[Determination of splenic size by ultrasonic scanning (author's transl)]. Two dimensional B-Scans make it possible to examine and measure the spleen. In 62 patients the size of the spleen was evaluated by ultrasound; the results were compared with the size of the organ after extirpation: In 58 of 62 cases there were correct results. Therefore, the ultrasonic determination of the splenic size is a reliable method for clinical questions.


[Congenital dyserythropoietic anemia type II. Another case report]. Hematologic evaluation of a 29-year old man with jaundice since childhood demonstrated the characteristic findings of congenital dyserythropoietic anemia (CDA) type II. This type is characterized by ineffective erythropoiesis, multinuclearity of erythroblasts, electron-microscopic abnormalities of the red cell membrane, and abnormal serological reactions. Because of severe anemia repeated transfusions were necessary. After splenectomy thrombosis of the portal vein occurred. The patient died from hemorrhage due to ruptured esophageal varices.


[Familial occurrence of chronic lymphocytic leukemia: report of three siblings (author's transl)]. Chronic lymphocytic leukemia was diagnosed in three siblings. Familiar occurrence speaks in favor of a predisposition in this disorder of unknown etiology. According to the present status of knowledge endogenous - genetically determined - factors combined with exogenous factors (viruses, radiation exposure, toxic substances) participate in the etiopathogenesis of the different forms of leukemia.


[Refractory anemia with hypercellular bone marrow and preleukemia (author's transl)]. In refractory anemia with hypercellular bone marrow and in preleukemia the primary cellular defect probably is located at the level of the morphologically not definable stem cell. This defect causes reduced proliferative activity and ineffectivity of the morphologically definable stem cell and consequently is accompanied by peripheral cytopenia. The disarrangement of cellular metabolism first of all manifests itself in morphological anomalies of bone marrow hemopoietic cells. Using 17 own observations and in reference to previous literature the manifold manifestations of this disturbance are described.


[The occurence of multiple diseases in high-aged patients (author's transl)]. Analysis of 1385 autopsies of 80-102 year-old patients was performed to investigate the frequency of simultaneous occurence of the following functionally pertinent diseases in one organism (polypathia): Severe aortic, coronary and cerebral arteriosclerosis, chronic pulmonary emphysema, contracted kidneys, fractures of the femur and malignant tumors. 80% of all patients of both sexes suffered from 2-4 of the above diseases. Even in the highest age group, however, 5 and more of the above diseases were very rarely developed. Patients with none of the above diagnoses were almost never encountered. The "polypathia" was stated also in patients who died by suicide or accident.


On the structure of the carbohydrate chains of different strains of the influenza virus. Structural features of the glycosyl chains of the influenca virus have been determined. It was found that fucose was solely terminal, whereas mannose and galactose were present at the terminal as well as subterminal and core positions. Mannose and glucose molecules were shown to be branching points in the glycosyl chains. Furthermore, linkage positions of carbohydrates within the chains were characterized.


The hamster as an experimental animal for the study of influenza. I. The role of antibody in protection. Hamsters were used to examine the role of serum antibody in protection against influenza virus infection. Following intranasal instillation, influenza viruses replicated well in these animals, and high, reproducible amounts of virus could be subsequently recovered from nasal washings and lung suspensions. A specific serum antibody response to the infecting virus was also observed; but no local antibody production was detected. The passive transfer of serum antibody gave some measurable protection, against homologous influenza virus challenge, to recipient hamsters. However, evidence that protection can occur in the absence of detectable serum antibody in individual hamsters, is also presented.


The hamster as an experimental animal for the study of influenza. II. The role of spleen cells in protection. Hamsters previously infected by influenza viruses, have been shown to have a cell-mediated immune response, as measured by the macrophage migration inhibition test. The participation of spleen cells in the protection of recipients against homologous influenza virus infection was also demonstrated using adoptive transfer experiments. However, the protection achieved by spleen cell transfer was marginal and not observed in every animal. The time at which the spleen cells were transferred following infection, and their number, affected the outcome. Evidence suggesting that transferred spleen cells protected recipient hamsters through specific antibody is presented.


[Distribution of species of Moraxella and moraxella-like organisms in the nasopharynx of healthy human adults (author's transl]. By means of a lincomycin containing selective medium, gram-negative, oxidase-positive, non-motile, non-saccharolytic, penicillin-sensitive rods have been isolated from 24 of 165 healthy adults (13,9%). Three strains were lost, 7 strains were Moraxella osloensis (4,2%), 12 strains were Neisseria elongata (7,3%) and 2 strains were considered to be a subspecies of N. elongata (1.2%). By agglutination and immunodiffusion could be demonstrated that N. elongata is a serologically heterogenous species. The nasopharynx seems to represent the natural habitat of M. osloensis and N. elongata.


A comparison of the evolution of transmitted IgG immunoglobulin and diphtheria antitoxin titers in the newborn. The evolution of the titers of transmitted IgG and diphtheria antitoxin was studied in 20 neonates during the first 2 months of life (6 serum samples for each). A rapid fall of the passive IgG titer was observed during the first weeks: as a rule the higher the initial titer the greater the fall. After the 15th day the rate of decline slows down. The evolution of the titer of transmitted maternal diphtheria antitoxin depends also on the initial level, and if it is low it can remain more or less constant for a long time. The initial level of passive IgG does not influence the drop in diphtheria antitoxin titre and vice versa. Therefore, the evolution of total IgG and diphtheria antitoxin levels appear not to be interdependent.


Comparison of the clinical course of Hodgkin's disease in children and adolescents. In this study the clinical features and response to therapy of 34 children, 4--10 years of age, and 54 adolescents, 11--20 years of age, were compared. The therapeutic response in patients in this series entered on a formal protocol was compared with nonstudy patients. The 2 age groups had similar sex ratios, characterized by male predominance, and age was not a determining factor in the extent of disease at diagnosis. By contrast, the distribution of histopathology varied between children and adolescents: mixed cellularity was most prevalent in the 4--10-year group (14/34), while nodular sclerosis predominated the older patients (23/55). Remission induction and duration were not age dependent, but remission duration did differ between study and nonstudy patients. Forty-five of 57 patients in the former group remain in continuous complete remission compared to 7 of 31 in the latter group. From these results we conclude that the clinical course of Hodgkin's disease is similar in children and adolescents and that the agressive therapy combined with careful staging used so successfully in adults should be adhered to in younger patients.


Improved prognosis in disseminated histiocytosis. The prognosis for children with disseminated histiocytosis, previously considered poor, has improved dramatically with the application of modern principles of chemotherapy. Fourteen children with histiocytosis were staged clinically as follows: those without organ dysfunction, stage I; those with organ dysfunction, stage II; and histologically (B, benign and M, malignant). They were treated with either oral chlorambucil or combination chemotherapy with vinblastine and other agents. Clinical staging was of value in predicting response to treatment and prognosis, while histologic staging was of less value. Thirteen of the 14 children responded to treatment and are alive 4 to 67 months (median 12 months) after diagnosis. Two of these relapsed on treatment, and they have responded to a change in therapy. Two children relapsed after stopping treatment and were reinduced with reintroduction of similar therapy. Initial response to treatment suggests a favourable outcome, for children who initially responded to treatment but relapsed subsequently responded to either reintroduction of the same treatment or a change in treatment.


Sporadic bilateral retinoblastoma and 13q- chromosomal deletion. Unilateral retinoblastoma (Rb) is usually a sporadic occurrence while bilateral (multifocal) cases are often familial. Sporadic bilateral Rb associated with a long-arm deletion of a D-group chromosome has been reported in 8 children. We have studied a 6-year-old female with bilateral sporadic retinoblastoma, treated during infancy by enucleation and radiotherapy. Chromosome banding studies on peripheral lymphocytes revealed an interstitial deletion from the long arm of a chromosome 13: del(13) (q12q14). Three additional patients reported in the literature had interstitial 13q- deletions, involving slightly different though overlapping regions. The only chromosomal region consistently missing in all of these 4 cases appears to be part of the lightly staining band 13q14. We, therefore, propose this site as the precise location of a gene (or genes) involved in retinal development. Our patient lacked features of the classic 13q- or 13-ring syndrome, which involves deletion of a more distal portion of the 13 long arm. When compared to reported patients with Rb and 13q-, it became apparent that there may be a separate recognizable syndrome consisting of moderate growth and developmental delay, characteristic facies and external ears, and bilateral sporadic Rb, which is associated with an interstitial 13q- deletion.


Evaluation of dose and schedule of L-asparaginase in multidrug therapy of childhood leukemia. Six regimens utilizing L-asparaginase in doses of 6,000 IU/M2, 2,000 IU/M2, and 500 IU/M2 in two separate schedules (consecutive and intermittent) along with vincristine and prednisone yielded remarkably similar response rates, approximating 70%, in 306 previously treated children with acute leukemia in relapse. The addition of daunorubicin to one regimen did not alter the response rate. Hypersensitivity reactions occurred in 5% and hyperglycemia in 7%. Lower doses of L-asparaginase significantly reduced the hypersensitivity rate but no such pattern was noted for hyperglycemia. A history of prior resistance to prednisone and vincristine significantly reduced the response rate.


Closed-system ionography for diagnostic radiology. Three methods are described whereby radiographic electrostatic images are transferred from inside of a liquid ionography chamber to the outside. One of these methods is implemented showing that multiple-charge images can be transferred from a single original without significant degradation of image quality and each copy may be developed with a different amount of edge contrast. This new method of imaging was applied to a radiograph of a test pattern and a hand phanton. An exposure of about 6 mR to the imaging chamber is needed to produce a useful image with a resolution of about 8 1p/mm.


Saturation curve in gases of high atomic number at pressures up to 8 atm. Part II: Freon 13-B1, and mixtures of Freon with xenon and krypton. The saturation curve has been studied in Freon 13-B1 (CF3Br) and in mixtures of Freon with xenon and krypton up to a pressure of 8 atm. The enhanced initial recombination due to the electron affinity of Freon has been evaluated and an empirical formula constructed that describes the fraction of current which escapes initial recombination over a wide range of voltages, pressures, and electrode spacings. After correction for this initial recombination, the general saturation curve for Freon and for mixtures of this gas with krypton and xenon has been derived and, again, convenient empirical formulae established which allow the current collection efficiency to be calculated for any given parameters within the range investigated. These formulae are of practical value in the design of image-forming ionization chambers.


On the application of a liquid-dielectric ionization chamber to 252 Cf dosimetry. Our investigations of an iso-octane-filled liquid-dielectric ionization chamber indicate that this dosimeter is well suited for the measurement of dose distributions at distances close to 252Cf interstitial implant sources. Initial research has shown that such an instrument provides good discrimination between the radiation components of a mixed field and possesses excellent sensitivity. Calculations indicate that iso-octane will yield a neutron and gamma-ray dose response independent of energy over a major part of the 252Cf spectral range, while transmission measurements have demonstrated that the liquid causes little perturbation of the radiation field.


NMR relaxation behavior in living and ischemically damaged tissue. A study by pulsed NMR techniques in living liver tissue has led to the discovery that the observed longitudinal relaxation decay behavior is strongly multicomponent. After death of the experimental animal, the relaxation decay curves evolve toward a single-component behavior. These changes can also be observed within a few minutes after the liver is excised and placed in a test tube, and they involve a high degree of quantitative and qualitative regularity and reproducibility. An excellent description of all observed NMR behavior is obtained from a dynamic two-compartment model. Rapidly relaxing volumes exchange water molecules with slowly relaxing volumes; associating only an increasing water molecule exchange rate with increasing ischemia accounts in quantitative detail for all observed changes. The exchange-rate values and their variation with tissue deterioration are in good agreement with that estimated for intra- to extracellular water exchange as limited by cell-membrane osmotic permeabilities. Possible applications of these results in different biomedical areas are discussed.


Nuclide parameters and S factors for 201Tl dosimetry estimates. The mean numbers per disintegration, n, and equilibrium-dose constants delta for the various emissions of 201Tl were computed. The sums of the penetrating and nonpenetrating equilibrium-dose constants are 0.1931 and 0.0874 g rad/muCi h, respectively. The S factor, the value of that portion of the MIRD dose equation which is independent of biological distribution, was calculated for various combinations of target and source organs.


Direct-response ultraviolet thermoluminescent dosimeter. An integrating solid-state dosimeter has been developed to detect ultraviolet radiation using the process of "direct" ultraviolet stimulation. This process yields a thermoluminescent signal after an exposure to ultraviolet radiation, without prior exposure to ionizing radiation. Magnesium oxide crystals were found to show a directly stimulated thermoluminescent glow peak at 145 degrees C which can be utilized as a linear, energy-independent ultraviolet dosimeter.


LambdacI mutants: intragenic complementation and complementation with a cI promoter mutant. Complementation for the maintenance of lysogeny was studied by superinfecting lambdacIts lysogens at 34 degrees C. and then heating to 43 degrees C. With certain exceptions, ts mutants with defects in the left half of the repressor complemented ts mutants with defects in the right half to produce a less heat-labile repressor (Fig. 3). All cI amber mutants failed to complement cIts mutants. The cI mutant c50 complements all ts mutants. Mutations in Pre (cy) or genes cII and cIII do not significantly affect the expression of cI by a superinfecting lambda genome in an immune lysogen. Mutants with very heat-labile repressors failed to complement lambdacy42 for the establishment of lysogeny at elevated temperatures, while those with less heat-sensitive repressors apparently did complement cy. According to a suggested model, the left side of the cI product is concerned primarily with subunit aggregation, while operator binding is the function of the right side of the oligomer.


Heat-sensitive DNA-binding activity of the cI product of bacteriophage lambda. The binding of lambda gene cI product to lambda DNA was studied at temperatures from 0 degrees C to 46 degrees C. Binding activity of the products of cIts mutants was higher at 22 degrees C than at 0 degrees C, 26 degrees C or 30 degrees C. Both cI+ and cIts products lost DNA-binding activity at 46 degrees C, but after subsequent cooling to 22 degrees C, they regained 50-100% of their activity.


Interconversion phenomena between two kinetic forms of class a pyruvate kinase from Ehrlich ascites tumor cells. 1. The regulatory properties of two interconvertible kinetic forms of class A pyruvate kinase from Ehrlich ascites tumor cells have been studied with a partially purified enzyme preparation free of interfering enzymatic activities. 2. The hyperbolic form shows Michaelis-Menten kinetics for P-pyruvate, with high affinity for this substrate and low affinity for the inhibitory amino acids alanine and phenylalanine. The sigmoidal form displays positive cooperativity respect to P-pyruvate (n=1.4), with lower affinity for this substrate and higher affinity for the inhibitory amino acids. 3. The equilibrium between the hyperbolic and the sigmoidal forms of the enzyme is affected by substraetes and effectors. P-pyruvate, ADP and Fru-P2 shift the equilibrium to the hyperbolic form while ATP, alanine and phenylalanine stabilize the sigmoidal form. 4. Effector metabolites affect the molecular weight of the protein, acting on an equilibrium between dimers and tetramers. P-pyruvate and ADP associate the enzyme to a tetramer while ATP, alanine and phenylalanine favor the occurrence as a dimer. The positive modifier Fru-P2 did not associate the enzyme to the tetramer, even at 1 mM concentration. 5. A tentative molecular model for pyruvate kinase A on the basis of the kinetic and aggregation interconversion is proposed.


Cell recognition among blood leukocytes: a new theory for cell recognition. Blood leukocytes exhibit specific cell type recognition. Neutrophils adhere to neutrophils, eosinophils to eosinophils, basophils to basophils and monocytes to monocytes. Rather large homotypic aggregates are formed. These are almost abolished by prior treatment of the cells with trypsin. It is assumed that a protein is involved in this type of cell recognition. Protein monomer-monomer interaction could provide the specificity required in homotypic aggregate formation.


Glycolytic metabolism in cultured cells of the nervous system. IV. The effects of thiamine deficiency on thiamine levels, metabolites and thiamine-dependent enzymes on the C-6 glioma and C-1300 neuroblastoma cell lines. C-6 glioma and C-1300 neuroblastoma cells were cultured in thiamine deficient and control media. Thiamine levels, transketolase and pyruvate decarboxylase activities, and high energy phosphate metabolites were all measured in deficient and control cells. Thiamine levels in the deficient cells were found to be below the level of detectability. Pyruvate decarboxylase activity was more susceptible to thiamine deficiency in both cell lines than transketolase. In spite of the large decrease in pyruvate decarboxylase activity, high energy phosphate metabolites were not decreased in either cell line. These data indicate that C-6 glioma and C-1300 neuroblastoma cells have the capacity to maintain normal energy metabolites in the presence of large changes in thiamine levels and thiamine dependent enzyme activity.


Studies on iron uptake and micelle formation in ferritin and apoferritin. Iron uptake and micelle formation in ferritin and apoferritin have been followed both spectrophotometrically and by means of sedimentation velocity experiments. Information was thus obtained on the molecular weight distribution of the reconstitution product. To achieve incorporation 'native' ferritin (whole ferritin as purified from horse spleen), 'native' apoferritin (apoferritin prepared by fractionation of ferritin preparations) and 'reduced' apoferritin (apoferritin prepared by reduction of ferritin by dithionite or ascorbic acid) have been incubated with ferrous salts in the presence of oxidizing agents under different experimental conditions. Although some iron is incorporated in 'native' ferritin, full saturation is not achieved and the molecular weight distribution of the incubated products remains heterogeneous. 'Native' and 'reduced' apoferritin show a similar iron incorporation, but the reconstitution products markedly differ in terms of their iron distribution. Ferritin reconstituted from 'native' apoferritin has a broad molecular weight distribution, while that reconstituted from 'reduced' apoferritin is characterized by a narrow, homogeneous molecular weight distribution. However treatment of apoferrition with reducing or oxidizing agents prior to the incubation alters the characteristics of the iron distribution without changing the iron incorporation properties. These results point to a role of the protein moiety not only in iron oxidation, but also in micelle formation.


Proton magnetic resonance spectroscopic studies of proteins containing deuterated tryptophan residues. The deuteration of the tryptophan residues of hen egg white lysozyme, bovine alpha-lactalbumin and bovine beta-lactoglobulin in d-TFA has been studied by PMR spectroscopy. It is found that short times of exposure to d-TFA allow selective deuteration at the C-2 position with only a small amount of deuteration at the C-5 position, as expected from studies on model peptides described in the previous paper. The proteins studied essentially regained their native structures after the treatment, except for broadening and shifting of the histidine resonances in the case of alpha-lactalbumin. Selective deuteration at the tryptophan C-2 position was readily observed by difference spectroscopy of the denatured protein, but PMR difference spectra of the same proteins in benign solvents did not contain resonances from all of the exchanged protons. Some resonances would not be observed because of line broadening, which causes the resonances to fall below the limit of sensitivity of detection at 100 MHz. Deuteration by brief exposure to d-TFA should be useful for the identification of tryptophan resonances in the PMR spectra of native proteins. The deuteration of all the aromatic protons of tryptophan residues in proteins by immersion in d-TFA for 4 hours at room temperature was studied. This technique is unlikely to be of general use for the simplification of the aromatic region of the PMR spectra of native proteins because of the degradation of tryptophan residues which results from the acid treatment.


Phosphorylation of casein by mitochondrial protein kinase(s). At least two protein kinase activities are bound to the rat liver mitochondrial membranes. Both activities are found to phosphorylate, besides endogenous proteins tightly bound to the membrane structures, also exogenous phosphoproteins such as casein and phosvitin. However one is able to phosphorylate both casein-bound serine and threonine residues, while the other is phosphorylating almost only serine residues.


Pyruvate kinase activity and gluconeogenesis in rat liver after glycogen depletion with nicotinic acid. Nicotinic acid administration, which depletes liver glycogen, leads to an increase of both pyruvate kinase L and phosphoenolypyruvate carboxykinase in liver by a factor of nearly two. The former is not prevented by either cycloheximide or actinomycin D. L-Cysteine, an allosteric inhibitor of pyruvate kinase L, favors gluconeogenesis from lactate in both nicotinic acid treated and starved animals.


Some properties of rat liver mitochondrial RNA polymerase. A rapid method suitable for purifying large amounts of mitochondria from rat liver using isopycnic zonal centrifugation is described. The RNA polymerase isolated from the purified mitochrondria was found associated with one peak when resolved by DEAE Sephadex chromatography. The enzyme was next fractionated on a phosphocellulose column followed by glycerol gradient centrifugation. A 600-fold purification was achieved when the enzyme was finally filtered through agarose gel. This final enzyme fraction consisted of one polypeptide chain as shown by polyacrylamide gel electrophoresis profiles. The enzyme has a greater preference for poly [d(A-T)] templates than for rat liver mitochondrial DNA. Inhibition of the enzyme activity required high concentrations of the inhibitors. The resistance of the enzyme to alpha-amanitin indicated that there was no contamination from nuclear RNA polymerase II. The conclusion is drawn that the mitochondrial RAN polymerase activity is associated with a single polypeptide.


Biochemical characteristics and biological significance of the genetically-distinct collagens. In recent years it has become evident that genetic polymorphism is dramatically expressed in the structural protein, collagen. Current information on the biochemical properties, biosynthesis, and tissue distribution of Type I, II, and III collagens is summarized with special reference to possible unique functional roles fulfilled by each of these collagens.


A study of histone-histone interactions by affinity chromatography. Homologous whole histone from calf thymus was adsorbed on Sepharose 4B columns with covalently coupled histone fractions H2a, H2b, H3 or H4 in 0.01 M phosphate buffer, pH 6.7 - 1 M NaCl. The adsorbed histones were eluted from the columns with 5 M urea in the same buffer. Electrophoretic analysis has shown that the different columns exhibit selective affinity to the histone fractions: the H2b column to histone H2b and H2a (with only weak affinity to histones H3 and H4), the H2a column to histones H2b and H3 (moderate affinity to histone H2b), and the H4 column to histone H3, H4 and H2b (weak affinity to histone H2a). Histone H1 displayed no fixation by either of the columns tested.


Free DNA stretches in histone H1-depleted chromatin and their possible relation to chromomere structure. Oligomers of chromatin subunits (oligonucleosomes) were prepared by a mild digestion of chromatin with staphylococcal nuclease followed by a purification of a high molecular weight material (hexanucleosomes and larger DNP particles) by gel chromatography. The main finding is that a mild removal of histone H1 from the oligonucleosome preparation by treatment with tRNA in the absence of any significant hydrodynamic shearing leads to the formation of free DNA molecules which constitute 5-6% of the total oligonucleosomal DNA. The size of nucleosome-free DNA stretches in H1-depleted hydrodynamically sheared chromatin is about 6000 base pairs and their content is apparently 10-12% of the total DNA. These and related findings are discussed in terms of the previously proposed "asymmetric hairpin" model of DNA packing in chromatin [1-4]. Different kinds of the asymmetric hairpin are considered and ambiguities in interpretations of experimental data are pointed out.


Processing of RNA by cytoplasmic extract. Synthesis and processing of RNA by isolated HeLa cell nuclei incubated with cytoplasmic extract. Nuclei are isolated from HeLa cells by a low speed centrifugation procedure. These nuclei can carry out RNA synthesis at 30 degrees. The effect of cytoplasmic extract on the transport and processing of RNA is measured. In the presence of cytoplasmic extract the precursor to 4S RNA is processed to 4S RNA and an RNA species OF 7-9S is transported outside the nuclei.


Crystallization of DNA fragments from water-salt solutions, containing 2-methylpentane-2,3-diol. Fragments of calf thymus DNA have been crystallized by precipitation from water-salt solutions, containing 2-methylpentane-2,3-diol (MPD). DNA crystals usually take the form either of spherulites up to 100 mu in diameter or of needles with the length up to 50 mu. No irreversible denaturation of DNA occurs during the crystallization process. X-ray diffraction from dense slurries of DNA crystals yields crystalline powder patterns.


Sedimentation studies on membrane vesicles. Analytical centrifugation was used in order to investigate the size distribution of vesicles in various membrane preparations. Under certain conditions depending among others on the speed of rotation and the temperature, a sedimentation profile was observed that was characteristic for membraneous material. Since the membrane vesicles exhibited a discontinuous distribution of sedimentation coefficients it was concluded that membrane vesicles only occur in a few size classes.


[ Polyclonal gammopathy in children with infectious mononucleosis (author's transl)]. Serum proteins and immunoglobulins were investigated in children with infectious mononucleosis. The results were as follows: 1. Most striking changes in serum protein patterns were increased levels of immunoglobulins. The resulting gammopathies are of symmetric and/or asymmetric type with a beta-gamma bridge.--2. Increased levels of immunoglobulins included all principal immunoglobulin classes IgG, IgM and IgA.--3. Polyclonal gammopathy in infectious mononucleosis did neither reflect the intensity of hepatic involvement nor was a sign for persisting or progressive hepatitis.--4. The type of gammopathies found seems to justify those clinicians, who did not consider to be usefull the application of gammaglobulin in the course of infectious mononucleosis. 5. Suggestion. If it is correct to assume according to Benyeschel-Melnick et al., that the raised production of antibodies in infectious monucleosis limits the further course of the disease, and is the defense against the development of leukemia, it would be necessary to reevaluate the application of corticoid therapy in infectious mononucleosis. This therapy should be reserved for life threatening complciations only.


[Acute renal failure in childhood (author's transl)]. From 1960 until 1975 we treated 88 children with acute renal failure. The majority of these patients were infants and children up to three years. In this report the etiology, symptomatology and prognosis of acute renal failure in childhood are discussed. During the last years the cases observed were more severe, especially when associated with the haemolyticuraemic syndrome. The overall mortality was 27%, and did not change since the introduction of dialysis. Important prognostic factors are discussed.


[Surgery in Diagnosis and therapy of infant rheumatoid arthritis (author's transl)]. In our hospital, diagnostic surgery is applied in as follows: confirmatory incisions of joints, excision of rheumatic nodulis, tissue excision of skin and muscles (dermatomyositis?), excision of mucosa of the rectum (amyloid?) and open biopsy of the kidney (amyloid?). Therapeutic measures are: total synovectomy of the knee joints or other joints, teno-synovectomy at the hands; treatment of contractions of the hip by myotenotomies and of the knee-joint by elongation of tendons and treatment of knock-knee by incision of the tractus ilio-tibialis and elongation of the tendon of the bicipital muscle.


Failure of X-rays to mutate class II histocompatibility loci in Balb/c mouse spermatogonia. Adult Balb/c Kh male mice were irradiated (pelvic region, 250 kVcp X-rays, 60 rad per min) and three months later were mated to untreated C57BL/6 Kh females. Their B6C F1 progeny were screened for mutations at the Class II histocompatibility loci, i.e. those that carry similar alleles in the parental lines and are therefore homozygous in the F1 progeny. The treatment groups were: single doses of 0, 350, 500, 650 and 800 rad; split doses 1 day apart, totalling 500, 650 and 800 rad; split doses averaging 52 days apart, totalling 650 and 800 rad. Thirty-six mutants were identified in 13,614 progeny. Twelve of them occurred in five clusters of two or three, presumably owing to five gonadal mosaics among 940 parents. Irradiation did not increase the spermatogonial mutation rate. The only effect of exposure appeared to be a decrease in the mutation rate of the 1-day split dose-groups compared to those with the same total doses in a single exposure or in two fractions, 52 days apart.


The effect of sodium fluoride on DNA synthesis, mitotic indices and chromosomal aberrations in human leukocytes treated with trenimon in vitro. Human leukocyte cultures were set up with Ham's F-10 medium and stimulated with PHA-M. Treatment of the cells in G1 from 15-20 h with 0.5 X 10(-6) M Trenimon resulted in a considerable cell cycle delay, as measured by [3H]-TdR autoradiography and determination of mitotic indices. Under these conditions only few cells incorporated the tracer at the same time as most cells did in untreated cultures. However, this did not lead to a mitotic activity at the same time as obtained in controls. Most of the treated cells started their DNA synthesis and mitotic activities with a delay of around 20 h, as compared with the controls. Continuous treatment of the cells with 10(-3) M NaF had no effect on [3H]TdR labelling or mitotic indices in otherwise untreated cultures, but led to an impressive effect on DNA synthesis in Trenimon-treated cultures, without a considerable effect on the mitotic indices. This finding could be explained as due to a lower alkylation in cellular DNA in the presence of NaF. More cells can start with their DNA synthesis, although they are, like Trenimon-treated cultures, incapable of completing it normally. Analysis of the effect of NaF on chromosome aberrations induced by Trenimon revealed that pre-, simultaneous and post-treatments significantly enhanced the frequency of undamaged mitoses. Continuous fluoride treatment also protected the cells from Trenimon-induced damage, but the effect was not significant, possibly because of heavily damaged mitoses which appeared under these conditions. We interpret our findings as an indication of a real anti-mutagenic activity of NaF.


A correlative study on the genetic damage induced by chemical mutagens in bone marrow and spermatogonia of mice. I. CNU-ethanol. Cytogenetic damage induced by a wide range of concentrations of CNU-ethanol in mice was evaluated by determining the frequencies of (a) micro-nuclei in polychromatic erythrocytes of the bone marrow, (b) chromatid aberrations in bone marrow, (c) chromatid aberrations in spermatogonia, and (d) reciprocal translocations induced in spermatogonia and scored in spermatocytes. For CNU-ethanol the following order of sensitivity was found between the tests performed: micronuclei greater than aberrations in bone marrow greaer than aberrations in spermatogonia greater than translocations in spermatocytes. Correlation coefficients were calculated for the first three parameters. Positive correlations existed (a) between micronuclei in polychromatic erythrocytes and chromatid aberrations in bone marrow on the first day after treatment, and (b) between chromatid aberrations in bone marrow and spermatogonia at the first day after treatment. Three reciprocal translocations were induced in spermatogonia and recorded in primary spermatocytes; all were of a rare type, namely between an X chromosome and an autosome.


Normal DNA strand rejoining and absence of DNA crosslinking in progeroid and aging human cells. We have measured by alkaline elution and alkaline sedimentation the rate of rejoining of X-ray induced DNA single-strand breaks in terminally senescent cultured WI-38 cells. Using the alkaline elution method, we have also measured the rate of ligation in cultured progeroid cells. In both cells and by both methods of measurement the rates of strand rejoining were normal. Alkaline elution failed to disclose any DNA crosslinking in these cells.


X-ray diffraction studies of circular superhelical DNA at 300-10,000-A resolution. X-ray diffraction studies on circular superhelical DNA from bacteriophage PM2 at a very low scattering angle show that it is possible to measure the superhelical scattering function of the molecule. The results suggest that in addition to the primary supercoil, a higher order of supercoiling of the DNA is present, an effect which can be interpreted with a simple analogue.


All oxygens in nucleic acids react with carcinogenic ethylating agents. Over 80% of ethylnitrosourea and ethylnitrosoguanidine modification of nucleic acids is on oxygens. The reactivity of oxygens (other than ribose and phosphate) in single-stranded RNA is: O2 of C greater than O2 of U greater than O6 of G greater than O4 of U. In double-stranded DNA the order is: O2 of T equals O6 of G greater than O4 of T greater than O2 of C. Oxygen reactivity of single-stranded DNA resembles RNA. The glycosidic bond of O2-alkylpyrimidines is labilised.


Cell surface distribution of lectin receptors determined by resonance energy transfer. The surface topography of concanavalin A (con A) bound to normal and transformed murine fibroblasts has been studied by a new technique involving fluorescence resonance energy transfer (RET), RET can provide a high resolution "map" of the distances separating con A-receptor complexes in single living cells. The distribution of con A is non-random in both normal and transformed cells, but sites are more closely approximated in the transformed. Approximation is induced by the con A but occurs at extremely slow rates indicating that the topography is not primarily determined by simple diffusion of complexes.


Crystallographic structure studies of an IgG molecule and an Fc fragment. The crystal structures of a human IgG antibody molecule Kol and a human Fc fragment have been determined at 4-A and 3.4-A resolution respectively, by isomorphous replacement. The electron-density maps were interpreted in terms of immunoglobulin domains based on the Rei and McPC 603 models (Kol) and by model-building (Fc). The Fab parts of Kol have a different quaternary structure from that observed in isolated crystalline Fab fragments, there being no longitudinal V-C contact in Kol. The Fc part C terminal to the hinge is disordered in the Kol crystals. It is suggested that the Kol molecule is flexible in solution, whereas fragments are rigid. In the Fc fragment both CH3 and CH2 show the immunoglobulin fold. The CH3 dimer aggregates as CH1-CL while CH2 are widely separated from each other. The carbohydrate bound to Fc is in fixed position. From these structures a hypothetical liganded antibody molecule has been constructed, which is assumed to be rigid.


Nuclease cleavage of chromatin at 100-nucleotide pair intervals. Digestion of mouse liver nuclei with DNase II leads to a novel cleavage pattern with a 100-nucleotide pair periodicity. From chromatin, this pattern or the standard 200-nucleotide pair repeat can be produced depending on the ionic conditions. The results are interpreted by assuming different conformational states of the nuclear material, including condensed and extended forms.


Significant journals of science.

Significant journals of science. In 1974 the Science Citation Index (SCI) covered about 401,000 articles and communications in 2,443 scientific and technical journals. They cited about 3.2 million different publications an average of 1.8 times each. In this article some results of an analysis of more than 5 million citations in the references of journal articles indexed for the SCI in 1974 are presented and an attempt is made to interpret of those results in the light of an earlier study of 1969 citations.


Spectral sensitivities and photopigments in adaptation of fly visual receptors. Chromatic adaptation and receptor-deficient mutants have been used to systematically eliminate specific receptor function to provide the first complete spectral sensitivity and photopigment characteristic data of all three receptor types (R1-6, R7 and R8) in Drosophila compound eyes. Different fly genera have different adaptation responses which allow characterization of photopigment spectra. Drosophila mutants with anomalous excitation also reveal mechanisms coupling photopigment activation with receptor excitation.


[Corrective steps in amino acid activation for protein biosynthesis]. Activation of aminoacids for proteinbiosynthesis is not absolutely specific. With tRNA modified at the 3' end we were able to show, that valine misactivated by isoleucyl-tRNA synthetase is transferred to tRNA(I1e). Val-tRNA(I1e) is then hydrolyzed by the enzyme prior to release of the wrong product. For this hydrolysis the nonaccepting 3'OH of the 3'-terminal ribose is essential. The role of the 3'OH is to activate a water molecule which, in the case of valine, is inserted into the place normally occupied by the methyl group of isoleucine. Hence hydrolysis is specific for misactivated valine while the correct substrate, isoleucine, is protected by its additional methyl group.


[Glomus caroticum. A model to understand chemoreception]. To understand the chemoreceptive process of the carotid body we have investigated under which conditions the chemoreceptor is stimulated and which part is taken over by its different cell elements in this process. In this way it was possible to open the "black box" as Torrance called the carotid body to prove all the hypotheses and models about the chemoreception in the carotid body.


[Biochemical and clinical aspects of alcoholic liver damage]. Alcoholism is the most common form of drug abuse and alcoholic liver disease is a major health problem which in terms of increasing incidence is only rivaled by viral hepatitis. Cirrhosis of the liver, most of which is probably alcoholic, is among the leading causes of morbidity and mortality between the ages of 25 to 65 in Western countries. Alcoholic liver disease includes adaptive and toxic ultrastructural alterations, alcoholic fatty liver, alcoholic hepatitis and alcoholic cirrhosis, later accompanied by hepatoma.


Effect of tetraethylammonium and barium on the release of noradrenaline from the perfused cat spleen by nerve stimulation and potassium. The effect of tetraethylammonium (TEA) and barium on release of noradrenaline (NA) from the cat spleen by nerve stimulation or potassium was investigated. 2. In spleens perfused with normal Krebs solution, the NA output at 5 Hz was barely detectable, and the output at 30 Hz was about 5-fold greater than the output at 5 Hz. 3. TEA (1 mM) or barium (2.5 mM) increased NA output at 5 Hz by 5-fold, but did not enhance it at 30 Hz. A maximal effect of TEA was obtained at about 1-3 mM. Enhancement of NA release by TEA was readily reversible. Output of NA induced by high potassium was not affected by TEA or barium. 4. The effect of TEA on release was related to the external calcium concentration. Insignificant outputs obtained at 5 Hz in 0.1 and 0.5 mM calcium-Krebs solutions were markedly increased by TEA, and were 2- and 5-fold greater than the control output at 5 Hz in normal Krebs solution containing 2.5 mM calcium. TEA enhanced release at all calcium concentrations up to 5 mM, but maximum output was still obtained at 2.5 mM. 5. Increasing the potassium concentrations of normal Krebs solution to 10, 15 and 20 mM depressed NA outputs at 5 Hz by 50, 55 and 75% respectively, TEA (1 mM) partially antagonized the inhibitory effect of potassium on release, and in zero potassium-Krebs solution it increased output by about 50% over that obtained in normal Krebs solution. 6. The ratio of NA outputs at 30 and 5 Hz during perfusion with Krebs solution containing TEA was about 0.6, and it approached the normal value as the calcium concentration of the perfusion medium was reduced. TEA facilitated release even at 30 Hz in low-calcium solutions. 7. It is suggested that the enhancement of NA release by TEA and barium is due to the greater influx of calcium ions into the sympathetic nerves during the course of an action potential.


Release of noradrenaline proposed as a mechanisms for the positive inotropic action of dipyridamole. In the arterially blood-perfused canine papillary muscle, i.a. injections of dipyridamole (10-300 mug) produced a dose-dependent increase in developed tension amounting to about 45% of the basal developed tension at 300 mug. The positive inotropic response to dipyridamole was greatly reduced by a prior i.a. injection of propranolol (10 mug) or by pretreatment with reserpine (0.2 mg/kg s.c. for 3 consecutive days) but not affected by a prior i.a. injection of tetrodotoxin (1 mug) or desmethylimipramine (3-10 mug). The positive inotropic response to dipyridamole reduced by pretreatment with reserpine was restored by i.a. infusion of noradrenaline (0.03 mug/min). Dipyridamole did not modify the positive inotropic responses to noradrenaline and tyramine. These results suggest that the positive inotropic response to dipyridamole is largely due to noradrenaline released from adrenergic nerve endings by a mechanism that differs from those operative in the action of tyramine or in liberation of noradrenaline upon excitation.


The peristaltic reflex: an analysis of the nerve pathways and their pharmacology. The enteric reflexes in isolated segments of the distal colon and rectum of the guinea-pig were studied by applying localized distensions and recording the consequent changes in circular muscle activity, and by recording tension changes in the circular muscle during the propulsion of a bolus in vitro. Lesions of the wall of the colon were made to locate nerve pathways involved in the reflexes and pharmacological tests were applied to investigate the natures of transmitters released and the types of receptors involved. Distension produced a transient contraction of the circular muscle on the oral side and sustained relaxation on the anal side. Both reflexes were nerve-mediated. They were elicited in segments deprived of mucosa and submucosa. Interruption of Auerbach's plexus, but not interruption of the submucosal plexus, prevented their conduction. The ascending excitatory reflex was partly blocked by hyoscine and was also partly blocked by methysergide or by making the preparation tachyphylactic to the excitatory action of 5-hydroxytryptamine. The ascending excitatory pathways apparently involve neurons releasing a 5-HT-like transmitter as well as cholinergic neurons. The descending inhibitory reflex was not antagonized by hyoscine, guanethidine, methysergide or mepyramine. It is assumed that the inhibitory neurons activated in this reflex are identical with the non-cholinergic, non-adrenergic, enteric inhibitory neurons found throughout the intestine. If both the ascending excitatory and descending inhibitory reflexes acted simultaneously on the same area of circular muscle, the inhibitory response tended to dominate. Pellets of faeces, covered by a thin layer of resin, were introduced into the oral ends of isolated segments of colon. They were propelled analwards at speeds of 0.5-1.6 mm/s. Tension records showed that the pellets were preceded by relaxation and followed by a ring of contraction. The propulsion was blocked by both hyoscine and methysergide. Descending waves of contraction were also observed in empty segments of colon. These occurred spontaneously or were initiated by stretch. They did not occur in the presence of hyoscine or tetrodotoxin. It is postulated that three factors may contribute to propulsion in the guinea-pig distal colon: ascending excitatory reflexes which evoke contractions above a bolus; descending inhibitory reflexes which cause relaxations below; and contractions which, once set up in the circular muscle, travel in an anal direction.


Release of prostaglandins by bradykinin as an intrinsic mechanism of its algesic effect. 1. The release of PGs from the isolated perfused rabbit ear was measured by means of a radioimmunoassay. 2. Bradykinin in dose dependent amounts released mainly PGE (presumably PGE1) and in much smaller amounts also PGF. 3. Bradykinin released similar amounts of PGE in innervated and chronically denervated ears. 4. Indomethacin completely prevented the PGE release by bradykinin. 5. ACh showed a much lower efficacy than bradykinin in releasing PGE and PGF. Synthetic substance P was devoid of any PGE releasing action. 6. It is concluded that bradykinin increases its own algesic action by a concomitant rapid stimulation of the PGE synthesis, thus providing a mechanism for the facilitation of its own algesic action.


The role of neuronal uptake at alpha- and beta-adrenoceptor sites in subcutaneous adipose tissue. Intravascular noradrenaline infusion may cause vasodilatation or vasoconstriction in subcutaneous adipose tissue, whereas sympathetic nerve activity causes vasoconstriction only. This discrepancy may be due to a differential distribution of alpha- and beta-adrenoceptors in relation to adrenergic nerve terminals in the adipose tissue vessels. In order to test this hypothesis the extent of prejunctional supersensitivity to noradrenaline was studied after blockade the neuronal uptake of noradrenaline with cocaine. In the autoperfused, isolated inguinal canine adipose tissue pretreatment with coacine (200-600 mug close i.a.) increased lipolysis following sympathetic nerve stimulation or close i.a. injection of noradrenaline. Cocaine also potentiated the vasoconstriction induced by nerve stimulation (1-3 Hz) or intraarterial noradrenaline (0.2-2 nmoles) as well as the vasodilatation induced by sympathetic nerve stimulation (1-3 Hz) after alpha-receptor blockade. However, the vasodilatation following close i.a. injection of noradrenaline after alpha-receptor blockade was not changed by cocaine. The results indicate that the functionally important vascular alpha-adrenoceptors in adipose tissue are in close contact with adrenergic nerve terminals, whereas most vascular beta-adrenoceptors seem to be unrelated to the nerve terminals. Thus, the alpha-adrenoceptors in the adipose tissue vessels may be classified as innervated receptors, in contrast to the vascular beta-adrenoceptors which may be more acessible to circulating catecholamines and may be classified as humoral receptors. Furthermore at least some of the beta-receptors on the adipocytes seem to be located close to sympathetic nerve terminals.


The effects of quipazine on 5-HT metabolism in the rat brain. Since quipazine is a potent 5-HT agonist in peripheral organs, its possible stimulatory effects on serotoninergic receptors in the rat brain were investigated. Quipazine administration (10 mg/kg, i.p.) induced a significant decrease in the synthesis and turnover rates of serotonin in the brain stem as well as in the forebrain. It is not likely that these changes were mediated by a negative feed-back mechanism triggered by a direct action of quipazine on central 5-HT postsynaptic receptors. Indeed, in contrast to LSD and 5-methoxy-N,N-dimethyltryptamine, this compound failed to activate the 5-HT sensitive adenylate cyclase in colliculi homogenates of newborn rats. However, quipazine exerted direct effects on serotoninergic terminals. It inhibited competitively the reuptake process in synaptosomes (Ki=1.38 X 10(-7) M) and stimulated the K+ evoked release of newly synthesized 3H-5-HT in slices of the brain stem. Injected in vivo in a dose which affected 5-HT uptake and release, quipazine did not modify MAO activity. However, this activity was non-competitively inhibited by high concentratin of the drug in vitro (Ki=3.0 X 10(-5) M). These actions are very likely indirectly responsible for the stimulation of central 5-HT receptors.


Influence of the flavonoid (+)-catechin on the permeability of Ehrlich mouse ascites tumour cell membranes. The effect of the flavonoid (+)-catechin and its hydrophilic derivative epicatechinsulphonate on the permeability of Ehrlich mouse ascites tumour cells (EMAT) was investigated. As a sensitive assay, the transmembrane fluxes of two different solutes were measured, the inwardly directed free diffusion of 14C-thiourea, and the carrier-mediated efflux of intracellularly accumulated 12C-1-aminocyclopentane-1-carboxylic acid. (+)-Catechn was found to reduce the permeability of EMAT membranes for both solutes. The primary target of the drug appears to be the membrane itself. The effectiveness of the drug was dependent on its concentration. Inhibition of fluxes was observed at 0.86 mM; the inhibition gradually increased as the concentration was increased. In contrast to (+)-catechin, epicatechinsulphonate was rather ineffective, even at a concentration as large as 10 mM. The effect of (+)-catechin was seen within a few minutes after its addition. However, it was considerably intensified as the incubation was prolonged. The effectivity of (+)-catechin decreased with increasing cell density. Thus, the drug appears to be absorbed by the cells. From the various data and the observation that incorporation of a strong lipophobic sulphonate residue into the moderately lipophilic catechin molecule markedly lowers the effectivity of the flavonoid, it is concluded that (+)-catechin, as a membrane stabilizing drug, interacts directly with certain constituents of the cell envelope, presumably membrane lipids.


Relaxation of splenic strips during wash out with amine-free solution after an exposure to noradrenaline. 1. Strips were prepared from the spleens of normal or of reserpine-pretreated cats or rabbits. The strips were first exposed to (-)noradrenaline and then washed out with amine-free solution. 2. After inhibition of monoamine oxidase by pargyline "secondary sensitization" was prominent during the incubation with noradrenaline, and the early phase of quick relaxation was followed by a late phase of slow relaxation. The latter was cocaine-sensitive and has to be attributed to a slowly declining efflux of noradrenaline from adrenergic nerve endings. 3. Inhibition of catechol-O-methyl transferase by U-0521 or inhibition of extraneuronal uptake by hydrocortisone (cat) or corticosterone (rabbit) failed to alter relaxation. Apparently, an efflux of noradrenaline from extraneuronal stores plays little or no role in the relaxation of splenic strips. 4. During prolonged exposure to noradrenaline strips become desensitized to noradrenaline; on wash out of the amine, sensitivity is restored. As a consequence of this temporary desensitization the response to noradrenaline is not well maintained during prolonged exposure to this amine (when MAO is intact), and the relaxation curve is distorted (whenever a late phase of slow relaxation is prominent). 5. Indometacin enhances the sensitivity of rabbit (but not of cat) splenic strips to noradrenaline but fails to substantially alter relaxation curves. 6. When the distribution of noradrenaline is restricted to the extracellular space and when the concentration of the amine is varied over a wide range, essentially parallel relaxation curves are obtained on wash out, provided the initial contraction does not exceed 80% of maximum. For higher initial contractions relaxation is slowed during the first minute of wash out, probably because of the sigmoid shape of the dose-response curve.


Inhibition of catecholamine release from the adrenal medulla by halothane. Site and mechanism of action. In isolated bovine adrenals perfused with Locke solution in a retrograde fashion we investigated the effects of halothane on the catecholamine release evoked by various secretagogues. 1. The catecholamine release induced by activation of the nicotinic receptors on the chromaffin cells with 1,1-dimethyl-4-phenylpiperazinium was almost completely inhibited (by about 90%) by 1.4 X 10(-3) M halothane. 2. It was shown by means of cumulative concentration-response curves of acetylcholine for its stimulating effect on catecholamine release (pD2 = 4.04) that halothane was a non-competitive antagonist (pD'2 = 3.17). 3. Halothane (1.4 X 10(-3) and 4.3 X 10(-3) M) did not decrease the catecholamine secretion in response to pilocarpine or histamine. 4. The 5-hydroxytryptamine-induced catecholamine release was not impaired by 1.4 X 10(-3) M halothane, but was significantly inhibited (by 44%) by 4.3 X 10(-3) M halothane. 5. At 1.4 X 10(-3) M halothane the catecholamine release induced by gamma-aminobutyric acid (GABA) was inhibited by 40%. 4.3 X 10(-3) M halothane completely blocked the secretion induced by GABA. 6. The catecholamine secretion in response to 56 mM KCl or to introduction of CaCl2 after perfusion with Locke solution deficient in CaCl2 was not reduced by halothane (1.4 X 10(-3) and 1.4 X 10(-2) M). 7. Halothane (1.4 X 10(-3) M) did not inhibit the catecholamine release evoked by acetaldehyde or tyramine from glands perfused with Ca2+ -free Locke solution throughout the experiments. It is concluded that the site of action of halothane is the cell membrane of the chromaffin cell. The anaesthetic does not impair the permeability of the membrane to calcium ions. Halothane may cause a conformational change of membrane proteins, particularly of the nicotinic receptor (and at higher concentrations of GABA and 5-hydroxytryptamine receptors); thus, stimulation may be prevented by an inhibition of agonist-receptor interaction.


Regional changes in the rate of turnover of acetylcholine in rat brain following diazepam or muscimol. Muscimol (8.8 mumol/kg i.v.) and diazepam (7.04 mumol/kg i.p.) decreased the rate of turnover of acetylcholine in midbrain and cortex of rat brain but failed to change acetylcholine turnover in striatum and hippocampus. The similarity in the profile of the action of diazepam and muscimol on acetylcholine turnover in various brain structures adds support to the view that GABA participates in mediating the actions of diazepam. Since the striatum contains an abundance of GABA neurones and intrinsic cholinergic neurones, it is inferred that the metabolism  of acetylcholine, and presumably the activity of striatal cholinergic neurones are not regulated by the activation of GABA receptors. Similar considerations apply to the cholinergic pathway projecting from the septum to the hippocampus.


Sensitization of the smooth muscle by prostaglandin E1 contributes to reversal of drug-induced inhibition of the guinea-pig ileum. Prostaglandin (PG)E1 reverses drug-induced inhibition of the electrically stimulated guinea-pig ileum. The effect of PGE1 is in part related to a sensitizing action on the smooth muscle and in part to an increased acetylcholine release from the myenteric plexus.


The cardiodynamic and metabolic effects of glucagon. The cardiac effects of a continuous infusion of glucagon at the rate of 10 mug/min were studied in the Starling heart-lung preparation, modified to measure coronary flow and myocardial oxygen consumption. A maximal increase in myocardial contractility, as reflected by maximal rate of rise of left ventricular pressure, dp/dt, of 31% was observed at a total dose of glucagon of 50 mug and was accompanied by an increase in heart rate and in myocardial oxygen consumption of 59% and 57%, respectively. At a total dose of glucagon of 100 mug, there was an additional and comparable increase only in heart rate and myocardial oxygen consumption of 11.2% and 6.4% respectively. Similarly, at a total dose of glucagon of 150 mug, only heart rate and myocardial oxygen consumption increased additionally by increments of 2.6% and 2.9% respectively. These effects occurred at constant aortic pressure and left ventricular volume. Further infusion of glucagon led to an additional increase only in myocardial oxygen consumption of 4.2%. When the increase in heart rate was largely prevented by prior treatment with veratramine, an increase in dp/dt, not significantly different from the maximal increase obtained with glucagon alone, was accompanied by much lower and closely comparable increases in heart rate and in myocardial oxygen consumption of 15% and 19%, respectively. Coronary flow increased more markedly when glucagon was administered alone and it paralleled the increase in myocardial oxygen consumption. It may be concluded from this study that, in the isolated dog heart preparation, glucagon increases contractility, heart rate and myocardial oxygen consumption and that the increase in myocardial oxygen consumption is related more closely to the increase in heart rate than to the increase in contractility, but a minor increment is referable to a calorigenic action. The increase in coronary flow is of a secondary nature, resulting from the increase in myocardial metabolic demands.


Relationship of antiarrhythmic to inotropic activity and antiarrhythmic qualities of the optical isomers of verapamil. 1. The relationship of antiarrhythmic to inotropic activity of the optical isomers of verapamil was studied by comparing their effects on functional refractory period and force of contraction in the isolated left atrium of the guinea pig and on maximum follow frequency and contractility in the dog heart. To evaluate the antiarrhythmic profile of the optical isomers of verapamil the relationship between threshold voltage and impulse duration in the left atrium of the guinea pig and the antagonistic action against ventricular arrhythmias in the rat were studied. 2. (-)Verapamil is nearly 10 times more effective than (+)verapamil in prolonging the functional refractory period in the isolated left atrium of the guinea pig. 3. In the dog heart (-)verapamil is about 8 times more active in reducing a maximum follow frequency at atrial pacing, as well as spontaneous heart rate and in prolonging PQ-duration. 4. In the guinea pig atrium (+)verapamil shows less negative inotropic activity than its enantiomorph. With (+)verapamil the concentration producing a 25% decrease in contractility is 3.7 times higher than that causing a 25% increase in refractory period. With (-)verapamil these concentrations are identical. 5. In the dog i.v. infusion of the isomers, at a dosage inducing identical reduction of maximum follow frequency, is accompanied by a decrease in left ventricular dp/dtmax with (-)verapamil, whereas with the (+)isomer a significant increase of dp/dtmax is observed at a certain dose level. 6. Because of the higher antiarrhythmic activity of (-)verapamil, the antiarrhythmic profile and the inotropic pattern of the racemic compound are mainly due to this isomer. 7. (+)Verapamil shifts the voltage duration curve of the isolated left atrium of the guinea pig to the right and leads to a significant increase in the chronaxie value. (-)Verapamil has no comparable effects on the excitability of the atrial myocardium. 8. In the intact animal (+)verapamil shows additional antiarrhythmic qualities. Like procainamide, but with higher activity, it antagonizes ventricular arrhythmias (ectopic beats, automaticity and flutter or fibrillation) which can be provoked in the rat by i.v. infusion of aconitine. (-)Verapamil and the racemic compound are ineffective against these ventricular rhythm disorders.


Catabolism of vasoactive polypeptides by perfused rat liver. Exsanguinated rat liver preparations perfused in situ with oxygenated saline solutions inactivated recirculating bradykinin (BK) at rates of 2.3 to 9.1 and isoleucyl5 angiotensin II (AII) at rates of 2.8 to 15.0 nmoles X min-1 X g-1 of liver, depending on the initial concentration of the peptides in the perfusion fluid (3.1 to 18.9 X 10(-6) M for BK and 8.5 to 17.0 X 10(-6) M for AII). On the other hand, at similar concentrations, recirculation of isoleucyl5 Angiotensin I (AI) for 8 min did not lead to decrease of its biological activity when assayed on the isolated rat uterus. Following a single passage through liver, picomole amounts of both BK and AII were inactivated by about 90% as revealed by assays on a superfused rat uterus. The potency ratio AI:AII, assayed on a superfused rat uterus was 1:22 and changed to 1:5 following a single passage of both peptides through liver. This finding and the separation of 4.9% of AII on carboxymethylcellulose columns following recirculation of AI through rat liver indicate a conversion of AI into AII. The dipeptides Phe-Arg, Ser-Pro and Gly-Phe were identified among the hydrolysis products of perfused BK. A peptidyldipeptide hydrolase (EC 3.4.15) may be responsible for both the BK inactivation and AI conversion. The inactivation of AII cannot be attributed to the same enzyme.


Evidence for stimulation of 5-HT receptors in canine saphenous arteries by ergotamine. Changes in tension of spiral strips from dog saphenous arteries were monitored isometrically. Dose-response curves for noradrenaline, 5-HT and ergotamine were established without and after a 30 min incubation with phentolamine or pizotifen. Phentolamine was about 15 times more potent in antagonizing responses to noradrenaline (pA2 value=7.4) than those to 5-HT (pA2 value=6.2) but it was nearly equipotent in antagonizing responses to ergotamine (pA2 value=6.5) and those to 5-HT. Pizotifen was about 500 times less potent in antagonizing noradrenaline effects than 5-HT but again nearly equipotent when tested against ergotamine and 5-HT. It is suggested that in canine saphenous arteries the stimulant activity of ergotamine is mediated mainly through 5-HT receptors.


The effect of corticosterone on the fluxes of 3H-normetanephrine into and out of the extraneuronal compartments of the perfused rat heart. 1. Hearts were obtained from pargyline-pretreated rats and perfused with 40 nM 3H-normethanephrine for 21 min. 87 muM corticosterone reduced the accumulation of 3H-normethanephrine in the heart. 2. When the initial perfusion with 3H-normetanephrine was followed by perfusion of the hearts with amine-free solution for 90 min, efflux of radioactivity was determined. Analysis of efflux curves showed that, apart from its distribution into extracellular space and fluid content of cardiac cavities, radioactivity distributed mainly into one corticosterone-sensitive, extra-neuronal compartment (compartment III, half time for efflux about 6 min). 3. When corticosterone was added to the wash out solution only, it failed to affect the efflux of radioactivity. 4. Although monoamine oxidase was inhibited, some deaminated metabolites of normetanephrine were detected in the efflux. Efflux of 3H-metabolites was monophasic in about half the hearts (short half time corresponding to that of compartment III) and biphasic in the other half. The early phase of efflux (short half time) seemed to represent efflux of newly formed metabolite(s), while the late phase (if present) appeared to be due to efflux of metabolites formed early in the experiment. 5. While corticosterone is known to inhibit the extraneuronal influx and efflux of catecholamines, it appears to impair the influx of normetanephrine without affecting the efflux.


Blood flow in intact and constricted coronary arteries under the influence of ouabain. The effects of ouabain on intact and experimentally constricted coronary arteries were investigated in anaesthetized, thoracotomized dogs. Ouabain decreased the blood flow in the intact artery without changing the flow per beat values and increased flow in the constricted artery. Since ouabain decreased left ventricular enddiastolic pressure, it is proposed that the drug-induced augmentation of flow in the constricted artery is related to an elevation of driving pressure to the endocardial layers of the myocardium which are supplied by the constricted artery.


Induction of platelet aggregation by the complement-derived peptides C3a and C5a. The effect of two complement-derived peptides, hog serum C3a and C5a, on platelet aggregation in platelet-rich plasma and suspensions in Tyrode solution was investigated. 1. Guinea-pig platelets were aggregated by both C3a and C5a; the spasmogenically inactive product of C3a, C3ai, also induced aggregation. Threshold concentrations were in the range of 10(-6)--10(-9) M depending on the peptide and platelet preparation. 2. Cat platelets were aggregated by C5a (threshold concentrations 10(-7)--10(-8) M) but not by C3a. 3. Platelets from pig, rabbit and man were not aggregated by either of the two peptides in concentrations of up to 5 X 10(-6) M. 4. When C5a was administered repeatedly in subthreshold doses guinea-pig platelets became tachyphylactic to C5a but were still aggregable by C3a or ADP. Conversely, platelets desensitized to C3a still reacted to C5a or ADP. Tachyphylaxis towards C5a developed also when platelets were incubated with C5a in the absence of free Ca2+ under which condition they do not react. The tachyphylaxis in this case became evident after recalcification of the medium. The lack of cross-desensitization indicates that C3a and C5a react via different receptors. 5. C3a and C5a were injected i.v. into guinea pigs. Histological examination of the lungs revealed that some of the smaller vessels (20-30 mu in diameter) were occluded by platelet aggregates. In addition signs of severe acute emphysema were seen in animals treated with C5a, but only slight emphysema in C3a-treated animals. Intravenous injections of C3a into guinea pigs caused but weak respiratory distress and drowsiness and never killed an animal (at doses of up to 20 mg per kg body weight), whereas C5a caused the well-known severe respiratory failure and death already at doses of 0.03 mg/kg body weight.


Effect of anesthetic doses of gamma-hydroxybutyrate on the acetylcholine content of rat brain. Gamma-hydroxybutyrate administered in anesthetic doses produces a time dependent increase in the levels of rat barin acetylcholine. A maximal increase in whole brain and subcortical levels of acetylcholine is observed about 15 min after administration of the lactone form of the drug. A similar GHB-induced increase in acetylcholine is observed in the striatum and a 75% increase in the hippocampus 15 min after administration of the drug. A good temporal correlation was not obtained between the increase in acetylcholine and the depth of anesthesia produced by the drug. Gamma-hydroxybutyrate did not cause a significant change in the striatal or hippocampal levels of choline. Possible mechanisms involved in the production of this increase in acetylcholine are discussed.


Muscle relaxation induced in the rabbit by intracerebroventricular taurine injection: a supraspinal effect. Taurine, given intracerebroventricularly to the consciou unrestrained rabbit, causes hypothermia and a reduction in skeletal muscle tone. Evidence has been produced that the latter effect is of a central, supraspinal origin.


Influence of viability on bromosulfophthalein uptake by isolated hepatocytes. The initial rates of BSP uptake by isolated hepatocytes were compared in cells of good and poor viability. Cells with impaired viability were obtained by ageing or by accident also in fresh preparations. Viability was judged by trypan blue stainability, membrane potential and respiratory parameters indicative for energy state, substrate supply and plasma membrane permeability changes. It was found that concomitant with impaired viability there was a decline of uptake rates at low and an increase at high BSP concentrations with a crossover point at 10 muM as manifest in an increase of Km and V. Simultaneously, the affinity and size of the membrane bound fraction decreases. The results give kinetic support to the supposition that it is the decreased uptake from plasma to liver that is responsible for the prolonged plasma retention times in the liver function test of patients with impaired hepatobiliary function.


Contribution to the mechanism of Stilbostat action. The hormone-cytostatic drug Stilbostat does not influence the estradiol binding capacity of the rat uterus tissue and tissues of human and experimentally induced mammary tumors. It exhibits an alkylating potency similar to that of other cytostatic drugs used in the therapy of neoplasia. An in vitro splitting of Stillbostat into diethylstilbestrol by tissue slices could not be detected. It was impossible to demonstrate an excretion of splitting products of Stilbostat by rat urine.


Preliminary experience with Mitolactol in advanced tumors of the orofacial region and the larynx. Mitolactol (Dibromodulcitol "DBD"; RlobromolR) an alkylating agent was applied in a clinical series of twenty advanced or relapsing cases of malignant tumors of the orofacial region and the larynx. It was administered orally in a mean total dose of 127 mg/kg/30 days. In 45% of the patients the treatment resulted in a diminution of tumors by more than 50%, with remission lasting 1-4 months. 30% of the patients responded by a retreat of the tumor volume smaller than 50%, while no therapeutic effect was noted in 25% of the patients, or the objective finding proved to be worse. Subsequent radiotherapy improved the results, and remissions which followed combined chemo-radiotherapy were prolonged up to 9 months. The effect of DBD treatment proved better in orofacial than in laryngeal carcinoma.


On surgical treatment of malignant melanoma. An early and adequate surgical intervention may have a favorable effect on the course of malignant melanoma (m.m.). Despite the focused publicity given to problems relating to m.m., faulty nonradical excisions of suspected pigmented lesions are still performed rather frequently in surgical outpatient departments. One of the reasons may be the rather difficult clinical diagnosis due to pleiomorphism of m.m., but a lack of experience of certain physicians is also responsible. The authors indicate what effective course to pursue in these patients. On the evidence of their set of 48 patients operated upon, they have shown a radical reexcision of the scar with its wide vicinity, following a nonradical intervention, to be justified. In certain cases, it may affect an eventful dissemination of tumorous cases, it may affect an eventual dissemination of tumorous cells in the close vicinity of the scar after an inadequate excision. In addition, they have delimitated indications valid for a radical reexcision.


Classification and survival rate of patients with serous cystadenocarcinoma of the ovaries. The comparative evaluation of two stage classifications including USSR Ministry of Health stage classification and TNM system was performed on the base of studies of the end results of 419 patients with serous cystadenocarcinoma of the ovaries. It has been established that TNM system is of a greater importance in establishing more accurate prognosis than the stage classification of the Ministry of Health. In TNM system four variants of the degree of extension correspond to each stage that allows to evaluate not only the extent of the primary tumor that also of the metastatic spread. The achieved results point to the superiority of the TNM system and serve as a base for transition to the TNM system in the classification of ovarian carcinoma.


Human neoplastic cells in tissue culture: two established cell lines derived from giant cell tumor and fibrosarcoma. The establishment and cultivation of two human neoplastic cell lines is described. The cell line B-5GT was derived from bone giant cell tumor and B-6FS from poorly differentiated fibrosarcoma. In comparison to the normal skin fibroblasts both cell lines have a potential for "indefinite" multiplication in vitro and they exhibit growth properties which are associated with malignant transformation. The parameters investigated included cell morphology, chromosome characteristics, terminal cell density, growth pattern, residual DNA synthesis and growth in soft agar. Both cell lines exhibited human karyotype with aneuploidy and differed in their karyotype from each other.


Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. III. Polarographic reduction potentials of carcinogenic nitrogen compounds in dimethylsulfoxide. The polarographic reduction of a series carcinogenic and noncarcinogenic polycyclic nitrogen compounds in anhydrous dimethylsulfoxide containing tetrabuthylammonium perchlorate as supporting electrolyte has been studied. The obtained results were compared with the number or with the position of nitrogen atoms in the molecules and with their carcinogenic activity. The values of half-waves potentials generally confirmed the mechanism proposed for the reduction of aromatic polycyclic carcinogenic hydrocarbons based on the polarographic experiments in dimethylsulfoxide. Agreement of the obtained results with the data reported by polarographic study in anhydrous dimethylformamide indicates, that the polarographic behavior of polycyclic nitrogen compounds in dimethylsulfoxide is very similar.


Contribution to the study of excision repair following UV irradiation in mammalian cells cultivated in vitro. The absence of pyrimidine dimer excision after UV irradiation in rat cell line was confirmed. The possibility of excision repair system depression by acidification of medium with H3PO4 in HeLa cells has been proved. The results obtained by two different methods of deproteinization and DNA isolation are in good conformity.


The effect of repeated dose of x-irradiation on the progress of HeLa cells through the cell cycle. In contradistinction to the increased fraction of HeLa S 3 cells in S phase after irradiation by a single dose in a range of 25--200 R, cultures irradiated by a second dose at time of morphologic restitution of mitotic activity exhibited decreased fraction of cells in S phase. The interpretation is that passage from G1 to S was reduced due to disturbances in subsystems which have not been fully repaired.


Deoxypyrimidineuria in the course of chemotherapy in M. Hodgkin. In patients with Hodgkin's disease the excretion of pyrimidine deoxyribonucleosides in urine was followed up within the course of 92 chemotherapeutical series with cytostatics of COOP group. In 14-day chemotherapy series, the excretion of deoxycytidine, deoxyuridine, thymidine, and their sum was significantly increased. In this paper the results are analyzed and a possibility of utilization of this finding for the judgment in the clinical course of the disease is considered.


Trends in morbidity on the basis of newly-reported cases of malignant skin melanoma (172 ICD) and other skin neoplasms (173 ICD) in Czechoslovakia during the period 1961--1972. According to newly-reported cases of all malignant neoplasms of the skin (172 + 173 ICD) morbidity rate for the period 1961--1972 showed a rising trend of statistical significance only in Bohemia; while in Slovakia it persisted at a practically steady level throughout the period followed. Malignant skin melanomas (172 ICD) were on the increase in both regions, the rate being of statistical significance only in men in Bohemia. Morbidity from other malignant skin neoplasms (173 ICD) during the same period showed a stable pattern in Slovakia while it rose steadily in a significant degree in both, males and females in Bohemia. The causes for these varying trends must be further analyzed.


Trends in mortality rate from malignant skin melanoma and other malignant skin neoplasms in Czechoslovakia during the period 1921--1970. Mortality from malignant skin melanoma (172 ICD) has an ascending trend in Czechoslovakia (CSSR) the rate being higher after the year 1960 in Bohemia (CSR) than the Slovakia (SSR). Mortality from other malignant neoplasms of the skin (173 ICD) declines; this decline for the whole of Czechoslovakia has been statistically influenced mainly by the lower death rate from this cause in Bohemia, for in Slovakia this mortality rate has risen, although significantly only in women. The proportion of deaths from malignant skin melanoma (172 ICD) out of the total number of deaths from malignant skin neoplasms (172 + + 173 ICD) is relatively low in Czechoslovakia--lower in Slovakia than in Bohemia.


Angiographic findings in basal tumours of the anterior and middle cranial fossa. Angiographic findings in tumours located near the skull base in the anterior and middle cranial fossa are described. It is possible to distinguish local and general changes, but in general these will indicate the localisation of the tumour rather than its type.


[Microsurgery in pre-pontine tumours (author's transl)]. On the basis of some selected examples, the problems of micro-surgical operations on parasellar and pre-pontine tumours are discussed. The tumours are divided into five types, according to their localisation. The particular anatomical aspects are discussed in detail.


[Observation of the course of craniopharyngioma]. A case of craniopharyngioma with an unusually long history is reported. The patient developed his first symptoms 44 years ago. After 2 to 3 years the patient became completely blind in both eyes. Now the tumour is calcified and as big as "a fist". Recessive processes seem to be the explanation for cessation of growth in the tumour.


Increased intracranial pressure associated with spinal cord tumours. Two cases of spinal cord tumour associated with increased intracranial pressure are reported and the 44 cases described in the literature are reviewed. The different hypotheses produced to explain the pathogenic mechanism of this syndrome are discussed. We think that several factors working together, rather than an isolated mechanism, take part in the production of this syndrome.


[Amitriptyline in the treatment of anxiety and insomnia anal as a tranquilizer]. Thirty out patients were selected in a psychiatric hospital among those presenting insomnia, anxiety, psychomotor retardation, loss of drive and anxiety with somatic manifestations. Amytryptyline was administered in 25 mg tablets, one to four times a day, for twelve weeks. Results were satisfactory as observed from the second week; side effects were minimal. We can conclude that amytryptyline is of great effectiveness in the treatment of the neurotic illnesses most commonly observed in clinical practice.


[Clinical evaluation of amitryptyline hydrochloride in the treatment of depression]. Thirty subjects between 18 and 66 years of age with overt symptoms of depression were followed during treatment with amytryptiline. Daily dose was 75 mg in three parts for a period of three months. Thirteen subjects showed total remission from the tenth week; 15 showed significant improvement from the third week; 2 showed no change. Side effects were mild and required no medical intervention.


[Effects of amitryptyline in the development of depression]. Considering depression as a condition that damages physical, mental and social wellbeing, in the individual as well as in the community, research was made in the evolution of symptoms of depressive syndromes of 33 subjects, when treated with amytryptiline compounds. Treatment was begun with 25 mg daily and increased to 150 mg; doses were divided to avoid somnolence, and maintained for 8 to 14 weeks. Depressive syndromes showed improvement in 100% of cases, with resolution of clinical depression in 80%.


[Clinical evaluation of amitriptyline in the treatment of psychogenic disorders]. Clinical evaluation of amytyptiline in the treatment of psychogenic disorders was performed, using one or more 25 mg doses daily per os. Of the patients, 19 were male and 11 female; ages were between 18 and 55. Treatment for each lasted 12 weeks, and clinical improvement was observed from the second to the fifth week, with mild side effects that did not require treatment. Psychotherapy was instituted during treatment. ;inal results were: 23 good improvement, 4 some improvement and 3, no change.


[Amitriptyline in the treatment of depression]. Oral tryptyline was evaluated clinically in the treatment of 14 male and 16 female patients; ages were 17 to 52 years the males and 32 to 59 years the females. Four had had no prior antidepressive treatment and the rest had had medication with poor to no results. The study ran for 12 weeks, with 15 patients showing improvement by the fourth week, 8 by the fifth week, 1 by the sixth; 5 showed no change. Side effects disappeared adjusting the dosage. Seventeen patients showed total improvement, 8 moderate improvement and 5 showed no change.


[Amitriptyline hydrochloride in the treatment of anxiety and insomnia and as a tranquilizer]. An open, non-comparative study with weekly clinical evaluations was made in 30 patients of both sexes aged between 16 and 70 years. The only medication used to treat anxiety was Amytryptiline HCl. 23 patients completed 12 weeks of treatment and 7 abandoned it before completion. Dosages varied between 25 and 100 mg daily, with median dose being 50 mg. Twenty-three patients showed mild side effects that disappeared without specific treatment. Improvement began the first or second week; at the end of 12 weeks, 17 patients were considered cured, 16 improved and 7 with no change.


[Structural therapy. Global therapeutic model of the psychotic child]. The authors report the means to manage the psychotic child throughout the out patients consult approaching directly the modalities of interpersonal relationships between the child and his family. The therapeutic plan includes an educational and formative program designed especifically, taking into consideration the needs and potencialties of each child and acting psychotherapeutically through a modality of individual psycotherapy directed to estimulate the psychological functions which are responsible of the development of the mental autorepresentation (ego boundaries). The treatment program is an adaptation of the one utilized for the management of autistic children in an institution for psychotic children. The type of individual psychotherapy is a modification of Des Lauriers' therapy, developed by him for the management of schizophrenic adolescents and adapted by Ward in 1969 to be applied to the psychotic child in the mentioned institution. The authors present the application and obtained results with the use of this therapy in the treatment of a psychotic girl.


[Psychosocial deliberations over the present man]. The first fact mentioned is the need which every society has had of forming directors or leaders, whether able or not, whom to hold responsible; and at the end, whom to blame for all the failures of said society. The seriousness which implies the wrong choosing of a leader is reviewed, and at the same time, both, the cautiousness that should be practiced and the characteristics which he should bear. The harmfulness that can be released by the mass-media means of communication in the election of leaders has been mentioned. At present, a vital importance has been given to success interpreted as power and wealth, without taking into consideration the moral and material crushing which comes along with it. The reason for a "generation gap" is considered as the lack of understanding between parents and children, although sometimes the money gifts and the material comforts are over and above; in any case, youth must modify the reason for the breaking up without having to take trips into artificial paradises, but instead mending those errors: this is their great commitment. The present tendency to consider the psychiatrists as a panacea and, therefore, able to solve all the problems of today's man is discussed. Although this is not true, the psychiatrist is able to remedy many maladies if and when he acquires, beforehand, absolute maturity and is able to pass over said maturity to the rest of the people.


Ergot alkaloid inhibition of melanophore stimulating hormone secretion. Ergonovine maleate inhibits melanophore stimulating hormone (MSH) secretion from the incubated frog, rat, and mouse pituitary gland. This ergot alkaloid is partially effective at a concentration as low as 10(-8)M. The inhibitory effect on hormone release is irreversible under the experimental conditions studied. Ergonovine inhibition of MSH secretion is blocked by Dibenamine and chlorpromazine as is dopamine inhibition of MSH secretion. At higher concentrations chlorpromazine as is dopamine inhibition of MSH secretion. Similarities between the cellular mechanisms controlling MSH and prolactin secretion will be discussed.


Dopaminergic control of adenohypophysial weight and serum ceruloplasmin level in rats. Twice a week male rats were given injections of 1 mg estradiol benzoate as an aqueous microcrystalline suspension; they were also given 0.1, 0.2 or 0.4 mg Pimozide (a dopamine receptor blocker) daily in their food. Only the maximum Pimozide dose potentiated the effect of estradiol on adenohypophysial weight and on the binding capacity of adenohypophysial proteins for thyroxine in vitro. The estrogen-induced increase in the serum ceruloplasmin level, however, was potentiated significantly by all 3 Pimozide doses.


Modifications of striatal dopamine levels by steroid contraceptive drugs in mice and rats. The effect of steroid contraceptive drugs (SCDs) on the concentration of dopamine (DA) in the striatum was studied in mice and rats. Mestranol was combined with each one of the three progestins, lynestrenol, norethindrone and norethynodrel. Treatments were given daily for 1, 4 or 30 days; animals were sacrificed 1 or 18 h after the last administration. In all groups, with the exception of the animals sacrificed 1 h after an acute treatment, striatal DA was significantly lower than in controls.


The effects of neurally active amino acids on pituitary gonadotropin secretion. Several neurally excitant amino acids were injected into the third ventricle of anesthetized male rats, and plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured. LH levels increased following injections of 2.0 mum glutamate, lysine, or beta-alanine. Glycine (2.0 mum), alpha-alanine (2.0 mum), and 0.9% saline were ineffective in altering LH levels. None of the amino acids tested significantly altered FSH levels. Of the 3 amino acids which raised blood LH levels following an intraventricular injection, i.e., glutamate, beta-alanine, and lysine, only lysine caused a significant increase in LH levels following injection into the pituitary. The present study provides evidence for a possible role for certain neurally excitant amino acids in the neuronal control of LH secretion.


Neurophysiological measures related to levels of 5-hydroxyindoleacetic acid, homovanillic acid and tryptophan in cerebrospinal fluid of psychiatric patients. In 26 patients with psychiatric disorders, EEG, and visual averaged evoked responses (VAER) were recorded. In the analysis of the EEG, the mean integrated amplitude (MIA), its within patient variance (WPV), and the coefficient of variation CV=(square root of WPV/MIA) X 100 were calculated. Patients were grouped as augmenters on reducers according to their tendency in the VAER recording to augment or to reduce the intensity of incoming signals with increasing stimulus intensity. The content of monoamine metabolites, 5-hydroxyindoleacetic acid, 5-HIAA, and homovanillic acid (HVA), and --for 17 patients-- tryptophan, in the cerebrospinal fluid was determined. In the analysis of the results, WPV in the alpha-band was found to be significantly correlated to HVA (r=0.45, p less than 0.02) and to 5-HIAA (r=0.34, p less than 0.05). In a multiple regression analysis, the correlation between WPV and HVA was found to be the most important. CV was found to be signfiicantly correlated to tryptophan (r=0.68, p less than 0.01). In the analysis of the results of the VAER, reducers were found to have higher levels of 5-HIAA and tryptophan and significantly higher values of HVA. The results are discussed in relation to earlier neurophysiological and biochemical theories about psychiatric patients.


Genetics of affective disorders. I. Familial incidence study of bipolar, unipolar and schizo-affective illnesses. 47 affectively ill psychiatric patients and their first-, second- and third-degree relatives were investigated by means of an interview and pedigree analysis to determine the incidence of psychiatric illness in their families. The percentage of psychiatric illness appeared greatest in families of bipolar and schizo-affective probands and least in families of unipolar depressives. In addition, we observed that often within a particular family constellation, more than one type of psychiatric illness (i.e., bipolar manic-depression, schizophrenia, alcoholism, etc.) was present. Morbidity risks varied from one affected family to another, indicating that the genetic risk components for some families are greater than for others. These findings are suggestive of multifactorial genetic disease but other genetic models are considered.


Genetics of affective disorders. II. Morbidity risk and genetic transmission. Morbidity risk and genetic transmission data on a small population of bipolar, unipolar and schizo-affective outpatients suggest a possible genetic overlap between bipolar and schizo-affective patients. There is a conspicuous absence of a homologous illness in the relatives of schizo-affective probands, although the incidence of schizophrenia was higher in these relatives as compared to the relatives of either bipolar or unipolar probands. The data, although tentative because of the relatively small numbers involved, suggest a multifactorial mode of transmission in some affective illnesses. These disease entities appear familial rather than 'genetically transmitted'. There are select families who show the heritable genetic penetrance previously recorded for these mental disorders.


Susceptibility to motion sickness and field dependence-independence as measured with the rod and frame test. This paper reports an experiment investigating the relationship between field dependence-independence and susceptibility to motion sickness in a normal volunteer and in a psychiatric patient population. Both variables have previously been related to psychiatric diagnosis and possible differential interaction between the cerebral hemispheres. Anticipated differences in field dependence according to degrees of motion sickness were not found; however, significant male-female and patient-control differences were observed and these occurred primarily in the non-motion sick and intermediate motion sick groups, suggesting that fundamental differences in field attitude do exist across in apparent spectrum of motion sickness.


The use of computed axial tomography (CAT) for the diagnosis and management of intracranial angiomas. The manifestations of angiomas on computed axial tomography (CAT) are described. Diagnostic changes were present in 66% and a focal abnormality, which was frequently suggestive of the diagnosis, in a further 27.5% of a consecutive series of 41 patients. It failed to show some focal abnormality in only two cases in which intravenous contrast was not given and in one case with a dural angiomatous malformation. The value of CAT in elucidating the nature of the complications of arteriovenous malformations is emphasized.


Intracerebral pneumatocele: an unusual complication following intraventricular drainage in case of benign intracranial hypertension. The development of an intracerebral pneumatocele following ventricular catheterization for benign intracranial hypertension is described. The importance of skull radiography in the diagnosis of this previously unreported complication ist emphasized. This case demonstrates that air can accumulate without the need to implicate increased pharyngeal pressure, and despite raised intracranial pressure.


Transverse anastomoses of the veins at the base of the brain. Venous anastomoses at the base of the brain are represented by the anterior and posterior communicating veins. The anterior communicating vein anastomoses with the anterior communicating vein anastomoses with the anterior cerebral veins. The posterior communicating veins join the basal veins through the interpenduncular veins. The functional value of these venous anastomoses is less important than that of the arterial polygon of Willis. This anastomotic function depends on anatomical constancy and on the calibre of these transverse veins. Under certain pathological conditions the variations of intracranial pressure result in contralateral venous drainage through these anterior and posterior anastomotic veins.


Changes in carotid flow velocity during catheterization of the aortic arch and common carotid artery. Quantitative percutaneous flow velocity measurements are possible in carotid arteries by means of a directional Doppler flow velocity device and registration on a polygraph. Carotid flow velocity changes were recorded during catheterization of the ascending aorta and common carotid artery and after infusion of 20 cc contrast medium in the ascending aorta. The results indicate an increase in the flow velocity in the right common carotid artery after infusion of the contrast medium in the ascending aorta, which is thought to be attributed to a diffuse vasodilatation, at least in the cerebral circulation. The catheterization of the ascending aorta and common carotid artery seems to interfere with the common carotid flow velocity.


Arachnoid cyst of the middle fossa with paradoxical changes of the bony structures. Two patients with an arachnoid cyst of the middle fossa showed paradoxical changes of the adjoining bony structures of the skull. There was a diminution of the middle fossa and hyperplasia of the sphenoid sinus (pneumosinus dilatans) as well as a marked bulging of the squamous part of the temporal bone. In one case in which scinticisternography was performed, communication between the cyst and the subarachnoidal space was proven as well as an extremely slow cerebrospinal fluid circulation in the cyst. The pathogenesis of the cyst is discussed, based upon the structural changes of the skull, the angiographic findings and the locally disturbed cerebrospinal fluid circulation. The primary disturbance seems to be a temporal lobe agenesis.


Comprehensive care revisited.

Comprehensive care revisited. Although the term comprehensive care has gone out of fashion in medical education, the concept has had a resurgence in attempts to teach primary care and family practice. Review of the early experiments in the teaching of comprehensive care in the 1950s reveals that much that was learned then is not being applied today. Surveys of medical school teaching and graduate training in primary care make it seem likely that there will be insufficient practitioners in the foreseeable future to meet the public need for personal physicians. Restructuring of both medical curricula and the delivery systems for personal health services may be necessary to apply effectively what has long been known about the teaching and practice of comprehensive primary care.