Synthesis of 11 beta,13 beta- and 13 beta,16 beta-propano steroids: probes of hormonal activity. Syntheses of 11 beta,13 beta- and 13 beta,16 beta-propano derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one are described. The 13 beta,16 beta bridge was constructed by intramolecular alkylation of the C-16 enolate anion from 3-methoxy-13 beta-[3'-(tosyloxy)propyl]gona-3,5-dien-17-one, the latter being obtained via Birch reduction of both aryl groups of 17 beta-hydroxy-3-methoxy-13 beta-(3'-phenoxypropyl)gona-1,3,5(10),8-tetraene (1). The 11 beta,13 beta bridge was constructed by Prins cyclization of 17 beta-acetoxy-3-methoxy-13 beta-(3'-oxopropyl)gona-1,3,5(10),9(11)-tetraene, itself obtained via Birch reduction of only the side-chain aryl group of 1. Binding affinities of certain of these compounds and substituted 13 beta-propyl derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one for the uterine cytosol receptor of progesterone are reported, and the origin of the high progestational activity of norgestrel and 11 beta-substituted progestins is discussed.


Photoaffinity labeling of the angiotensin II receptor. 3. Receptor inactivation with photolabile hormone analogues. It has been shown that the receptor of angiotensin II (AT) in rabbit aorta strips, rat aorta, and rat stomach can be blocked specifically and irreversibly by several photolabile analogues of Sar-Arg-Val-Tyr-Val-His-Pro-Phe ([Sar1]AT) with irradiation. The effectiveness of a photolabel with light of wavelength 365 nm depends on the labeling amino acid (L-4'-nitrophenylalanine, L-4'-diazoniumphenylalanine, or L-4'-azidophenylalanine) and on its position in the peptide (replacing Tyr4 and/or Phe8). The 4'-azido)Phe-containing analogues are all good to fair photoinactivators. Their decreasing order of effectiveness is as follows: [Sar1,(4'-azido)Phe8]AT, [Sar1,(4'-azido)Phe4,8]AT, and [Sar1,(4'-azidoPhe4]AT. The (4'-nitro)Phe analogues show the opposite relation: the good ligand [Sar1,(4'-nitro)Phe8]AT is almost ineffective, but the nonligand [Sar1,(4-nitro)Phe4]AT exhibits good, specific photoinactivation. This can be explained by the existence of a different photolysis pathway for (4'-nitro)Phe: this analogue probably undergoes a multiphoton decay with a long-lived first excited state. A peptide in this state may differ in its pharmacological properties from the ground state and become a ligand.


Synthesis and biological properties of N2-substituted spin-labeled analogues of actinomycin D. We have synthesized N2-[4-(2,2,6,6-tetramethyl-1-piperidinyloxy)]actinomycin D And the related 1,2-diaminoethane and 1,3-diaminopropane derivatives and evaluated their biological properties. Binding studies with the spin-labeled actinomycin D analogues and DNA were carried out by using circular dichroism, electron spin resonance, and thermal denaturation. These studies have suggested that the derivatives bind to DNA and that their DNA-binding modes are similar but not identical. Spin-labeled actinomycin D derivatives were less potent in inhibiting Escherichia coli DNA-dependent RNA polymerase reaction than actinomycin D and were less toxic to L1210 cells in vitro than the parent compound. Spin-labeled actinomycin D derivatives were more common than the parent compounds against P-388 leukemia cells in vitro with little or no toxicity.


Crystal-induced inflammation, enzyme release and the effects of drugs in the rat pleural space. The pleural space of the rat has been used to study the acute inflammatory response to crystals of monosodium urate monohydrate, calcium pyrophosphate dihydrate and hydroxyapatite. Each crystal caused a brisk inflammatory response accompanied by crystal phagocytosis and release of lysosomal enzymes. These responses were modified by the anti-inflammatory drugs indomethacin, dexamethasone, colchicine and cyclophosphamide. The results of these experiments suggesting that the resting cell population of the pleural space contributed to the response, and that lysosomal enzyme release may play only a minor role in the mediation of increased vascular permeability.


Frequency sweep analysis of neuromuscular junction continuity. A new technique for measuring neuromuscular junction continuity is described. Junctional transmission is evaluated by integration of the electromyographic (EMG) response induced by intramuscular electrical stimulation. The unique characteristics of this monitoring technique are the use of intramuscular stimulation and a varying stimulation rate. The stimulus frequency is made to increase exponentially from 1 to 100 pulses per second over a period of 10 or 15 seconds. Thin coiled wire electrodes are used for stimulation and recording of the EMG response. The frequency sweep electromyogram (FS-EMB) response was measured in uncurarized and curarized tibialis anterior muscle of cat. In the uncurarized preparation, the FS-EMG response was only slightly decreased with an increasing stimulus frequency. During neuromuscular blockade with d-tubocurarine the FS-EMG response diminished with increasing frequency. The response failed at successively lower frequencies during deeper levels of neuromuscular block. Recovery proceeded in the reverse order. The frequency sweep technique provides quantitative assessment of neuromuscular junction continuity over a broad spectrum of driving frequencies without inducing fatigue. This method does not require force measurements nor voluntary effort. Intramuscular stimulation minimises painful stimuli thus making the frequency sweep technique suitable for evaluating neuromuscular transmission in either conscious or unconscious individuals.


Conformational changes of membrane-bound (Na+--K+)-ATPase as revealed by trypsin digestion. To distinguish ligand-induced structural states of the (Na+--K+)-ATPase, the purified membrane-bound enzyme isolated from rat kidneys was digested with trypsin in the presence of various combinations of Na+, K+, Mg++ and ATP. It was found that first the large and then the small polypeptide chain of the (Na+--K+)-ATPase was degraded, indicating that the lysine and arginine residues of the large chain are more exposed than are those of the small one. The (Na+--K+)-ATPase activity was inactivated in parallel with the degradation of the large polypeptide chain. After the degradation of the large polypeptide chain, about 75% of the (Na+--K+)-ATPase protein remained bound to the membrane, demonstrating that the split protein segments were only partially released. It was found that the combinations of ATP, Mg++, Na+ and K+ present during trypsin digestion influenced the time course and degree of degradation of the (Na+--K+)-ATPase protein. The degradations of the large and the small polypeptide chain were affected in parallel. Thus, certain ATP and ligand combinations influenced neither the degradation of the large nor the degradation of the small polypeptide chain, whereas by other combinations of ATP and ligands the degree of susceptibility of both polypeptide chains to trypsin was equally increased or reduced. In the absence of ATP the time course of trypsin digestion of the (Na+--K+)-ATPase was the same, whether Na+ or K+ was present. With low ATP concentrations (e.g., 0.1 mM), however, binding of Na+ or K+ led to different degradation patterns of the enzyme. If a high concentration of ATP (e.g. 10 mM) was present, Na+ and K+ also influenced the degradation pattern of the (Na+--K+)-ATPase, but differentially compared to that at low ATP concentrations, since the effects of Na+ and K+ were reversed. Furthermore, it was found that the degradation of the small chain was only influenced by certain combinations of ATP, Mg++, Na+ and K+ if the large chain was intact when the ligands were added to the enzyme. The described results demonstrate structural alterations of the (Na+--K+)-ATPase complex which are supposed to include a synchronous protrusion or retraction of both (Na+--K+)-ATPase subunits. The data further suggest that ATP and other ligands primarily alter the structure of the large (Na+--K+)-ATPase subunit. This structural alteration is presumed to lead to a synchronous movement of the small subunit of the enzyme. The structural state of the (Na+--K+)-ATPase is regulated by binding of Na+ or K+ to the enzyme-ATP complex. The effects of Na+ and K+ on the (Na+--K+)-ATPase structure are modulated by the ATP binding to "high affinity" and to "low affinity" ATP binding sites.


Phosphorylation of casein by human erythrocyte membrane-bound protein kinase: competition of casein with endogenous substrates. The possibility that spectrin and band-3 protein are phosphorylated by the same membrane-bound protein kinase was investigated by adding casein to unsealed erythrocyte ghosts and examing competition of the three proteins for phosphorylation. The extent of spectrin and band-3 protein phosphorylation was reduced by up to approximately 55%. This indicated that casein was competing with these endogenous substrates for phosphorylation and was most probably phosphorylated by the same protein kinase(s). Furthermore, the extent of inhibition of the phosphorylation of the two endogenous substrates was indistinguishable over the range of casein concentrations tested (0.1 to 5 mg/ml). This indicates that spectrin and band-3 protein may be phosphorylated by the same protein kinase. In contrast, casein was found to have no effect on the cAMP-dependent phosphorylation of band 4.5. This result indicates that casein only competes with the endogenous proteins phosphorylated by the cAMP-independent protein kinase(s). The extent of reduction of endogenous substrate phosphorylation in the presence of casein was found to be constant over incubation periods of 1 to 15 min, indicating that this reduction was not due to consumption of ATP. Since the spectrin and band-3 protein phosphorylations were specifically and identically reduced by casein and these reductions were not due to the ATP consumption or to a general alteration of the membrane, we conclude that the two substrates are likely phosphorylated by one kinase which also phosphorylates casein.


Amino acid and 22Na+ uptake in membrane vesicles from confluent simian virus 40 transformed Balb/c3T3 and Balb/c3T3. The studies reported here were carried out to characterize further previously described changes in membrane localized amino acid transport associated with simian virus 40 transformation of the mammalian cell line, Balb/c3T3. Membrane vesicles were prepared from confluent cultures of both simian virus 40 transformed Balb/c3T3 (SV3T3) and the untransformed parent line, Balb/c3T3 (3T3). An initial, externally imposed out greater than in, 100 mM a+ gradient produces acceleration of early ingress of alpha-aminoisobutyric acid (AlB) in vesicles from both cell lines, but transient, concentrative uptake (overshooting) only in SV3T3 vesicles. Early ingress of L-leucine is also accelerated in SV3T3 vesicles by a Na+ gradient, and overshooting is also demonstrable. Na+-gradient independent AIB permeability of SV3T3 and 3T3 membranes was estimated using uptake data, a first order rate equation and measurements of vesicle size derived from quasi-elastic light-scattering studies. AIB permeability of SV3T3 membranes is greater than that of 3T3 membranes (113 A/min and 43 A/min, respectively), suggesting that overshooting in 3T3 vesicles is not attenuated by a Na+-independent AIB "leak". Na+ permeability of the two membranes is similar, ruling out the possibility that a slower rate of Na+ equilibration across the SV3T3 membrane allows development of the overshoot. In SV3T3 vesicles the height of a Na+-gradient dependent overshoot varies with the initial [Na+]o/[Na+]i ratio, and ln[Na+]o/[Na+]i is linearly related to ln AIB uptake at overshoot peak/AIB uptake at equilibrium, consistent with the possibility that for [Na+]o/[Na+]i ratios in the range studied, AIB overshoot is energized by a constant proportion of the energy available from the initial electrochemical gradient for Na+. These results are consistent with the possibility that Na+-gradient dependent overshooting in SV3T3 vesicles is produced by Na+-amino acid carrier interactions resulting in either an increase in maximum transport velocity or an increase in carrier affinity for AIB.


A mathematical model for membrane transport of amino acid and Na+ in vesicles. A model with a carrier having sites for both amino acid and Na+ can account for AIB (alpha-aminoisobutyric acid) transport kinetics observed in membrane vesicles from SV3T3 (simian virus 40-tranformed Balb/c33 cells) and 3T3 (the parent cell line). The main feature of this cotransport model is that Na+ binding to carrier decreases the effective Km for AIB transport. Na+ transport kinetics observed in both vesicle systems can be described by passive (possibly facilitated) diffusion. The lag of Na+ transport across the membrane compared to that for AIB, coupled to the Na+-dependent decrease in the Km for AIB, accounts for the overshoot in intravesicular AIB observed for SV3T3 in the presence of an initial Na+ gradient. Extra-vesicular Na+ maintains a decrease in the Km for AIB influx before intra-vesicular Na+ has accumulated to balance it with a comparable decrease in the Km for AIB efflux. 3T3 vesicles display little overshoot, and this finding can be explained mostly by a lower carrier affinity for Na+.


Identification of differences between the surface proteins and glycoproteins of normal mouse (Balb/c) and human erythrocytes. The topography of the external surface of the Balb/c mouse erythrocyte has been investigated and compared to the human erythrocyte by using a series of protein radiolabeling probes. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the pattern of Coomassie Blue stained proteins was very similar for mouse and human erythrocyte ghosts, as was the distribution of radioactivity in protein bands after lactoperoxidase catalyzed radioiodination. The mouse erythrocyte glycoproteins identified by periodic-acid-Schiff and 'Stains-All' reagents, sialic acid analysis of gel slices, binding of 125I-wheat germ agglutinin and 125I-concanavalin A to the gels, and glycoprotein radiolabeling techniques, differed markedly from the sets of proteins labeled by radioiodination, and also differed from the human erythrocyte glycoproteins. Instead of the PAS I to PAS IV series of sialoglycoproteins characteristic of human erythrocytes, the mouse erythrocyte possesses a broad band of sialoglycoproteins with several peaks ranging in mol wt from 65,000 to 32,000. The same group of sialoglycoproteins were labeled by the periodate/B3H4-technique specific for terminal sialic acid, and the galactose oxidase/B3H4-method (plus neuraminidase) specific for galactosyl/N-acetylgalactosaminyl residues penultimate to sialic acid. These results emphasize the necessity to employ a variety of protein radiolabeling probes based on different labeling specificities, to study the membrane topography of cells which are poorly understood compared to the human erythrocyte membrane.


Further evidence for the existence of an intrinsic bicarbonate-stimulated Mg2+-ATPase in brush border membranes isolated from rat kidney cortex. The aim of this study was to provide further evidence for the existence of a nonmitochondrial becarbonate-stimulated Mg2+-ATPase in brush border membranes derived from rat kidney cortex. A plasma membrane fraction rich in brush border microvilli and a mitochondrial fraction were isolated by differential centrifugation. Both fractions contain a Mg2+-ATPase activity which can be stimulated by bicarbonate. The two Mg2+-ATPases are stimulated likewise by chloride, bicarbonate, and sulfite or inhibited by oligomycin and aurovertin, though to different degrees. In contrast to these similarities, only the Mg2+-ATPase activity of the mitochondrial fraction is inhibited by atractyloside, a substance which blocks an adenine nucleotide translocator in the inner mitochondrial membrane. On the other hand, filipin, an antibiotic that complexes with cholesterol in the membranes inhibits exclusively the Mg2+-ATPase of the cholesterol-rich brush border membranes. Furthermore it could be demonstrated by the use of bromotetramisole, an inhibitor of alkaline phosphatase activity, that the Mg2+-ATPase activity in the membrane fraction is not due to the presence of the highly active alkaline phosphatase in these membranes. These results support the assumption that an intrinsic bicarbonate-stimulated Mg2+-ATPase is present in rat kidney brush border membranes.


Membrane pathways for water and solutes in the toad bladder: I. Independent activation of water and urea transport. Vsopressin activates a number of transport systems in the toad bladder, including the systems for water, urea, sodium, and other small solutes. Evidence from experiments with selective inhibitors indicates that these transport systems are to a large extent functionally independent. In the present study, we show that the transport systems can be separately activated. Low concentrations of vasopressin (1 mU/ml) activate urea transport with virtually no effect on water transport. This selective effect is due in part to the relatively greater inhibitor action of endogenous prostaglandins on water transport. Low concentrations of 8-bromoadenosine cyclic AMP, on the other hand, activate water, but not urea transport. In additional experiments, we found that varying the ratio of exogenous cyclic AMP to theophylline activated water or urea transport selectively. These studies support the concept of independently controlled systems for water and solute transport, and provide a basis for the study of individual luminal membrane pathways for water and solutes in the accompanying paper.


Membrane pathways for water and solutes in the toad bladder: II. Reflection coefficients of the water and solute channels. Urea and water transport across the toad bladder can be separately activated by low concentrations of vasopressin or 8 Br-cAMP. Employing this method of selective activation, we have determined the reflection coefficient (sigma) of urea and other small molecules under circumstances in which the bladder was transporting urea or water. An osmotic method for the determination of sigma was used, in which the ability of a given solute to retard water efflux from the bladder was compared to that of raffinose (sigma = 1.0) or water (sigma = 0). When urea transport was activated (low concentration of vasopressin), sigma for urea and other solutes was low, (sigma urea, 0.08--0.39; sigma acetamide, 0.55; sigma ethylene glycol, 0.60). When water transport was activated (0.1 mM 8 Br-cAMP) sigma urea approached 1.0 sigma urea also approached 1.0 at high vasopressin concentrations. In a separate series of studies, sigma urea was determined in the presence of 2 x 10(-5) M KMnO4 in the luminal bathing medium. Under these conditions, when urea transport is selectively blocked, sigma urea rose from a value of 0.12 to 0.89. Thus, permanganate appears to "close" the urea transport channel. These findings indicate that the luminal membrane channels for water and solutes differ significantly in their dimensions. The solute channels, limited in number, have relatively large radii. They carry a small fraction (approximately 10%) of total water flow. The water transport channels, on the other hand, have small radii, approximately the size of a water molecule, and exclude solutes as small as urea.


Growth of short bones of the hand in children with Down's syndrome. In this study, we report the elongation of the diaphyses of the short bones of the hand in an institutionalised sample of children with Down's syndrome. These diaphyses are significantly shorter than normal which is typical of other physical dimensions of individuals with Down's syndrome. Sex differences were generally lacking in diaphyseal lengths; this is in agreement with earlier reports. Pubescent spurts were not detected, but their absence cannot be certain. Roche (1965) reports the common absence of pubescent spurts in stature in children with Down's syndrome. However, only the magnitude of growth in stature of a small sample of these Down's children differed from normal; this dissimilarity was the result of differences in adult statures of normal and Down's individuals (Rarick, Wainer, Thissen and Seefeldt, 1975). Benda (1960) speculates that growth of the short bones of the hand stops early; thus, the pubescent spurt may be prevented by premature, epiphyseal closure. This would be in partial agreement with reports for stature (Roche, 1965). In this sample of children with Down's syndrome the extra chromosome, No. 21, appears to affect the growth of short bones of the hand before seven years of age. The diaphyses of short bones of the hand in these children are shorter than normal by seven years of age and significantly so after eleven years of age; but thereafter, these bones grow normally except for the absence of a pubescent spurt. This pattern is similar to reports of growth in length of other parts of the skeleton in children with Down's syndrome.


Long-term survival in a case of stage IV carcinoma of the ovary treated with a single chemotherapeutic agent. A case of stage IV carcinoma of the ovary is presented which was treated approximately six years ago in the Department of Radiation Therapy at Queens Hospital Center. On September 12, 1972, the patient had a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a papillary scirrhous cystadenocarcinoma of the left ovary. At the time of the operation, the patient was found to have stage IV carcinoma of the ovary due to metastases of the liver and rectum. She was scheduled to receive pelvic-abdominal postoperative radiation therapy via the moving strip technique. Unfortunately, after completion of two strips, the patient could not tolerate treatment. She then began chemotherapy with a single agent, chlorambucil.Chlorambucil, 0.2 mg/kg/day×25 days/course was administered. The patient received 18 courses. Treatment dosage on a few occasions was decreased and increased again, due to drops in hemoglobin level and white blood cell and platelet counts. At the time of this presentation, the patient has no signs or symptoms of the disease. The introduction of megavoltage radiotherapy and adjuvant chemotherapy postoperatively has significantly improved the prognosis for patients with ovarian carcinoma. However, despite progress in radiotherapy, some patients cannot sustain this kind of treatment due to the unwanted side effects. Such was the case in this patient. She was switched to chemotherapy with excellent results in response and survival, even cure.


Therapeutic trial of four amoebicide regimes in rural Zaire. A prospective comparative trial of four amoebicide regimes was carried out with protozoological control using 300 patients presenting with symptomatic intestinal amoebiasis at a tropical rural hospital during a five month period. 195 (76.2%) of 256 treated supplied three follow-up stools. Of those treated with Metronidazole and Oxytetracycline 10.9 per cent continued to excrete Entamoeba histolytica while with Di-iodohydroxyquinoline and Oxytetracycline the figure was 25.5 per cent falling to 20.0 per cent when Dehydroemetine was added and with Clioquinol and Oxytetracycline 27.5 per cent continued to excrete Entamoeba histolytica. These figures with the absolute numbers of patients involved do not show any one of the regimes used to be significantly more effective than the others in unclassified symptomatic intestinal amoebiasis. We conclude therefore that in the rural situation the cheapest regime should be preferred as the standard one, namely Clioquinol and Oxytetracycline. However, in view of the reported serious side-effects of Clioquinol, Di-iodomydroxyquinoline and Oxytetracycline could be considered as the second cheapest and with slightly better results.


Brain metastases in small cell carcinoma of the lung. The records of 177 patients with small cell carcinoma of the lung were reviewed to determine parameters associated with brain metastases. Complete autopsy, including examination of the brain, was done in each case. Of the 70 cases of brain metastases, only two patients (3%) were aged 70 years or more as compared with 19 (18%) aged 70 years or more who did not have brain metastases. Patients with brain metastases had a longer median survival as compared with those without brain metastases. Patients with brain metastases had involvement of the thyroid and kidney more frequently (23% and 34%, respectively) compared with patients without brain metastases (8% and 13%). Thus, patients who have brain metastases tend to (1) be less than 70 years of age; (2) have a longer survival; and (3) have a higher incidence of metastases to the thyroid and kidney.


High-density lipoprotein-cholesterol in survivors of myocardial infarction. High-density lipoprotein-cholesterol (HDL-Chol) levels were higher in a group of 83 myocardial infarction survivors who participated in a moderate, graded exercise program (47 +/- 13 mg/dL) than in 103 nonexercising coronary heart disease patients (40 +/- 11 mg/dL, P less than .001), reaching levels undistinguishable from those of 181 population controls (44 +/- 12 mg/dL). The level of exercise and concentration of HDL-Chol were correlated (r = .24, P less than .05). In 18 patients studied longitudinally, HDL-Chol levels increased from 35 +/- 8 mg/dL before participation to 40 mg/dL (P less than .001) after one week, and remained at that level for six months. Concurrently, functional aerobic impairment decreased from 31% +/- 29% to 11% (P less than .01). These observations suggest that participation in a moderate exercise program increases HDL-Chol levels in myocardial infarction survivors and may contribute to lowering the risk for subsequent infarction.


Moderate exercise and high-density lipoprotein-cholesterol. Observations during a cardiac rehabilitation program. The effects of a 13-week moderate exercise program on fasting plasma insulin, lipids, and lipoprotein cholesterol concentrations were studied in 32 sedentary, middle-aged men with coronary artery disease. The preponderant component of the exercise program was walking or slow jogging. There was no significant change in the systolic blood pressure and pulse rate product response to a standard exercise load. The high-density lipoprotein-cholesterol (HDL-C) level increased, and the fasting plasma insulin concentration decreased. There were no significant changes in plasma triglycerides or low-density lipoprotein cholesterol levels. In sedentary subjects with coronary artery disease, a modest increase in activity can result in an increase in the HDL-C level and a decrease in the plasma insulin concentration. These changes occurred in the absence of variations in diet, smoking habits, adiposity, or plasma triglyceride concentrations and did not require a cardiovascular training effect.


Effects of estrogens on sleep and psychological state of hypogonadal women. A double-lind crossover study involving 16 hypogonadal women compared the effects of placebo and conjugated estrogens, 0.625 mg daily, on gonadotropin levels, symptoms, sleep patterns, and psychological state. After one month, serum concentrations of follicle-stimulating hormone fell 31%, and levels of luteinizing hormone, 19%; the number of vasomotor flushes also decreased. The administration of estrogens was also associated with a shorter mean sleep latency, a longer period of rapid eye movement sleep, and a positive correlation between psychological intactness (as clinically ranked) and latency to sleep onset. Psychological testing, including the Clyde Mood Scale, and the Gottschalk-Gleser Test indicated that estrogens caused this group to be less outwardly aggressive but more inwardly hostile.


Giant cell formation in the brain of suckling mice infected with mouse hepatitis virus, JHM strain. After intranasal inoculation with a neurotropic mouse hepatitis virus, JHM strain, suckling mice less than 2 weeks of age died in 4 or 5 days postinoculation, while those 3 weeks or more of age survived. In the brain lesions of mice 8 days or less of age, there appeared two different types of multinucleated giant cells. One of them which was irregular in shape with many virus particles, appeared mostly in the subependymal or perivascular areas after 72 h postinoculation and it seemed to have resulted from a fusion of two or more infected macrophages. The other type of giant cells which was oval in shape with a small number of virus particles, appeared within degenerative lesions at 96 h postinoculation. It consisted of two morphologically different parts and seemed to be a complex of infected neurons and reacting macrophages. In the cerebral lesions of mice 2 to 4 weeks of age, only the former type of giant cells appeared.


[Effects of orciprenaline on the responses to Ca, K, acetylcholine and Ba in the isolated seminal vesicles of guinea pigs, especially in relation to cyclic AMP (author's transl)]. By using the isolated seminal vesicles of guinea pigs, the effects of dibutyryl cyclic AMP and beta-stimulant, orciprenaline, on the responses to Ca, K, acetylcholine and Ba were investigated, especially in relation to cyclic AMP. The following results were obtained. 1. Orciprenaline inhibited the contraction produced by Ca, K, acetylcholine and Ba in a dose-dependent manner, and the inhibition became larger in the order of Ca, K, acetylcholine and Ba. 2. Dibutyryl cyclic AMP showed the same results as those of orciprenaline. That is, dibutyryl cyclic AMP inhibited the contractions produced by acetylcholine and Ba. 3. Orciprenaline showed the increased level of cyclic AMP in a dose-dependent manner. But the increase was not remarkable in the concentration in which the contractions produced by the tested contractile agents were inhibited by about 50%. From these results, the following suggestions were obtained; (1) there exists beta-receptor in guinea pig seminal vesicles and (2) a part of actions of orciprenaline is due to a mechanism unrelated to cyclic AMP.


[Study of the effect of various intermediate products and enzymes of carbohydrate metabolism on erythrocyte aggregation]. The effect of some substances on the aggregation of red blood cells induced by gamma-globulin and fibrinogen was studied in vitro. Fructose 1,6-diphosphate, glucose 6-phosphate, glyceraldehyde dehydrogenase, insulin and prostaglandin E1 inhibited aggregation of red cells. Glucose, glucose 1,6-phosphate and ACTH had different effects in various concentrations on red cell aggregation, while fructose, prednisolon and D-oxy-prostaglandin E1 alpha and E1 beta caused no effect.


[Comparative analysis of incidence of main risk factors, behavior characteristics and work activity in ischemic heart disease with normolipemia and hyperlipoproteinemia type II and IV]. Examination was conducted of 180 healthy males 35 to 44 years of age, working as leading engineers, and of 174 patients with ischemic heart disease selected according to sex and occupation. A comparative analysis was made of the frequency of the main risk factors and some peculiarities of the labour activity and behaviour of patients with types II and IV hyperlipoproteinemia and those with normal lipid level. It is shown that a combination of known risk factors, behaviour peculiarities and conditions of labour activity is typical of patients with type IV hyperlipoproteinemia, which may promote the development of ischemic heart disease. Patients with normal blood lipid livel merit special attention. Additional factors contributing to the development of ischemic heart disease in these cases should be searched for.


[Myocardial scintigraphy with pyrophosphate-99mTc in transitory myocardial ischemia in chronic ischemic heart disease]. Scintigraphy of the myocardium with pyrophosphate-99mTc was used in the examination of 45 patients with chronic ischemic heart disease and 3 patients with vegetovascular dystonia. A direct dependence of the character of the scintigram on the anginous attack was revealed. Accumulation of pyrophosphate-99mTc in the myocardium was observed in all patients with the agent injected just before the attack, during the attack or in the first 8 hours after it. Pyrophosphate-99mTc accumulation in the myocardium demonstrated on the scintigrams of the myocardium was less intense but more diffuse and extensive in chronic ischemic heart disease than in the focus of acute myocardial infarction.


Effect of indomethacin and adrenocorticotrophic hormone on renal function in man: an experimental model of inappropriate antidiuresis. The effect of prostaglandin synthesis inhibition on basal and ACTH-stimulated adrenal and renal function was investigated in normal volunteers. Data were collected during control and experimental study periods (13 days each). Adrenocorticotrophic hormone (Cosyntropin, 80 U/day) was administered i.v. on days 8 and 9 of each period. Indomethacin (150 mg/day) was given on days 5 through 13 of the experimental period. The subjects ate a constant diet containing 9 mEq of sodium, 100 mEq of potassium, and 2,500 ml of fluid daily. Indomethacin markedly inhibited urinary PGE excretion and plasma PGE concentration. The effect of ACTH alone as compared to the effect of ACTH and indomethacin showed: plasma sodium concentration, 139 +/- 1 vs. 131 +/ 3 mEg/liter (P less than 0.01, mean +/- SEM); plasma osmolality, 287 +/- 3 vs. 270 +/- 3 mOsm/liter (P less than 0.01); free water clearance, 97 +/- 66 vs. -1100 +/- 380 ml/24hr (P less than 0.01); urine volume, 2,000 +/- 60 vs. 950 +/- 200 ml/day (P less than 0.01); and urine osmolality 282 +/- 12 vs. 720 +/- 144 mOsm/liter (P less than 0.01). We conclude that the effects of ACTH and prostaglandin synthesis inhibition interact to result in inappropriate antidiuresis.


[Glomangioma in the eyelid. A clinical and histological case report (author's transl)]. A glomangioma of the eyelid is presented. This localisation of such a tumor is considered to be an extremely exceptional one. Clinical and histological details are described. The differential diagnosis is discussed.


Lipid-protein interactions in membranes: effect of lipid composition on mobility of spin-labeled cysteine residues in yeast plasma membrane. In order to gain direct evidence for lipid-dependent protein conformation in membrane, effects of modification of lipid composition on mobility of spin-labeled cysteine residues were investigated in the plasma membrane of the yeast Saccharomyces cerevisiae. Conversion of the bulk of phospholipids to diglycerides by treatment of the membrane with phospholipase C substantially enhanced spectral anisotropy. However, alterations of the viscosity of the lipid-bilayer by enriching the membrane with palmitelaidic or oleic acid had no effect on mobility of spin-labeled cysteine residues. These observations indicate that while the spin-labeled residues are not in direct contact with the lipid core of the membrane, there are lipid-protein interactions to the extent that removal of the polar portion of the bulk of phospholipids induces conformational changes in proteins, which in turn restrict mobility of these residues. It is concluded that conformation of membrane proteins on lipid structure and that phospholipids have a role in preserving the native conformation of proteins.


Malignant fibrous histiocytoma arising in a patient with multiple neurofibromatosis: a case report and a literature review. A case report of a 56-year-old man with the characteristic clinical and histologic features of multiple neurofibromatosis is presented. This patient was also diagnosed as having a malignant fibrous histiocytoma involving the right thigh with metastasis to the lung. A definite association between Von Recklinghausen's disease and various sarcomas (most commonly neurofibrosarcomas) of the peripheral nerves and the somatic soft tissues is well-known. This is apparently the first report in the literature of a malignant fibrous histiocytoma arising in a patient with multiple neurofibromatosis. The phenomenon of sarcomatous change in Von Recklinghausen's disease and the clinical and pathologic features of malignant fibrous histiocytoma are also discussed.


Experimental opacification of mediastinal lymph nodes by intraperitoneal injection of an iodinated fatty emulsion. Absorption and lymphatic drainage of several lipiodol emulsions injected intraperitoneally have been studied in the rabbit and rat. Good opacification of the lymphatic channels and mediastinal lymph nodes is obtained in several hours with fine emulsions and in several days with coarse emulsions. The tolerance is related to dose, and the peritoneal reaction was moderate with the low doses, similar to that caused by the administration of physiologic saline alone. Computerized tomography in detecting low contrasts attained with small doses could render this method of indirect lymphography possible in man.


5-HT induced accumulation of 3',5'-AMP and the phosphorylation of paramyosin in the ABRM of Mytilus edulis. In Mytilus edulis 5-Ht induced relaxation of a muscle in catch is preceded by an increase in 3',5'-AMP content. In vitro two proteins of the contractile apparatus are phosphorylated by 3',5'-AMP dependent protein kinases. The 295000 dalton protein cannot be identified, the other one is paramyosin. Phosphorylated paramyosin inhibits actomyosin ATPase of smooth mollusc muscles at low and high Ca++ concentrations.


The re-formation of connections in the nervous sytem of Lymnaea stagnalis after nerve injury. Changes in the tentacle reflex pathway of the pond snail Lymnaea stagnalis induced by peripheral nerve injury were studied with behavioural and electrophysiological techniques. After nerve injury regeneration of sensory axons is obtained in 6-12 days, suggesting an axonal outgrowth at a rate of 1 mm per day. Recovery of the tentacle reflex takes much more time indicating that synaptic efficacy is affected considerably by the period of sensory deprivation following nerve injury.


Functional characteristics of an identified pair of neurones in the CNS of the pond snail (Lymnaea stagnalis L.). The properties of 2 giant electrically coupled neurones (A10 and P1) identified in the visceral and right parietal ganglia of Lymnaea stagnalis were examined. The active and passive electrical parameters of the neurones, as well as the junction between them were measured. The main peripheral and interneuronal connections of the neurones were demonstrated using both electrophysiological and morphological methods. It is shown that the coupled cells are not neurones of the same function, but they are asymmetrical ones. This finding is supported by the following results: (1) the axonal pathways of neurones A10 and P1 are different; (2) there are significant differences in their afferent and efferent connections; (3) though the electrical junction between them is bidirectional, the junctional electrical characteristics prefer P1-A10 transmission. According to the electron microscopic results both neurones are possible neurosecretory cells. The differences demonstrated between the 2 giant neurones may have significance concerning their role in a special neuronal network.


Receptors for insulin and epidermal growth factor-urogastrone in adult human fibroblasts do not change with donor age. The ligand binding and biological responsiveness of cultured fibroblast monolayers were measured for porcine insulin and for murine epidermal growth factor--urogastrone in skin fibroblast cultures derived from young (22 to 31 years) and old (65 to 80 years) normal male volunteer donors. The receptor characteristics of the cells studied from the two groups of donors were not found to differ. In contrast with previous data, suggesting that there may be a genetically programmed aging of the insulin binding system, it is concluded that for both insulin and epidermal growth factor, receptor characteristics do not change with adult donor age.


[Mediastinoscopy and thoracotomy in bronchogenic carcinoma (V) (author's transl)]. The opinion of the Bronchogenic Carcinoma Cooperative Group is that mediastinoscopy is at present an irreplaceable method for the determination of the resection limits in patients with bronchogenic carcinoma. Mediastinoscopy cannot be replaced by roentgenologic or isotopic studies of the mediastinum, since the invasion of the ganglionar capsule or of the mediastinal fat can only be determined by histopathologic examination. Following a classification based on macro- and microscopic morphological criteria, surgery has achieved a 64 percent of thoracotomies with "presumably curative" resections. Patients with epidermoid carcinomas were the main candidates to surgery. Lastly the role of the so-called bronchogenic carcinoma "markers" or substances that can indirectly indicate the course of the disease is discussed. The value of humoral and cell-mediated immunologic studies for introducing other therapeutic variants after curative surgery is pointed out. The definite conclusions regarding the clinical and surgical therapeutic aspects of the Bronchogenic Carcinoma Cooperative Group are detailed.


[Experimental induced pancreatic carcinoma after choledochojejunostomy (author's transl)]. The pancreatic carcinogen DHPN (dihydroxypropylnitrosamin) was administered to Syrian golden hamsters. By intragastric administration more pancreatic carcinomas in the head of the gland were induced than by subcutaneous injections. After choledochojejunostomy the incidence of carcinomas was only 5--7% and the lesions were similar in multiplicity and distribution without relationship to the way of administration. The importance of biliary reflux in pancreatic tumor induction is discussed and the role of bile concerning the preferred localisation of the tumors in the head of the pancreas.


[Significance of the exfoliative cytodiagnosis in cases of Paget's disease of the nipple (author's transl)]. 8 cases of Paget's disease of the nipple were diagnosed by means of cytological examination: in 6 patients by exfoliative, in 2 patients by aspiration biopsy cytology. The diagnoses were verified histologically. Early exfoliative cytology is recommended for early diagnosis in all cases of Paget's mamillae. This method is quick, safe, easily to be carried into effect and to apply repeatedly; but, if the process is suspected of malignancy, a trial-excision has to be carried out. A well-trained cytologist rarely needs the latter. This simple method will reduce the development of advanced Paget's disease.


Lipoproteins in experimental nephrosis: plasma levels and composition. Experimental nephrosis was induced in rats by administration of puromycin aminonucleoside and the levels of plasma lipoproteins were examined 7 days later and compared to controls. As determined by density ultracentrifugation, VLDL, IDL, LDL, and HDL protein levels were increased by 8, 4, 5, and 5 times, respectively. These increases were accompanied by changes in lipid and apoprotein composition. The VLDL, IDL, and LDL fractions contained less triglyceride and more phospholipid and cholesterol, while HDL lipid composition was not altered. The apoprotein composition of VLDL and IDL were not measurably altered, but LDL contained less apoE. HDL had a markedly abnormal composition characterized by an almost complete absence of apoA-IV and apoE, increased apoA-1, and decreased apoC. While increased hepatic synthesis can account for much of the observed hyperlipoproteinemia in nephrosis, the changes in lipoprotein composition suggest impaired catabolism as a contributory factor.


Adipose tissue lipoprotein lipase activity in type III hyperlipoproteinemia. An impairment in the catabolism of chylomicron and very low density lipoprotein remnants appears to cause the lipid abnormalities in type III hyperlipoproteinemia. A reduction in the activity of lipoprotein lipase (LPL) has been suggested as the catabolic defect. Results in this study indicate that the activity of adipose tissue LPL measured in the fasted and fed states are in the normal range in type III hyperlipoproteinemia (fasted: type III = 2.7 +/- 1.8 mU/10(6) cells, N = 8; normals = 3.4 +/- 2.5, N = 23, p, not significant; fed: type III = 3.6 +/- 2.1, N = 7; normals = 4.8 +/- 1.8, N = 12, p, not significant). This suggests that perhaps another mechanism, such as the interaction between LPL and its lipid substrate, is abnormal, or that the activity of LPL derived from another tissue source is deficient.


[Tuberculosis in tropical Africa. Tuberculosis primary infection: some clinical aspects in tropical Africa]. A review of 140 cases of tuberculous patent primary infections from the hospital of Abidjan University and from an antituberculous unit. The disease begins slowly, general condition is rapidly altered, ventilation troubles are very frequent and so are complications as meningitis and miliary dissemination. In 11,4 p. cent of the cases, measles occurred before the primo-infection. In 38 p. cent of the cases the source of contamination could be identified and in one out of two cases, the mother proved to be responsible for it.


Cigarette smoking, alcohol intake, and oral contraceptives: relationships to lipids and lipoproteins in adolescent school-children. The effects of cigarette smoking, alcohol intake, and oral contraceptives on plasma cholesterol, triglyceride, high density lipoprotein cholesterol (C-HDL), and low density lipoprotein cholesterol (C-LDL) were assessed in 965 12--19-year-old school-children in the Cincinnati Lipid Research Clinic's Princeton school survey. After pair matching for age, sex, race, and total plasma cholesterol, adolescent children who smoked had mean C-HDL 6.1 mg/dl lower, and mean C-LDL 4.1 mg/dl higher, than nonsmokers (p less than 0.01). These findings for C-HDL were replicated by covariance analysis, adjusting for age, race, sex, alcohol intake, and triglyceride levels. Adolescents who drank alcohol had higher C-HDL and triglyceride levels and lower C-LDL than nondrinkers, but the differences were not significant. Adolescent females taking oral contraceptives had higher triglyceride, C-HDL, and C-LDL levels than matched controls, but the differences were not significant. If a portion of smoking's contribution to coronary heart disease risk is mediated through its inverse association with C-HDL, and if smoking habits initiated in adolescence continue into adulthood, this report provides additional physiologic data relevant to programs designed to prevent, reduce, or stop cigarette smoking in the adolescent years.


Pieiotropic effect of two cell wall mutants on the activity of some cell wall enzymes in the yeast Saccharomyces cerevisiae. The two mutants (abs) and (wal) affecting the cell morphology of yeast lead also to higher in vivo activities of the cell wall enzymes acid phosphatase, invertase and melibiase.


Characterization of a plasmid mutation affecting maintenance, transfer and elimination by novobiocin. We have isolated a mutant H group plasmid temperature-sensitive for plasmid maintenance. Unlike the wild type plasmid (pSD114), the mutant (pDT4) was eliminated at 37 degrees C and also at 30 degrees C after novobiocin treatment. The mutant plasmid interfered with host cell growth at the non-permissive temperature. Conjugative transfer of the mutant was reduced at 30 degrees C compared to the wild-type plasmid. Introduction of a coumermycin-novobiocin resistance DNA gyrase (cou) mutation into Escherichia coli prevented pDT4 elimination by novobiocin but did not affect the temperature-sensitive phenotype. The evidence indicates that the mutant plasmid used bacterial DNA gyrase for replication. Models to account for the behaviour of this unusual mutant are discussed.


Dual regulation of the synthesis of the arginine pathway carbamoylphosphate synthase of Saccharomyces cerevisiae by specific and general controls of amino acid biosynthesis. The synthesis of the arginine pathway carbamoylphosphate synthase (CPSase A) of Saccharomyces cerevisiae is subject to two control mechanisms. One mechanism is specific for CPSase A and is exerted by arginine; it probably involves a repressor-operator type of interaction. This "specific" mechanism regulates the expression of gene cpaI coding for the small "glutaminase" subunit of CPSase A but has little influence on the production of the large subunit of the enzyme, a product of gene cpaII. This large component, which alone has no biological significance, accumulates freely under conditions of arginine repression. The second mechanism is general: it controls enzyme synthesis in a number of amino acid biosynthetic pathways in addition to the arginine sequence. Two types of evidence that this "general" mechanism participates in the control of CPSase A synthesis are presented: (1) Derepression upon starvation for any amino acid of which the synthesis is subject to this general control; and (2) repression during growth in amino acid-rich medium. In contrast to the specific mechanism, the "general" mechanism regulates the expression of both the cpaI and cpaII genes.


Disturbance of tryptophan metabolism and its correction during oestrogen treatment in postmenopausal women. A relative pyridoxine deficiency was found in all of 12 women using conjugated oestrogens unopposed by progestagsns. This was due to disturbed tryptophan metabolism, expressed in increased xanthurenic acid (XA) excretion (greater than or equal to 60 mumol/8 h) during 8 h following oral administration of 2 g L-tryptophan. The intake of synthetic oestrogens such as ethinyl oestradiol has already been found to lead to a disturbance of tryptophan metabolism and to a deficiency of vitamin B6. Now we have evidence that this is the case not only in women taking oestrogens in oral contraceptives but also as replacement therapy during the postmenopause. This disturbance is clear after 1 yr of oestrogen treatment. Xanthurenic acid excretion was only slightly increased in 3 women who used progestagens in high dosages at the same time. The biochemical changes induced could easily be corrected by administration of vitamin B6. Our cyclic treatment regimen now consists of 25 days of oestrogens per month. In the remaining days a 250 mg tablet per day of vitamin B6 is prescribed.


The effect of long-term oestrogen treatment on the development of osteoarthrosis at the small hand joints. The effect of long-term oestrogen treatment of at least 5 yr on the development of osteoarthrosis was studied in 48 postmenopausal women. Osteoarthrosis at the hand joints was graded according to Kellgren's criteria, using hand X-rays. Data obtained in a normal population of 155 women served as controls as well as data obtained in 24 postmenopausal women who didnot receive oestrogen replacement therapy. No significant difference in osteoarthrosis between the treated and non-treated groups was found. The development of osteoarthrosis at the hand joints seems to be independent of the hormonal status in postmenopausal women.


Effect of postmenopausal estrogen therapy on diastolic blood pressure and bodyweight. The effect of two forms of exogenous estrogen and a placebo on diastolic blood pressure and bodyweight was evaluated in 50 oophorectomized women. There was no significant change in bodyweight on any form of treatment, nor was there any significant elevation in mean diastolic blood pressure. However, 2 out of 49 females on conjugated estrogen showed a marked elevation of the diastolic blood pressure. It is therefore recommended that all women on exogenous estrogen treatment have their blood pressure checked at least once every 6 months. Provided this precaution is observed, changes in bodyweight or diastolic blood pressure need not be considered as potential disadvantages in the evaluation of indications for long-term estrogen treatment.


Psychosomatic aspects of the effect of conjugated estrogens in patients with postoperative ovarian deficiency syndrome. Fifty-three uterine cancer patients who complained of the syndrome dur to vasomotor manifestations or psychosomatic response after ovariectomy were given Premarin tablets, 1.25 mg per day or placebo for 3 weeks and improvement in their complaints was compared from the psychosomatic aspects by the double-blind method. Premarin was significantly more effective than placebo (P less than 0.001) in the psychologically normal patients. On the other hand, no difference in the effectiveness of these drugs were found in the psychologically abnormal patients (P = 0.119). According to the self evaluation by the patients, Premarin was significantly more effective than placebo (P less than 0.05) in the psychologically normal patients. However, there was no difference in the effects of these agents in the psychologically abnormal patients.


[Electron microscopic preparation of DNA on uncharged carbon films (author's transl)]. DNA is adsorbed with densities sufficient for electron microscopy on thin uncharged carbon films. Superhelical SV 40 DNA remains superhelical on the supporting film on the contrary to the relaxation of DNA on films treated with alky dimethylbenzyl ammonium chloride (BAC). The number of superhelical turns increases to the two- or threefold of the value in solution. Investigations with a structural resolution below 1nm are possible with this preparation method.


Hypothesis:presynaptic receptors controlling renin release. Presynaptic receptors have recently been identified on nerves supplying vascular smooth muscle. Renin is stored in juxtaglomerular cells in the wall of the afferent glomerular arteriole and the JG cell is probably derived from vascular smooth muscle. Nervous stimuli exert an important influence on release of renin, but the nature of the receptors involved is not agreed. We propose that there are presynaptic receptors associated with the JG apparatus as with vascular muscle and that a mechanism of this sort gives a better account of data on renin release.


Sources of energy for the brain and physical dependence on ethanol. This paper describes a proposed biochemical mechanism to account for physical dependence on ethanol. Long-term exposure to a continuous and plentiful supply of ethanol-derived hydrogens in NADH and ethanol-derived acetyl-CoA (AcCoA) may lead to a decreased rate of production of endogenous hydrogens in NADH and endogenous AcCoA in compensation. It is proposed that physical dependence on ethanol occurs when ketolytic- and glycolytic-based NADH and AcCoA synthetic rates fall below the rate of utilization by the brain; the brain then "depends" on alcohol-derived NADH and AcCoA for normal function.


Increased resistance to influenza as a possible source of heterozygote advantage in cystic fibrosis. Cystic fibrosis is the most common lethal or semi-lethal genetic disease in Caucasians of Central European origin, among whom it is inherited as an autosomal recessive trait at a frequency approximately 10 times that expected from recurrent mutation alone. A decreased sialic acid content has been observed in cell surface glycoproteins on cystic fibrosis fibroblasts and in numerous soluble glycoprotein preparations from cystic fibrosis homozygotes. Sialic acid residues on cell surface glycoconjugates play an essential role in the binding and infectivity of myxoviruses and paramyxoviruses, including those causing pandemic influenza. It is suggested that increased resistance to these viruses conferred by similar but quantitatively smaller alterations in sialoglycoconjugate structure in cystic fibrosis heterozygotes may have provided a selective advantage to maintain the high frequency of the cystic fibrosis gene in Caucasian populations.


Enterotoxins of Escherichia coli and epilepsy. Evidence exists that cyclic nucleotides play an important role in the stabilisation of developing synapses during the early postnatal period, and later on participate in the generation of the slow excitatory and inhibitory postsynaptic potentials. It is postulated that enterotoxins of Escherichia coli, due to their long-lasting and specific action on cyclic nucleotide-dependent processes, provide a unique mechanism for selective impairment of synaptogenesis in the abscence of cell loss. Therefore it seems possible that early enteritis, when caused by certain pathogenic strains of Escherichia coli, might be an aetiological factor in the genesis of idiopathic epilepsy.


Evidence for an aetiological role for adenovirus type 7 in the mesenteric adenitis syndrome. Previous research has established the relationship between viral infection with adenovirus, influenza B virus and Coxsackie B virus, and mesenteric adenitis. A prospective controlled survey of the incidence of viral infection in mesenteric adenitis was undertaken in children attending a children's hospital over a period of 13 months. Eighteen patients, together with 18 controls who were matched for age, sex, and date of presentation, were studied. There were five cases of adenovirus type 7 infection in the mesenteric adenitis group and none in the control group (P=0.023--Fisher's exact test). The clinical problem at presentation is in differentiating mesenteric adenitis from appendicitis. If further work shows that viral infection is indeed more common in mesenteric adenitis, and is limited to a narrow range of viruses, then rapid identification of these viruses in children with "acute abdomens" would be a valuable aid to differential diagnosis.


[Computerized tomographic localization of insulinomas (author's transl)]. Computerized  tomographic localization of insulinomas utilises the differences in radiodensity between the tumor and the adjacent pancreatic tissue. With the aid of this new technique four insulinomas have been localized preoperatively. All of the tumors had the same radiodensity. Firm, well encapsulated beta-islet-cell tumors were detected with the same ease as an insulinoma, which was soft and almost without encapsulation. The smallest tumor detected was 1.0 cm in diameter. Of the four insulinomas, localized by computer tomography of the body, only one was also detected angiographically and only two were detected sonographically.


Lymphotropic papovaviruses isolated from African green monkey and human cells. A lymphotropic papovavirus was isolated from a lymphoblastoid cell line of African green monkey (AGM) cells which also contained a herpesvirus and a paramyxovirus-like agent. The papovavirus was analyzed by restriction endonuclease cleavage; its biochemical and serological crossreactivity with SV40 and host range have been determined. Thus far, only B-lymphoblasts of primate and human origin have been found to be susceptible to infection. Although more than 50% of the tested monkey sera were reactive with antigens of this virus, all human sera tested failed to react. Cleavage patterns and hybridization studies with the viral DNA indicate that the virus represents a novel member of the papovavirus group that is characterized by its lymphotropic host range. Papovavirus particles were also demonstrated in a human lymphoblastoid cell line (CCRF-SB) originally derived from a leukemic child. These cells revealed nuclear fluorescence when tested with human sera, but failed to react with AGM sera. Although characterization of this agent has not yet been completed, available evidence suggests that it represents another lymphotropic papovavirus which seems to be spread within the human population.


Further studies of antibody levels to Herpes simplex virus, cytomegalovirus, measles virus, and adenovirus type 5 in Burkitt's lymphoma patients. Sera collected from Burkitt's lymphoma (BL) patients before and after tumor manifestation were tested for antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), measles virus (MV) and adenovirus type 5, using the immunofluorescent (IF) techniques in all instances except for MV where complement fixation (CF) was used. It was found that none of these viruses showed higher antibody levels in BL patients than in controls, either before or after the appearance of the tumor. The patients came from the West Nile District of Uganda.


The location of SV40 specific sequences in the heterogeneous nuclear RNA of transformed mouse cells. Rapidly labelled nuclear RNA from an SV40 transformed mouse 3T3 line was isolated, and different molecular size classes pooled. The fractions were treated with Ehrlich ascites exonuclease III for various lengths of time, and the digestion of the 3' ends of the RNA measured by the appearance of TCA-soluble material. The resulting partially degraded RNA populations were then hybridised to SV40 DNA. The data suggest that a high proportion of the viral specific sequences are located near the 3' ends of heterogeneous nuclear RNA.


Purification and properies of cAMP dependent and independent histone kinases from human leukocytes. Histone kinase activity was purified from human polymorphonuclear leukocytes by ammonium sulphate precipitation of a 180 000 x g supernatant, followed by DEAE-cellulose chromatography and gelfiltration. On DEAE-cellulose cAMP dependent kinase activity eluted in two peaks, I and III, at 1.2 mmho and 6.5 mmho, respectively. Catalytic subunit (C) from both peaks had Mr 33 000, 3.0S. Regulatory subunit (R) from peak I and III both had Mr 33 000 upon gelfiltration, but sedimented at 2.8--3.0S and 3.0--3.2S, respectively. R2 and R4 subunits were identified. The R-C dimer from peak I and III sedimented at 4.8S and (4.8)--5.1S, respectively. The holoenzyme from peak I had Mr 165 000, 6.7S, which suggest a R2C2 structure, while that of peak III sedimented at 6.7S, but eluted at Mr 330 000 (2R2C2) by gelfiltration. The Kmapp for peak I and III enzymes were, respectively: histone IIA 0.5 mg/ml (both forms), ATP 18 microM and 23 microM, and cAMP 5 X 10(-8) M and 6.3 x 10(-8) M. Both enzymes had pH optimum 6.7--6.9 and were equally sensitive to Ca2+, temperature and protein kinase inhibitor. The substrate specificity was histone VS greater than histone IIA = histone VIS greater than casein greater than phosvitin. Peak I enzyme, but not peak III enzyme, was dissociated by histone and high ionic strength and reassociation of R and C subunits were facilitated by ATP-Mg. It is concluded that peak I and III enzymes represent type I and II cAMP dependent protein kinases, respectively. Type I comprises 20--30% of cAMP dependent protein kinase activity and is absent from the 180 000 x g supernatant of gently disrupted cells. Purified catalytic subunit had Kmapp (ATP) 20 microM with rabbit muscle glycogen synthease I as substrates. Synthase I from rabbit muscle and human leukocytes were phosphorylated by catalytic subunit to synthase D (ratio of independence less than 0.07). cAMP independent histone kinase activity eluted in one peak (Peak II) at3 mmho. The enzymatic activity sedimented at 3.4S and eluted from gelfiltration with Mr 78 000. Kmapp for ATP was 78 microM and for histone IIA 0.5 mg/ml. The enzyme was sensitive to temperature, but less sensitive than cAMP dependent protein kinase to Ca2+, and insensitive to protein kinase inhibitor. The substrate specificity was histone IIA greater than histone VS = histone VIS, while casein and phosvitin were poor substrates. Glycogen synthase I was not phosphorylated. The cAMP independent histone kinase activity comprised 15% of the total histone kinase activity in a crude homogenate of leukocytes. Its physiological substrate is unknown.


Determination of phosphodiesterase activity in the presence of phosphomonoesterase using bis-p-nitrophenyl phosphate. In the presence of phosphomonoesterase contaminations the use of bis-p-nitrophenyl phosphate to measure phosphodiesterase activity gives inconclusive values because one of the products of the phosphodiesterase or nuclease reaction becomes a substrate of the contaminating enzyme. A direct determination of the hydrolyzed phosphodiesterase substrate in the UV range is possible at the isosbestic points of the transformation of the phosphomonoesterase substrate.


The glucocorticoid domain of response: measurement of pleiotropic cellular responses by two-dimensional gel electrophoresis. In this article, we have provided two examples of pleiotropic regulation by specific effector molecules as assayed by two-dimensional gel electrophoresis. In one case, catabolite repression in the bacterium Escherichia coli was examined by measuring the response to cyclic cAMP. In the other, the effect of dexamethasone on the rate of synthesis of over a thousand cell proteins was analyzed in HTC cells. It was found that in E. coli, cAMP regulates the synthesis of about 10 percent of the cell's proteins; both inductions and repressions are observed, but inductions clearly predominate. In HTC cells, dexamethasone induces the synthesis of seven proteins, or about 0.7 percent of the total cellular proteins; repression was not consistently observed. In another rat hepatoma line (FAZA) a similar number but essentially different set of proteins was induced. These data are discussed in terms of the notion of domains of response originally proposed by TOMKINS [1].


Regulation of mouse mammary tumor virus gene expression by glucocorticoid hormones. Several laboratories have documented that glucocorticoid hormones markedly stimulate the expression of mouse mammary tumor virus genes in a variety of mouse mammary tumor cells and in infected heterologous cells. The effect of the hormone appears to be a rapid and specific augmentation of the synthesis of viral RNA, mediated by interaction with glucocorticoid receptor proteins. The availability of virus-specific reagents and recent developments in the molecular biology of RNA tumor viruses now permit a highly refined analysis of hormonal regulation in this experimental system.


Influences of adrenocortical hormones on pituitary and brain function. Adrenocortical secretions influence neuroendocrine function and behavior, and it is possible to recognize separate physiologic actions of gluco- and mineralocorticoids. The search for neuroanatomical sites and cellular modes of adrenocorticoid action has revealed a system of putative glucocorticoid receptors in neurons of the hippocampus, septum, amygdala, and entorhinal cortex, and in the pituitary. No part of the brain is totally devoid of receptor activity, however, and glial cells may also contain glucocorticoid receptors. Mineralocorticoid receptors are less well characterized neuroanatomically or biochemically. One reason for this is the considerable degree to which both gluco- and mineralocorticoids bind to both classes of receptors in vitro. Another reason may be the overwhelming quantitative predominance of glucocorticoid over mineralocorticoid receptors in neural tissue. Glucocorticoid receptors of the pituitary, which have a high avidity for dexamethasone, appear to participate in the delayed negative feedback effects of glucocoticoids. Functional correlates of neural glucocorticoid receptors remain to be clearly established. Among the possibilities are several reported effects on hippocampal neural activity that have an onset latency of 20--30 min and a duration of several hours. The relative rapidity of such effects does not preclude genomic mediation, as genomic effects of glucocorticoids on thymus lymphocytes have been detected within as little as 15 min of steroid application [117]. What are not so far explained by the intracellular receptor mechanism are the extremely rapid effects of glucocorticoids such as the rate-sensitive negative feedback on CRF and ACTH secretion. These may involve a direct action of the steroid on cell membranes in the pituitary and hypothalamus.


Inhibition of glucose transport in fat cells and activation of lipolysis by glucocorticoids. The major effects of glucocorticoids on white fat are shown in Fig. 1. The glucocorticoid diffuses into the cytosol of fat cells where it binds to a soluble receptor. The steroid-receptor complex then enters the nucleus where RNA synthesis is increased. The next step may be a selective increase in synthesis of protein(s). In any event, there is an inhibition of the membrane-bound glucose transport system and an increase in the ability of lipolytic agents to activate triglyceride lipolysis. There is also a decrease in phosphoenolpyruvate carboxykinase, lipoprotein lipase, and fatty acid synthetase that occurs after a somewhat longer lag period than is required for inhibition of glucose transport or lipolysis activation. Whether these effects are independent or secondary to the glucose transport inhibition and lipolysis activation remains to be established.


[Vitamin D-metabolism and rickets (author's transl)]. By new methods Vitamin D metabolites can now be determined in small quantities of biological fluids. These methods have revealed further details about Vitamin D metabolism as well as the pathogeneses and therapy of the various types of rickets. A review of this topic will be presented.


[Urethrotomy of urethral strictures in adults (author's transl)]. The late results of optical "cold" urethrotomy so far have shown that this method of treatment of urethral stenoses and strictures of any type and location is superior to all other operative possibilities, the more so as the operation, carried out under local anesthesia, scarcely distresses the patient and he can easily recover. The danger of secondary injury is certainly reduced by the optical control yet bleeding may occasionally occur later. It should also be borne in mind in making the indication that with a relatively narrow urethra a high degree of iatrigenic scar stricture may develop. Relapses (ca. 12 to 47%) occur relatively seldom compared with other procedures. The relapse rate is affected by chronic urinary tract infections, the nature and duration of subsequent indwelling catheter treatment and the length and severity of the stricture.


Survival of apurinic SV40 DNA in the d-complementation group of xeroderma pigmentosum. The survival of depurinated Form I SV40 DNA was studied in normal human fibroblasts and in D-complementation Xeroderma pigmentosum (XP) fibroblasts. Survival was measured with an infective center assay. Heat-acid and methyl methanesulfonate (MMS) were used as depurinating agents. After 3 hrs of depurination by heat--acid treatment, infectivity in normal cells was less than 15% of the controls compared to more than 50% for the XP D cell strains. Similar results were obtained with MMS-treated DNA. These results are contrary to expectation since apurinic endonuclease activity, which is presumed to be involved in the repair of apurinic sites, is much lower in XP D cell strains than in normal cell strains. Our results indicate that another mechanism for the repair of apurinic sites could exist.


Increase in lipoprotein lipase during clofibrate treatment of hypertriglyceridemia in patients on hemodialysis. In 11 hypertriglyceridemic patients on hemodialysis, clofibrate (1 to 1.50 g per week) reduced plasma triglyceride (-40 +/- 20%, P less than 0.001), very-low-density-lipoprotein triglyceride (-44 +/- 20%, P less than 0.001) and very-low-density lipoprotein cholesterol (-39 +/- 25%, P less than 0.01), and it increased high-density-lipoprotein cholesterol (82 +/- 106%, P less than 0.005). Low pretreatment lipoprotein-lipase activity in adipose-tissue specimens and postheparin plasma increased to normal with clofibrate, whereas low hepatic triglyceride lipase activity did not change. The reduced very-low-density-lipoprotein triglyceride correlated with the increased lipoprotein-lipase activity in adipose tissue (rs = 0.792, P less than 0.02, n = 8) and postheparin plasma (rs = 0.851, P less than 0.02, n = 8), whereas increased high-density-lipoprotein cholesterol correlated with changes in this activity in adipose tissue (rs = 0.696, P less than 0.06) and post-heparin plasma (rs = 0.679, P less than 0.10). There was no correlation between changes in hepatic triglyceride lipase activity and plasma lipids during treatment. Reduced lipoprotein-lipase activity may cause hypertriglyceridemia and decreased high-density-lipoprotein cholesterol in patients on hemodialysis; clofibrate may correct these abnormalities by increasing lipoprotein-lipase activity to normal.


Increased endoneurial fluid pressure in galactose neuropathy. Edema and increased endoneurial fluid pressure developed in peripheral nerves of rats that received a diet containing 40% galactose during a study of the role of sugar alcohols in producing neuropathy. Fluid pressure was elevated starting in the third month and progressed to a fivefold increase over control values by the fifth month. Microscopic examination confirmed the presence of edema as predicted by the sorbitol theory, which is often invoked to explain the pathogenesis of diabetic neuropathy.


Activation of suppressor T cells during Epstein-Barr-virus-induced infectious mononucleosis. Infectious mononucleosis is caused by the Epstein-Barr virus (EBV), an unusual human pathogen because it preferentially infects B lymphocytes and consequently activates them to produce immunoglobulins. When cultures of lymphocytes from patients with infectious mononucleosis were stimulated with polyclonal activators, unseparated cells failed to produce immunoglobulins, whereas purified B cells responded normally. Cocultures demonstrated profound suppressor T-cell activity in blood from patients with infectious mononucleosis. Early in this disease, circulating immunoglobulin-secreting cells were elevated, but during the second week their number was strikingly depressed. These data indicate that during infectious mononucleosis, EBV causes polyclonal activation of B cells, reflected by hypergammaglobulinemia and increased circulating immunoglobulin-secreting cells. Next, suppressor T cells become activated and inhibit further B-cell activation. Thus, activation of suppressor T cells in infectious mononucleosis provides a unique additional mechanism of host defense because these T cells inhibit the activation and proliferation of an important target of the causative virus.


Treatment of denervated muscle by gangliosides. Short-duration cooling of the nerve to the extensor digitorum longus muscle of the rat in vivo induced partially reversible denervation of the muscle and atrophy in the type 2 muscle fibers. Increases in cyclic adenosine monophosphate, cyclic guanosine monophosphate phosphodiesterase, adenylate cyclase, and guanylate cyclase were observed in the denervated muscle. Treatment with gangliosides of the bovine brain cortex seemed to improve the excitability of the surviving motor units and to encourage recovery of neuromuscular trophic control, but it did not affect the nerve conduction velocity or the contractile properties of the denervated muscle.


Studies on a strain of Fusarium solani (Mart.) Sacc. Isolated from a case of mycotic keratitis. A strain of Fusarium solani (Mart.) Sacc. (IMI-216517), isolated from a patient of mycotic keratitis, produced experimental keratomycosis in albino rabbit cornea and survived in internal tissues of albino mice for varying periods. Alantolactone, isolated from the plant - Inula racemosa Hook. f. exhibited marked in vitro fungistatic activity against this strain of F. solani at 100-200 microgram/ml concentrations. The strain was less sensitive to amphotericin B and showed more acid than alkaline proteinase and phosphatase activities.


[Effect of tin on rats. 1. Inverse voltammetric determination of tin in the presence of lead in biological material after extraction]. By means of inverse polarography, the authors determined tin selectively after double extraction with diethylammonium diethyl dithiocarbamate (DADDTC) in perchloric solution. The recovery rates were: in potatoes, 91.7 +/- 5.8%; in beef kidney, 85.0 +/- 22.7%; in beef liver 79.9 +/- 13.8%; and in milk, 69.8 +/- 11.4%. Possible interferences from other elements with the tin determination are discussed.


Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. The RNAs of seven replication-defective leukaemia virus (DLV) strains contain three types of unique sequences, which correlate with the capacity of a given virus strain to transform erythroblasts, macrophage-like cells and myeloblasts, respectively. These sequences, termed erb, mac and myb, have their counterparts in the normal DNA of avian and mammalian species. Our results indicate that DLVs represent recombinants between a common 'vector' related to a chicken endogenous virus and one of three types of cellular gene possibly involved in haematopoietic differentiation.


T4 DNA topoisomerase: a new ATP-dependent enzyme essential for initiation of T4 bacteriophage DNA replication. A novel ATP-dependent DNA topoisomerase which makes reversible double-strand breaks in the DNA double helix has been purified to near homogeneity from T4 bacteriophage-infected Escherichia coli cells. Genetic data suggest that this activity is essential for initiating T4 DNA replication forks in vivo.


Combined effects of adrenaline and insulin on active electrogenic Na+-K+ transport in rat soleus muscle. Both beta 2-adrenoreceptor stimulants (such as adrenaline and salbutamol) and insulin can increase active Na+-K+ transport and hyperpolarise skeletal cells. Thus, adrenaline and insulin, which are otherwise antagonistic regulators of several metabolic processes, have one action in common, namely, stimulation of active ion translocation. This is especially interesting as cyclic AMP stimulates Na+-K+ transport, whereas a lowering of the cytoplasmic concentration of cyclic AMP has been proposed as an early signal in the action of insulin. Here we report the results of experiments in which the active Na+-K+ transport and membrane potential (EM) of rat soleus muscles were studied during the action of supramaximal doses of insulin and beta 2-adrenoreceptor stimulants, alone and in combination. We conclude that the stimulant action of insulin on active electrogenic Na+-K+ transport is unlikely to be evoked by a lowering of the intracellular concentration of cyclic AMP.


A different genetic code in human mitochondria. Comparison of the human mitochrondial DNA sequence of the cytochrome oxidase subunit II gene and the sequence of the corresponding beef heart protein shows that UGA is used as a tryptophan codon and not as a termination codon and suggests that AUA may be a methionine and not an isoleucine codon. The cytochrome oxidase II gene is contiguous at its 5' end with a tRNAAsp gene and there are only 25 bases at its 3' end before a tRNALys gene. These tRNA'S are different from all other known tRNA sequences.


Pharmacological characteristics of beta-adrenoceptor binding sites in intact and sympathectomized rat spleen. [3H]-(--)-Dihydroalprenolol ([3H]-DHA) binds to rat spleen membranes with a dissociation equilibrium constant (KD) of about 0.7 nM and a maximal number of binding sites of 272 fmoles x mg protein-1. Approximately 90% of the sites labelled by 1 nM [3H]-DHA possess classical properties of beta-adrenoceptors. The labelled ligand is stereospecifically displaced by the isomers of propranolol and the order of potency of agonists is: isoprenaline greater than adrenaline greater than noradrenaline. Highly selective beta 1 antagonists such as practolol and atenolol displaced [3H]-DHA from spleen membranes in a biphasic manner indicating the co-existence of beta 1 and beta 2 sites (30--35% beta 1; 65--70% beta 2) in this tissue. Support for this classification was provided by the binding of the beta 2 agonist procaterol to spleen membranes. This drug possessed high affinity only for those sites that have low affinity for the beta 1 selective agents. Chemical sympathectomy induced by chronic 6-hydroxydopamine administration did not alter the number or the pharmacological properties of beta-adrenoceptor binding sites. The results suggest that both beta 1 and beta 2 adrenoceptors are probably postsynaptic in spleen.


Metabolism of red blood cells in chronic renal failure. I. Glycolytic enzyme levels. This paper starts a series on red blood cell (RBC) metabolism in patients with chronic renal failure (CRF). The glycolytic enzyme levels and in vitro half-lives of these patients' RBCs were determined. A number of enzymes (hexokinase, glucose-6-phosphate isomerase, fructose-6-phosphate kinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase) showed higher activities than in normal control RBCs. Other enzyme activities were normal. These results were discussed and several possible mechanisms considered. We favour the point of view of a shortened life span of the RBCs in CRF, making the most unstable enzymes of the glycolytic sequence appear increase as compared with normal controls.


Collagenase activity of rat kidney with glomerulonephritis is inhibited by erythromycin. Collagenolytic activity of rat kidney with glomerulonephritis (GN) of Masugi's type was determined by a series of biological experiments. The determination was carried out during the heterologous phase of the disease together with inhibition studies in vivo and in vitro. Erythromycin has been tested in vivo for its inhibitory activity and an activity of collagenase was found in untreated rats with GN only, the panel treated with erythromycin did not show any collagenolysis. Statistical calculations indicate the significance of the inhibition (p less than 0.001). In addition, kidneys of test animals with GN have been investigated for their enzymatic activity and the inhibition by erythromycin in vitro where the kidneys failed to show collagenolytic activity. It can be concluded that erythromycin is able to inhibit in vivo and in vitro the activity of the collagenolytic enzyme produced by polymorphonuclear leukocytes during the heterologous phase of the nephritis, an effect which leads to the recovery of the physiological equilibrium of the protease and its inhibitor.


Influence of theophylline on concentrations of cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate of rat brain. The influence of theophylline (2.5--100 mg/kg p.o.) on cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) in brain of Sprague-Dawley rats (0.5--3.0 hr after administration of theophylline) was investigated. It was found that theophylline increases cAMP and cGMP levels when administered in a dose of 25 mg/kg or higher. A significant decrease of cGMP level was observed after administration of 10 mg/kg. The results of this study suggest that the influence of theophylline on cyclic nucleotide levels of rat brain is the result of two factors: (a) inhibitory properties of theophylline on cAMP and cGMP phosphodiesterases and (b) competition of theophylline with adenosine.


Effect of intraventricular histamine on hormone secretion in dogs. In pentobarbital-anesthetized dogs, infusion of a low dose of histamine directly into the third ventricle increased plasma ACTH concentration. The increase was unaffected by metiamide, a drug which blocks H2 receptors, but was abolished by mepyramine, a drug which blocks H1 receptors. Mepyramine alone did not produce a decrease in plasma ACTH concentration in stressed dogs. Infusion of the H1 agonist 2-methylhistamine increased plasma ACTH concentration, whereas infusion of the H2 agonist 4-methylhistamine decreased plasma ACTH concentration and blocked the response to surgical stress. Histamine, 2-methylhistamine and 4-methylhistamine had no statistically significant effect on plasma renin activity, blood pressure, or heart rate, and histamine had no effect on plasma prolactin concentration. There were no consistent, specific effects on growth hormone secretion. We conclude that activation of central H1 receptors increases ACTH secretion in dogs, and that activation of central H2 receptors decreases ACTH secretion. Some of the reported effects of cyproheptadine and other drugs on ACTH secretion may be due to their antihistamine activity.


Effects of neonatal hydrocortisone treatment of pituitary and adrenocortical response to stress in young rats. Administration of corticosteroids to rat pups within the first several days of life results in retardation of several behavioral, neurophysiological, and biochemical developmental patterns. At 25 days of age, animals treated neonatally with 1.0, 0.5, or 0.1 mg hydrocortisone acetate showed dose-dependent decreases in plasma ACTH following 2.5 min continuous exposure to ether. On day 20, plasma corticosterone values did not differ between these groups 15 min after ether stress, but lower values were seen 60 min after ether in animals treated at birth with 0.5 mg hydrocortisone. At 45--48 days of age, hydrocortisone-treated animals exposed to one of 2 different stressors showed decreased plasma corticosterone response to stress; females had lower corticosterone levels following both stressors, while males showed suppressed corticosterone levels following exposure to the mild (novelty) but not to the intense (ether) stress. These data demonstrate that neonatal exposure to hydrocortisone results in decreased CNS-pituitary responsivity to stress at 20--25 days of age, and that the adrenocortical response to stress in impaired at 45--48 days of age.


Overnight sleep EEG and cerebrospinal fluid monoamines in seizures induced by movement. Clinical, electrical and biochemical studies in an eight years old boy with movement-induced seizures were reported. The attack was usually triggered by sudden initiation of movement, but rarely occurred without any apparent movement. Repeated jumping provoked attacks constantly, which was recorded cinematographically. No abnormality was found either in ictal or interictal EEGs. Haloperidol aggravated the condition, but 1-DOPA had no effect, while DPH (100 mg/day) controlled attacks perfectly with the serum DPH concentration of just 2.0 ug/dl. In overnight sleep analysis, sleep rhythms and characters of REM sleep were not differed significantly from the standard. After DPH therapy, stabilization of sleep in general was noticed; that is, total sleep time prolonged, number of sleep stages decreased and interrupting awakening disappeared. Probenecid loading test revealed that 5-HIAA was normal, HVA high, and large amount of octopamine was detected in CSF.


High density lipoprotein cholesterol and other serum lipids in New Zealand Maoris. The pattern of fasting serum lipids, with emphasis on high density lipoprotein cholesterol, and the relationship of the lipids with each other and with other risk factors is examined in a population based sample of New Zealand Maoris. There are no sex differences in the distribution of total cholesterol and cholesterol fractions but triglycerides are higher in men. High density lipoprotein cholesterol levels are lower in Maoris than reported in other populations. High density lipoprotein cholesterol is negatively correlated with low density lipoprotein cholesterol but not associated with total cholesterol. High density lipoprotein cholesterol is negatively correlated with body mass index and in men high density lipoprotein cholesterol levels are higher in current alcohol drinkers. The possible relationship between the low levels of high density lipoprotein cholesterol and the high risk of coronary heart disease in Maoris requires investigation.


Trigeminal neuralgia: an overview.

Trigeminal neuralgia: an overview. Facial pain is a perplexing problem confronting all who practice the healing arts. The purpose of this article is to concentrate on one aspect of facial pain--trigeminal neuralgia. An overview of this entity is presented by demonstrating current concepts in its etiology, diagnosis, and treatment. Classically, trigeminal neuralgia has been described as a paroxysmal, lancinating, knifelike pain which is limited to the anatomic pathways of the fifth cranial nerve. It is a chronic facial pain that is amenable to medical and surgical treatment when correctly diagnosed. A knowledge of the anatomy of the fifth cranial nerve is essential for a correct diagnosis of trigeminal neuralgia. A description of the anatomy is not within the scope of this article, and the reader is referred to any of the standard anatomy textbooks for review.


The effects of abdominal loading on rib cage distortion in premature infants. The action of the diaphragm in inspiration is to decrease intrathoracic pressure and raise abdominal pressure, which elevates the rib cage. In the supine position, the rise in abdominal pressure is smaller because of the lack of abdominal muscle tone. In premature infants the inward pull of the diaphragm on the very compliant ribs causes inward movement on inspiration (ie, distortion) which is exacerbated by the lack of intercostal muscle activity during rapid eye movement (REM) sleep, their predominant state. We raised abdominal pressure by means of an inflatable cuff in 12 newborn infants (gestation 28 to 40 weeks) to try to improve inspiratory coupling of the rib cage and diaphragm. There was no significant change in minute ventilation, indicating no ventilatory impairment. In all studies in which there was distortion, abdominal loading produced a reduction or abolition of distortion (P less than .01). Abdominal loading may be useful in reducing diaphragmatic activity in premature infants.


Granular cell tumors of the tongue.

Granular cell tumors of the tongue. We have presented a series of 19 new cases of granular cell tumors of the tongue. This benign condition is often difficult to diagnose if an adequate biopsy specimen has not been obtained. Insufficient biopsy material that includes only the overlying pseudoepitheliomatous hyperplasia may distort the pathologic picture. Review of frozen sections should provide an accurate diagnosis, and local surgical excision should resolve the problem completely.


Malignant fibrous histiocytoma of the maxillary sinus. A malignant fibrous histiocytoma from the maxillary sinus of a 51-year-old woman was treated surgically with adjuvant chemotherapy and radiation. The maxillary sinus is an unusual site for this rare and controversial neoplasm, as a review of the literature shows.


Diagnosis of juvenile nasopharyngeal angiofibroma by computed tomography. Juvenile nasopharyngeal angiofibroma is a highly vascular neoplasms that tends to spread in the various fissures and foraminia of the nasopharynz. Polytomography and angiography have added greatly to the diagnosis and management of this tumor through accurate preoperative assessment. Computed tomography has given an additional sophisticated, precise method for evaluating the extent of juvenile nasopharyngeal angiofibroma. Computed tomography shows, in detail, the extension of the tumor into the pterygopalatine fossa with widening of the pterygopalatine fossa and anterior bowing of the posterior wall of the maxillary sinus. With this correct information about tumor location, surgical or radiation treatment can be appropriately planned, with a probable improvement of cure rates and reduction of recurrences.


The diagnosis of insulinoma in a child in the absence of fasting hyperinsulinemia. This report concerns an 8-year-old girl with fasting hypoglycemia caused by a functional islet cell adenoma. During two separate fasting studies the blood glucose concentrations decreased to abnormally low levels yet the serum concentrations of insulin were consistently within the accepted range of normal. This report illustrates the diagnostic value of three simple functional tests--the inhibitory effect of insulin on ketogenesis and on glycogenolysis and the stimulatory effect of leucine on insulin secretion.


Triglyceride and cholesterol concentrations in whole serum and in serum lipoproteins in Reye syndrome. Triglyceride and cholesterol concentrations in whole serum and in the serum lipoprotein fractions were measured during the course of hospitalization in six patients with Reye syndrome, four of whom survived. Very low density lipoprotein (VLDL) triglycerides were significantly lower on admission than on the last day of hospitalization. However, no VLDL triglyceride value was below the normal range. Triglyceride transport was increased in low density lipoprotein (LDL) and high density lipoprotein (HDL) fractions. LDL and HDL cholesterol concentrations were low on admission and decreased further during hospitalization. The changes in LDL and HDL cholesterol concentrations were more severe among nonsurvivors. No HDL cholesterol was detected in nonsurvivors on the last day of hospitalization. These results suggest that decreased VLDL triglycerides may not play an important role in the development of fatty liver and that decreased LDL and HDL cholesterol concentrations may be of prognostic value in Reye syndrome.


[The treatment of Cushing's syndrome by selective excision of pituitary adenoma. 3 cases (author's transl)]. In three patients suffering from Cushing's disease, exploration revealed an enclosed pituitary adenoma in one case and a microadenoma in two cases. Selective excision via a transphenoidal approach resulted in cure of Cushing's disease as reflected by complete regression of clinical signs and the restoration of circadian rythm of cortisol. Regular follow-up over a period of more than two years showed the persistence of normal regulation of the corticotrophic sector of the pituitary.


[Acetylcholine receptors (author's transl)]. The actions of acetylcholine can be classified as nicotine-like or muscarine-like. Nicotinic actions of acetylcholine are seen at the skeletal neuromuscular junction and at autonomic ganglia whereas muscarinic transmission occurs at parasympathetic effector organs and in the brain. The sites on the membrane surface of a neuronal cell body or dendrite where acetylcholine acts is called a receptor site. There has been marked progress in the last few years in the identification and quantification of acetylcholine receptors by biochemical methods by means of specific radioactive ligands of very high activity and very high affinity for these receptors. Using these techniques it has been possible to: determine the regional distribution of nicotinic and muscarinic receptors in the brain, evaluate new drugs acting on these receptors, and determine the concentration of these receptors in neurologic disorders.


Electron microscopic mapping of proteins bound to herpes simplex virus DNA. Exonuclease digestion experiments have suggested that there is a protein(s) bound close to one or both ends of herpes simplex virus-1 (HSV) DNA. The existence of such bound proteins has been positively demonstrated and their positions on the HSV genome determined by application of a newly developed method for electron microscopic mapping of proteins bound to nucleic acids. Purified HSV DNA was treated with dinitrofluorobenzene under conditions that covalently attach the dinitrophenyl (DNP) group to the proteins in a protein-nucleic acid complex. The HSV DNA-protein-(DNP)n complex was treated with rabbit anti-DNP IgG, and, in some cases, additionally treated with monovalent Fab fragments of goat anti-rabbit IgG, and mounted for examination in the electron microscope. Electron opaque dots representing the protein-(DNP)n-(IgG)m complex were seen on the HSV DNA. Direct measurements of the positions of the protein, as well as partial denaturation mapping, indicate that there are four positions for protein bound to HSV DNA: two near but not at the two ends and two at sites corresponding to the internal inverted repeats of the ends. These results suggest that there is a specific protein binding sequence within the direct terminal repeat of HSV DNA. The previous observation that HSV DNA is more sensitive to digestion by a 3' than by a 5' exonuclease then indicates that the bound protein(s) is more intimately associated with one strand of the specific sequence than with the complementary strand.


Nonhistone proteins HMG1 and HMG2 unwind DNA double helix. In a previous communication we have shown that both HMG1 and HMG2 nonhistone proteins change the DNA helical structure and the binding of HMG1 and HMG2 to DNA induces a net unwinding equivalent of DNA double helix (Javaherian, K., Liu, L. F. and Wang, J. C. (1978) Science, 199, 1345-1346). Employing melting absorption technique, we now show that in the presence of salt HMG1 and HMG2 destabilize DNA whereas in the absence of salt, they both stabilize DNA molecules. Consequently the folded structure of HMG must play an important role in melting DNA. Furthermore, by measuring topological winding number using competition unwinding experiments, we conclude that HMG1 has a higher affinity for a single-stranded DNA relative to double-stranded DNA. These results together suggest that HMG1 and HMG2 unwind DNA double helix by local denaturation of the DNA base pairs. The net unwinding angles have been measured to be 22 degrees and 26 degrees per molecule of HMG1 and HMG2 respectively.


Salt-and histone H1-induced structural changes of reconstituted minichromosomes. Structural changes of reconstituted SV 40 minichromosomes have been studied in relation to the salt concentration and addition of histone H1 by sedimentation and electron microscopy. Sedimentation data are represented as functions of the NaCl concentration and the Debye-Hückel electrostatic screening radius 1/alpha. The latter representation which proved to provide more information revealed three structural states of the SV 40 reconstitutes which can be additionally characterized by electron microscopy as follows: Expanded or relaxed conformation including free DNA spacers between the nucleosomes at low salt concentration (approx. 0.001 M-0.05 M NaCl), increasing condensation at moderate salt concentration (approx. 0.05 M-0.3 M NaCl) and expansion of this condensed state above approx. 0.3 M NaCl. The condensation of the reconstitutes at moderate salt concentration does not require the presence of histone H1. H1 seems to stabilize the condensed state against electrostatic expansion. The condensation might be promoted by salt-dependent conformational changes of naked superhelical DNA as revealed by sedimentation measurements.