of the motor cortex evoked excitatory and inhibitory PSP in reticulospinal neurons of the cat gigantocellular nucleus. EPSP were recorded in 94.3% of the investigated neurons and IPSP in 5.7%. Analysis of the presynaptic pathways showed that 77.4% of EPSPs appeared through monosynaptic and 22.6% through polysynaptic corticoreticular connections. According to latency, duration and rise time all monosynaptic EPSP were divided into two groups (fast and slow). Obviously, fast EPSPs are generated by fast corticobulbar fibres and slow ones by slow fibres. IPSP were recorded in neurons which were also inhibited by stimulation of the ventral funiculi of the spinal cord. It is suggested that motor cortical signals can be transmitted to the spinal cord through both mono- and polysynaptic connections of the fast and slow pyramidal neurons with reticulospinal neurons.


Studies with bromocriptine: III. Concomitant administration of caffeine to patients with idiopathic parkinsonism. Caffeine was administered to six patients with idiopathic parkinsonism in an attempt to potentiate the therapeutic response of bromocriptine, a dopamine (DA) receptor agonist, by inhibition of phosphodiesterase. In a double-blind study at doses of 1,000 mg daily, caffeine failed to enhance the antiparkinsonian action of bromocriptine (40 mg daily) given concomitantly. Although effective in potentiating the action of levodopa and other agonists in animal models of parkinsonism, caffeine is inactive in parkinsonism in man.


Viruslike particles in granulomatous angiitis of the central nervous system. Neuropathologic examination of the brain of a 67-year-old woman with a 5-month history of progressive multiple neurologic deficits showed granulomatous angiitis of the small parenchymal and leptomeningeal blood vessels of the brain and spinal cord. Electron microscopy of formalin-fixed brain disclosed intranuclear viruslike particles resembling herpesvirus. Although definitive proof cannot be established without further virologic tests, this previously unreported finding suggests that some cases of granulomatous angiitis of the central nervous system may result from viral infection.


Experimental myasthenia due to alpha-bungarotoxin. Neuromuscular transmission was studied electrophysiologically in rabbits intoxicated by alpha-bungarotoxin, a specific inhibitor of acetylcholine receptor. The findings consisted of a slight reduction in amplitude of single evoked muscle action potentials, a decrement in amplitude of successive evoked muscle action potentials post-tetanic potentiation and exhaustion, edrophonium reversal, and no change of muscle action potentials evoked by direct stimulation of the muscle. These were similar to characteristic electrophysiologic phenomena seen in 40 patients with myasthenia gravis. The receptor abnormality may be responsible for the underlying defect of myasthenia.


Hyperthyroidism and myasthenia gravis with features of Eaton-Lambert syndrome. In a 50-year-old man with hyperthyroidism and myasthenic weakness electrophysiologic phenomena similar to Eaton-Lambert syndrome were seen in classical myasthenia gravis. The orbicularis oculi showed an abnormally small muscle action potential in response to nerve stimulus and unusual facilitation of the response with activity. These signs are compatible with Eaton-Lambert syndrome, but the findings obtained from the adductor pollicis were typical of classical myasthenia. A possible common basis for hyperthyroidism and such an electrophysiologic complexity of transmission failure was considered as a pathogenic hypothesis.


Some metabolic effects of prolonged feeding of starch, sucrose, fructose and carbohydrate-free diet in the rat. Male rats of the ASL Wistar strain were fed from weaning on starch, fructose or carbohydrate-free diets for 4 and 12 weeks. In addition, further groups were fed for 24 weeks on starch, sucrose or carbohydrate-free diets. Livers were examined for gross composition, glucose-6-phosphatase activity and in vitro lipogenesis and glucose oxidation. Intestinal sucrase was also measured. Dietary fructose and the carbohydrate-free diet induced an enlargement of the livers after 12 weeks feeding, when expressed per 100g body weight, and at the same time, an increased fat content. Fructose caused an increase in liver glucose-6-phosphatase after 4 weeks, which persisted after 12 weeks, and a similar increase was observed after 24 weeks feeding on sucrose. Fructose produced an increase in intestinal sucrose after 4 weeks, but this did not persist and there was no increase evident after 12 weeks feeding, nor after 24 weeks feeding on sucrose. Fructose markedly depressed the in vitro lipogenesis and glucose oxidation in liver slices. This was evident after 4 weeks feeding and also after 12 weeks when the effect of age showed as a fall in both these parameters in the control group of animals. The carbohydrate-free diet caused an increase in liver glucose-6-phosphatase after 4 weeks, a smaller increase after 12 weeks, and there was no increase apparent when feeding was continued for 24 weeks. Apparently due to the absence of substrate, the intestinal sucrose activity fell to less than half after 4 weeks and to negligible levels after 12 and 24 weeks on carbohydrate-free diet. In vitro liver lipogenesis and glucose oxidation were depressed after 4 and 12 weeks in a similar way to the fructose diet. On both these diets the rise in liver glucose-6-phosphatase appeared to parallel the fall in liver lipogeneis and glucose oxidation.


Mass screening for breast disease. Results, problems, and expectations. The first 18 months' experience of the Breast Diagnostic Center of Jefferson Medical College have been reviewed. Almost 14,000 patients were screened for breast disease, using a combination of clinical examination. Xeroradiography, and thermography. In this group of 14,000 women, 106 cases of cancer were discovered, in incidence of almost 8 per 1000 women screened. Of these 106 cases of cancer, 45.3% were clinically occult or not recognized by clinical examination, and within this group at the time of mastectomy only a small percent had any evidence of axillary lymph node metastases. The combination of several technics of examination is proving to be more reliable for the early detection of breast cancer than any of the technics alone, and programs such as these may make a significant difference in the death rate from breast cancer.


Surveillance of hydatidiform mole with the Milan-Markley helix. A case of complicated trophoblastic disease followed by quantitative radioimmunoassay and endometrial cytology is presented. Despite the fall of the postevacuation hCG titer to zero, trophoblastic elements were still detected cytologically with the helix technic. A second curettage performed 60 days postevacuation because of a rising serum hCG titer and persistent trophoblastic elements on the endometrial smears was histologically negative. Subsequent helix cytologic studies continued to reveal trophoblastic cells. Chemotherapy with methotrexate and hysterectomy were carried out. A solitary 7-mm lesion was found deep in the myometrium. Titers dropped abruptly postoperatively. Photomicrographs of the cytologic findings are presented.


Methotrexate with citrovorum factor rescue for nonmetastatic gestational trophoblastic neoplasms. Fifteen patients with nonmetastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor. Complete and sustained remission was achieved in 14 of the 15 patients. Response to treatment was determined solely on the basis of serial serum human chorionic gonadotropin levels as measured by the beta subunit radioimmunoassay. All patients developed nonmetastatic gestational trophoblastic neoplasms following evacuation of a molar pregnancy. The known histologic diagnosis in all cases was hydatidiform mole. No significant toxicity was encountered despite careful monitoring of marrow, hepatic, renal, neurologic, and mucocutaneous parameters. Up to January 31, 1976, duration of remission ranged from 2 to 14 months.


[Absorption of testosterone-7 alpha-3H by tissues of organ-targets in male rat embryos]. The dynamics of consumption of testosterone-7alpha-3H by different tissues of the differentiating reproductive system, as well as by suprarenals, brain, hypothalamus and muscles was studied in the in vivo experiments with the rat male embryos beginning from the 14th and till the 20th days of development. The specific consumption of the labelled androgen related to the metabolic processes was observed at all developmental stages under study. The selective consumption of testosterone-7alpha-3H was noted prior to the beginning and during the morphogenesis of the organs-targets' rudiments. The radioactivity in tissues increased already 1--2 days following the castration of 18 days old embryos. Estrone, testosterone, testosterone-propionate, cyproterone-acetate competitively decreased the consumption of testosterone-7alpha-3H. The problem of reception of tissues of the rat male embryos to the male sex hormone is discussed.


[Sensitivity and specificity of the passive hemagglutination reaction applied to titration of herpes antibodies]. 52 human sera were checked for herpes virus hominis type 1 antibodies by passive hemagglutination, complement fixation, neutralization tests and plaque reduction in presence of complement. A good correlation was observed among the results obtained by the passive hemagglutination test and the plaque reduction in presence of complement. The rapidity of the indirect hemagglutination test and the sensitivity of the reaction are in favour of its routine use.


[Structural and biochemical alterations of human diabetic dermis studied by H-lysine incorporation and microscopy]. The alteration of the structural organization of dermal connective tissue was studied by light and electron microscopy and by biochemical techniques in normal human and in diabetic patients using skin biopsies. Part of the tissue was used for light and electron microscopy, the rest was incubated in the presence of 3H-lysine for four hours. The 3H-lysine labelled biopsies were submitted to a sequential extraction procedure in order to obtain representative macromolecular fractions containing the matrix macromolecules. The extracts were analyzed for their chemical composition and radioactivity. Electron microscopy revealed ultrastructural modifications of the fibroblasts, of the collagen and elastic fibers in the diabetic dermis. Fibroblasts contained an increased amount of electron dense deposits in the cytoplasm and dilated endoplasmic reticulum. The collagen bundles were dissociated. Elastic fibers under the epithelial basal laminae were fragmented or absent. The incorporation pattern of 3H-lysine into these macromolecular fractions was different in the normal and diabetic skin biopsies. The percentage of total radioactivity incorporated increased significantly in the 1M CaCl2 extractable fraction an in the 6M urea extractable fraction and decreased significantly in the collagenase and elastase extracts in diabetic skin biopsy. These results demonstrate the existence of morphological and biochemical alterations in diabetic connective tissue (dermis) reflecting alterations in the relative rates of synthesis and/or degradation of the intercellular matrix macromolecules as well as of their microarchitectural arrangement.


[Relation between urinary cyclic AMP, PTH and histomorphometric resorption parameter. A study of 44 human iliac crest bone biopsies]. Daily urinary cyclic AMP (AMPcU) has been compared to pth plasma level and to bone resorption parameters in 44 cases of metabolic bone disease. In 14 cases of primary hyperparathyroidism, AMPcU was always increased likewise in 4 cases of osteomalacia with secondary hyperparathyroidism. On the whole series of cases a significant correlation has been found (1) between PTH plasma level and AMPcU and (2) between bone resporption surfaces and AMPcU. Conversely, no correlation between PTH and periosteocytic lacunae size, nor between AMPcU and periosteocytic lacunae has been found.


[Histochemical study of the cysticercoids of cestodes of the genus Aploparaksis Clerc, 1903 (Hymenolepididae)]. Hystochemical methods were employed in order to study the distribution of succinic dehydrogenase, glucose-6-phosphate-dehydrogenase, alcaline, acidic phosphatases, lipids, fatty acids, glycogen and neutral. mucopolysaccharides in larvae of three species of cestodes: A. birulai, A. polystictae, A. xemae. A high concentration of succinic dehydrogenase was recorded from the tissue of the tail, scolex and neck. Glycose-6-phosphatdehydrogenase was found in great quantity only in the external parenchyma of the neck of A. polystictae. Here accumulations were observed of lipids which apparently are the products of excretion. The glycogen localization coincides with the distribution of succinis dehydrogenase. The activity of phosphatases is concentration in the structures of the tail and external membranes of cysticercoids, the acidic phosphatase being dominant. It was concluded that aerobic oxidation dominates in larvae and substances are principally transported through the tail area and excretory aperture.


Fetal lung maturation IV: the release of phosphatidic acid phosphohydrolase and phospholipids into the human amniotic fluid. The relationship between surface active material and phosphatidic acid phosphohydrolase (PAPase) activity was examined in human amniotic fluid after centrifugation at 105,000 X g for one hour. The distribution of PAPase activity between the pellet and supernatant fractions was similar to that of phospholipids in the amniotic fluid. The majority of the PAPase activity was found to be associated with the pellet fraction. Similarly, 82% of the phospholipid was also present in this fraction. Of the total palmitate present in the original sample, approximately 90% was found in the pellet after centrifugation. Palmitic acid constituted 75% of all fatty acids present in the phosphatidylcholine identified in the pellet. By sharp contrast only 4% of the total protein was pelletized by centrifugation. The pelletized fraction isolated from amniotic fluid after 105,000 X g centrifugation closely resembles the lamellar bodies in: (1) its phospholipid pattern; (2) palmitate concentration in phosphatidylcholine; and, (3) the presence of PAPase activity with a high specific activity. Collectively, these findings lend strong support to the concept that a lamellar-like body is released from fetal lung into the amniotic fluid.


Vitamin D: the discovery of its metabolites and their therapeutic applications. Our understanding of the role of vitamin D in calcium-phosphorus metabolism has changed considerably in the last decade. Studies performed in tissue culture, animal, and man have firmly established that the natural compound requires hydroxylation in the liver at the C-25 position and in the kidney at the C-1 position to form the biologically active derivative 1,25-(OH)2D3. These hydroxylation reactions are finely regulated to maintain normal calcium-phosphorus homeostasis: We now regard 1,25-(OH)2D3 as a hormone which is released by the kidney during periods of hypocalcemia. This hormone acts on the intestinal mucosa to facilitate calcium absorption and on bone to increase calcium mobilization. Its function in other tissues is still being evaluated. The active metabolites of vitamin D and several closely related analogs have been synthesized. It has been clearly demonstrated that 1,25-(OH)2D3 and 1alpha-OH-D3 promote healing in uremic bone disease. Administration of small amounts of these compounds has corrected the biochemical disturbances in vitamin D-dependency and hypoparathyroidism. Limited clinical experience with 25-OH-D3 and 1,25-(OH)2D3 in children with familial hypophosphatemia has failed to show convincing evidence of a therapeutic effect. Further clinical studies are needed to fully evaluate the therapeutic potential of this new family of compounds.


Long-term management of a case of carbamyl phosphate synthetase deficiency using ketanalogues and hydroxyanalogues of essential amino acids. A 13-year-old girl with congenital deficiency of carbamyl phosphate synthetase has been treated intermittently for one year with a restricted protein diet supplemented by various mixtures of the alpha-ketoanalogues of valine, leucine, isoleucine, and phenylalanine, the D,L-alpha-hydroxyanalogue of methionine, and five amino acids (lysine, arginine, histidine, threonine and tryptophan). Numerous adjustments in the composition of this mixture were made. Eventually normal levels of plasma ammonia and most amino acids were achieved, with three exceptions: slightly increased glutamine, pronounced alloisoleucinemia, and persistently low phenylalanine. Alloisoleucine was shown not to be incorporated into plasma protein and not to be excreted in the urine; hence this abnormality was viewed as being clinically insiginificant. Hypophenylalaninemia was unexplained, and failed to respond to increased phenylpyruvate dosage or phenylalanine itself; renal clearance of phenylalanine was high but could not account for the low plasma level. Compared to the pretreatment period her clinical status has improved markedly. Physical and mental development has continued at the same rate. Temporary withdrawal of the supplements led to prompt increases in plasma ammonia, glutamine, and alanine. We conclude that this therapy provides safe and effective long-term management for this patient's disorder and may be useful in other cases of congenital hyperammonemia.


The mechanism of DNA strand breakage by vitamin C and superoxide and the protective roles of catalase and superoxide dismutase. Vitamin C breaks DNA only in the presence of oxygen. Superoxide dismutase has no effect on the reaction but catalase suppresses it. Superoxide also gives rise to breaks in DNA suppressible by both superoxide dismutase and catalase. The hydroxyl radical seems to be the agent responsible for strand cleavage itself.


Isolation and characterization of poly(A)-containing intranuclear polyoma-specific "giant" RNA'S. Heterogeneous polyoma giant RNA molecules have been isolated by oligo(dT)- cellulose chromatography during the late phase of a lytic cycle of infection of mouse kidney cell cultures. These RNAs have sedimentation coefficients in denaturing Me2SO gradients that are greater than 26S and thus apparently correspond to RNA molecules larger than one strand of polyoma DNA. Approximately 15% of total nuclear polyoma late giant RNAs  contained tracts of poly(A) and were retained by oligo(dT)-cellulose. The polyoma late giant RNAs as well as heterogeneous nuclear RNAs (HnRNAs) were found to have a slightly lower sedimentation rate in Me2SO-chloral hydrate density gradients than sedimentation values in sucrose gradients indicated. Even when synthesis of viral DNA and the production of capsid protein are blocked by 5-fluorodeoxyuridine (FdU), 10% of polyoma-specific RNA (as determined by sedimentation analyses under aqueous conditions) was shown to contain tracts of poly(A). In contrast to our findings on polyoma late giant RNA, nuclear polyoma RNA synthesized in the presence of FdU sedimented in denaturing Me2SO-chloral hydrate gradients considerably slower (from 15 to 30S) in relation to HnRNA and ribosomal precursor RNA. The sedimentation pattern in denaturing Me2SO gradients suggest that Py RNA synthesized late in lytic infection in the presence of FdU may be no longer than one transcript of Py DNA.


Search for potential amoebicides. Part V. N-substituted 2-nitro-4,5-dimethoxybenzamides and anils of 2-amino-3-methoxy and 2-amino-4,5-dimethoxybenzoic acids. The authors in all have synthesised 28 new N-substituted 2-nitro, 4,5-dimethoxy-benzamides, and anils of 2-amino-3-methoxy and 2-amino-4,5-dimethoxybenzoic acids with a view to obtain potent amoebicides. Their work is based on the observation that a large number of dimethoxyphenyl substituted derivatives occupy an important place as antiamobic agents. Fourteen belonging to different series subjected to in vitro screening for amoebicidal activity against E. histolytica failed to show any significant activity.


Studies on the relationship between intestinal flora and cecal coccidiosis in chicken. The bacteriological and histopathological changes in the ceca of young chickens after being infected with sporulated oocysts of Eimeria tenella were investigated. Lactobacilli and bifidobacteria showed remarkable decrease in number on the 5th day after infection, when shizont and gametocyate came to appear, and destruction of mucosa along with severe haemorrhaging was noticed. Other predominant bacteria like bacteroidaceae, catenabacteria and peptostreptococci showed only moderate and temporal decrease in number during the infection. Clostridium perfringens prolifereated after the 5th day post infection following the decline of lactobacilli and bifidobacteria. Proliferation of clostridia was so intense that the number was almost million times greater than that of the uninfected chicken at its peak on the 7th day after infection. Enterobacteria also showed a moderate but persistent increase in number. Most bacteria came to the normal population on the 10th day after infection. As for lactobacilli, bifidobacteria, clostridia and enterobacteria, the disturbances were still noticeable on the 17th day after injection. Antagonism between proliferated bacteria (clostridia and enterobacteria) and lactic acid bacteria (lactobacilli and bifidobacteria) whose intensity is suppose to be related to the cecal mucosa is suggested during cecal coccidiosis in chickens.


Variant infectious bronchitis virus isolated from Indiana chickens. Infectious bronchitis virus (IBV) associated with a catarrhal tracheitis, sudden decline in egg production, and reduced shell quality was isolated from an Indiana White Leghorn breeder flock. It was found to be serologically different from Massachusetts, Connecticut, Iowa 97, Iowa 609, Florida, Arkansas 99, JMK, Holte, Gray and SE 17 IBV serotypes. Two different Massachusetts vaccine strains protected chickens from respiratory signs but not against virus infection using the isolant for challenge in laboratory trials. The isolant was passed through a 0.22 mu. filter. It was heat (56 C), acid pH (3.0), ether and chloroform labile. In embryos it produced deaths or lesions of infectious bronchitis in one to five days after inoculation. It is suggested that this IBV isolant be designated Indiana-type.


Reduced symptoms of anaphylaxis in chickens by ACTH or heat. Exogenous ACTH, when administered intramuscularly in four equal doses of 2 I.U./100 gm. of body weight at 24, 23, 22, and 21 hours prior to challenge with BSA, reduced the severity of anaphylaxis in BSA sensitized juvenile chickens. Additionally, a single heat exposure (45 degrees C.) of 30 minutes at 24 hours prior to challenge consistently reduced the severity of anaphylaxis. Single heating exposures at 24 hours prior to sensitization or at 48 hours prior to challenge did not influence the anaphylactic response. In one of two experiments single heat exposures at one hour prior to challenge reduced the severity of anaphylaxis. The levels of anti-BSA antibody which existed immediately prior to challenge were not affected by the heat treatments. These data demonstrate clearly that exogenous ACTH and a single, non-lethal heating episode, when applied 24 hours prior to the induction of anaphylaxis, reduced the severity of the symptoms associated with this particular hypersensitive reaction in the domestic chicken.


The nature of the phosphorus linkage in component I, a phosphoprotein isolated from the blood serum of DES-treated cockerels. The  nature of the phosphorus linkage in electrophoretic component I of the blood serum of DES-treated cockerels was investigated by enzymatic and partial acid and alkali dephosphorylation. The C-P bond was excluded because this bond is stable to 6 N HCl at 110 degrees C. for 20 hours, and all  the phosphorus was released under these conditions. No phosphorus was released when diesterase, pyrophosphatase and 0.25 N HCl were employed, and this excludes the diester, pyrophosphate and N-P bonds. The presence of the O-P bond was supported by the release of phosphate by the phosphatases and 0.25 N NaOH. The hydrolysate produced upon hydrolysis with pronase and papain contained phosphoserine. No phosphothreonine was present.


Isolation and partial charcterization of a cytochrome b complex and cytochrome oxidase from yeast mitochondria. A cytochrome b complex and cytochrome oxidase have been purified 14- and 20-fold respectively from yeast submitochondrial particles by a simple procedure involving their spontaneous precipitation from a deoxycholate extract. The recovery of both proteins was almost quantitative. The specific heme contents were 11 and 8 nmoles/mg protein for the cytochrome b complex and cytochrome oxidase respectively and both were spectrally pure. Sodium dodecyl sulfate gel electrophoresis resolved the cytochrome b complex into seven distinct subunits with molecular weights 42,000, 33,000, 27,500, 23,000, 15,500, 13,000 and 10,500. Cytochrome oxidase contained five bands with molecular weights 42,000, 26,500, 21,000, 14,000 and 10,500.


A model for cytochrome oxidase.

A model for cytochrome oxidase. A model is proposed for the active center of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) in which cytochrome a is a low-spin ferrihemoprotein and cytochrome a3 is a high-spin ferrihemoprotein antiferromagnetically coupled to one of the two Cu2+ ions present in the enzyme. It is further proposed that reduction is accompanied by a conformational change in the enzyme thus exposing the sixth coordination site of cytochrome a3 to ligands. With this model it is possible to account for a variety of outstanding observations including the results of magnetic circular dichroism, Mossbauer, and electron paramagnetic resonance spectroscopies, as well as magnetic susceptibility measurements.


Effect of Fv-1 gene product on proviral DNA formation and integration in cells infected with murine leukemia viruses. The amounts of unintegrated murine leukemia virus-specific DNA detected by molecular hybridization in extracts of Fv-ln/n (strains NIH/3T3, SIM) or Fv-lb/b (strains JLS-V9, SIM.R) mouse cells after infection with N- or B-tropic viruses were found to be the same in both permissive and resistant cells. Therefore, formation of DNA products from the viral RNA template does not appear to be grossly affected by the Fv-l gene product. Integration of virus-specific DNA into chromosomal cellular DNA was assayed by hybridization of radioactive complementary DNA to DNA from infected cells. With either NIH/3T3 or SIM.R cells infected with N- or B-tropic viruses, integration of proviral DNA could be detected in permissive cells but not in nonpermissive cells. The Fv-l gene product therefore appears to prevent integration of proviral DNA.


Monomer molecular weight of T antigen from simian virus 40-infected and transformed cells. T-antigens from simian virus 40 (SV 40)-transformed and lytically infected cells have been isolated by immunoprecipitation and their molecular weights estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. T-antigen from SV40-transformed mouse and hamster cells has an apparent molecular weight of 94,000 whereas that from several lines of SV40-infected monkey cells is 84,000. In a wheat germ cell-free system, mRNA from either transformed or productively infected cells is translated into a 94,000 species. Experiments with the protease inhibitors L-l-(tosylamide-2-phenyl)ethylchloromethyl ketone HCl and N-alpha-p-tosyl-L-lysylchloromethyl ketone HCl suggest that the 84,000 species of T-antigen found in infected cells is derived from the larger species by proteolytic cleavage. Further, the cleavage pathway probably involves a two-step reaction with an 89,000 intermediate. The biological significance of the two molecular weight forms of T-antigen is unknown, but the possibility that they have different physiological activities is discussed.


Independent regulation of endogenous and exogenous avian RNA tumor virus genes. 3H-Labeled complementary DNA specific for the envelope glycoprotein (env) gene of avian leukosis-sarcoma viruses was isolated by selective nucleic acid hybridization techniques, and used to analyze the expression of the endogenous provirus. The endogenous provirus in certain cell types termed chicken helper factor positive (chf+) can synthesize the envelope glycoprotein. Env DNA sequences were present in both chf+ and chf- cells, but env RNA was detectable only in positive cell types. When these cells were infected with the Bryan strain of Rous sarcoma virus (BH-RSV), a defective virus which is deleted in the env gene, the levels of endogenous env RNA remained unchanged, although exogenous BH-RSV specific RNA was synthesized in very high amounts. Thus, the infecting virus did not appear to influence the expression of the endogenous virus. Likewise, the endogenous virus did not influence the exogenous virus expression, since similar amounts of BH-RSV specific RNA were present in all infected cell types, regardless of the level of endogenous virus expression.


Localization of low density lipoprotein receptors on plasma membrane of normal human fibroblasts and their absence in cells from a familial hypercholesterolemia homozygote. Monolayers of normal human fibroblasts were observed to bind ferritin-labeled low density lipoprotein (LDL-ferritin) at specific receptor sites on the cell surface membrane. When fibroblasts were incubated with LDL-ferritin at 4 degrees, more than 70% of the surface-bound ferritin cores were localized by electron microscopy to short segments of the plasma membrane where the membrane appeared indented and coated on both of its sides by a fuzzy material. These membrane segments corresponded to "coated regions" previously described in other cell types. Unver the conditions of these experiments, an average of 55 LDL-ferritin particles were bound to each millimeter of plasma membrane in normal cells. In the presence of a 15-fold excess of native LDL, the number of bound ferritin cores was reduced by 75%, suggesting that the LDL-ferritin was binding to specific LDL receptor sites. Although fibroblasts from a patient with the homozygous form of familial hypercholesterolemia contained the same number of indented, coated membrane regions per millimeter of cell surface as did normal cells, no LDL-ferritin was observed to bind to the cell membrane in these mutant cells. The present ultrastructural data are consistent with previous biochemical and genetic evidence indicating that LDL exerts its regulatory action on cellular cholesterol metabolism in fibroblasts through an interaction with a specific cell surface receptor and that this receptor is defective in homozygous familial hypercholesterolemia fibroblasts. Moreover, the data suggest that the LDL receptor is localized to indented, coated regions of the plasma membrane that appear to participate in the adsorptive endocytosis of proteins.


Increase of AKR-specific sequences in tumor tissues of leukemic AKR mice. AKR mice produce, from shortly after birth, high titers of their endogenous Gross type murine leukemia virus, and develop a thymus-derived leukemia at 7-9 months of age. We show that this oncogenesis is accompanied by an increase in the number of AKR-specific DNA sequences in the tumor tissues, whereas the "non-target" organs are not affected. Sequence increase was determined by kinetic analysis of DNA reassociation using an AKR-murine leukemia virus (MuLV)-specific cDNA and also by hybridization with excess AKR cDNA. The AKR cDNA was selected to recognize AKR sequences without significant crossreaction with DNA sequences of other endogenous viruses. The results show that during the development of the leukemia, the number of AKR-MuLV-specific genes increases in tumor tissues by a factor of 1 1/2 to 2.


Natural antibodies in sera from healthy humans to antigens on surfaces of type C RNA viruses and cells from primates. Sera from healthy humans contained naturally occurring antibody against group- or subgroup-specific antigen on the envelope of the following type C viruses isolated from primates: gibbon ape leukemia virus, simian (woolly monkey) sarcoma virus, baboon endogenous type C virus, and putative human type C viruses [HL23V isolated from blood cells of a patient with acute myelogenous leukemia (HL23) and HEL-12V from human embryonic diploid cells (CIH-32)]. Two sera also reacted with C57BL/6 mouse leukemia induced by Friend virus. These results were obtained by indirect immunoelectron microscopy with various virus-producing cells and by absorption tests using as targets gibbon lymphosarcoma cells that release gibbon ape leukemia virus. In a previous report, the presence of natural antibody in sera from healthy gibbon apes was demonstrated. When the specificities of the human and gibbon natural antibodies were compared, the human natural antibody reacted with two nonproducing culture cell lines of human lymphocytic leukemia (CEM-A and MOLT) and with human embryonic diploid (CIH-1(V-) cells [which became type C virus-producing CIH-32(V+) cells after many passages], but did not react with normal gibbon spleen monolayer cells. In contrast, gibbon natural antibody showed no reaction with CEM-A, MOLT, and CIH-1(V-) cells but reacted with gibbon spleen monolayer cells. Neither human nor gibbon natural antibody  that was reactive with gibbon ape leukemia virus crossreacted with feline leukemia virus and mouse wild-type AKR leukemia virus. The gibbon lymphosarcoma cells releasing gibbon ape leukemia virus were used in a screening study of sera from healthy  humans. Out of 72 sera screened by indirect immunoelectron microscopy using this system, 55 were positive (76%), i.e., 26 out of 35 males (74%) and 29 out of 37 females (78%). The highest incidence of antibody production was in 1- to 10-year-olds and 31- to 40-year-olds, with the adults exhibiting higher levels. Differences in incidence of natural antibody were not found to be sex-linked. These findings suggest that type C RNA viruses related to the gibbon ape leukemia virus and simian (woolly monkey) sarcoma virus family as well as the baboon endogenous type C virus family may be widespread in humans.


In vivo fate of a behaviorally active ACTH 4-9 analog in rats after systemic administration. In vivo fate of a threefold substituted ACTH 4-9 analog with a markedly potentiated behavioral activity, 4-Met(O2), 8-D-Lys, 9-Phe-ACTH 4-9, was investigated. The radioactive labeled [7-3H-Phe] ACTH 4-9 analog was administered IV, SC and orally in a dose of approximately 40 mug. Plasma concentrations of total radioactivity and intact peptide were determined at various periods after administration in urethane anesthetized rats. Oral administration was also performed with conscious animals. Maximal plasma concentrations were found 8 min after SC injection. After oral administration in anesthetized rats maximal plasma levels were reached 8 hr after administration; in conscious animals this took 4 hr. The initial volume of distribution was 5.9% of body weight and the initial half-life (t1/2) for intact peptide 4 min. Shortly after IV and SC administration relatively high and stable plasma levels of intact peptide were obtained, reflecting metabolic stability. This stability was also apparent from the metabolite patterns, which were determined in trichloroacetic acid extracts of plasma and brain by paperchromatography and paperelectrophoresis. The plasma profiles indicated increased stability of the labile 8Lys-9Phe bond by the introduction of an 8D-Lys residue in the peptide analog. Enzymatic attack of the analog took place predominantly at 6His-7Phe and 7Phe-8D-Lys. Formation of tritiated water occcurred in brain and the gastro-intestinal tract and was considerable; proteolysis in these compartments was higher than in plasma. High uptake of radioactivity was found in the kidney, but urinary excretion was low during the first 30 min. Uptake in brain was low and paralleled uptake in cerebrospinal fluid. Intact peptide concentrations/g fresh tissue were in the order of 10(-5)-10(-4) times the administered dose for all three routes.


The radiology of lung cancer.

The radiology of lung cancer. Double reading of radiographs increases the likelihood of detecting pulmonary disease and, accordingly, physicians have an obligation to view the radiographic examinations performed on their patients, either with the radiologist or independently. It is also essential that the radiologist be proved with the clinical findings before he interprets the radiographs, a practice which will result in significant improvement in the accuracy of radiologic  reports.


[Mechanism of action and kinetics of lithium. I. Biochemical and experimental pharmacological findings after administration of lithium-conclusions on the mechanism of the therapeutic effect of lithium]. A comprehensive consideration of biochemical and pharmacodynamic lithium (Li) effects enabled an explanation of the Li mechanism (Fig 1). According to this concept, Li might possibly affect the activity of membrane-bound ATPases in dependence on the initial situation, dose and duration of application. Research into Li-kinetics suggested the participation of active process in the transport of the ion through the organism. Li-kinetics describes distribution within a multiple-compartment system and, with the exception of the resorption phase, its independent of the anion used. The elimination (half-life time 22 to 25 hrs) is limited by backward flow form the tissue.


[Plasma ACTH, STH and other hormone levels in various groups under chlormethiazole, haloperidol or reserpine load in alchohol delirium, alcoholic hallucinations, and chronic alcoholism]. Studies of 135 men with safely diagnosed alcohol delirium mostly revealed increased ACTH blood values when sober and increased T4 values in about 1/3 of these patients. There is a correlation between the psychiatric clinical picture of the alcohol delirium and the ACTH content of the plasma. Under load with chloromethiazole, halperidole or with reserpine, there is a significant drop in the increased ACTH and T4 values. In an acute alcoholic hallucinosis (n=16) similar endocrinological changes as in most cases of safely diagnosed alcohol delirium were observed. In a chronic alcoholic hallucinosis (n=11) and in chronic alcoholics (n=31) the endocrinological values were similar to those of patients after alcohol delirium.


[Biochemistry of depression].

[Biochemistry of depression]. 1. In patients with endogenous depression a functional deficiency of noradrenalin and serotonin is presupposed. This hypothesis is based on examinations of the metabolites of these transmitter substances in the cerebrospinal fluid and in the urine. 2. Attempts to compensate the deficiency by means of precursors of the transmitter show a great variety of therapeutic effects. Possible metabolic regulations are discussed. 3. Changes of hormone metabolism are involved in the disease, these are discussed. 4. At present valid statements on the causes of a biochemical defect in depressive illness are not possible.


Comparative study of the gamma-radiation-induced changes in the tissular levels of acyclic and cyclic adenosine phosphates. Periodical measurement of total adenosine phosphates and cAMP in liver, intestinal mucosa and brain carried out in rats after irradiation with either 500 rads or 750 rads generally revealed high intratissular levels of these compounds, suggesting both a stimulated cellular synthesis and an abnormal redistribution in different tissues. The most interesting findings were those regarding the brain considering their close relationships with the clinical evolution of the animals and other previously described biochemical observations.


Antinociceptive action of quipazine: relation to central serotonergic receptor stimulation. Quipazine, a serotonin receptor stimulant, inhibited the response of rats to painful stimuli in two methods currently used to measure antinociception in these animals: the hot plate and tail compression test. The antinocicptive action was observed with doses ranging from 5 to 20 mg/kg i.p according to the test situation. The effect was significantly antagonized by a pretreatment with methergoline, a potent serotonin antagonist. An electrolytic lesion placed in the nucleus raphe medianus, which produced a marked decrease of serotonin in the forebrain did not, or only slightly, affected the effect of quipazine, depending on the method used to measure antinociception. It is suggested that quipazine can produce antinociceptive action in rats by interacting with a serotonergic mechanism. The action appears to be due mainly to a direct action on postsynaptic serotonin receptors, although a presynaptic component can also contribute to the effect of quipazine.


An unusual upper abdominal gas pattern.

An unusual upper abdominal gas pattern. The case history of one patient is discussed to illustrate radiographic features, etiology and prognosis of gas bubbles in the gastric wall.


Evaluation of ultrasonic and scintigraphic studies of the liver. Ultrasonic and scintigraphic examination of the liver took place in 148 patients. 29 had normal livers, 36 had cirrhosis, 11 had obstructive jaundice, 12 had fatty livers, 60 had focal liver defects. In case of diffuse liver disease the accuracy of both methods is about the same except for fatty liver which is poorly diagnosed by scintigraphy. Focal liver disease is determined with a relative high percentage false-negative for scintigraphy and a relative high percentage false-positive for echography. It is recognized that previous knowledge of the scintigraphic result may raise the accuracy of ultrasound examination of the liver. As echography could distinguish cystic from solid lesions both methods of liver imaging are considered complementary.


Kinetics and imaging characteristics of 99mTC-labled complexes used for bone imaging. Activity levels of 99TC-labeled compounds, 18F, and 85Sr were obtained at 1, 3, and 5 hr. postinjection in normal and healing fractured bone and in soft-tissue rat specimens. Serial diagnostic bone images and blood and urine kinetics were obtained in patients with each of the TC-labeled compounds. Computer-processed images were used to evaluate in vivo kinetics. 99mTC pyrophosphate provides the best overall characteristics for bone imaging. Improved quality and bioassay procedures are required, however, before any one agent can be designated the radiopharmaceutical of choice for diagnostic bone imaging.


Imaging of tumors involving bone with 13N-glutamic acid. Nitrogen-13 labeled L-glutamic acid was evaluated as an imaging agent for tumors involving bone. The enzymatically prepared labeled compound was administered intravenously to dogs with spontaneous tumors, and tumor uptake was determined with a gamma camera and rectilinear scanner. These tumors were well visualized with 13N-glutamic acid, and the results compared favorably with uptake studies performed on the same animals with 99mTc-diphosphonate.


Effect of pentagastrin, histalog, glucagon, secretin, and perchlorate on the gastric handling of 99mTc pertechnetate in mice. Pentagastrin, histalog, glucagon, secretin, and perchlorate were intravenously injected into mice in order to investigate the hormonal regulation of 99mTc pertechnetate uptake by gastric mucosa. Pentagastrin significantly increased uptake; the effect of histalog was weaker. Secretin did not alter the uptake. Glucagon produced some diminution, and perchlorate significantly inhibited gastric uptake. Hormones may play a role in improving the sensitivity and specificity of diagnostic tests for Meckel's diverticulum.


Elective whole lung irradiation.

Elective whole lung irradiation. Whole lung irradiation has been effective in 10 of 17 patients irradiated solely electively (no demonstrable metastatic nodules) who are alive and well 2 to 5 years. Of an additional 17 patients with only one or two demonstrable pulmonary metastases (treated with resection or boost therapy plus whole lung irradiation), 6 are alive and well 5 to 8 years. Only one patient developed clinically significant postirradiation pneumonitis and this case proved to be fatal. Elective whole lung irradiation, especially in conjunction with modern adjuvant chemotherapy, shows promise in improving the survival of patients with tumors having a high propensity for metastasizing to the lungs.


Metabolism and effect of prostaglandin H2 in adipose tissue. Prostaglandin H2 (PGH2) inhibited noradrenaline induced cyclic AMP accumulation in isolated rat fat cells in a dose-dependent manner. IC50 was 10-25 ng/ml both in the absence and in the presence of theophylline. The degree of inhibition produced by PGH2 increased with time of incubation. A stable PGH2 analog did not inhibit cyclic AMP accumulation. PGH2 was rapidly converted by isolated fat cells to PGD2, PGE2 and PGF2alpha' but no formation of thromboxane B2 was found either in vitro or in vivo. PGE2 was a more potent inhibitor than PGH2 of noradrenaline induced cyclic AMP accumulation. PGD2 enhanced cyclic AMP accumulation in a limited concentration interval, while PGF2alpha was essentially uneffective. Our results suggest that PGH2 is an inhibitor of cyclic AMP formation in isolated rat fat cells only after conversion to PGE2. A physiological role for PGH2 as a modulator of lipolysis is considered unlikely.


Ultrastuctural study on the relations among nerve elements and ependymal cells of the "Bradypus tridactylus". On hand of the electonmicroscope, the authors study 24 parts of the encephalic ventricles in samples of Bradypus tridactylus, relating the nervous structures to the ependymal lining, chiefly emphasizing the presence of intraventricular unmyelinated fibres. In various of these regions, typical nerve fibres and other intraventricular cell projections, that cannot be taken as nerve structures, because of the continuity they show along with ependymal cells, were observed. Finally they make an analysis of some functions related to arrangements of this nature.


In vitro cytochrome b5 binding to microsomal membranes: functional and non-functional levels. A comparison of the apparent level of cytochrome binding b5 to liver and kidney microsomes was undertaken comparing values obtained by dithionite vs. NADH reduction. Significant differences both in the extent and specificity of binding to microsomes from liver and kidney were found. These results suggest careful consideration of the apparent binding site availability based on means of reduction is in order.


Isolation of a cytopathic calf rotavirus. The isolation and serial passage in secondary and continuous cultures of calf kidney cells of a cytopathic calf rotavirus is described.


Detection of immune complexes in the serum of dogs infected with canine adenovirus. Evidence for the presence of circulating virus-immune complexes in dogs experimentally infected with canine adenovirus was found when deposits of canine IgG were present in the glomeruli of recipient mice. This passive transfer of complexes occurred only with serum taken at the height of the disease when antibody titres were low and when deposition of complexes in the donor dogs was maximal. Transfer of complexes was not obtained early in the disease (no circulating antibody and minimal deposition of complexes) nor later in the disease (high circulating antibody and minimal complex deposition).


[Chemodectomas of the vagus nerve. Pathogenic hypothesis based on a review of 100 cases]. In connection with a personal case, 100 chemodectomas of the vagus described in the literature have been collected: revealing themselves in 75p. 100 of the cases in the form of cervical and pharyngeal tumours, 50p. 100 of the tumours of the vagal glomus involve some neurological manifestations mainly in the form of lesion of the lower cranial nerves. These appear to be either affected in isolation (41 p. 100) or in a dissociated manner (59 p. 100). Intra-cranial extension is rare (7 p. 100 of the cases) and delayed. Carotid angiography is characteristic. 76 p 100 are intra-vagal, 24 p. 100 are para-vagal and 60 p. 100 are located in the plexiform ganglion. Multifocal forms which account for 17 p. 100 of the cases are more usually, but not exclusively, familial. Surgical treatment is followed by sequelae or complications in more than half the cases. Close attention has been paid to pathogenetic theories: chemodectomas of the vagus may develop from type I chemoreceptor cells of the carotid glomera or from distinct cells with different properties (S.I.F. cells). They may equally well develop from nonchromaffin paraganglionic cells which have not migrated in the normal manner. The finding of such cells in the nerves of new-born babies and adults supports this theory, at least for some chemodectomas of the vagus.


[Ultrastructural aspects of peripheral nerve lesions in one case of Farber's disease]. The patient is a girl who had amyotrophia, dyspnea and juxta-articular nodes. She died at the age of 14 months. Ultrastructural examination of a sural nerve biopsy revealed anormal inclusions in the cytoplasm of numerous myelinated fibres. They are round or oval, and empty, sometimes with a great diameter. Some histiocytes show also such bodies. These are different from those seen in the other neurolipidosis.


[The risk of tuberculosis in students of professional schools]. In four technical schools in a Burcharest district, the first grade scholars were tested at the beginning of the term with 2 units PPD; those with a reaction of 0--9 mm received BCG vaccine. After 6 months, in the 3rd term, they were controlled by MMR examination which was repeated in the second year. The incidence of tuberculosis detected by X-ray and clinically was of 298.8 per 100 000 in the frist year and 283.6 per 100000 in the second year. In all disease cases but one the intradermoreation and greater than or equal to 15 mm which may thus be considered the risk group (a risk of 9.5 per thousand); there were no cases among the children revaccinated with BCG. In conclusion it is recommended to apply in adolescent communities tuberculin testing and BCG revaccination of the non-infected children 0--9 mm) in their first term and periodical X-ray control of the risk group, i.e. those with a reaction of 15 mm or more.


[Problems concerning the etiopathogenesis of bronchopulmonary suppurations]. The data supplied by analysis of more than 1 000 patients pointed to the wide range of the causal factors, the role of focal infections of the upper respiratory and digestive tracts and the mechanisms that interfere in the determinism of the bronchopulmonary suppurative syndrome, the septic particles migrating as a rule along the bronchogenic route.


[Current incidence of the aged among hospitalized tuberculosis patients]. A survey including 10 442 tuberculosis patients hospitalized in a sanatorium showed that 1 086 (10.42%) were 65 years old or older, the proportion increasing from 5.21% in 1964 to 12.78% in 1973 (p less than 0.001). The patients over 70 represented 3.73% of the total, increasing twofold in the course of ten years, from 2.37% to 4.15% (p less than 0.05). There was a rural prevalence, i.e. 11.9% as against 6.85% from urban areas (p less than 0.001), and in the over 70 years age group 4.13% as against 2.74% (p less than 0.001).


[Respiratory consequences of thoracopulmonary surgical operations in children and adolescents]. Spirographic investigations were carried out in a lot of 125 children and adolescents with surgical exeresis or collapse, performed between 1965 and 1972 for suppurations, tuberculosis and other thoraco-pulmonary diseases. Spirographic determinations before and 1--2 months after surgery showed that the postoperative sequelae were milder in children than in adults. Recovery of the ventilation function was more complete than that of the pulmonary circulation. The necessity of a correct postoperative care and systematic, prolonged respiratory kinesitherapy is emphasized.


[Experience in the field of microbial allergic asthma]. The present paper reports on the effect of prolonged microbial hyposensitization applied in 206 cases of microbial allergic asthma in comparison to 95 asthmatic patients of the same category in which this treatment was not applied; improvement was obtained in 78% of the former lot as against 17% in the latter. The quanlity of the improvement obtained and the dependence of the results upon the various diagnostic criteria used are discussed. Microbial hyposensitization has proved efficient in asthmatic patients although its mechanism of action is not yet known, nor the difference that exists from this point of view with the current microbial vaccination. The data obtained suggest that microbial hyposensitization acts by the mechanism of microbial vaccination in all the variants of infectious asthma.


[Inter-relations between pulmonary tuberculosis and diabetes mellitus]. The glucose tolerance test was applied in 50 patients with cavitary pulmonary tuberculosis. In 8 cases chemical diabetes was found representing a proportion of 16% as compared to 2.13% in the rest of the population. Certain possible etiopathogenic factors are discussed: sex, age, environment, nutritional status, age of the disease and tuberculostatic medication. Tuberculosis may be considered as a "diabetogenic risk" factor.


Effect of cortisone and acth on the phospholipids of human amniotic fluid and lung tissue in early gestation. Fifteen physically healthy women who received permission for legal abortion on sociomedical grounds in the second trimester of pregnancy were given either cortisone acetate per os or adrenocorticotrophic hormone (ACTH) intramuscularyly for 3 days previous to hysterotomy. Eight other patients served as controls. The phospholipid composition of amniotic fluid, fetal lung washings, and lung tissue was analyzed. In the cortisone group there was a significant increase in the proportion of palmitic acid in the lung tissue lecithins linked to a corresponding decrease in the oleic acid. A similar tendency was observed in the ACTH group, but the changes were not significant. The investigation suggests that the human fetal lung already at this early stage of development is capable of responding to the action of cortisone by a relative increase in the synthesis of dipalmitoyllecithin.


Cord blood cholesterol, triglyceride, and lipoprotein pattern from two districts in Norway. Lipid levels of cord blood from two districts in Norway were studied. Although the mean levels of cholesterol and triglycerides in the two populations were similar, high cord blood lipid levels were more frequently found in a population in Finnmark in northern Norway than in Bergen in western Norway. In Bergen the 95-percentile value for both cholesterol and triglycerides was 90 mg/100 ml. In Finnmark the corresponding values were 100 and 115 mg/100 ml. The lipid levels in cord blood from children of Norwegian, Finnish, and Lappish origin were nearly identical. The frequency of lipoprotein subfractions as distinct bands between beta and pre-beta fractions in polyacrylamide gel electrophoresis was the same in the two populations. Thus no genetic difference was found in lipoprotein patterns of cord blood in the populations of western and northern Norway.


Precipitation of plasma lipoproteins by PEG-6000 and its evaluation with electrophoresis and ultracentrifugation. A neutral polymer precipitation procedure for fractionation of human plasma lipoproteins is described. The method was also tested preliminarily for fractionation of rat plasma lipoproteins. Polyethylene glycol-6000 (PEG-6000) at a concentration of about 12% and at pH 7.9 precipitated human plasma very low density (VLDL) and low-density (LDL) lipoproteins completely. Precipitation was independent of time and temperature. VLDL and LDL could not be precipitated separately. Polyethylene glycol-6000 precipitation can be used for rapid determination of high-density (HDL) lipids and of the ratio of HDL to LDL lipids.


Radioimmunoassay of triiodothyronine in human serum with special reference to methodological problems. A radioimmunoassay for measuring the level of triiodothyronine in human serum has been developed and studied with respect to interference from hormone-binding substances present in human serum. Dextran-coated charcoal was used for the separation of free and antibody-bound hormone. ANS (8-anilino-1-naphthalenesulfonic acid) was used to reduce the interference from hormone-binding substances in serum. Extraction of the hormone by ethanol before the radioimmunoassay did not solve the problem of interference, even in the presence of an internal standard. The protein concentration in the assay system strongly influenced the charcoal adsorption of free and antibody-bound hormone, and optimal concentrations for both proteins and ANS had to be worked out to get a reliable assay for unextracted serum.


Importance of associated viral and bacterial infections in the production of acute pneumonias. Bacteriologic and virologic investigations carried out in a group of 85 patients with acute pneumonia have allowed the determination of the etiologic agent in 52.9% of the cases. Of these, 40% showed combined viral and bacterial infections. Mixovirus infections were frequently associated with staphylococcic ones (7 out of 8 cases) and adenovirus infections with the pneumococcic ones (6 out of 7 cases). The most severe and longdrawn clinical pictures with frequent pleuropulmonary complications (in 22.24% of the cases) had a biphasic evolution in only 6 of the 18 pneumonias of mixed etiology. For their high frequency and their clinical peculiarities, mixed etiology pneumonias might be considered as distinct clinical entities.


A protein-binding assay for direct determination of adenosine 3',5'-monophosphate in amniotic fluid, cerebrospinal fluid, plasma, and urine. An adenosine 3',5'-monophosphate (cyclic AMP)-binding protein was isolated from bovine skeletal muscle. This preparation showed maximum binding capacity for cyclic AMP at the physiological pH of amniotic fluid, cerebrospinal fluid, and plasma and had a high association constant of 1.4x10(9) 1/mol. This preparation of binding protein, together with albumin and EDTA in the assay buffer, gave a sensitive and specific competitive protein-binding assay that permitted direct determination of cyclic AMP in the biological fluids mentioned above.


Effects of granulocyte neutral proteases on complement components. The proteolytic effects of collagenase and elastase from human granulocytes were investigated on the human complement components C3 and C5 in serum and with purified components. The conversion of C3 was analyzed with crossed immunoelectrophoresis as described by Ganrot, and the conversion of C5 was detected with immunoelectrophoresis according to Scheidegger's method. Collagenase converted C3 to C3b but had no detectable effect on C5. Elastase converted C3 to C3b and converted C5 to a C5b-like fragment. The proteolysis by collagenase and elastase in serum was not detectable until the molar ratio for enzyme to the protease inhibitors alpha1-antitrypsin and alpha2-macroglobulin was greater than 1.


Sustained tolerance to a specific effect of ethanol on posttetanic potentiation in Aplysia. Perfusion with 0.8 molar ethanol in a seawater specifically accelerates the rate of decay of posttetanic potentiation observed after repetitive electrical stimulation of an identified synapse in the abdominal ganglion of Aplysia californica. Repeated perfusion with seawater alternately with and without ethanol leads to a progressive diminution of this specific effect of ethanol, such that after the third application ethanol no longer has any effect on the rate constant of decay of posttetanic poteniation. This tolerance to the specific effects of ethanol persists for at least 11 hours after the last application of ethanol.


Dopamine-sensitive adenylate cyclase occurs in a region of substantia nigra containing dopaminergic dendrites. The zona reticulata, the subdivision of the substantia nigra containing dendrites of the dopaminergic nigro-neostriatal neurons, contains dopamine-sensitive adenylate cyclase activity. This nigral dopamine receptor is similar to the striatal dopamine receptor. These and previous data suggest a physiological role (or roles) for dopamine in the substantia nigra.


Ischemic areas in perfused rat hearts: measurement by NADH fluorescence photography. Fluorescence emission of reduced nicotinamide adenine dinucleotide (NADH) from the surface of perfused rat hearts was photographed to provide a two-dimensional recording of NADH levels. Sodium Amytal inhibition of NADH oxidation resulted in a homogeneous increase in NADH fluorescence, while lowering perfusion pressure from 55 to 10 torr caused a heterogeneous increase in NADH fluorescence, reflecting the heterogeneous oxygen delivery at this low pressure. Local ischemia resulted in a well-defined region of high NADH fluorescence that corresponded to the region of ischemic inslut. The sharp transition between the ischemic and normoxic areas demonstrated that the hypoxic interface separating the two areas must be quite small.


Herpesvirus infections in renal allograft recipients. 17 of 37 immunosuppressed renal allograft recipients developed clinical and/or serological evidence of herpes simplex virus infections, 7 of 83 developed a zoster rash, 85 of loo had evidence of cytomegalovirus infection and in 3 of 30 an active Epstein-Barr virus was seen.


Selective in vitro growth of T lymphocytes from normal human bone marrows. Selective growth of T lymphocytes occurred when unfractionated normal human bone marrow cells were cultured with conditioned medium obtained from phytohemagglutinin-stimulated normal human lymphocytes (Ly-CM). Cultures of up to 90 percent T cells have been maintained for more than 9 months. The T cells exhibited a strict growth dependence upon Ly-CM and were consistently negative for Epstein-Barr viral information.


[Ligation of lymphatic ducts in treatment of arteriosclerosis. 550 operated cases reported over a period of 9 years]. In all diseases where there is an important loss of lymph, e.g. chylothorax, chyloperitoneum, exsudative enteropathy chyloduodenal fistula, we observed not only a fall in the serum proteins and calcium, but also a fall in lipids and cholesterol. We first carried out ligature of the lymphatic ducts in numerous dogs. Since 1966, we have carried out this ligature in 550 arteriosclerotic patients, aged less than 52 years. The metabolic changes observed over a period of 9 years were very marked. Clinically, in 100 patients who underwent classical reconstructive arterial surgery, the association of ligature of the lymphatic ducts reduced by half, after a period of 6 years, the complications normally observed.


[Acute agranulocytosis induced by pyramidon or phenothiazines. Apropos of 31 cases]. The authors present 31 cases of acute agranulocytosis due to drugs. 27 resulted from amidopyrine poisoning and 4 were due to phenothiazines. The clinical picture in most cases, was that of severe septicemia with lesions of the mucosae. On blood count agranulocytosis was complete, associated on bone marrow examination with an appearance of selective hypoplasia of the granular series or an aspect of maturation blockage at the stage of the myelocyte or the metamyelocyte. The course was fatal in 6 cases. A search for leukocyte agglutinating antibodies, carried out in 29 cases, was positive in only 5 cases. These facts correspond, on the whole, to the, clinical and etiological data found in the literature. Although the agranulocytoses induced by phenothiazines, seem to be mainly of toxic origin, the agranulocytoses induced by amidopyrine associated both an immunological mechanism and a toxic mechanism. Among all the biological tests proposed, the most useful is the le ukocyte agglutination test, but the serological diagnosis is rarely conclusive.


[Study of circulation of cerebro-spinal fluid using indium 111 DTPA. Apropos of 300 cases]. A study of the C.S.F. circulation by intrathecal injection of radioactive tracers has become a common technic of neurological exploration. Among the molecules used at present, Indium111 DTPA has numerous advantages for this type of study. It is a chelating agent, the renal clearance of which is rapid and which has no toxicity at the dose injected. Indium111 is a product of the cyclotron and the physical period (2.8 days) is compatible with the duration of the examination. Finally the dose of radioactivity delivered by this isotope is less than that Iodine131, Technetium99m and Ytterbium169. In normal subjects after injection by the lumbar route, the average biological period measured by external counting lies between 20 and 28 hours. A study of the circulation of the C.S.F. is particularly useful in patients suspected of hydrocephalus. It permits finer diagnosis and shows the indications and type of by pass operation that may be neccssary. A marked increase in the biological period of Indium111-DTPA seems to be a good indication for such an operation. Our experience of 300 patients has shown the interest of the use of Indium111-DTPA which now seems to be the best radio-isotope for the study of the subarachnoid space.


[Bacteroides infections].

[Bacteroides infections]. The authors analyse 42 cases of bacteroides infection regrouping bacteremia and localised infection collected over a period of one year. The route of entry was almost always digestive. The prognosis seems mainly to depend on the background. The bacteriological diagnosis is now easy and germ-sensitivy is stereotyped.


[Cerebral gigantism. Review of the literature apropos of one case]. The authors report a case of cerebral gigantism and review 83 cases found in the world literature. The diagnosis depends on the association of several factors, none of which alone are specific but which, on the whole, form a fairly characteristic picture. Large size at birth, leading only rarely to gigantism at adult age. Facial dysmorphia of acromegaloid type. Ecephalopathy with mental deficiency without any neuroradiological abnormality. Finally, endocrine investigations and somatotropic function were normal. No etiology has been found up to now. The most satisfactory theory is that of a hypothalamopituitary disturbance. Treatment may simple avoid excess height at adult age and is based on sex hormone therapy to accelerate bony maturation.


Angiographic evaluation of hepatoma for surgical treatment. Celiac and superior mesenteric arteriography of 60 patients with primary carcinoma of the liver was evaluated retrospectively to select patients properly for hepatic lobectomy, ligation of the hepatic artery or temporary occlusion of the hepatic artery. The angiograms were studied from the viewpoints of origin of the hepatic artery, location of hepatomas, macroscopic type of hepatomas, tumor supplying arteries, patency of the portal vein and coexistence of cirrhosis of the liver. It is stressed that an exact knowledge of these items before operation is important in performing any type of surgical treatment for patients with hepatomas. Resectability of the tumor in the present series of patients was possible in 11 patients, and in the recently seen patients with nonresectable hepatomas, ligation or repeated temporary occlusion of the hepatic artery or both have been performed with postoperative infusion chemotherapy.


Lack of specificity for detection of breast lesions with radioactive cesium chloride. Detection of breast disease at an early stage was evaluated with 131CsCl. The tissue distribution study showed that malignant tumors could be distinguished from both benign and normal tissue by the degree of 131Cs concentration. However, the external counting method was not sensitive enough to warrant general application to patients with a suspected malignant tumor of the breast. False-positive breast study findings using radionuclides, such as 131CsCl, require close follow-up study in view of possible malignant changes in benign disease of the breast.


The role of cell receptors in tumor biology. A general review of the role of receptors in tumor biology is presented. Nonhormonal receptors on the normal cells of the host are extremely important in the attempts to discern the origin and role of similar receptors on malignant cells. The most intriguing of these receptors is the Fc receptor which, in many respects, seems identical to the Fc receptor on B lymphocytes and macrophages. Recent data suggest chemical means of differentiating the Fc receptor of malignant cells from normal cells of the milieu. Such data are essential to resolve a controversy of the significance of the receptor and to help define the role of the receptor in the biology of tumors.


Hypersensitivity pneumonitis after exposure to isocyanates. Four patients exposed to isocyanate vapour developed dyspnoea associated with restriction and reduced gas transfer as well as moderate airways obstruction on lung function testing. In one patient bilateral radiographic shadowing was present and an open lung biopsy was performed. The microscopic appearances ranged from acute inflammation to end-stage fibrosis but the centribular accentuation of disease and the presence of areas resembling bronchopulmonary aspergillosis suggested that the process was a hypersensitivity response to inhaled allergen. Challenge tests with albumin and toluene diisocyanate-albumin were carried out in sensitized and control rabbits. The sensitized animals developed extensive lung damage of the type associated with an Arthus reaction. It is suggested that patients exposed to isocyanates may occasionally develop a hypersensitivity pneumonitis rather than the more usual asthmatic syndrome.


Bronchial adenoma: review of 18-year experience at the Brompton Hospital. Continued uncertainty about the prognosis for patients with bronchial adenomata led to a review of the experience of this condition in the Brompton Hospital. Of 72 patients seen between January 1955 and December 1972, 39 were women and 33 men, mean age 45 years, range 9-73 years. The commonest presenting symptoms were haemoptysis, cough, sputum, and repeated chest infections. Positive bronchoscopic biopsy occurred in 35 of 43 cases; five of these were originally reported as carcinomata, of oat-cell type in four. Plain chest film abnormality occurred in 69 patients. Seventy-three operative procedures comprised two endoscopic removals, two wedge resections, six bronchotomies, five pneumonectomies, and 58 lobectomies (seven with sleeve resection). Recurrence in three of six bronchotomies--two with adenoid cystic carcinomata (cylindromata)--necessitated further surgery. Lobectomy and lymph node dissection is usually the operation of choice. Histology confirmed 67 carcinoids (eight with atypical histology or lymph node metastases), two adenoid cystic carcinomata, one muco-epidermoid, and two mucous gland adenomata. Prolonged follow-up is especially indicated in patients with adenoid cyst carcinoma and in those with atypical or metastatic carcinoid histology. Although such pathology is not incompatible with long survival, of 10 patients in these categories, all five late deaths were probably related to the tumour. However, of 57 patients considered to have had typical carcinoid histology and adequate removal of the tumour, there has to date been no tumour-related death, but one patient developed radiosensitive atypical carcinoid tracheal tumours nine years later. The actuarially assessed survival of 71 patients undergoing surgery for bronchial adenomata was 75% at 15 years. Specific tumour types should replace the term bronchial adenoma.


Cancer of the lung in women.

Cancer of the lung in women. A study from Wales of 132 women with cancer of the lung admitted consecutively during the five years 1964-68, and of 13 other women submitted to surgery at an earlier period, showed that the prognosis for women was worse than for men. Every woman except one was followed up for more than five years. Of the 132 women in the consecutive series only five survived for five years, while the five-year survival rate after resection in 35 women was less than one-half of that of men. The cause of the worse prognosis for women in Wales appears to be due to some sex-linked factor. It cannot be explained by the age of the patient or by the histology, location, early or resectability of the growth. The prognosis of cancer of the lung in English, French, and American women is considered. The relative incidence of the disease in women and men is discussed. Sex and nationality appear to be of importance, but the influence of tobacco and other atmospheric carcinogens is obscure.


[Aujezky's disease in the field and vaccination against the disease (author's transl)]. A rather extensive outbreak of Aujeszky's disease in the area served by the above veterinarians is reported. Of 252 pig-breeding farms, eighty-two were contaminated. The other herds (170) were partly (81) vaccinated against the disease with the Bartha strain. Unlike de non-vaccinated group, the immunized herds showed few of any losses. In view of this fact it is concluded that Aujeszky's disease vaccination is a useful procedure (even in a contaminated environment).


Effects of epinephrine and theophylline on lipolytic response in hereditary diabetic mice. In non-obese but diabetic 15-week-old KK mice which showed fatty liver histopathologically, the content of liver lipids and the levels of blood glucose and plasma IRI were greater than those in the control ICR mice of the same age and were quite similar to those in GTG-obese mice. In 6-week-old KK mice which excreted no glycosuria and showed normal hepatic tissues, only plasma IRI level was slightly elevated as compared with that in the control mice. The cyclic 3',5'-AMP stimulators like epinephrine and theophylline exerted far less potent stimulatory effects on lipolytic activity in 6-week-old KK mice than in the control mice, as in diabetic 15-week-old KK mice and GTG-obese mice. Theophylline potentiated the lipolytic effect of epinephrine lineraly in KK mice, the tendency being different from that in the control mice, and only the submaximal rate was obtained. Furthermore, the inhibitory effect of theophylline on PDE from the epididymal adipose tissue was less potent in 6-week-old KK mice than in healthy ICR mice of the same age.


Experimental study of dibutyryl cyclic AMP: its antishock effects observed in traumatic shock rats. Antishock effect of N6, O2-dibutyryl cyclic AMP (DBcAMP) Was investigated in rats subjected to Noble-Collip drum trauma and compared with effects of hydrocortisone and Trasylol. Results obtained are as follows. 1)Hydrocortisone and Trasylol administered 1 hr before initiating drumming improved the survival rate from traumatic shock with concomitant reducton of levels of acid phosphatase and beta-glucuronidase in circulating blood. DBcAMP administered i.p. immediately after trauma also improved the survival rate to the same extent as did Traylol or hydrocortisone, while no inhibitory effects were observed on acid phosphatase and beta-glucuronidase. 2)The rectal temperature fell significantly after suffering trauma, and the rats with greater fall in rectal temperature had poorer chance for survival. The fall in rectal temperature was considerably prevented by DBcAMP in a dose of 0.5 mg/100 g body weight (b.w.). 3)DBcAMP induced a rise in plasma insulin level (IRI) and insulin/glucose ratio (I/G) in shock rats, and the elevation in blood lactate/pyruvate ratio (L/P) and excess lactate otherwise observed after trauma were satisfactorily prevented by DBcAMP administration. It is concluded that the antichock effects of DBcAMP primarily resulted from improvements of the intracellular metabolism induced by its easy passage through the cell membrane and its cAMP like action, while any preventive action was not observed against elevation of lysosomal enzymes in the circulating blood.


An outbreak of epidemic keratoconjunctivitis due to adenovirus type 8 in a babies home. Between October and December, 1973, an outbreak of epidemic keratoconjunctivitis occurred in a babies home in Sapporo. 28 out of 58 infants and children suffered from the disease. Infection seemed to have been transmitted within a room by hands of nursing staff with spread into other rooms through the dispensary. Clinical manifestation in almost all of the patients was pseudomembraneous conjunctivitis without apparent corneal opacities. None of them showed systemic symptoms. Virus isolation was attempted from eye swabs of 4 patients between 5 and 8 days after onset of the disease, and adenovirus type 8 was isolated from all of the specimens. It was found that there was no case of subclinical infection by the serologic tests. Consecutive serologic studies revealed a good neutralizing antibody response to adenovirus type 8 in the patients tested.