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Biomedical subjects

H Blum

Publications and source records attributed to H Blum.

At least 55 records · Page 3Linked to original sources
PubMed1989

Rat liver metabolism in hemorrhagic traumatic shock.

Rats were bled to a mean arterial pressure of 40 mm Hg until the onset of decompensatory shock (marked by the need to return some blood in order to maintain the blood pressure) at which time all the shed blood was returned. 31P-nuclear magnetic resonance (NMR) spectra of their livers were collected during the shock and a subsequent 60 min recovery period. Adenosine triphosphate (ATP) levels fell linearly with time, in some instances to zero during shock. ATP recovery was very rapid after return of shed blood but did not return to its preshock values. Levels of ATP remained stable during the 60 min of recovery. From the rapid recovery after total depletion of ATP in this study and in other NMR studies on perfused ischemic livers, as well as the discrepancy in residual levels of ATP during shock and ischemia as measured by in vivo NMR or by extraction techniques, we argue in favor of metabolically inaccessible pools of adenine nucleotides during these hepatic stresses.

Adenosine Triphosphate↗
PubMed1989

[An unusual slow course of systemic vasculitis with multiorgan involvement].

This paper reports on an unusually slowly progressing course seen in systemic vasculitis of the median and smaller arteries and small veins associated with dermatomyositis, chronically active hepatitis, glomerulonephritis of the immune complex and restrictive cardiomyopathy in a 35-year-old patient. The authors discuss the difficulties in establishing the diagnosis and in finding the exact classification of this disease.

Adult↗
PubMed1988

Intracellular sodium flux and high-energy phosphorus metabolites in ischemic skeletal muscle.

We have employed concurrent 31P- and 23Na-nuclear magnetic resonance (NMR) spectroscopy in conjunction with the paramagnetic shift reagents dysprosium-chelated tripolyphosphate and triethylenetetramine-hexa-acetic acid to observe the intracellular sodium and phosphorus signals in rat leg muscle. With induced ischemia in the leg, we find slowly falling phosphorylation potential. At a critical value of, associated with energetic failure of the Na+-K+ antiport, the intracellular sodium signal begins to increase. We find the following critical values: log, 3.12 +/- 0.32; pH, 6.86 +/- 0.13; Na+ influx with and without ouabain, 5.1 +/- 4.3 and 4.0 +/- 1.3 mol.l-1.h-1, respectively.

Adenine Nucleotides↗
PubMed1988

Metabolic and ionic changes in muscle during hemorrhagic shock.

We have employed concurrent noninvasive 31P and 23Na NMR spectroscopy in conjunction with the paramagnetic shift reagent dysprosium triethylenetetramine hexaacetic acid to observe the intracellular sodium and phosphorus signals in rat leg muscle. Male Wistar rats were bled to a mean arterial blood pressure of 40 mm Hg and were maintained at that pressure. Until decompensatory shock was reached, no increase in intracellular sodium (Nai) was found. Although the high energy storage metabolite phosphocreatine fell with time during shock, ATP did not decrease until decompensation. When the phosphorylation ratio, PR = [ATP]/[ADP][Pi], fell below log(PR) = 3.21 +/- .42, Nai increase commenced at a rate of 7.97 +/- 0.60 meq/l/hr. This corresponds to a two-fold increase in Na permeability compared to normal muscle. A calculation of the free energy available from hydrolysis of ATP at the above value of PR yields -11.7 kcal/mol which is essentially equal to the value of 11.8 kcal/mol which we calculate is needed to run the Na+-K+ antiport through one cycle under normal physiologic conditions.

Adenosine Triphosphate↗
PubMed1987

In vivo noninvasive observation of acute mesenteric ischemia in rats.

Acute intestinal ischemia remains a catastrophic event even with the advent of modern diagnostic and vascular surgical techniques. An early noninvasive test would be valuable since early operation yields better survival rates. We have used an in vivo rat model to study acute intestinal ischemia after occlusion of the superior mesenteric artery (SMA). 31Phosphorus magnetic resonance spectroscopy (MRS), a noninvasive nondestructive technique, can detect the phosphorus metabolites most likely to be altered in ischemia: adenosine triphosphate, phosphocreatine (PCr), inorganic phosphate (Pi) and phosphomonoesters and phosphodiesters. Furthermore, intracellular pH can be estimated from the pH dependent position of the Pi spectral line relative to PCr. A tourniquet was loosely placed around the SMA in five Wistar rats through a transabdominal approach to the retroperitoneum. The abdomen was immediately closed. A 20 millimeter MRS surface coil was placed on the abdomen and 31Phosphorus spectra were accumulated. The SMA was then occluded and additional 31Phosphorus spectra were taken for the next 75 minutes. Significant (p less than 10(-4) changes in the position and magnitude of the spectra lines occurred within 20 minutes; the Pi position indicates severe intracellular acidosis and rapidly increases to three times its original magnitude. The PCr line decreases in magnitude. In a similar experiment, occlusion of the superior mesenteric vein (SMV) produced equivalent results. Occlusion of vessels other than the SMA or SMV not accompanied by transmural ischemia resulted in spectra unaltered from control. These findings support the application of phosphorus MRS to clinical studies.

Adenosine Triphosphate↗
PubMed1986

Synthesis, antitumor activity, distribution and toxicity of 4-[4-[bis(2-chloroethyl)amino]phenyl]-1-hydroxybutane-1 1-bisphosphonic acid (BAD), a new lost derivative with increased accumulation in rat osteosarcoma.

The aim of this study was to investigate whether the newly synthesized bisphosphonic acid-linked N-Lost derivative BAD retains bone-seeking and cytostatic properties. The paper describes experiments on mutagenicity in vitro and on toxicity in vivo. BAD is characterized by very low mutagenic activity toward histidine auxotrophic Salmonella typhimurium strains. Cytotoxic effects were tested in rat osteosarcoma and in Walker carcinosarcoma 256B. The LD50 of i.v. injected BAD was 146 mg/kg. Acute toxicity is probably caused by calcium complexing of the bisphosphonate part of the molecule. Labeling experiments showed moderate accumulation in bone and osteosarcoma, as well as in lung metastases. BAD effected high tumor growth inhibition in osteosarcoma and Walker carcinosarcoma-bearing rats and marked prolongation of survival; histologic and radiographic examination revealed rapid calcification of osteosarcoma and lung metastases. BAD-pretreatment produced protective effects against osteolysis induced by intratibially implanted Walker carcinosarcoma ascites cells. The cytostatic efficacy of equitoxic doses of BAD in rat osteosarcoma is comparable to that of dacarbazine and in Walker carcinosarcoma to that of melphalan.

Animals↗
PubMed1986

Acute intestinal ischemia studies by phosphorus nuclear magnetic resonance spectroscopy.

31P nuclear magnetic resonance (NMR) spectroscopy has been used to follow the metabolism of acutely ischemic rat small intestine and its recovery after reversal of ischemia. Loops of small intestine were subjected to occlusive external pressure for up to 60 minutes, followed by a recovery period. The depletion of PCr and ATP is rapid and complete within 20 minutes. Recovery from ischemia is also rapid but with recovery ATP levels lower than initial values after prolonged ischemic periods. Intestinal shock was avoided. Clinical recovery correlated with shorter ischemic periods. 31P NMR spectroscopy thus appears to be a suitable technique for studying the effects of pharmacological agents and other treatments for amelioration of ischemic effects on the bowel.

Adenine Nucleotides↗
PubMed1985

Combined macroscopic and microscopic detection of viral genes in tissues.

A hybridization technique has been devised for detecting and quantitating viral genes in tissues that combines macroscopic and microscopic analyses in the same section. The method is based on dual labeling virus-specific probes with 125I and 35S to generate signals that can be detected both with X-ray films and nuclear track emulsions. The regions of increased hybridization evident in the X-ray film serve as a guide to the portion of the section that warrants microscopic examination. Detection of viral RNA in tissues with visna virus and viral DNA with hepatitis B virus are illustrated, and potential applications of this technique in virology and other disciplines are discussed.

Animals↗
PubMed1985

Detection of two viral genomes in single cells by double-label hybridization in situ and color microradioautography.

Double labeling and color microradioautography were used in a new method of hybridization in situ to identify different genes in individual cells. The method is based on the unequal penetration of 3H and 35S into two layers of nuclear track emulsion separated by a thin barrier film. Hybridization of a 35S-labeled probe specific for one kind of gene results in silver grains over cells in both layers of emulsion; a 3H-labeled probe for a second gene provides grains only in the first layer of emulsion. Silver grains are converted to magenta-colored grains in the first layer and to cyan-colored grains in the second to facilitate enumeration of grains in each layer. This technique should be widely applicable in analyses of differential gene expression in single cells or in discrete populations of cells.

Autoradiography↗
PubMed1985

Natural history of restricted synthesis and expression of measles virus genes in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a slow infection caused by measles virus in which several years separate recovery from typical acute measles and the development of a slowly progressive neurological disease. We have investigated replication of measles virus in brain tissue obtained after the onset of neurological disease and in the terminal phase. With a hybridization tomographic technique that combines in situ hybridization with macroradioautographic screening of large areas of tissue, we analyzed the spatial and temporal distribution of virus genes in vivo, using region- and strand-specific probes for the nucleocapsid and matrix genes. We show that early in the course of SSPE there is a global repression in the synthesis and expression of the genome. In the final stage of SSPE most infected cells still have depressed levels of plus- and minus-strand viral RNA and contain nucleocapsid protein but lack matrix protein. These findings provide further evidence for a unified view of slow infections of the nervous system, where the general constraints on virus gene expression provide an explanation for persistence of virus in the face of the host's immune response, and the slow evolution of pathological change. In the final phases of SSPE the more specific block in virus replication accounts for the cell-associated state of the virus and the difficulty in virus isolation.

Brain↗
PubMed1984

Slow virus visna: reproduction in vitro of virus from extrachromosomal DNA.

Under permissive conditions of growth in tissue culture, the retrovirus visna multiples over the course of a few days to high titer and kills the host cell. We show that in this lytic life cycle, viral DNA is tightly associated with, but not covalently linked to, chromosomal DNA. This finding provides explanations for a number of the unusual properties of the lentivirus subfamily of retroviruses, and suggests potential mechanisms for the block in virus gene expression in vivo responsible for the slow infection in nature.

DNA Replication↗
PubMed1983

Chronic psychiatric patients in the community.

A feasibility study is presented which describes a cohort of 102 chronic psychiatric patients. The cases were selected on the criterion of four or more new admissions to psychiatric services in the Hamilton-Wentworth region during the year 1977. The group was predominately in the age 20-39 year range and both sexes were represented about equally. The diagnostic labels were personality disorder, schizophrenia, depression and alcoholism in descending order of frequency. The large majority were socially isolated and had contact with social agencies and the police. Seven deaths occurred in the cohort during the year of study.

Adult↗
PubMed1981

Iron-sulfur N-1 clusters studied in NADH-ubiquinone oxidoreductase and in soluble NADH dehydrogenase.

Two N-1 type iron-sulfur clusters in NADH-ubiquinone oxidoreductase (Complex I, EC 1.6.5.3) were potentiometrically resolved: one was titrated as a component with a midpoint oxidation-reduction potential of -335 mV at pH 8.0, and with an n-value equal to one; the other as an extremely low midpoint potential component (Em 8.0 less than -500 mV). These two clusters are tentatively assigned to N-1b and N-1a, respectively. Cluster N-1b is completely reducible with NADH and has a spin concentration of about 0.8/FMN. Its EPR spectrum can be simulated as a single rhombic component with principal g values of 2.019, 1.937, and 1.922, which correspond to the Center 1 reported earlier by Orme-Johnson, N. R., Hansen, R. E., and Beinert, H. (1974) J. Biol. Chem. 249, 1922-1927. At extremely low oxidation-reduction potentials (less than -450 mV), additional EPR signals emerge with apparent g values of gz = 2.03, gy = 1.95, and gx = 1.91, which we assign to cluster N-1a. It is difficult, however, to simulate the detailed spectral line shape of this component as a single rhombic component, suggesting some degree of protein modification or interaction with a neighboring oxidation-reduction component. EPR spectra of soluble NADH dehydrogenase, containing 5-6 g atoms of non-heme iron and 5-6 mol of acid-labile sulfide/mol of FMN, were examined. Signals from at least two iron-sulfur species could be distinguished in the NADH-reduced form: one of an N-1b type spectrum; the other of a spectrum with g values of 2.045, 1.95, and 1.87 (total of about 0.5 spin equivalents/FMN). This is the first example of an N-1 type signal detected in isolated soluble NADH dehydrogenase.

Binding Sites↗
PubMed1981

Thermodynamic and electron paramagnetic resonance characterization of flavin in succinate dehydrogenase.

Thermodynamic parameters of succinate dehydrogenase flavin were determined potentiometrically from the analysis of free radical signal levels as a function of the oxidation-reduction potential. Midpoint redox potentials of consecutive 1-electron transfer steps are -127 and -31 mV at pH 7.0. This corresponds to a stability constant of intermediate stability, 2.5 x 10(-2), which suggests flavin itself may be a converter from n = 2 to n = 1 electron transfer steps. The pK values of the free radical (FlH . in equilibrium Fl . -) and the fully reduced form (FlH2 in equilibrium FlH-) were estimated as 8.0 +/- 0.2 and 7.7 +/- 0.2, respectively. Succinate dehydrogenase flavosemiquinone elicits an EPR spectrum at g = 2.00 with a peak to peak width of 1.2 mT even in the protonated form, suggesting the delocalization in the unpaired electron density. A close proximity of succinate dehydrogenase flavin and iron-sulfur cluster S-1 was demonstrated based on the enhancement of flavin spin relaxation by Center S-1.

Anaerobiosis↗
PubMed1981

Magnetic interactions between dysprosium complexes and two soluble iron-sulfur proteins.

A tetranuclear ferredoxin from Rhodopseudomonas gelatinosa [4Fe-4S](+2,+3) has been examined by electron paramagnetic resonance techniques. The temperature-dependence and relaxation characteristics of the spectral lines indicate that the spin-lattice interaction is described at low temperatures by a T2 law which gives way to a T9 Raman relaxation as the temperature is raised. At higher temperatures an Orbach process becomes dominant. In the presence of dysprosium complexes the relaxation and line widths are modified. From crystallographic structure determinations of similar proteins we are able to relate the dysprosium effects to the spatial separation between the complex and the tetranuclear cluster. This scale is then tested against a ferredoxin from Clostridium pasteurianum which contains two tetranuclear clusters, [4Fe-4S](+1,+2). We find that for these soluble iron-sulfur proteins the dysprosium complexes form a shell at the protein surface. The magnetic interaction between the clusters and the complexes altering the relaxation time goes as r-6, while the low temperature line broadening is described by an r-3 dipole interaction.

Clostridium↗