Growth hormone and prolactin secretion in the carcinoid syndrome.

We evaluated plasma growth hormone (GH) and plasma prolactin (PRL) levels in ten patients with metastatic carcinoid tumors and the carcinoid syndrome ("active tumors") and seven patients with metastatic carcinoid tumors without the carcinoid syndrome ("inactive tumors"). The patients with active tumors had elevated serum serotonin levels and increased urinary 5-hydroxyindoleacetic acid (5-HIAA) while these values were normal in patients with inactive tumors. Forty-five per cent of patients with active tumors had elevated fasting plasma GH levels that were either not suppressed or showed a paradoxical increase in response to I.V. glucose. There was a positive correlation between the plasma GH levels and serotonin production by the tumor. Twenty-eight per cent of patients with inactive tumors had elevated fasting plasma GH levels. GH levels were decreased by the administration of serotonin antagonists in some but not all of the patients. Parachlorophenylalanine (PCPA) an inhibitor of serotonin synthesis caused a paradoxical rise in GH levels. GH release in response to insulin hypoglycemia was normal. Plasma prolactin levels were normal in most of the patients with metastatic carcinoid tumors. PCPA administration did not systematically alter plasma prolactin levels. We conclude that elevated plasma GH levels are frequently present in patients with the carcinoid syndrome. Both serotonin produced by the tumors and the tumor itself may be responsible for the elevated GH levels.


Dissociation of Na-K-ATPase specific activity and net reabsorption of sodium.

Prevoius studies have suggested that the increase in specific activity of Na-K-ATPase in renal tissue during treatment with glucocorticoids occurred as a result of aconcurrent rise in net tubular reabsorption of sodium.  Since recent data have indicated a specific effect of glucocortiocoids on epithelial cells, experiments were performed to determine whether enzyme activity and net sodium reabsorption could be dissociated. Evidence is provided demonstrating that base-line specific activity of Na-K-ATPase in rat renal cortex and outer medulla does not correlate directly with net sodium reabsorption since enzyme activity did not change after a chronic reduction in glomerularfiltration rate and the rate of sodium reabsorption.  Further studies showed a markedrise in Na-K-ATPase after 4 days of treatment with methylprednisolone despite a fall in sodium absorption.  These results suggest a direct effect of glucocorticoids onrenal Na-K-ATPase and illistrate the difficulty in assigning a transport role tothis enzyme from the correlation of specific activity with rates of net electrolyte transport.


Pathogenesis of acute avian malaria. III. Antigen and antibody complexes as a mediator of anemia in acute Plasmodium gallinaceum infections of chickens.

In a study of antigens and antibodies found in malarious chicken blood, antigen activity was found in plasma, and in hypertonic saline eluates of blood cells. A soluble antigen was extracted from parasites liberated from erythrocytes. Two classes of antigen were differentiated, one a globulin associated "serum antigen" which was found to show identity with a serum antigen from blood of rats with acute Babesia rodhaini infection, and another that was associated with the Plasmodium gallinaceum parasite. The plasma also contained antibody to both classes of antigen. Study of blood cells from normal chickens made anemic by injections of autohemagglutinin-free malarious plasma indicated that both serum antigen and its antibody were present in eluates of the washed blood cells. Direct immunofluorescent tests of these cells with conjugated antibody to serum antigen, and with conjugated antibody to P. gallinaceum parasite antigen showed that they reacted with the antibody to serum antigen but gave no reaction with antibody to parasite antigen. From this information it is suggested that soluble complexes of serum antigen and its antibody combined with the erythrocytes, and that these complexes acted as opsonin to cause the cells to be sequestered and destroyed in the spleen, or may have fixed complement to cause intravascular hemolysis. The serologic identity of serum antigen from malarious chickens and from rats with babesiosis, and its distinction from parasite antigen, led to the speculation that it might be an autoantigenic macroglobulin.


Failure of thiabendazole and metronidazole in the treatment and suppression of guinea worm disease.

Guinea worm disease is endemic in West Africa. In 1973 a field drug trial was conducted to compare effectiveness, cost, and side-effects of thiabendazole and metronidazole in treating active guinea worm disease and preventing latent worms from emerging. A mass chemotherapy campaign was planned to follow the drug trial. Only 15.5% of the treated patients expelled the worm completely, and in 28.4% of the cases worms continued to appear. Both drugs were equally unsatisfactory in their anti-helminthic effect. Consequently, our efforts to control guinea worm have shifted from chemotherapy to chemical control of cyclops and improvement of rural water supplies.


Mebendazole in the treatment of dracontiasis.

In a controlled field trial of treatment for dracontiasis, mebendazole (Vermox) was found to be effective in eliminating the adult worm and preventing clinical relapses, but it did not achieve significant amelioration of symptoms, subsidence of inflammation, or healing of ulcers. The failure is attributed to poor absorption and lack of anti-inflammatory action of the drug. Mebendazole was well tolerated and although two patients reported mild gastrointestinal disturbances, which may be attributed to the drug, the study confirms that mebendazole is one of the safest anthelmintics in current use and is in that respect ideal for mass therapy.


Comparison of two geographic strains of Leishmania donovani by resistance of mice to superinfection.

Groups of mice were injected with Leishmania donovani strains Et (Burma) or IS (Sudan) and the courses of infection were followed. Between days 20 and 30 after infection by treatment with pentostam. Et- and 1S-recovered mice were challenged by intravenous injection of amastigotes of each strain. Although resistance to superinfection was apparent the L. donovani strains could not be differentiated by this method.


Central alveolar hypoventilation in a child: an evaluation using a whole body plethysmograph.

A disorder in the central nervous system control of breathing is thought to be responsible for the clinical syndrome of "primary" or central alveolar hypoventilation.  Only 2 of the 7 reported cases in children have included any functional evaluation of this control system disorder.  We report the case of a 2-year-old girl with central alveolar hypoventilation attributed to an abnormality in be central nervous system of unknown etiology.  In evaluating her ventilatory control system, we used a method (whole body pleildren and small animals but has since received little clinical use.  The findings included an irregular respiratory rhythm and a diminished ventilatory response to inhaled CO2, which suggested a functional abnormality of brainstem neurons responsible for rhythmic effective breathing and the CO2 response.  A relatively normal change in breathing with sleep and exercise as well as qualitively normal peripheral chemoreceptor function suggested that these aspects of the control system were undisturbed.  These findings are contrasted to those in other children; it is suggested that the syndrome of central alveolar hypoventilation may reflect a variety of functional abnormalities in the nervous system control of ventilation.


Value of laparoscopy in hepatobiliary disease.

A prospective study was made of the value of laparoscopy in hepatobiliary disease. The pathology was accurately diagnosed by laparoscopy alone in 21 out of 33 consecutive cases of cholestatic jaundice (36% failure rate). Laparoscopy gave a slightly better diagnostic yield for secondary tumour deposits than hepatic scintiscanning, and the simultaneous use of both procedures reduced the false negative rate to 2/18 (11%). Laparoscopic liver biopsy was superior to blind percutaneous biopsy in the retrieval of secondary malignant tissue, but it had no obvious advantage over the latter when performed on patients with diffuse disease (cirrhosis) or primary hepatic tumours.


The effect of thiols on Saccharomyces fragilis.

Treatment of cell suspensions of Saccharomyces fragilis with 0.01 M beta-mercaptoethanol or dithiothreitol released a variety of substances of high and low molecular weight. Twenty-two high-molecular-weight glycoproteins were separated by a combination of chromatography on DEAE cellulose and polyacrylamide gel electrophoresis in presence of sodium dodecylsulphate. The carbohydrate components consisted of at least 95% mannose and the protein components had threonine and serine as the major amino acids. Only very small amounts of phosphorus were associated with the high-molecular-weight components. The low-molecular-weight substances werr probably released from the internal cell pool and uracil and hypoxanthine were identified as components of this fraction. It is suggested that in addition to breaking disulphide bridges in the cell wall the thiols may also render the plasmalemma permeable to certain low-molecular-weight substances. Such effects are not lethal since the yeast can be trained to grow in presence of 0.01 M mercaptoethanol.


DDT: effect of continuous exposure on ATPase activity in fish, Pimephales promelas.

Fat head minnows, 45-days old, were continuously exposed to DDT using continuous water flow and constant temperature conditions. Exposures were to 0.5 and 2.0 ppb of DDT in water, and combinations of the two concentrations with 50 ppm in food, and 50 ppm in food alone, using C1 4-DDT in food. Brain homogenates were analyzed for enzyme activity from fish treated for 56, 118, 225, and 266 days; and gill analysis was made at 225 and 226 days exposure. Enzyme reductions were greatest in oligomycin-sensitive (mitochondrial) Mg2+ ATPase, with pronounced effects (over 50% inhibition) at the 266th sampling day. In contrast, Na+-K+ ATPase and oligomycin-insensitive Mg2+ ATPase activities were activated by as much as 28% and 40%, respectively. Mitochondrial Mg2+ ATPase of fish brain has been inhibited to the greatest extent in previously reported in vitro studies. All three ATPase enzymes were reduced in gill tissue sampled at the 266th day, with mitochondrial Mg2+ ATPase showing the greatest decline.


Lymphocyte reactivity in rheumatoid arthritis. Mixed lymphocyte culture.

Lymphocyte function in rheumatoid arthritis has been assessed by the mixed lymphocyte culture assay. In contrast to previous studies, no difference was found between lymphocytes from healthy volunteers and patients with rheumatoid arthritis. An occasional patient's lymphocytes failed to respond on a given day, but were normal on restudy. All 44 arthritic patient's lymphocytes underwent blast transformation on stimulation with lymphocytes from unrelated donors. By reaction in mixed lymphocyte culture, lymphocytes from patients with rheumatoid arthritis appear to be normal and no different from normal cells studied simultaneously.


Bleeding in pregnancy due to retroplacental situtation of guinea worms.

Two cases of retroplacental guinea worms causing bleeding in the early and late months of pregnancy are reported. In one case, habitual abortions may have been due to the presence of a guinea worm. These situations and manifestations have not been previously reported. It is suggested that larval worms can invade the vagina, that the acid vaginal exudate destroys the Cyclops and releases the larvae which then penetrate the tissues and migrate to the retroplacental region corresponding to the migration from the stomach. This probably explains the higher incidence among females compared with males and of the pelvis over other regions.


The effects of gonadectomy on monoamine metabolism in three regions of mouse brain.

The concentrations 5-hydroxytryptamine, noradrenaline, their precursors and metabolites have been determined in three regions of mouse brain following gonadectomy; the rates of depletion of 5-hydroxytryptamine and noradrenaline following synthesis blockade have also been examined. Previous investigations have shown that gonadectomy results in changes in hypothalamic catecholamine metabolism; this report shows that changes are not confined to the hypothalamic area and suggests that the effects in other areas of the brain may contribute to the increased incidence of mental disturbances in man when hormone levels are drastically altered. Gonadectomy results in reduced 5-hydroxytryptamine and 5-hydroxyindoleacetic acid concentrations in all regions of the mouse brain. Normetanephrine concentrations are significantly increased and the rate of depletion of noradrenaline from the brain following synthesis blockade is markedly accelerated following gonadectomy; this suggests that circulating steroid sex hormones may exert a stabilising effect on brain catecholamine stores.


Allosteric activation and competitive inhibition of yeast phosphofructokinase by d-fructose.

Purified phosphofructokinase from bakers yeast is activated by D-fructose in low concentrations (up to 1 mM) and inhibited by high concentrations. The stimulatory effect of D-fructose is similar, but smaller than that of AMP. In the presence of AMP (0.4 mM or higher) D-fructose does no longer stimulate, but its inhibitory effect persists (KI = 8 mM). Its dualistic action on phosphofructokinase activity indicates that D-fructose might induce low frequency in glycolytic oscillations by direct interaction with the enzyme.


Enzymes of D-fructose catabolism in species of Beneckea and Photobacterium.

Cell-free extracts of strains representative of the genera Beneckea and Photobacterium catalyzed a P-enolpyruvate dependent phosphorylation of D-fructose. The resulting product, fructose-1-P, was converted to fructose-1,6-P2 by 1-P-fructokinase. Both activities were inducible, being present in D-fructose-grown cells and reduced or absent in D-gluconate-(or succinate-) grown cells.


Death resulting from unbalanced growth in a temperature-sensitive mutant of Neurospora crassa.

A temperature-sensitive mutant of Neurospora crassa was found to undergo rapid death on minimal medium at 35 degrees C.  The loss of viability in this mutant was prevented by various factors which retard growth, including deprivation of carbon sources or interruption of protein synthesis.  Synthesis of nucleic acids and protein in this mutant was normal at the early stages of germination and then depressed at 35 degrees C.  The active transport of glucose and the respiration rate in this mutant were depressed at 35 degrees C.  Phopholipid synthesis was significantly repressed at 35 degrees C.  The possible significance of the characteristics of this mutant is discussed in terms of membrane biosynthesis.


Conidiation of Neurospora crassa induced by treatment with natrium fluoride in submerged culture.

A transient treatment of pregerminated conidia of Neurospora crassa with NaF induced young, submerged cultures to prematurely differentiate conidia. The inductive treatment decreased the rate of respiration (with lower RQ), reduced the relative concentration of nucleoside triphosphates, and inhibited leucine incorporation into protein and adenosine incorporation into RNA.


Interaction of a coupling factor from Rhodospirillum rubrum with coupling factor deficient chromatophores.

A coupling factor necessary for the photophosphorylation and Mg2+-ATPase activities in Rhodospirillum rubrum chromatophores has been separated from these particles. Although the redox potential of coupling factor deficient chromatophores is slightly more oxidized than of the control, the addition of the coupling factor for reconstitution does not alter the redox potential. Phenazine methosulfate cannot restore or significantly enhance the photophosphorylation activities of uncoupled or reconstituted chromatophores compared to the control. The coupling factor can bind to coupling factor deficient membranes without addition of magnesium ions and thus restore the photophosphorylation and Mg2+-ATPase activities of these vesicles. The Ca2+-ATPase in the coupling factor preparation shows binding characteristics similar to those of the coupling factor.


Prophylactically administered phenytoin. Effects on the development of chronic cobalt-induced epilepsy in the cat.

In chronic cobalt-induced experimental epilepsy in the cat, there are alterations in behavior, electroencephalograms, and brain sodium, potassium adenosine triphosphatase (Na,K ATPase) activity. The electrographic and enzymatic changes occur both in focus and homotopic cortex, and are time related. The onset of EEG paroxysms consistently precedes increases in Na,K ATPase activity, indicating that the enzymatic change is adaptive. Prophylactic treatment with phenytoin (formerly diphenylhydantoin) prevents these chronic alterations from developing, although some early changes do occur. After the drug is withdrawn following 28 days of therapy, treated animals still demonstrate no evidence of epileptiform discharges or changes in Na,K ATPase activity, although these changes persist in untreated cats. Given properly, phenytoin may prevent alterations in brain, which can result in the formation of a hyperexcitable population of cells. These data support the efficacy of early pharmacologic prophylaxis in posttraumatic epilepsy.


Human epileptic brain Na, K ATPase activity and phenytoin concentrations.

An abnormal flux of monovalent cations may be related to the epileptogenic process in man. One possible mechanism for deranged electrolyte metabolism in epileptic brain is an abnormality in sodium, potassium-dependent adenosine triphosphatase (Na, K ATPase). We found the activity of Na, K ATPase to be significantly less in epileptic human corfex than in nonepileptic cortex. Histological changes have been simultaneously evaluated in epileptic brain. A second membrane-bound enzyme, acetylcholinesterase (AChE), was also assayed as a marker for neuronal membranes and found not to correlate with the epileptogenicity of human brain. In addition, the concentrations of the anticonvulsant compound phenytoin have been determined in the serum and cerebral cortex of epileptic and nonepileptic patients. The ratio of phenytoin in cortex to serum concentration is significantly lower in epileptic patients than in nonepileptic controls.


Primary actinomycosis of the abdominal wall.

A rare case of primary actinomycosis of the abdominal wall presenting as a tumour is described. The patient responded to penicillin therapy well. A brief account of the literature is included.


A double blind trial of lithium carbonate and haloperidol in Huntington's chorea.

Six patients with a family history of Huntington's chorea (HC) participated in a double blind crossover trial involving four treatments--lithium carbonate, haloperidol, lithium carbonate and haloperidol, and placebo. Each treatment was administered for three weeks and, at the end of each treatment period, assessments were made of chorea and a number of psychological variables. None of the treatments significantly affected chorea measurements. With regard to the psychological variables, the levels of irritability, the frequency of angry outbursts and depression did appear to be affected in some patients by the treatment. Three patients improved on a combination of lithium carbonate and haloperidol while the remaining three did not. Haloperidol alone significantly raised depression ratings above levels for other treatments including placebo. It is suggested that lithium carbonate and haloperidol together should be seriously considered in the treatment of HC when patients are excessively irritable and impulsive.


[Histogenesis of the immune system of the "nude" mouse. III. Postnatal development of lymph nodes and spleen: a light microscopical study (author's transl)].

In neonatally thymectomized mice, the intermediate cortical zones of the lymph nodes as well as the central portions of the spleen follicles (=thymus dependent areas, TDA) are depleted of lymphocytes within a few weeks (Parrott et al., 1966). The TDA's in the lymphatic tissues of mice homozygous for the gene "nude" (nu/nu) contain also a very small number of lymphocytes. Since only a few developmental stages of the lymphatic tissues in nude mice have been studied, an investigation of the postnatal differentiation of their lymph nodes and spleen seemed worthwhile. The mice (BALB/c) were maintained under specific pathogen-free (spf) conditions. Heterozygous (nu/ plus) females were mated with homozygous (nu/nu) males in order to obtain the homo- and heterozygous offsprings used in this study. Two nu/nu and two nu/ plus female mice were sacrificed at the following postnatal stages: day 1, 7, 14, 21, 35, 42, 49, 63 and 84, respectively. Newborn and 7 day old mice were fixed in toto in Bouin's solution and embedded in paraffin. From the other animals, spleen and mesenteric lymph nodes were removed and processed in an identical manner. Serial sections were cut at 5 mum and stained with hematoxylin and eosin. The mesenteric lymph nodes of the nu/ plus mice studied were indistinguishable from those of other mouse strains. In the nu/nu mouse, outer cortex and medulla of the mesenteric lymph nodes were found to develop as in normal (nu/ plus) animals, while the intermediate and deep cortex underwent characteristic changes...


Fractionation of proteoglycans from bovine corneal stroma.

Proteoglycans were extracted from bovine corneal stroma with 4M-guanidinum chloride, purified by DEAE-dellulose chromatography (Antonopoulos et al., 1974) and fractionated by precipitation with ethanol into three fractions of approximately equal weight. One of these fractions consisted of a proteoglycan that contained keratan sulphate as the only glycosaminoglycan. In the othertwo fractions proteoglycans that contained chondroitin sulphate, dermatan sulphate and keratan sulphate were present. Proteoglycans which had a more than tenfold excess of galactosaminoglycans over keratan sulphate could be obtianed by further subfractionation. The gel-chromatographic patterns of the glucosaminoglycans before and after digestion with chondroitinase AC differed for the fractions. The individual chondroitin sulphate chains seemed to be larger in cornea than in cartilage. Oligosaccharides, possibly covalently linked to the protein core of the proteoglycans, could be isolated from all fractions. The corneal proteoglycans were shown to have higher protein contents and to be of smaller molecular size than cartilage proteoglycans.


The proteoglycans of the human intervertebral disc.

The methods of Hascall & Sajdera (1969) were used to compare the proteoglycans of human intervertebral disc with those of bovine nasal cartilage. In contrast with cartilage, most of the hexuronate of disc could be extracted at low shear with water or dilute salt solutions. Extracts of disc with 4M-guanidinium chloride were centrifugated in 0.4M-guanidinium chloride in a CsCl gradient. Analytical ultracentrifugation of the hexuronate-containing heavy component revealed two fractions. both more polydisperse than those of cartilage. Also the more rapidly sediminting component was a much smaller fraction of the total. After prior extraction with 0.4M-guanidinium chloride, 4M-guanidinium chloride extracts of disc were found, by ultracentrifugal analysis, to be enriched in components resembling the proteoglycan monomer and aggregating factors of cartilage.


Interaction of cartilage proteoglycans with collagen-substituted agarose gels.

1. Rat tail-tendon collagen was coupled to activated Sepharose 4B at 2.5 mg of collagen/ml of gel. Chromatographic columns of this gel were calibrated with T2 virus (Vo) and Dnp-alanine (Vt). 2. The chromatographic behaviour of cartilage proteoglycans on the collagen-substituted gel was studied under conditions of varying ionic strength. Proteoglycan subunit obtained from bovine nasal cartilage, the proteoglycan obtained after digestion with chondroitnase ABC and purified chondriotin sulphate were all retarded on the collagen gel by an interaction that abolished at I0.17. Purified keratan sulphate and hyaluronic acid were not retarded. 3. A strong ionic interaction between cartilage proteoglycan and collagen was demonstrated to depend on the structure of the protein core of the proteoglycan.


Functional polarity of the rat hepatocyte surface membrane. Isolation and characterization of plasma-membrane subfractions from the blood-sinusoidal, bile-Canalicular and contiguous surfaces of the hepatocyte.

1. Six rat liver plasma-membrane subfractions of different density and morphological, enzymic and chemical properties were prepared from homogenates by a combination of differential, rate-zonal and density-gradient centrifugation. They consisted of three vesicular 'light' subfractions of density 1.12-1.13 and three 'heavy' subfractions of density 1.16-1.18 containing membrane strips and intercellular junctions. 2. All six subfractions contained a basal adenylate cyclase activity. One of the 'light' subfractions that showed the highest glucagon-stimulated adenylate cyclase activity was identified as deriving form the blood-sinusoidal face of the hepatocyte. This subfraction, unlike the others, was contaminated by Golgi components, as indicated by its morphological properties and the presence of galactosyl- and sialyl-transferase activities. 3. All the six subfractions showed high activities of the following plasma-membrane marker enzymes: 5'-nucleotidase, alkaline phosphodiesterase (nucleotide pyrophosphatase), alkaline phosphatase, leucine naphthylamidase and Mg2+-activated adenosine triphosphatase. A 'light' subfraction that showed the highest specific activities of all the above marker enzymes, but lacked a glucagon-stimulated adenylate cyclase activity, was identified as deriving from the bile-canalicular face of the hepatocyte. 4. The 'heavy' subfractions, which showed generally the lowest activities of the above plasma-membrane enzyme markers, and were characterized by the presence of desmosomes and gap junctions, were taken to originate from the contiguous faces of the hepatocyte. 5. The protein composition of the six subfractions was generally similar, as shown by polyacrylamide-gel electrophoresis. Differences in the amounts of various protein and glycoprotein bands among the subfractions correlated with their morphology, enzymic composition and sialic acid content. 6. Hormonal and histochemical evidence supporting the identification of a bile-canalicular subfraction, a blood-sinusoidal subfraction and contiguous-face subfractions is discussed.


Membrane-lipid unsaturation and mitochondrial function in Saacharomyces cerevisiae.

The lipid composition of yeast cells was manipulated by the use of an unsaturated fatty acid auxotroph of Saccharomyces cerevisiae. There was a 2-3-fold decrease in the concentration of cytochromes a+a3 when the unsaturated fatty acid content of the cells was decreased from 60-70% of the total fatty acid to 20-30%. The amounts of cytochromes b and c were also decreased under these conditions, but to a lesser extent. Further lipid depletion, to proportions of less than 20% unsaturated fatty acid, led to a dramatic decrease in the content of all cytochromes, particularly cytochromes a+a3. The ATPase (adenosine triphosphatase), succinate oxidase and NADH oxidase activities of the isolated mitochondria also varied with the degree of unsaturation of the membrane lipids. The lower the percentage of unsaturated fatty acid, the lower was the enzymic activity. Inhibition of mitochondrial ATPase by oligomycin, on the other hand, was not markedly influenced by the membrane-lipid unsaturation. Npn-linear Arrenius plots of mitochondrial membrane-bound enzymes showed transition temperatures that were dependent on the degree of membrane-lipid unsaturation. The greater the degree of lipid unsaturation, the lower was the transition temperature. It was concluded that the degree of unsaturation of the membrane lipids plays an important role in determining the properties of mitochondrial membrane-bound enzymes.


Metabolite transport in mutants of Escherichia coli K12 defective in electron transport and coupled phosphorylation.

1. The uptakes of Pi and serine by whole cells of mutant strains of Escherichia coli K12, grown under both aerobic and anaerobic conditions, were studied. 2. Uptake by aerobic cells was low in a ubiquinone-less mutant but normal in two mutant strains unable to couple phosphorylation to electron transport. 3. One of these uncoupled strains, carrying the unc-405 allele, does not form a membrane-bound Mg2+-stimulated adenosine triphosphatase aggregate, and it is concluded that the Mg2+-stimulated adenosine triphosphatase does not serve a structural role in the aerobic active transport of Pi or serine. 4. The other uncoupled strain, in which aerobic uptake is unaffected, carries a mutation in the uncB gene, thus distinguishing this gene from the etc gene, previously shown to be concerned with the coupling of electron transport to active transport. 5. The uptakes of Pi and serine by anaerobic cells were normal in the ubiquinone-less mutant, but defective in both the uncoupled strains. 6. The uptake of Pi and serine by anaerobic cells of the uncB mutant could be increased by the addition of fumarate to the uptake medium. The unc-405 mutant, however, required the addition of fumarate for growth and for uptake. 7. The uncB mutant, unlike the unc-405 mutant, is able to grow anaerobically in a minimal medium with glucose as sole source of carbon. Similarly a strain carrying a mutation in the frd gene, which is the structural gene for the enzyme fumarate reductase, is able to grow anaerobically in a glucose-minimal medium. However, a mutant strain carrying mutations in both the uncB and frd genes resembles the unc-405 mutant in not being able to grow under these conditions.


Metabolic interactions of dichloroacetate and insulin in experimental diabetic ketoacidosis.

1. The infusion of sodium dichloroacetate into rats with severe diabetic ketoacidosis over 4h caused a 2mM decrease in blood glucose, and small falls in blood lactate and pyruvate concentrations. Similar findings had been reported in normal rats (Blackshear et al., 1974). In contrast there was a marked decrease in blood ketone-body concentration in the diabetic ketoacidotic rats after dichloroacetate treatment. 2. The infusion of insulin alone rapidly decreased blood glucose and ketone bodies, but caused an increase in blood lactate and pyruvate. 3. Dichloroacetate did not affect the response to insulin of blood glucose and ketone bodies, but abolished the increase of lactate and pyruvate seen after insulin infusion. 4. Neither insulin nor dichloroacetate stimulated glucose disappearance after functional hepatectomy, but both agents decreased the accumulation in blood of lactate, pyruvate and alanine. 5. Dichloroacetate inhibited 3-hydroxybutyrate uptake by the extra-splachnic tissues; insulin reversed this effect. Ketone-body production must have decreased, as hepatic ketone-body content was unchanged by dicholoracetate yet blood concentrations decreased. 6. It was concluded that: (a) dichloroacetate had qualitatively similar effects on glucose metabolism in severely ketotic rats to those observed in non-diabetic starved animals; (b) insulin and dichloroacetate both separately and together, decreased the net release of lactate, pyruvate and alanine from the extra-splachnic tissues, possibly through a similar mechanism; (c) insulin reversed the inhibition of 3-hydroxybutyrate uptake caused by dichloroacetate; (d) dichloroacetate inhibited ketone-body production in severe ketoacidosis.


Stimulation of glycosaminoglycan biosynthesis by amyloid fibrils.

Since amyloid-laden organs have an increased glycosaminoglycan content, the effect of amyloid fibrils on glycosaminoglycan metabolism by normal fibroblasts was examined. In comparison with controls, synthesis of glycosaminoglycans, primarily hyaluronic acid, was increased by an average of 48 and 93% respectively when 0.1 and 1.0 mg of amyloid fibrils/ml was added to the cultures.


The effect of uncouplers on catecholamine incorporation by vesicles of chromaffin granules.

It is shown that uncouplers inhibit the incorporation of catecholamines by vesicles of chromaffin granules in parallel with their stimulatory effect on the membrane-bound adenosine triphosphatase.


Structure and metabolism of glycoproteins and glycosaminoglycans secreted by organ cultures of rabbit trachea.

1. When cultured in medium 199 in an atmosphere of O2+CO2 (95:5) rabbit tracheal explants retained their viability for up to 21 days. 2. The explants secreted into the culture medium three electrophoretically separable components which were eluted in the non-retarded fraction from Sephadex G-200. 3. Digestion with papain and fractionation with a LiCl gradient on DEAE-cellulose resulted in the separation of these components, which were identified as a sialic acid-rich glycoprotein of epithelial origin, and chondroitin sulphate and hyaluronic acid from sub-epithelial cartilage and connective tissue. 4. Incorporation of radioactive precursors (  D-[U-14-C]glucose, D-[1-14-C]glucosamine, D-[1-14-C]galactose and Na2-35SO4) into these secreted macromolecules was indicative of their active biosynthesis by the tracheal tissue.


Effect of D-penicillamine on lymphocyte function.

Lymphocyte stimulation by different stimulating agents was dose dependently inhibited by D-penicillamine (Metalcaptase-R). The influence of D-penicillamine on the lymphocyte metabolism after the stimulation was established, was time dependently reduced. After preincubation of lymphocytes with D-penicillamine the lymphocyte metabolism was dose dependently reduced. The inhibition of the mixed lymphocyte cultures was by far less extensive after preincubation of the stimulator cells than of the responder cells. HeLa-cells were dose dependently inhibited by D-penicillamine, too. From these results there is much to be said for the assumption that D-penicillamine acts at the level of the cell membrane. D-Penicillamine seems to affect "membrane dependent" metabolic processes rather than block antigenic or other immunologically relevant structures.


The ground substance of the arterial wall. Part 1. Extractability of glycosaminoglycans and the isolation of a proteoglycan from bovine aorta.

Water and glycosaminoglycan contents were measured in upper and lower thoracic aortas of claves and steers. The ability of various molarities of guanidine hydrochloride to extract glycosaminoglycans from these tissues was assessed. Some glycosaminoglycans seem to be more resistant to extraction than others. A procedure is described for the isolation of a proteoglycan. The molecule appears to contain both dermatan sulfate and chondroitin sulfate. It also seems to be less dense than cartilage proteoglycans extracted by similar methods as assessed by its behavior in centrifugal fields. The properties, locus and biological activities of this molecule are currently being studied.


'Posterior' transposition reconsidered.

Seven cases of transposition with an unusually posterior aorta and mitral-aortic fibrous continuity are described. The cases are similar to four cases published by Van Praagh et al. in 1971. The use of the term 'p' transposition is suggested to distinguish this unusual form of transposition from cases with a subaortic conus ('d' and 'l' transposition). The use of the term 'transposition' is considered justifiable on both semantic and morphogenetic grounds and a possible common embryological mechanism for all forms of transposition is discussed.


Plasma beta-MSH levels in acne vulgaris.

Plasma beta-MSH levels and sebum excretion rates (SER) were measured in thirty male and twelve female patients with acne vulgaris. The mean SER in both male and female patients was significantly increased as compared to normal control levels. Plasma beta-MSH levels were normal in male and female patients with acne and showed no correlation with the SER. The SER that occurs in acne cannot therefore be explained by an increased secretion of beta-MSH.


Seborrhoeic keratoses and carcinoma of the large bowel. Three cases exhibiting the sign of Lester-trélat.

Three patients who rapidly developed multiple seborrhoeic keratoses and were found to have adenocarcinoma of the large bowel are described. In two cases the discovery of the neoplasm was prompted by skin manifestations.


Isothiocyanates. A new class of uncouplers.

This paper describes the uncoupling effect of three isothiocyanates: p-bromophenylisothiocyanate, 4,4'-diisothiocyanatebiphenyl and beta-naphtylemthylisothiocyanate on the respiration of Ehrlich-Lettré cells and isolated mitochondria. The isothiocyanates are similar to other uncouplers (such as 2,4-dinitrophenol and carbonyl cyanide p-trifluoromethoxyphenylhydrazone) in that they: 1. stimulate respiration of state 4 mitochondria; 2. stimulate mitochondrial ATPase activity; 3. release the inhibition of mitochondrial respiration by oligomycin and 4. inhibit both mitochondrial respiration and mitochondrial ATPase activity at higher molar concentrations. The incoupling activity of these isothiocyanates correlates well with their biological activity. Maximal activation of a latent mitochondrial ATPase activity of rat liver mitochondria in the presence of p-bromophenylisothiocyanate was found at a concentration of 15 muM. The investigated isothiocyanates differ significantly in their solubility in organic solvents and their chemical reactivity. We assume that the greater the partition coefficient in a series of isothiocyanates grouped according to the increasing value of log P (partition coefficient for the system octanol/water, 25 degrees C), the greater will be their uncoupling activity, but only up to a certain degree. Any further increase of log P will be marked by a decrease of this activity.


Interaction of phosphofructokinase with antibodies. Kinetic properties of phosphofructokinase in complexes with antibodies.

The allosteric properties of phosphofructokinase (EC 2.7.1.11) from rabbit muscle are influenced by enzyme concentration, most probably due to changes in the association state of the enzyme. In this study, the behaviour of dispersed pre-cipitates of phosphofructolinase as produced by treatment with antibodies has been investigated. The enzyme is not capable of rapid dissociation in the precipitated state as is confirmed by the lack of inactivation upon dilution and by the absence of shifts in substrate saturation curves as measured in the presence of different concentrations of the enzyme. The Hill coefficient of phosphofructokinase is decreased from 1.96 to 1.04 by antibody treatment. The V at neutral pH is increased 3-fold while the K0.5 for fructose 6-phosphate is reduced significantly. On the other hand, antibody-treated phosphofructokinase retains its sensitivity to allosteric activation by glucose 1,6-bisphosphate in the rpesence of high ATP concentrations.


Complementarity in the regulation of phosphoglucomutase, phosphofructokinase and hexokinase; the role of glucose 1,6-bisphosphate.

ATP and citrate, the well known inhibitors of phosphofructokinase (ATP: D-fructose 6-phosphate 1-phosphotransferase, EC 2.7.1.11), were found to inhibit the activities of the multiple forms of phosphoglucomutase (alpha-D-glucose 1,6-bisphosphate: alpha-D-glucose 1-phosphate phosphotransferase, EC 2.7.5.1) from rat muscle and adipose tissue. This inhibition could be reversed by an increase in the glucose 1,6-bisphosphate (Glc-1,6-P2) concentration. Other known activators (deinhibitors) of phosphofructokinase, viz. cyclic AMP, AMP, ADP or Pi, had no direct deinhibitory action on the ATP or citrate inhibited multiple phosphoglucomutases. Cyclic AMP and AMP, could however lead indirectly to deinhibition of the phosphoglucomutases, by activating phosphofructokinase which catalyzes the ATP-dependent phosphorylation of glucose 1-phosphate to form Glc-1,6-P2, the la-ter then released the multiple phosphoglucomutases from ATP or citrate inhibition. The Glc-1,6-P2 was also found to exert a selective inhibitory effect on hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) type II, the predominant form in skeletal muscle. This selective inhibition by Glc-1,6-P2 was demonstrated on the multiple hexokinases which were resolved by cellogel electrophoresis or isolated by chromatography on DEAE-cellulose. Based on the in vitro studies it is suggested that during periods of highly active epinephrine-induced glycogenolysis in muscle, the Glc-1,6-P2, produced by the cyclic AMP-stimulated reaction of phosphofructokinase with glucose 1-phosphate, will release the phosphoglucomutases from ATP or citrate inhibition, and will depress the activity of muscle type II hexokinase.


Human platelet 6-phosphofructokinase. Relation between inhibition by Mg-ATP2-and cooperativity towards fructose 6-phosphate and investigations on the formation of a ternary complex.

Human platelet 6-phosphofructokinase (EC 2.7.1.11) shows cooperativity towards Fru-6-P and is allosterically inhibited by high Mg-ATP2- concentrations. No relation could be demonstrated between the cooperativity towards Fru-6-P and the inhibition by Mg-ATP2-. Increasing the concentrations of Mg-ATP2- only raised the apparent Km values for Fru-6-P, but did not change the Hill constants. A possible formation of a Mg-ATP2--enzyme-Fru-6-P complex during catalysis was investigated. Our calculations suggest that such a ternary complex is indeed formed during the reaction.


Association of basal ATPase activity and cholesterol with a distinct group of rabbit skeletal muscle microsomal particles.

Basal ATPase is readily separated from the Ca2+-ATPase of the sarcoplasmic reticulum. The median density distributions of cholesterol and basal ATPase activities are almost identical. Digitonin has been successfully employed in determining the association of cholesterol with specific vesicles in rat liver microsomal preparations. Treatment of rabbit skeletal muscle microsomal preparations with digitonin alters the density distribution patterns of basal ATPase activity and cholesterol in an identical fashion. Protein distribution displays a less marked change in median density. Enzymic activity associated with calcium transport, measured under differing conditions, is largely unaffected. It is concluded that cholesterol and basal ATPase activity are associated with a distinct group of rabbit skeletal muscle microsomal particles.


Improved purification and partial characterization of (Na+, K+)-ATPase from cardiac muscle.

A method is described for purification of (Na+, K+)-ATPase which yielded approximately 60 mg of enzyme from 800 g of cardiac muscle with specific activities ranging from 340 to 400 mumol inorganic phosphate/mg protein per h (units/mg). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated the presence of a major 94 000 dalton polypeptide and four or five lesser components, one of which was a glycoprotein with an apparent molecular weight of 58 000. The enzyme preparation bound 600-700 pmol of [3H]ouabain/mg protein when incubated in the presence of either Mg2+ plus Pi, or Mg2+ plus ATP plus Na+, and incorporated more than 600 pmol 32P/mg protein when incubated with gamma-32P-labelled ATP in the presence of Mg2+ and Na+. The preparation is approximately 35% pure.


Carrier-mediated transfer of D-glucose in brush border vesicles derived from rabbit renal tubules. Na+-dependent versus Na+-independent transfer.

A brush border preparation from rabbit renal tubules containing a high yield of vesicles has been used to study the transfer of D-glucose through the brush border membrane. In the presence of an Na+ gradient across the vesicular membrane, the vesicles could concentrate D-glucose to a factor of 1.5, whereas in the absence of an Na+ gradient, only equilibrium with the medium was achieved. Two types of transfer could be distinguished by their requirement of Na+, their sensitivity to phlorizin and their pH optimum. The Na+-independent transfer was about 100 times less sensitive to phlorizin than the Na+-dependent path and exhibited a pH optimum between 7 and 8, whereas the Na+-dependent transfer was highest at a pH between 8 and 9. The brush border preparation could be freed of most of the contaminating material derived from the basal and lateral tubular cell membrane by a discontinuous density gradient centrifugation. It still showed both forms of transfer to a similar extent, indicating that both are located in the brush border membrane. A study of the sensitivity of D-glucose transfer to phlorizin, in the presence and absence of Na+ at different temperature, suggests a single carrier species functioning in two interchangeable conformational states with different affinities for phlorizin rather than two transfer systems working independently.


Calcium uptake by placental plasma membrane vesicles.

The placental plasma membrane vesicles are capable of accumulating up to 190 mM Ca2+. This is 24-fold higher than the external Ca2+ concentration. This process is dependent on ATP hydrolysis by the placental Ca2+-ATPase. The Pi/Ca ratio is dependent on the external Ca2+ concentration, and reaches the value of 2 at 10 mM Ca2+. Phosphate (5 mM) can double Ca2+ uptake when measured in the presence of 5 mM Ca2+. Mg2+ increased Ca2+ uptake only at low Ca2+ concentrations, and had no significant effect at 5 mM Ca2+.


Mathematical analysis of multienzyme systems. II. Steady state and transient control.

The control theory of steady states, previously presented for linear enzymatic systems (Heinrich and Rapoport, 1974) is extended to nonlinear systems. On the basis of three theorems a new procedure for the calculation of the control strength and of the control matrix is developed. The theory is applied to the extended model of glycolysis of erythrocytes, which includes also ATP-consuming processes. Also in this model the glycolytic flux is mainly controlled by the hexokinase-phosphofructokinase-system. The control strengths of the pyruvate kinase and of the enzymes of the 2.3 P2G-bypass are negligibly small. The control strength of the ATPase is negative, i.e. an activation of this enzyme leads to a decrease of the flux. For transition states of multienzyme systems definitions are given for the mean time required for the transition of the metabolites and for the "transient control" of enzymes. Enzymes with a pronounced influence on the transition time are called time-limiting enzymes. Enzymes which excert strong control on the time-dependent processes may have little influence under steady state conditions and vice versa. The transition times of ATP have been calculated for transient states of glycolysis.


Activity of eight antimicrobial agents in vitro against N. Gonorrhoeae.

The sensitivity of four groups of gonococcal strains to ampicillin (Am), penicillin (P), tetracycline (T), rifampicin (Ri), spectinomycin (Sp), sulphamethoxazole (Su), trimethoprim (Tr), and a combination of Su and Tr in the ratio 5:1 (Su/Tr 5:1) has been determined. The various groups of strains were isolated from male civilians (MC), female civilians (FC), and sailors (S) in Rotterdam (R) in 1972, and from FC in Amsterdam (A) in 1967. The S-R strains, which may be regarded as mainly imported, were compared with the MC-R and FC-R (which may be considered as mainly of Dutch origin). Also investigated was whether the incidence of relative resistance to the antibiotics investigated among Dutch strains has changed in the period from 1967 to 1972. For this purpose, the FC-A and FC-R strains were compared. The MC-R and FC-R strains were also compared with one another. Finally, Spearman's rank correlation coefficient r were calculated between the sensitivity distributions for each pair of antibiotics investigated, for all strains. The S-R strains were significantly less sensitive to Am, P, T, Ri, and Tr than the MC-R and FC-R strains. Comparison of the FC-A and FC-R strains revealed that the FC-R strains were significantly less sensitive only to Su/Tr 5:1. A possible explanation for this finding is given. With the exception of one FC-A strain, all gonococcal strains were sensitive to Sp. High values of r (larger than or equal to 0.50) were found between Am and P, Am and T, and P and T for all groups of strains. The values of r between any pair of the antibiotics Am, P, T, Ri, and Tr (with the exception of the pair Am-P) were always highest for the S-R strains. High values of r (larger than or equal to 0.50) were found between Su and Su/Tr 5:1 for all groups of strains. The FC-A strains, unlike the R strains, gave low values of r between Su and Tr and between Tr and Su/Tr 5:1. A possible explanation for this is given. Finally, a hypothesis is put forward to explain the fact that no significant changes were found in the sensitivity of Dutch gonococcal strains to Am, P, T, Ri, Sp, Su, and Tr in the period from 1967 to 1972, while the S strains (which may be regarded as imported) showed a significantly higher percentage of strains relatively resistant to Am, P, T, Ri, and Tr.


Spectinomycin in gonorrhoea.

Of 104 male and nine female patients with uncomplicated acute gonorrhoea who were treated with spectinomycin (males 2 g., females 4 g.), two patients (one male and one female) were considered to be treatment failures. No conclusions can be drawn from the small numbers of female patients investigated. Of the 104 male patients, 93 were followed for 2 weeks or more, giving a failure rate of 1-1 per cent. The drug was well tolerated. Sensitivity tests were carried out on 44 strains of N. gonorrhoeae; 42 strains were sensitive to 2-5 mug./ml. spectinomycin and all strains were sensitive to 5 mug./ml.


Arsenic and cancer.

Palmar and plantar keratoses developed in seven patients many years after ingeston of trivalent inorganic arsenic. Six had basal cell carcinoma (superficial multicentric type in five), carcinoma "in situ" or squamous cell carcinoma of the skin. Two had systemic carcinoma--one, bilateral breast adenocarcinoma and one, carcinoma of the colon. From these observations and from the findings of a review of the literature, there seems no question that long-term arsenic ingestion can cause palmar and plantar keratoses and skin cancer, particularly basal cell carcinoma of the superficial multicentric type, usually on the torso. It is suspected but not proved to cause other cancers. Although over the last 50 years general exposure to arsenic has greatly decreased, particularly that from insecticides, this element is still found occasionally in drinking water (naturally or as a smelter byproduct), in certain foods and in cigarette smoke.


The chemotherapy of urologic cancer.

A review of the status of evaluation of chemotherapeutic agents in the urologic malignancies reveals a largely neglected area of investigation. Except for testicular carcinomas, which are highly responsive to drug therapy, active agents have not been clearly established for the other urogenital tumor sites. Published information and data on file in the Cancer Therapy Evaluation Program of the National Cancer Institute are reviewed, and studies currently in progress are outlined. Adequate clinical testing of the standard antitumor agents that are active against other human malignancies should receive high priority in future therapeutic trials in urologic cancer.


Mechanism of action of 2,2'-(methylenediimino)bis-1,3,4-thiadiazole (NSC 143019), an antitumor agent.

The mechanism of action of 2,2'-(methylenediimino)bis-1,3,4-thiadiazole (NSC 143019) was clarified by studies on its effects on monolayer cultures of growing cells of the mouse cell line BALB/3T3. At concentrations below 50 muM, NSC 143019 specifically inhibited DNA and RNA syntheses without appreciably affecting protein synthesis. The syntheses of DNA and RNA were inhibited equally and concomitantly by the compound. The inhibition was reversed by removal of the compound and was prevented competitively by an equimolar amount of nicotinamide. It was also reversed completely by guanosine (0.1 mM) or deoxyguanosine (0.1 mM) and was reversed partially by xanthosine (1 mM). Other nucleosides did not influence the inhibition. The inhibition of DNA synthesis by NSC 143019 was not due to inhibition of RNA synthesis, and vice-versa. NSC 143019 inhibited the conversion of [8-14C]hypoxanthine to acid-soluble and -insoluble guanine nucleotides but not to adenine nucleotides. It was strongly suggested from these results that at concentrations of NSC 143019 below 50 muM the primary action of this compound might be due to the inhibition of GMP biosynthesis at the step of conversion of IMP to xanthosine 5'-phosphate.


Sequential histological and histochemical study of the rat liver after single-dose aflatoxin B1 intoxication.

Rats were given a single dose of aflatoxin B1 lethal to 50% of the animals (7.20 mg/kg). Their livers were examined histochemically in correlation with sequential histological lesions. Early periportal liver cell necrosis and marked biliary cell proliferation were observed. Periportal cytoplasmic glycogen and RNA depletion occurred during this early period and subsequently extended to the whole lobule. The enzymes investigated decreased or disappeared in the periportal area; but alkaline phosphatase increased strikingly in the centrolobular area, whereas canalicular adenosinetriphosphatase completely disappeared throughout the liver lobule. The histochemical changes reverted to normal after cessation of the necrosis. Histochemical techniques were more sensitive in detecting the vulnerability of the periportal parenchyma to aflatoxin. After the necrosis, regenerative foci appeared. They showed a variable content in glycogen and RNA and were characteristically enzyme deficient. This reflects the immaturity of regenerating hepatocytes. These early foci subsequently disappeared and are thus considered irrelevant to hepatomagenesis.


[Biosynthesis of macromolecules of the intercellular matrix in aorta organ culture. Influence of the age of the animal].

Rabbit aorta organ cultures were used as a model for the study of the modifications of the rate of biosynthesis of intercellular matrix macromolecules with age. Aortas of new born (100 g), young (400 g) and adult (2 kg) rabbits were maintained in culture for several weeks. 14C-lysine is incorporated in all the macromolecular fractions of the aortas, even in polymeric elastin. The change with age of the distribution of proteins of the aorta-explants in successive extracts obtained by a "chemical dissection" procedure and the decrease of their specific radioactivity wtih age enabled us to characterise biochemically the "aging program" of the arterial wall.


[Alloantigens directed by the SL-A region control the mixed lymphocyte reaction in swine].

Immunizations between a pig bearing a recombined SL-A haplotype and related animals revealed serological defined antigens under the MLR region control. These antigens seemed to be carried by all types of lymphocytes so far studied, but with large quantitative differences. The blood nonadherent on nylon fiber lymphocytes carried very few antigens and platelets none at all. The data are compatible with the assumption that these newly discovered antigens are equivalent to the mouse Ia antigens.


Volume ejected in early systole. A sensitive index of left ventricular performance in coronary artery disease.

Indices based on early systolic ejection rates are theoretically more sensitive to ventricular performance than indices based on the entire systolic ejection (SE) period (mean ejection phase indices-MEPI): mean systolic ejection rate (MSER), mean normalized systolic ejection rate (MNSER) and mean velocity of circumferential fiber shortening (MVcf). The volume ejected in early systole is an indicator of the early rate of ejection. Accordingly, ventricular volume changes were determined by ventriculographic analysis for each thrid of SE in ml/sec (SER), as normalized systolic ejection rate (NSER), and as percent of stroke volume (PSV). In ten normal controls all these indices were higher in the first third compared to the other thirds of SE. Seven patients with diffuse ventricular disease had depressed values in the first third of SE. Despite "normal ventriculograms and normal MEPI, eight patients with left anterior descending coronary artery stenoses (greater than 60%) also had definitely depressed ejection indices during first third of systole. Detailed wall motion analysis in this group showed anteroapical hypokinesis isolated to the first third of SE. These data show that indices based on early SER are more sensitive than MEPI (MVcf, MNSER) for detecting abnormalities in ventricular performance in coronary artery disease;


Complete interruption of the aortic arch. 1. Characteristic radiographic findings in 21 patients.

The radiographs of 21 patients with complete interruption of the aortic arch are reviewed, together with the literature, to emphasize characteristic radiographic features previously not recognized or discussed. In addition to the nonspecific radiologic findings of a left-to-right shunt through the invariably present ventricular septal defect, charateristic and unique features noted on chest radiograph and barium swallow that may suggest the diagnosis prior to catheterization include: a) a midline trachea; b) a hypoplastic ascending aorta with direct vertical ascent toward the neck; c) absence of the aortic "knob;" d) termination of the descending thoracic aortic shadow at the level of the main pulmonary artery; e) a "low arch" on lateral or left anterior oblique projections; and f) absence of the normal aortic impression on the barium-filled esophagus. Rib notching, when present, in association with the above findings indicates a stenotic or closed ductus arteriosus with collateral circulation through intercostal arteries to the descending aorta. The bilateral or unilateral location, right or left side, of the notching is dependent on the site of interruption and origin of the subclavian arteries and may permit differentiation into types and subtypes on chest radiograph.


Biosynthesis of oestrogens and their inter-conversion in human placentae from normal and toxaemic pregnancies.

In vitro biosynthesis of oestrogens in microsomal and 10,000 g supernatant fractions of placentae, ten each, from normal and toxaemic pregnancies has been investigated. Dehydroepiandrosterone sulphate (DHAS), dehydroepiandrosterone (DHA) and androstenedione were used as substrates and their conversion to oestrone and oestradiol studied. In all the placental preparations the relative efficiency of the conversion of these androgens to oestrogens, though differing greatly between subcellular fractions as well as between normal and toxaemic placentae, was invariably in the order of DHAS greater than DHA greater than androstenedione. The conversion of these androgen precursors to oestrone and oestradiol was reduced in toxaemia compared with the normal placenta. Moreover, formation of oestradiol was much more reduced than that of oestrone. The free oestradiol level in the serum was also found to be lower in toxaemic pregnancies as compared with the normal range. The inter-conversions of oestrogens further showed a significantly reduced conversion of oestrone to oestradiol in toxaemic placentae compared with normal placentae. The results may explain the lowered blood oestradiol levels observed in toxaemia of pregnancy and thus provide an explanation of the usefulness of the estimation of the oestradiol level as an index of feto-placental function.


Studies of in vitro steroid metabolism by testis tissue from 'complete' and 'incomplete' forms of testicular feminization.

The in vitro steroid metabolism of testicular tissue from seven cases of testicular feminization was studied. Using radioactive steroid substrates of both C21 and C19 configurations, kinetic studies of these tissues showed that the major pathway of testosterone production was via the delta5 pathway, i.e. pregnenolone leads to 17 alpha-hydroxypregnenolone leads to dehydroepiandrosterone leads to androstenedione and androstenediol leads to testosterone, with the accumulation of dehydroepiandrosterone and androstenediol. This accumulation of dehydroepiandrosterone and androstenediol does not occur in similar incubations of normal human testis tissue. The seven cases of testicular feminization were classified as 'complete' or 'incomplete' forms of the syndrome by reference to clinical data and the histology of the testicular tissue. It was concluded that the biochemical differences between the two forms of the syndrome were the greater production and accumulation of C21 and C19 delta 4 steroids from the C21 and C19 delta 5 steroid precursors indicating the relatively greater activity of the C21-3beta-hydroxysteroid dehydrogenase-isomerase enzyme in the 'incomplete' form.


A new consideration in athletic injuries. The classical ballet dancer.

The professional ballet dancer presents all of the problems of any vigorous athlete. The problems include osteochondral fractures, fatigue fractures, sprains, chronic ligamentous instability of the knee, meniscal tears, impingement syndrome, degenerative arthritis of multiple joints and low back pain. Attention to minor problems with sound conservative therapy can avoid many major developments and lost hours. Observations included the extraordinary external rotation of at the hip without demonstrable alteration in the hip version angle and hypertrophy of the femur, tibia and particularly the second metatarsal (in female dancers). Careful evaluation of the range of motion of the extremities, serial roentgenographic examination, and systematic review of previous injuries, training programs and rehearsal techniques have been evaluated in a series of cases to provide the basis for advice to directors and teachers of the ballet.


The treatment of thoracic intervertebral disc protrusions.

A series of seventeen patients with a protruded thoracic intervertebral disc is reported. In many cases a trauma, which was sometimes mild, seems to have played a role. This and signs and symptoms (of which pronounced numbness and obtrusive paraesthesiae are the most important) should suggest the diagnosis. In such patients myelography and tomography of the thoracic region is indicated. Twelve of the seventeen patients operated upon improved and nine of them made a good or excellent recovery.


[Unusual clinical forms of pseudo-LE syndrome: an induced immune-complex disease? (author's transl)].

Two of nine patients with pseudo-LE syndrome had previously undescribed organ manifestations. In one there was the full-blown picture of cutaneous lupus erythematodes, with renal and CNS involvement, ending fatally. Immunohistologically there was severe vasculitis and nephritis, histologically generalised necrotizing angitis. It is possible that the dramatic clinical picture was due to alpha-methyldopa. In the second case lymphadenopathy with bihilar involvement and splenomegaly predominated. Histologically there was no evidence of Boeck's sarcoid. Further studies revealed systemic involvement with immune-complex nephritis, electron-dense deposits in the glomerular basal membrane, and the typical changes of lupus erythematodes in the marrow. In a third case there were similar changes in kidney and marrow. These findings support the view of an immune-complex disease which can be fatal. An unusual feature in seven of the nine patients was the proven intake of Venopyronum¿ coated tablets in temporal relationship to the manifestation of the disease. It is possible that the described cases of pseudo-LE syndrome were drug-induced. The immunological mechanism of the disease would, in that case, be analogous to penicillamine nephropathy.


Pituitary fibroblast growth factor as a stimulator of growth in cultured rabbit articular chondrocytes.

Growth promoting activity for rabbit chondrocytes has been described as a contaminant of partially pruified TSH and LH prepared from bovine and ovine pituitaries. We have investigated fibroblast frowth factor (FGF), a small growth promoting peptide isolated from bovine pituitary tissue, in a rabbit chondrocyte system. The results suggest to us that FGF is the factor or one of the factors responsible for chondrocyte growth stimulating activity previously described in the pituitary hormone preparations. DNA synthesis in these cells is stimulated by FGF at final medium concentrations of 10(-9) g/ml. Bovine NIH-LH is not stimulatory below concentrations of 10(-7) g/ml. FGF also stimulates cell growth in the presence of 10% fetal bovine serum. Dexamethasone, at concentrations of 10(-5) to 10(-9) g/ml exerts a synergistic effect with FGF on both DNA synthesis and cell growth. Over a concentration range of 10(-6) to 10(-9) g/ml, FGF does not stimulate synthesis of sulfated mucopolysaccharides.


Enzymatic oxidation and reduction of C19-delta5-3beta-hydroxysteroids by hepatic microsomes. V. Testosterone as a neonatal determinant in rats of the 7- and 16alpha-hydroxylation and reduction of 3beta-hydroxyandrost-5-en-17-one (DHA).

The oxido-reductive metabolism of [14C]dehydroepiandrosterone (DHA) by hepatic microsomes from 40- or 70-day-old rats of either sex castrated neonatally has been compared after several treatment regimens with testosterone propionate (TP). The low transformation rate of DHA to 16-oxygenated metabolites produced by neonatal orchiectomy (0.09 +/- 0.04 nmoles min-1 mg-1), was not restored in 70-day-old males by either neonatal or pubertal treatment with TP. The rates were only partially restored (0.74 +/- 0.44) toward nromal adult levels (1.30 +/- 0.16) by the combination of neontal and pubertal treatments, in increments that maintained normal body weight but produced no visible growth of the male accessory glands. The combination of neonatal and pubertal treatments with larger doses of TP enough to produce normal accessory gland growth, stimulated the enzymatic rates of 16alpha-7alpha-, or 7beta-hydroxylases to levels that exceeded those of intact adult males. In 40-day-old males, the 16-oxygenation rate was restored by the latter regimen, but only to the levels characteristic of yound males (0.56 +/- 0.24), and young females responded more (1.03 +/- 0.33) than the males. The 7-oxygenation rate of DHA responded in both age groups to smaller doses of TP than did that of the 16-oxygenation. None of these manipulations altered the reduction of DHA to androst-5-ene-3bets-17beta-diol. We conclude that testosterone activates hepatic DHA hydroxylases in pubertal male rats only if neonatal imprinting by testosterone preceeds the subsequent stimulus. In addition, the DHA 16alpha-hydroxylase of young males is less sensitive than that of young females, but this pattern is reversed by 70 days of age. The hepatic males are both sensitive to testosterone, but the response of the glands is diminished by age.


Initiation of precocious sexual maturation in the immature rat treated with dehydroepiandrosterone.

Administration of dehydroepiandrosterone (DHA) to immature female rats on day 27 for 3 days resulted in an increase in uterine weight within 6 h of injection and a surge of FSH, LH and prolactin occurred on day 30 resulting in premature ovulation. Increase in ovarian weight and vaginal patency also occurred on day 30. Ovulations occurred at various times on day 30 and some as late as day 33 and these could be synchronized by the administration of pregnant mare serum gonadotropin (PMSG). The gonadotropin surge resulting in ovulation could be blocked by central nervous system blocking agents like phenobarbital and reserpine. The action of DHA in inducing precocious ovulation appeared to be mediated through conversion to estrogens because DHA and testosterone both of which can be aromatized to estrogens at appropriate dose elvels caused potentiation of the effect of PMSG on the secretion of gonadotropins. They also induced vaginal patency in the castrated immature rat. Dihydrotestosterone, an androgen not aromatized to estrogens did not induce precocious ovulation, vaginal patency or potentiation of the effect of PMSG in the release of gonadotropins. Furthermore, cyanoketone an inhibitor of 3beta-hydroxysteroid dehydrogenase and thus the conversion of DHA to estrogens, prevented vaginal patency and DHA-induced precocious ovulation.


The treatment of horses with chronic back pain by resecting the summits of the impinging dorsal spinous processes.

This paper describes the surgical treatment of 14 horses exhibiting chronic back pain attributed to impaction and overriding of the dorsal spines in the thoracolumbar region. The technique involved the resection of the summits of one or more dorsal spines following midline division of the supraspinous ligament. All the horses returned to full work after a convalescent period of at least four months, and 12 of them showed considerable improvement in their form and performance. A post-surgical complication encountered in one case was the development of new bone on the edge of a resected spine. This lesion, which pressed on the dorsal spine immediately caudal to it, was removed subsequently at a second operation and no further sequelae occurred.


Fetal testicular homografting for bilateral congenital anorchism.

Fetal testicular homografting, performed on a 27-year-old man with histologically proven congenital anorchism, is reported. The clinical and laboratory findings 4 and 12 months after the operation suggested that the grafted testicles were viable. No similar case has been encountered in a review of the literature.


Dehydroepiandrosterone-induced polycystic ovaries and acyclicity in the rat.

Administration of dehydroepiandrosterone (DHA) to the immature female rat resulted in one precocious ovulation followed by ovulatory failure. The animals exhibited either "constant-estrus" or "constant-diestrus" vaginal smears, and the ovaries were either polycystic or contained corpus luteum-like structures. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed an ovulatory type surge on day 30, at the time of the precocious ovulation. Thereafter, serum FSH levels were comparable to those of control rats, whereas the LH levels were very low. Serum prolactin was elevated significantly in DHA-treated animals. The ovaries of DHA-treated animals were responsive to gonadotropins and the pituitary was responsive to luteinizing hormone-releasing hormone. Withdrawal of androgen treatment resulted in restoration of cyclicity. This animal model demonstrates that an androgen insult can cause ovulatory failure and polycystic ovaries in spite of normal ovaries, adrenals, and hypothalamic-pituitary mechanisms. That such ovulatory failure is a result of the androgen administration is further substantiated by restoration of cyclicity after androgen withdrawal. This animal model in several ways is similar to the human polycystic ovary syndrome and has a potential application in the study of the mechanism of androgen-induced ovulatory failure.


The role of the dental specialist in the hospital.

As can be seen from this incomplete list of dental specialties and functions they perform in the hospital, there is an increasing participation of dental specialists in the delivery of total health care to the hospitalized patient. In order to disseminate knowledge further of the special protocols of hospital practice and of special hospital dentistry problems, the American Association of Hospital Dentists was formed and publishes a journal containing this special information.


[Study on the mode of action of dithranol: increased lipid peroxidation and enzyme inhibition].

The results reported in connection with previously published data suggest the importance of increased lipid peroxidation in the epidermis after Dithranol treatment. Malonaldehyde, one of the main products of lipid peroxidation, reacts with epidermal phosphofructokinase and glucose-6-phosphate dehydrogenase to cause enzyme inactivation by cross-linking of the enzyme protein demonstrated by dodecyl sulphate electrophoresis. Enzyme inactivation leads to an inhibition of hexose monophosphate shunt and glycolysis. The effect on energy donating metabolism in psoriatic lesions is discussed.


Observations on sodium retention related to insulin treatment of experimental diabetes.

Streptozotocin (STZ)-diabetic rats regularly retained sodium (Na+), and tended to retain potassium (K+) as well, in response to insulin. Diabetic patients have also been reported to exhibit antinatriuresis and antikaliuresis early in the course of insulin therapy. Insulin-related Na+ retention can occur without a marked reduction in blood glucose level and does not appear to be attributable to preexisting Na+ depletion, mineralocorticoid effect, or suppression of glucosuria. The decrease in urinary Na+ excretion (UNaV) in the rats incident to insulin administration was appreciably greater than the decrease in chloride (Cl-) or water excretion. The significance of this observation is uncertain. It may be, in part, a consequence of the nephrotoxicity of STZ. Insulin-related Na+ retention may be closely related pathogenetically to the Na+ retention of refeeding and may reflect a direct renal action of insulin or, less likely, an alteration of renal tubular metabolism in response to insulin-mediated changes in sytemic metabolism.


Glucose intolerance in the carcinoid syndrome.

We assayed glucose tolerance and insulin secretion in ten patients with metastatic carcinoid tumors and the carcinoid syndrome ("active tumors") and in seven patients with metastatic carcinoid tumors without the carcinoid syndrome ("inactive tumors"). The patients with "active tumors" had elevated serum serotonin levels while the patients with "inactive tumors" had normal serum serotonin levels. Of the ten patients with "active tumors," five had diabetic and three had borderline intravenous glucose disposal rate constants (KG = 0.88 +/- 0.07, M. +/- S.E.M.). Their KG was significantly lower (p less than 0.01) than a group of age-matched normals. All of the patients with "inactive tumors" had normal KG values (KG = 1.67 +/- 0.24). Their KG did not differ from that of age-matched normal subjects. Both groups of carcinoid patients had a comparable decrease in their insulinogenic index. Two days' administration of the serotonin antagonist cyproheptadine (Cypro) to eight of the patients with "active tumors" resulted in a significant increase in the "insulinogenic index" (50%) but a nonsignificant increase in the KG (12%). Administration of p-chlorophenylalanine, a compound that blocks serotonin synthesis, resulted in an increase in both the KG (60%) and the "insulinogenic index" (55%). The insulin half-life (t1/2) of patients with "active tumors" (6.1 +/- 0.4 min.) did not differ from the t1/2 of normal subjects (6.6 +/- 0.4 min.), suggesting that the decreased plasma insulin levels following intravenous glucose were due to impaired insulin secretion rather than accelerated insulin destruction. Seven of the patients received treatment with the antitumor agent streptozotocin (Strepto). The patients received cumulative doses of from 70 to 300 mg. of Strepto per kilogram body weight with no impairment in glucose tolerance or insulin secretion. We conclude that there is high incidence of glucose intolerance (80%) and impaired insulin secretion in patients with the carcinoid syndrome and that serotonin plays a role in producing these alterations.


Operant approaches to group therapy in a school for handicapped children.

In order to determine the effectiveness of operant approaches to group therapy with children with cerebral palsy or mental retardation, four boys aged between 4 years 10 months and 5 years 7 months were given a total of 23 twice-weekly 30-minute treatment sessions. After treatment there was considerably improvement in the children's attention-to-tasks and they showed some increase in social interactions, though to a lesser degree. Teacher ratings also showed some improvement in classroom behavior.


[Effect of prostaglandin E1 on the isolated stomach, small intestine, bronchus and uterus of experimental animals and its intestinal effect in vivo].

The stomach, intestine and uterus were contracted by PGE1. Stimulating effects of ACh and serotonin were augmented in some of these organs, especially in guinea pig uterus. ACh- and serotonin-induced bronchial contraction, however, decreased after administration of PGE1. Bronchial relaxation induced by adrenaline or noradrenaline was unaffected or increased. Antiadrenergic effects were not detected in the organs tested. ACh-induced contractions of frog rectus abdominus was augmented by PGE. The potentiating effect of PGE1 was almost the same in degree as that of physotigmine, although cholinesterase inhibitory effect was not detected in PGE1. Intravenous injection of PGE1 (10 mug/kg) into rabbits caused a relaxation of the intestine, which was contrary to the result with the isolated organ. Administration of PGE1 (1 mug/100 g, i.p. or 0.1, 1 mug/100 g, i.v.) did not show any curative effects on intestinal paralysis in cecectomized rats. The mechasism of action of PGE1 on rat uterus was found to be calcium-dependant.


[Inhibitory effect of taurine on ouabain-induced arrythmia].

Myocardial taurine level was found to be greater in the rat than in the guinea-pig. Taurine inhibited the development of arrhythmias caused by the i.v. infusion of ouabain in the rat. When ouabain induced arrhythmias, the myocardial taurine level decreased. Both effects were blocked by pretreatment of propranolol. The uptake of taurine into the heart did not necessarily result in the reversal of the PR interval prolonged by ouabain. The protecting effect of taurine against ouabain toxicity was not dependent upon the change in myocardial total ATPase activity.


[A comparison of radiology and endoscopy in the diagnosis of gastric and duodenal ulcers(author's transl)].

The results of endoscopy and radiology were compared in 455 patients, 250 with gastric ulcers and 205 with duodenal ulcers.  Accuracy of endo- scopy for gastric ulcers was 95% and for duodenal ulcers 92%.  Findings were judged on  the results of endoscopy.  The radiological findings were related to the endoscopic diagnosis and radiological examinations were carried out on out-patients as well as in-patients.  20% of gastric ulcers in out-patients were missed, and 10% of those in in-patients.  Of duodenal ulcers, 27% of out-patients and 8% of in-patients were missed.  Gastric ulcers missed radiologically were usually small or superficial and situated predominantly in the upper third of the stomach or in the antrum.  Duodenal ulcers tended to escape radiological diagnoSIS if they were linear in shape.  Improved technique and greater experience of the examiner increased the radiological accuracy significantly.


[False positive tumour diagnosis in the caecum(author's transl)].

Radiographic appearances simulating tumours were found in 25 patients; the causes of the mistaken diagnosis are critically analysed.  The commonest mistake was caused by inflammatory process (eight patients), caecal contents (seven patients) and an enlarged ileo-caecal valve (five patients).  Ways of avoiding such misinterpretation are described.author


[The valve of selective retrograde cholangiography in the radiological diagnosis of diseases of the biliary passages(author's transl)].

The value of selective endoscopic retrograde cholangiography in the radiological diagnosis of diseases of the biliary passages and neighbouring organs is discussed on the basis of 400 retrograde pancreatocholangiograms.  The results of this endoscopic examination were compared with the findings of all the other preoperative examinations carried out.  The diagnostic usefulness and limitations of various methods are discussed in relation to stenosis of the papilla, pancreatitis, carcinoma of the pancreas, tumours of the extrahepatic bile ducts and postoperative bile duct abnormalities.  The diagnostic accuracy of 97% emphasises the value of co-operation between radiologists and endoscopists.


[The value and limitation of echotomography in the diagnosis of abdominal lymphomas in malignant diseases(author's transl)].

The indication for ultrasonic examination in addition to endolymphatic methods is discussed.  In 23 histologically proved advanced cases the accuracy of lymphography was 77% and in echotomography 74%.  In the diagnosis of lymphonodal enlargements in the area of the liver and spleen hilium echotomography proved to be a valuable diagnostic method independent from endolymphatic methods.  In X-ray treatments echotomography enables us to estimate the therapeutic result and to evaluate the lymphonodal status.  The controls are performed in an out-patient manner.


[Xero-radiography of the thorax(author's transl)].

In over 150 patients, comparative chest examinations were carried out using films and xerography.  The following results were obtained: Using xerography, image quality depends significantly on the size and shape of the imaging structure and on its marginal sharpness.  Using a sectional technique and xerography, pulmonary vessels, bronchi, hilar structures and various linear changes are more clearly demonstrated than with ordinary film.  Xerography has no advantage in showing changes occupying a large area.  Routine use of xerography for chest examinations is limited by the size of the selenium plates and the higher radiation dose required.


[Evaluation of the pneumomediastinum for the diagnosis of tumours in the anterior mediastinum(author's transl)].

Using a correct retrosternal technique, adequate insufflation of negative contrast material and good radiography, a pneumo-mediastinum is the method of choice for the investigation of retrosternal tumours with respect to their position, size and shape.  By means of experiments on cadavers, a suitable needle was developed.  The method of air insufflation and radiographic positioning are described.  The results of our examinations are detailed and the method is discussed.


[Mucus plugs.  Phantom tumour of the major air passages.  The tomographic appearances(author's transl)].

During tomography of the major air passages, the radiologist is occasionally surprised by an appearance which is indistinguishable from an intraluminal tumour.  In addition to a genuine tumour, one must then consider the possibility of a mucus plug.  One can distinguish between these possibilities by repeating the appropriate cuts after the patient has coughed several times.  It will then be found that the position or appearance of the mucus plug will have altered, or that it will have disappeared completely.  This phenomenom occurs primarily in older patients, or patients unable to cough.  We report ten such cases.


[The intrathoracic rib(author's transl)].

The intrathoracic rib belongs to the group of additional ribs, hence the 'english synonym "supernumerary rib".  Two cases are reported.  The mode of inheritance could not be established.  Knowledge of this rare and bizarre anomaly is important in order to avoid unnecessary treatment (occasionally even a thoracotomy).


[Calcification and ossification of the posterior and longitudinal ligament of the cervical spine(author's transl)].

Three patients with calcification or ossification of the posterior longitudinal ligament of the cervical spine are described.  This abnormality is very common in Japan.  Descriptions from non-Japanese sources vary considerably.  The practical significance of this abnormality consists of narrowing of the spinal canal, which may result in a myelopathy.  Two of our patients are Chinese, the third was a white Dutchman.


[Radiological features of the rectal manifestations of myelofibrosis(author's transl)].

In addition to the well known changes in bone structure, myelofibrosis can result in extramedullary tumour formation; in the gastr-intestinal tract, proliferation of reticulum can lead to fibrotic changes.  This results in appearances similar to linitis plastica or Crohn's disease.  In the discussion, the authors refer to tumours in other organs which have been described in the literature and which can be demonstrated radiologically.


[New principles and theories for improving angio-cinedensitometry.  I. The physical principles of quotient densitometry(author's transl)].

The physical basis of quotient densitometry is described.  All stages are discussed, beginning with the production of the x-rays, their attenuation by the patient, their effect on the radiographic film, and the evaluation of the film by projection and its measurements by a photo cell in a Wheatstone bridge.  Two values were obtained, one consisting of the signal together with background fog, the other of the background alone.  By an analysis of the relationships of these measurements, obtained from specially separated points on the radiograph, it is possible to eliminate artefacts to a large extent.


[Clinical application of iodine 123 with special consideration of radionuclide purity, measuring accuracy and radiation dose(author's dose)].

Iodine 123 is a nearly "ideal" radionuclide for thyroid imaging.  The production of Iodine 123 requires cyclotrons or accelerators.  The production of multicurie amounts of Iodine 123 has been suggested through the use of high-energy accelerators (less than 60 MeV).  Most of the methods for the production of Iodine 123 using a compact cyclotron result in contamination with f.e. Iodine 124 which reduces the spatial resolution af imagining procedures and increases the radiation dose to the patient.  The radiation dose has been calculated for three methods of production.  The various contamination with Iodine 124, Iodine 125, and Iodine 126 result in comparable radiation dose of Iodine 131, provided that the time between production and application is more than four half-live-times of Iodine 123.


[Compensatory mechanisms in intra- and extracranial vascular occlusions (author's transl)].

Intra- and extracranial collaterals are described and are illustrated radiographically. The significance of these collaterals for cerebral blood flow, particularly in respect to possible surgery, is discussed.


[Changes in the vessel wall in the region of the carotid syphon (author's transl].

The present paper reviews changes in the vessel wall in the carotid syphon, including variations in calibre, stenoses, post-stenotic dilatation and aneurysms. Particular attention is paid to a supraclinoid circular stenosis, which corresponds in its localisation to the emergence of the internal carotid artery from the dura. Reference is made to new anatomical findings in this region. The haemodynamic basis of poststenotic dilatations and the development of acquired aneurysms as a result of this mechanism are discussed. Examples of post-stenotic aneurysms are demonstrated.


[Advantages in the use of teflon-catheter cannulas, compared with needles, for direct carotid angiography (author's transl)].

A method for direct carotid puncture, using a Teflon-catheter cannula, is described. The complication rate of this method is compared with the usual technique using a rigid cannula. The significant advantage of using the Teflon-cannula consists in: 1. In the absence of sub-intimal contrast injection and 2. The possibility of selectively demonstrating the internal or external arteries from the common carotid.


[Detailed demonstration of aneurysms at the base of the brain by angiotomography (author's transl].

Exact knowledge of the morphology and topography of arterial aneurysms at the base of the brain is of great importance to the neurosurgeon. Angio-tomography can provide more detailed information than any other method, particularly in the case of saccular aneurysms with short necks and aneurysms in close proximity to large, thin-walled vessels. It can also clarify the situation in the case of several vessels lying close together. Angio-tomographic examinations were performed in fifteen patients, with seventeen aneurysms. The value of angiotomography in the detailed diagnosis of basal, cerebral aneurysms, particularly of the anterior communicating artery, is illustrated by four selected case reports.


[Postural scintimyelography of the cervical spine (author's transl)].

This study discusses the clinical validity of 101 postural scintimyelograms as a screening method for cervical myelopathy. The RIHSA or Ytterbium isotope-examination are not an extra burden to the patient if the radiopharmacon is introduced into the dural sac following Queckenstedt's test. If there is a normal rise and fall of CSF pressure after bilateral jugular compression and postural scintimyelography is judged normal as well, a cervical subarachnoid obstruction may be excluded. If both examinations yield pathological results an obstructive process in the cervical spinal canal is made certain; and in cases of spondylotic myelopathy a positive contrast myelogrpahy may thus be superfluous. If the results of these two examinations are contradictory then further neuroradiolocal studies are indicated.


[The addition of nucleography to discography as an extended method of examination (author's transl)].

The information provided by discography concerning morphological changes in the disc can be increased by serial observations with estimation or rate of resorption. This occasionally makes it possible to differentiate between traumatic and degenerative disc lesions.


[Complications of cervical discography (author's transl)].

The report deals with 1,005 discographic examinations in 380 patients with a cervical syndrome. Three cases of a discitis were observed, of which two had to be regarded as complications of the examination. The aetiology, clinical features, diagnosis and differential diagnosis are described: therapeutic and prophylactic problems and possible complications are discussed. With a complication rate of 0.2%, the authors recommend contrast demonstration of the cervical disc as a supplementary radiological method for the investigation of the cervical syndrome.


[Pantopaque-myelographic findings in brachial plexus root avulsion (author's transl)].

The myelograms of 7 patients with traction injury of the brachial plexus are compared with the operation findings. It appears that not only the roentgenological sign of the "traumatic meningocele" but also other myelographic abnormalities are to be considered as indications of a nerve root lesion. These changes are demonstrated. The myelogram of a 6-months-old child showing a nerve root avulsion due to birth trauma is represented. Myelographic examination of each patient with posttraumatic brachial palsy should be performed as soon as possible. A sufficient myelographic diagnosis of the nerve root lesion can be achieved only in considering also the less impressive radiological signs.


[Neurogenic gastric tumours. Schwannomas and neurofibromas (author's transl)].

The literature concerning the definition, frequency, development and morphology of neurogenic gastric tumours is reviewed. The clinical, radiological and histological findings in eleven cases seen by the authors are described. The radiological differential diagnosis and errors in diagnosis are discussed. The significance of tumour perforation in making a type diagnosis is pointed out. There are few angiographic reports available at present.


[Disturbance of gastric emptying in diabetes mellitus (author's transl)].

The author discusses abnormalities in gastric emptying due to diabetes mellitus, and in particular, diabetic gastroparesis, on the basis of his own experience and the relevant literature. Diabetic gastroparesis is a result of a diabetic neuropathy of the vagus. Even in the presence of mild abdominal symptoms, particularly with repeated hypoglycaemic episodes, this condition should be considered and the stomach should be examined readiologically. A diabetic phytobezoar may develop. It may be presumed that these changes are more common than had previously been realized. The author has observed six cases. The gastric atony associated with diabetic coma has to be differentiated from the condition under discussion. Conservative treatment is recommended.


[The radiological diagnosis of ulcer recurrence following drainage operations (author's transl)].

Organ preserving operations for treatment of duodenal ulcers are being more widely used. Amongst the possible late post-operative complications, one must reckon with ulcer recurrence. The radiological diagnosis of a recurrent ulcer after pyloroplasty is usually difficult. An accurate knowledge of the type of drainage operation is necessary. The typical radiological findings are demonstrated in 11 cases. The localization of the ulcer niche and stenosis in the drainage territory is considered of particular significance.


[Cystitis emphysematosa (author's transl)].

Two cases of cystitis emphysematosa are described and the literature is reviewed. The aetiology, course and diagnosis are discussed, the radiological appearances being of particular importance. The cystoscopic and laboratory findings are mentioned. Cystitis emphysematosa is analogous to other conditions which cause gas to collect in abdominal organs and has similar aetiological factors.


[Intravenous cholegraphy and diaphragmatic movements in the differential diagnosis of acute cholecystitis (author's transl)].

Intravenous cholegraphy was performed in 79 patients with abdominal symptoms suggestive of acute cholecystitis. Three excretion patterns were found: 1. Opacification of the gall bladder and common bile duct. 2. Opacification of the common bile duct. 3. No opacification of the gall bladder or common bile duct. 29% showed opacification of the gall bladder and common bile duct; none of these had acute cholecystitis. 51% of cases showed opacification of the common bile duct only; 82.5% of these had acute cholecystitis. 79.4% of patients with this excretion pattern were shown to have acute cholecystitis at operation. In the other cases, absence of opacification of the gall bladder was due to obstruction of the cystic duct, caused either by concretions or fibrosis. The biliary tree was not visible in 21% of cases. The most common diagnosis was acute cholecystitis, but this excretion pattern is of limited value in differential diagnosis. The value of this examination is stressed, but it must be carried on for an adequate period. Mobility of the right diaphragm was examined preoperatively in 34 patients. Compared with patients with other diagnoses, there was a significant number of patients with acute cholecystitis who showed limited movement. The examination may be regarded as supplementary to intravenous cholegraphy in the diagnosis of acute cholecystitis.


[Planimetric volumetry of human brains].

1) Coronal sections measuring exactly 4 mm in thickness of 106 human brains (212 cerebral hemispheres) were cut with the Göttinger Hirnmakrotom. Planimetric volumetry of various macroscopically delineated structures was performed on photographs of the sections. 2) The volumes ovtained from 58 "normal cases" were used for determining preliminary standards as well as mean values and standard deviations for age and sex. The female-male ratio of the structures measured varies between 86 and 92%. Comparing right and left a predominance of the left pallidum for both sexes is apparent showing an error probability of less than 5%. In "normal" men a significant predominance of the rightsided frontal structures, located anterior to the anterior commissure, have been found (error probability of less than 1%). 3) Regarding the 48 "abnormal cases", striatum and pallidum show a uniform picture in Huntington's disease, namely an extreme shrinkage. The pallidum shrinks to a similar extent as the striatum, although its neurones are not substantially affected by this system atrophy. Other structures do not display similarly uniform changes in this disease. 4) In Parkinson's syndrome a tendency of the pallidum to enlarge -- though statistically not significant -- is seen. This raises the question whether a constitutional hyperplasia of this structure is sometimes involved in the pathogenesis. 5) In Pick's disease, it is not only the histologically impressive centers of shrinkage of the cerebral cortex that are atrophic, but, to a somewhat lesser degree, also the whole telencephalon. 6) In an 18-year-old girl with malignant obsessional neurosis (schizophrenia?) the volume of the striatum was highly above average values enlarged. 7) Bibliographical data of macroscopic-quantitative brain research reveal many problems which can be solved today due to improved methods.


Responses of guinea-pig lymphocytes to mitogens, an antigen, and mixed leucocyte culture in media with and without mercaptoethanol and foetal calf serum.

The ability of guinea-pig spleen and lymph node cells to undergo a proliferative response in vitro in the presence of mitogens (concanavalin A and lipopolysaccharide), a specific antigen (oxidized ferredoxin), and allogeneic cells was assessed under a variety of conditions. Time and dose dependency of the responses was measured in RPMI 1640, RPMI 1640 plus mercaptoethanol (ME), RPMI 1640 plus foetal calf serum (FCS), and RPMI 1640 with ME and FCS. Mitogen responses were also measured after treatment of the cells with sheep antiguinea pig immunoglobulin (SaGPIg) and complement (C') or after passage through nylon wool columns. Lipopolysaccharide (LPS) stimulated the cells under all media conditions over a wide range of concentrations but over a narrow time period. Nylon wool treatment of the cells eliminated the LPS response while SaGPIg and C' reduced it. Concanavalin A (con A) stimulated the cells under all test conditions and demonstrated a dose-time interrelationship in terms of maximum response. Pre-treatment of cells with SaGPIg and C' enhanced the response to con A while nylon wool fractionation diminished it somewhat. Only lymph node cells responded in vitro to oxidized ferredoxin (OFd). In serum-free media the OFd responses were maximal at 48 hours whereas in media containing FCS proliferative responses were supported for a prolonged period and appeared to be bimodal. Except for an early response with RPMI 1640 and ME, only media containing FCS supported stimulation in the mixed leucocyte culture.