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Biomedical subjects

B Martin

Publications and source records attributed to B Martin.

At least 217 records · Page 12Linked to original sources

[Do antioxidants protect against myocardial infarct? Swiss contribution to the EURAMIC Study].

There is a growing interest in the function of antioxidants and free radicals and their roles in the development of arteriosclerosis. Oxidised LDL-cholesterol and polyunsaturated fatty acids may be involved in the development of arteriosclerotic lesions. The potential of antioxidant vitamins to prevent cardiovascular disease has been the subject of many studies. Up to now the results of different in vitro and in vivo studies remain controversial. For the first time, measurements of the concentrations of lipophilic antioxidants alpha-tocopherol (vitamin E) and beta-carotene (provitamin A) in fat-tissue have been used as an approach. This method is believed to provide an average of the antioxidant intake over a longer period of time and probably reflects steady-state levels rather than intake. A case-control study was conducted using first occurrence of myocardial infarction in men as disease endpoint. In the swiss part of EURAMIC, cases were recruited in collaboration with the hospitals of Zurich. Controls were chosen randomly from the population register of Zurich. Fifty-seven male cases and 74 male controls were enrolled in the protocol. The classical risk factors showed the expected pattern. Levels for beta-carotene were significantly lower in the patient group (0.36 microgram/g biopsy versus 0.52 microgram/g biopsy in controls, p < or = 0.02). In contrast, levels for alpha-tocopherol were similar in both groups (237.5 micrograms/g biopsy in patients and 233.4 micrograms/g biopsy in controls). The Swiss alpha-tocopherol levels were the highest of all participating centres. Analyses of the questionnaires showed significantly higher consumption of vitamin C supplements in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Effects of phosphorylation and nucleotides on the conformation of myosin II from Acanthamoeba castellanii.

The actin-activated Mg(2+)-ATPase activity of filamentous Acanthamoeba myosin II is inactivated by phosphorylation of a short non-helical tailpiece at the C-terminal end of each heavy chain even though the catalytic sites are in the N-terminal globular head. Consistent with this effect, phosphorylation at the tip of the tail alters the conformation of the head as shown by a shift in the principal site of cleavage by endoproteinase Arg-C (Ganguly, C., Martin, B., Bubb, M., and Korn, E. D. (1992) J. Biol. Chem. 267, 20905-20908). We now show that the sedimentation coefficient of monomeric phospho-myosin II is 1.3-4.6% lower than that of dephospho-myosin II, which suggests that phosphorylation produces a less compact conformation with a small increase in frictional coefficient. As shown by changes in papain digestion patterns, bound nucleotide also affects the conformation of the head region of monomeric phospho- and dephospho-myosin II, the conformation of the head region of filamentous phospho- and dephospho-myosin II, and the conformation of the C-terminal region of the tail of filamentous phospho-myosin II. Conformational differences between the dephospho- and phospho-forms of myosin II in the presence of nucleotide, as detected by susceptibility to proteolysis, therefore, appear to be greater in filaments than in monomers. These results provide additional evidence for communication between the N-terminal heads and C-terminal tails of Acanthamoeba myosin II.

Acanthamoeba↗

The initiation cascade for chromosome replication in wild-type and Dam methyltransferase deficient Escherichia coli cells.

'Newborn' Escherichia coli B/r cells, obtained by membrane elution, were used to study the cell cycles of wild-type and Dam methyltransferase mutants. In wild-type cells, initiation of chromosome replication was synchronous and tightly controlled. In dam mutants, initiation was altered, but not random. We propose that this is due to the absence of an initiation cascade caused by liberated DnaA molecules, and that this cascade normally synchronizes initiation. The dam- cells contained mainly two, three or four replication origins, and this affected nucleoid partitioning as well as cell division. In cultures growing with a 50 min doubling time, a variety of cell cycles were present and half the origins were used every 25 min. Some cells had a 25 min interdivision time, whereas others had an interdivision time longer than the generation time. Partitioning of nucleoids containing unequal numbers of replication origins could also be readily observed by fluorescence microscopy in the dam mutant. Based upon these observations we propose that the dam mutant is also an initiation cascade mutant.

Bacterial Proteins↗

Purification of a novel DBI processing product, DBI39-75, and characterization of its binding site in rat brain.

This report describes the purification and characterization from rat brain of DBI39-75, a novel, biologically active processing product of diazepam binding inhibitor (DBI). We have shown that DBI39-75 in nM concentrations stimulates pregnenolone synthesis in mitochondria of rat brain. Using cross-linking of 125I-DBI39-75 in steroidogenically active concentrations we have demonstrated for the first time that the DBI fragment has a specific high affinity binding site in rat brain. Displacement of [3H]PK 11195 and [3H]Ro5-4864 by DBI39-75 indicates more complex interaction than the competitive inhibition. Collectively, the data suggest that the function of DBI39-75 is mediated through a mitochondrial receptor complex which includes binding sites for PK 11195 and Ro5-4864.

Amino Acid Sequence↗

Mathematical model for the mineralization of bone.

A mathematical model is presented for the transport and precipitation of mineral in refilling osteons. One goal of this model was to explain calcification "halos," in which the bone near the haversian canal is more highly mineralized than the more peripheral lamellae, which have been mineralizing longer. It was assumed that the precipitation rate of mineral is proportional to the difference between the local concentration of calcium ions and an equilibrium concentration and that the transport of ions is by either diffusion or some other concentration gradient-dependent process. Transport of ions was assumed to be slowed by the accumulation of mineral in the matrix along the transport path. The model also mimics bone apposition, slowing of apposition during refilling, and mineralization lag time. It was found that simple diffusion cannot account for the transport of calcium ions into mineralizing bone, because the diffusion coefficient is two orders of magnitude too low. If a more rapid concentration gradient-driven means of transport exists, the model demonstrates that osteonal geometry and variable rate of refilling work together to produce calcification halos, as well as the primary and secondary calcification effect reported in the literature.

Animals↗

Evidence for a multigenic system controlling methyl-beta-carboline-3-carboxylate (beta-CCM)-induced seizures.

beta-CCM is a beta-carboline known to have properties opposite to those of benzodiazepines. Our approach was to analyze, in mice, the genetic mechanisms involved in beta-CCM-induced myoclonic seizures using recombinant congenic strains and F1 hybrids issued from these strains. Our aim was to define the extent of the multigenic character of beta-CCM-induced myoclonic seizures, while also evaluating the distribution of the strength of the genes implicated in this trait. The results show that the control of reactivity to beta-CCM is multigenic with notable epistatic involvement.

Animals↗

Association of autosomal loci with the grooming activity in mice observed in open-field.

We studied the reactions of mice when placed in an open-field environment and counted the grooming score in response to novelty. We used animals from Mendelian F2s and backcrosses, obtained from the parental strains ABP/Le and C57BL/6By, to test the hypothesis that the differences in this behavior were due to genetic variation at loci associated with visible recessive markers. Furthermore, the analysis of the segregating populations by means of non parametric Collins' method was used to test the one segregating unit hypothesis. We provide evidence for genes involved in the variation of grooming activity and situated close to the locus se on chromosome 9. Although the one-locus hypothesis was ruled out in the general analysis, a possible major gene effect in some crosses suggests a maternal environment effect.

Animals↗

Physiological perturbation of ocular and cerebral blood flow as measured by scanning laser ophthalmoscopy and color Doppler imaging.

Retinal blood flow regulation in health remains poorly described. We hypothesized that retinal perfusion is controlled to provide constant O2 delivery to that tissue, and that changes in retinal blood flow in response to chemical stimuli parallel changes in carotid and retrobulbar perfusion. Accordingly, in 11 young adults with normal eye examinations, we measured retinal blood flow indices (via scanning laser ophthalmoscopy [SLO] during fluorescein angiography) and carotid, ophthalmic, and central retinal arterial blood flow indices (via Doppler imaging [CDI]) under control, hypoxic (alveolar PO2 = 55 +/- 3 mmHg) and hyperoxic (alveolar PO2 = 655 +/- 18 mmHg) conditions. The three conditions were counterbalanced in order and isocapnia was maintained in each. Retinal arterial mean dye velocity and arteriovenous passage time, as measured by SLO, were slowed by hyperoxia and accelerated by hypoxia, in rough proportion to the changes in arterial O2 content (+/- 10%; p < 0.05). In the seven subjects in which relative measurements of retinal arterial diameters were obtained, neither hypoxia nor hyperoxia significantly altered vessel diameter. At the same time, mean retinal capillary transit velocity was independent of PO2, suggesting that, in health, retinal capillaries may be recruited as PO2 falls. O2-induced changes in carotid, ophthalmic, or central retinal arterial blood flow velocities (via CDI) were not found, though a wide coefficient of variation (30% for CDI vs. 14% for SLO) may have contributed to this failure. We conclude that, under isocapnic conditions, retinal perfusion may be regulated to provide constant O2 delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Assessing adherence to asthma medication and inhaler regimens: a psychometric analysis of adult self-report scales.

Poor adherence to recommended regimens is a substantial problem in the clinical management of adults with asthma and other chronic diseases. Research on adherence assessment is complicated by methodological difficulties including limitations associated with the use of self-report measures. In this study, psychometric techniques were used to analyze two self-report scales for assessing adherence to recommended medication and inhaler use regimens in adults with asthma. Results indicated that the two scales had standard deviations large enough to detect variation adherence, had adequate reliability, and reflected the impact of an intervention designed to improve adherence. The results supported the usefulness of these scales for research on adherence. Additional analyses indicated that the two scales could be combined if the research goal required an overall measure of adherence.

Administration, Inhalation↗

Biologic activities of retinoic acid and 3,4-didehydroretinoic acid in human keratinocytes are similar and correlate with receptor affinities and transactivation properties.

The biologic activities of retinoic acid and 3,4-didehydroretinoic acid, two endogenous vitamin A derivatives in various tissues, were compared to their affinities for the nuclear retinoic acid receptors and their ability to induce transcriptional activation. Both retinoids were equipotent inducers of differentiation of F9 teratocarcinoma cells. In a morphologic assay, using reconstructed skin, retinoic acid and 3,4-didehydroretinoic acid inhibited keratinization at a concentration of 100 nM. In cultured keratinocytes, a 50% inhibition of the production of the keratinocyte transglutaminase enzyme was achieved with about 20 nM for both retinoids. The in vitro binding to the nuclear retinoic acid receptors alpha, beta, and gamma showed that retinoic acid and 3,4-didehydroretinoic acid had almost equal affinities for the receptors with Kds ranging from 3 to 47 nM. The transcriptional activation resulting from the addition of the two retinoids to cells co-transfected with alpha, beta, or gamma retinoic acid receptor expression vectors and a retinoic acid responsive element linked to the chloramphenicol acetyltransferase reporter gene was similar. Finally, it was demonstrated that retinoic acid did not metabolize to 3,4-didehydroretinoic acid, and a slow conversion of 3,4-didehydroretinoic acid into retinoic acid was not sufficient to explain the biologic effects produced by the former compound. In conclusion, the present study demonstrates that retinoic acid and 3,4-didehydroretinoic acid have the same activity in several different test systems, but their metabolism differs depending on the cell type used.

Cells, Cultured↗

Direct evidence for SAA deposition in tissues during murine amyloidogenesis.

To study the mechanism of amyloid deposition, the nature of amyloid proteins formed in experimental murine amyloidosis, was examined. Spleen specimens, 15-60 mg, were homogenized and extracted using aqueous acidic acetonitrile, in a recently developed procedure, making it possible to obtain amyloid proteins from minute amounts of tissue. The extracted material, 1.5-4 mg, was analysed by Western blotting and ELISA using antibodies recognizing differentially proteins AA and SAA. Two immunoreactive proteins of 8 and 12 KDa were isolated and subjected to amino acid analysis and N-terminal sequence determination. The results of immunochemical and chemical examination showed that the 8 and 12 KDa proteins represented proteins AA and SAA, respectively. The data obtained provide new direct evidence for SAA in tissues during murine amyloidogenesis.

Amino Acid Sequence↗

The Alcoholism Denial Assessment Tool (ADAT): a study of interrater reliability.

The purpose of this study was to develop and test a tool for assessing alcoholic denial. The primary author devised the Alcoholism Denial Assessment Tool (ADAT) based on 2 years of experience. The tool was tested for interrater reliability using chart data of 42 recently discharged alcoholism patients. The test for significance of a proportion, using z scores, indicated significance at the .001 level. Item analysis showed strong interrater reliability on all but 1 of the 16 tool items. The ADAT provides nurses with a practical assessment tool that can be used daily to monitor progress. Recognition that a patient is in denial can allow meaningful and appropriately planned treatment.

Adolescent↗

[Kienboeck disease: treatment by shortening osteotomy of the radius].

INTRODUCTION: A series of twenty eight cases of Kienbock's disease treated by a shortening osteotomy of the radius are reported. MATERIAL AND METHODS: The series consisted of sixteen male and twelve female patients with an average age of twenty-five and followed for an average of five years. Seventeen patients were manual workers. The dominant side was affected in twenty cases; there were no bilateral cases. The clinical grades before surgery were one case in stage I, ten stage II, thirteen stage III, and four stage IV, using the Decoulx classification. The preoperative distal radio ulnar index was greater than 0 in only one case. Average radial shortening was three millimeters. The osteotomy was stabilized by using dynamic compression plates in fourteen cases, pinning in twelve cases, and staples in two cases. RESULTS: In all the cases, the results on pain relief and muscular strength were satisfactory. During preoperative review, pain was a major complaint in seventeen cases, moderate in nine cases, and slight in two cases. Joint range of motion (ROM) was, in seven cases, greater than seventy-five percent when compared to the opposite hand; in fourteen cases greater than fifty percent; less than fifty percent in five cases and less than twenty-five percent in two cases. Muscular strength, measured by J.A.M.A.R. test, was decreased in six cases by seventy-five percent when compared with the healthy side; in nineteen cases decreased by fifty percent and in three cases decreased by twenty-five percent. On the post-operative review, pain was decreased in all cases: twenty patients were pain free, seven felt slight pain during forced movements. Only one patient showed no improvement: he had a work related injury, with reflex dystrophy. A twelve percent increase in postoperative ROM was noted. Muscular strength improved by an average of forty one percent: 8 cases recovered normal strength, fifteen cases improved strength to seventy-five percent, and five cases improved to fifty percent. The overall clinical result did not seem to depend on the age of the patient or the preoperative radiological stage. They were evaluated using the criteria described by Michon. We obtained fourteen excellent results, ten good, four average. Twenty-five patients have been able to their previous job, three changed jobs. For the preoperative radiological assessment, we followed the Decoulx and the Lichtman scales and considered the distal radio ulnar index, the radial slope, the Linscheid lunate bone dimple incline and the Young and Mac Murtry measurement of the carpal collapse. Radiological assessment showed lunate bone remodeling in the ten cases rated stade II. Nine out of the thirteen patients rated stade III improved: two of them were rated stade II and seven cases presented an improvement of the radiological aspect. Four cases worsened. DISCUSSION: There was no parallel between the radiological evolution of the lunate bone and clinical results. Furthermore, radiological assessment did not show any true relationship between changes in the distal radio ulnar index and radiological evolution. The post-operative distal radio ulnar index was zero in eight cases, greater than one in fourteen cases and greater than two in six cases. Only the obliquity of the radial dimple opposite to the lunate bone is related with the radiological evolution. In the nine cases of stage III that have improved, the radial dimple slope was increased. The four cases of stage III that worsened, it was decreased. CONCLUSION: A shortening osteotomy of the radius is a satisfactory procedure independently of whatever the disease's age, the lunate bone radiological stage and the distal radio ulnar index. The only factor we think capable of modifying the radiological result of necrotic evolution is the lunate bone slope. It appears necessary, during the osteotomy, to increase this slope in order to reduce local pressure.

Adolescent↗

Correlates of acute exercise-induced ocular hypotension.

PURPOSE: To understand those factors that determine the decrease in intraocular pressure (IOP) that occurs during acute dynamic exercise. METHODS: Three aspects of the exercise-IOP relationship were studied. These included graded exercise, with and without CO2 addition for isocapnia; comparison of the IOP response of trained and sedentary subjects to a fixed external work load; and exercise after ocular beta-adrenoceptor blockade. Graded exercise consisted of 7 minutes each at 30 and 90 watts on a cycle ergometer, then progressive work to exhaustion. Trained and sedentary subjects were defined on the basis of the blood lactate response to fixed external work (10 minutes at 90 watts). Selective beta 1-adrenoceptor blockade (betaxolol) and nonselective beta-adrenoceptor blockade (levobunolol) were superimposed on graded exercise. Intraocular pressure was measured using applanation tonometry. RESULTS: Graded exercise: Intraocular pressure decreased in proportion to exercise intensity. Hypocapnia developed in the last minutes of exhausting work, but preventing hypocapnia with CO2 addition failed to lessen the decrease in IOP. Response to fixed external work load: Intraocular pressure decreased significantly more in sedentary than in trained subjects; this decline was correlated with elevations in blood lactate but not with changes in metabolic rate or plasma osmolarity. Selective and nonselective beta-adrenoceptor blockade: Both drugs lowered IOP at baseline and throughout graded exercise; the drugs and exercise had apparently additive ocular hypotensive effects. CONCLUSIONS: Acute dynamic exercise lowers IOP in a graded fashion proportional to relative, not absolute, work load. The IOP decline is correlated with blood lactate but not with PCO2 or plasma osmolarity changes, and exercise potentiates the ocular hypotensive effects of beta-adrenoceptor blockade.

Betaxolol↗

The reduced unsubstituted pteroate moiety is required for folate toxicity of cultured cerebellar granule neurons.

The proconvulsive and putative excitotoxic properties of folates led us to study folate toxicity in cultured rat cerebellar granule neurons. Exposure of these neurons to tetrahydrofolate (THF) (EC50 = 263 +/- 12 microM) and dihydrofolate (EC50 = 709 +/- 29 microM), but not to folate, formyl-THF, methyl-THF or methotrexate, resulted in a concentration-dependent neurotoxicity. THF and dihydrofolate toxicity were characterized by prominent neuronal swelling and early loss of neurite networking and could not be blocked by glutamate receptor antagonists, L-channel calcium blockers or anticonvulsants. Cleavage of THF into glutamate and tetrahydropteroate by glutamate carboxypeptidase in the presence of 1 microM MK-801 and 5 microM 6-cyano-7-nitroquinoxaline-2,3,dione shifted the concentration-toxicity curve to the left (EC50 = 47 +/- 4 microM). These results suggest (1) that the glutamate moiety is not necessary for folate toxicity, (2) that the unsubstituted reduced pteroate moiety is required for folate toxicity and (3) that unsubstituted reduced pteroates are previously unrecognized neurotoxins. Because there is no endogenous glutamate carboxypeptidase activity in cerebellar granule neuron cultures and no increase of glutamate levels in the medium of cultures exposed to THF or dihydrofolate, pteroate metabolites are unlikely to mediate the THF or dihydrofolate toxicity of cultured cerebellar granule neurons.

Animals↗

MK-801 and memantine protect cultured neurons from glutamate toxicity induced by glutamate carboxypeptidase-mediated cleavage of methotrexate.

Cleavage of methotrexate into glutamate and diaminomethylpteroate by intrathecal glutamate carboxypeptidase is a new approach to the treatment of acute methotrexate neurotoxicity. The simulation of glutamate carboxypeptidase rescue from high-dose methotrexate in neuron astrocyte cocultures of rat cerebellum or cerebral cortex resulted in a selective, concentration-dependent neurotoxicity. The neurotoxicity was caused by the enzymatic release of glutamate from methotrexate at lower concentrations of methotrexate, and by both glutamate and diaminomethylpteroate at concentrations of methotrexate exceeding 200 microM. The good neuroprotection afforded by MK-801 and memantine suggested that glutamate toxicity was mediated by N-methyl-D-aspartate receptors. Methotrexate alone was not toxic to astrocytes, neurons, or the neurite networking. [3H]thymidine and [3H]deoxyuridine incorporation studies showed that astrocyte proliferation in the presence of methotrexate was maintained by the reutilization of pyrimidine bases for DNA synthesis. N-methyl-D-asparate receptor antagonists should be coadministered in future experimental and clinical trials examining intrathecal glutamate carboxypeptidase rescue of methotrexate toxicity.

Animals↗