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Biomedical subjects

J L Martin

Publications and source records attributed to J L Martin.

At least 307 records · Page 17Linked to original sources

Insulin-like growth factor-binding protein from human plasma. Purification and characterization.

Insulin-like growth factor (IGF)-binding protein (BP) has been purified from Cohn fraction IV of human plasma by acidification, ion exchange to remove endogenous ligands, and affinity chromatography on agarose-IGF-II. The pure protein appeared as a single peak by high performance reverse-phase and gel permeation chromatography (molecular mass, 45-50 kDa), but on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave a major band at 53 kDa and a minor band at 47 kDa, unreduced, or 43 and 40 kDa, respectively, reduced. The two bands stained for both protein and carbohydrate. After storage at 2 degrees C for 5 months at pH 3, two additional bands, at 26 and 22 kDa on unreduced gels, were also present. Autoradiography after affinity labeling with IGF-I or IGF-II tracer revealed a single labeled band of 61 kDa. BP, quantitated using a specific radioimmunoassay, was retained by agarose-immobilized IGF-I, IGF-II, concanavalin A, and wheat germ lectin, but not Helix pomatia lectin. Competitive binding curves using pure BP and human IGF-I and IGF-II as both labeled and unlabeled ligands indicated association constants of 2-3 X 10(10) liters/mol for both peptides, with a slightly higher affinity for IGF-II than IGF-I, and 0.9 binding sites for either peptide per 53-kDa protein. The exact relationship of this acid-stable IGF BP to the 150-kDa complex from which it is derived remains to be determined.

Chromatography, Affinity↗

[mono[125I]iodo-Tyr10,MetO17]-vasoactive intestinal polypeptide. Preparation, characterization, and use for radioimmunoassay and receptor binding.

Vasoactive intestinal polypeptide (VIP) was labeled with sodium [125I]iodide using the chloramine-T method and subsequently purified by reverse-phase high performance liquid chromatography. Three main 125I-labeled peaks designated A, B, and C resulted from the radioiodination and purification procedures. They were characterized by electrophoresis of tryptic fragments; Edman degradation (for Peaks A and C); enzymatic digestion to amino acids by leucine aminopeptidase, carboxypeptidase Y and Pronase; and treatment with cyanogen bromide. Peak A corresponds to VIP monoiodinated on Tyr10 and with the Met17 residue oxidized to methionine sulfoxide. This [mono[125I]iodo-Tyr10,MetO17]VIP displays the following characteristics. 1) It constitutes quantitatively the major product of the iodination procedure (62.5%); 2) it is well resolved from other labeled and unlabeled products; 3) it is stable (2 months at -20 degrees C); 4) it possesses a high specific activity (2050 Ci/mmol); 5) it maintains the biological activity of native VIP; and 6) it binds to antibody and membrane recognition sites in a specific, saturable, and reversible manner. Reduction of [mono[125I]iodo-Tyr10, Met-O17]VIP to [mono[125I]iodo-Tyr10]VIP does not improve the performance of the tracer in a radioimmunoassay. The method described in this article is simple and rapid and yields a molecular form of 125I-labeled VIP that has been fully characterized and is suitable for use in biological studies.

Animals↗

Effects of nitroglycerin in patients with angina, normal coronary arteries, and left ventricular hypertrophy.

The coronary hemodynamic and left ventricular mechanical responses to nitroglycerin were studied in eight patients with angina, normal coronary arteries, and pressure overload left ventricular hypertrophy (POLVH) and in five control subjects. Elevated mean and end-diastolic pressure and end-diastolic meridional stress characterized the POLVH group, although systolic meridional stresses were not significantly different from the control group. Thermodilution coronary sinus flow and estimated myocardial oxygen consumption declined significantly following nitroglycerin in both patient groups. Systolic and diastolic mechanical loads also decreased in both groups, although diastolic tone remained elevated in the patients with POLVH. The decrease in coronary sinus flow in the POLVH group was in excess of that expected from the decrease in systolic mechanical load, which suggests a combination of perfusion pressure-dependent decreases in coronary flow as well as an increased resistance to coronary inflow in these patients. The beneficial clinical response to nitroglycerin may reflect the lowered myocardial metabolic demand as well as the decrease in diastolic myocardial tensile and compressive forces.

Adult↗

Nutrients, platelet function and composition in nine groups of French and British farmers.

In 260 male farmers (40-45 years) divided into 9 groups from different areas in France and Britain, coagulation, platelet aggregation, lipemia, fatty acids from plasma lipids and platelet phospholipids were determined in relation to the food intake evaluated by recall, weighing and chemical analysis of the diet. The clotting activity of platelets and their response to thrombin aggregation was significantly correlated on an individual basis with the intake of saturated fatty acids both in subsamples as well as in the whole study. Serum cholesterol was also significantly correlated with saturated fats but only on a group basis or on the totality of the study. Calcium, linolenic acid and alcohol in the diet were inversely related to certain platelet functions. Linoleic acid was inversely related to serum cholesterol and triglycerides. Dietary saturated fats were associated, with an increase in the platelet phospholipids not in saturated fatty acids but in 20:3 (n-9), known to promote platelet aggregation to thrombin, with a decrease in platelet cholesterol, also apparently regulating platelet functions. The present studies indicate that dietary saturated fats, calcium (hard water) and alcohol, influence platelet behaviour in a way strictly parallel to their known effect on coronary heart disease.

Adenosine Diphosphate↗

Actions of VIP, hGRF, PHI and secretin: comparative studies in cerebral cortex and adenohypophysis.

We have examined the effects of hGRF on cyclic AMP and glycogen levels in mouse cerebral cortical slices. hGRF-44-NH2 and hGRF-28-OH did not stimulate cyclic AMP formation nor glycogenolysis and did not antagonize the stimulatory effects of VIP on cyclic AMP formation and glycogenolysis. These observations indicate that despite the structural homologies with VIP, hGRF does not interact with VIP receptors coupled to adenylate cyclase in mouse cerebral cortex. This is in contrast with observations in other tissues and species, such as rat and human intestinal epithelial membranes and rat pancreas. We have also compared the effects of hGRF, VIP, PHI and secretin on Growth Hormone (GH) release and cyclic AMP levels in anterior pituitary cells in vitro. VIP and PHI, but not secretin, promote at a high concentration (10(-6) M) a small but significant release of GH. This GH release is accompanied by increases in cyclic AMP levels. The concentration of VIP and PHI required to elicit these effects is high and suggests that VIP and PHI act as low affinity pharmacological analogs of hGRF on hGRF pituitary receptors.

Animals↗

Femtosecond spectroscopy of excitation energy transfer and initial charge separation in the reaction center of the photosynthetic bacterium Rhodopseudomonas viridis.

Reaction centers from the photosynthetic bacterium Rhodopseudomonas viridis have been excited within the near-infrared absorption bands of the dimeric primary donor (P), of the "accessory" bacteriochlorophylls (B), and of the bacteriopheophytins (H) by using laser pulses of 150-fsec duration. The transfer of excitation energy between H, B, and P occurs in slightly less than 100 fsec and leads to the ultrafast formation of an excited state of P. This state is characterized by a broad absorption spectrum and exhibits stimulated emission. It decays in 2.8 +/- 0.2 psec with the simultaneous oxidation of the primary donor and reduction of the bacteriopheophytin acceptor, which have been monitored at 545, 675, 815, 830, and 1310 nm. Although a transient bleaching relaxing in 400 +/- 100 fsec is specifically observed upon excitation and observation in the 830-nm absorption band, we have found no indication that an accessory bacteriochlorophyll is involved as a resolvable intermediary acceptor in the primary electron transfer process.

Journal Article↗

Femtosecond spectroscopy of electron transfer in the reaction center of the photosynthetic bacterium Rhodopseudomonas sphaeroides R-26: Direct electron transfer from the dimeric bacteriochlorophyll primary donor to the bacteriopheophytin acceptor with a time constant of 2.8 +/- 0.2 psec.

The primary light-induced charge separation in reaction centers from Rhodopseudomonas sphaeroides R-26 has been investigated after excitation with laser pulses of 150 fsec duration within the longwave absorption band of the primary donor at 850 nm. An excited state of the primary donor, characterized by a broad absorption spectrum extending over the whole spectral range investigated (545-1240 nm), appeared within 100 fsec and gave rise to stimulated emission in the 870- to 1000-nm region with a 2.8-psec lifetime. The photooxidation of the primary donor, as measured at 1240 nm, and the photoreduction of the bacteriopheophytin acceptor, monitored at 545 nm and 675 nm, have been found to proceed simultaneously with a time constant of 2.8 +/- 0.2 psec. Kinetics of absorbance changes at other probe wavelengths gave no indication that an accessory bacteriochlorophyll is involved as a transient electron acceptor.

Journal Article↗

Influence of long-term diet modification on platelet function and composition in Moselle farmers.

Platelet function and composition, lipemia, and dietary habits were evaluated yearly in 98 male farmers from Moselle (East of France) before and after decreasing, in half of them, dietary saturated fats from 16.2% to 9.9% of calories (P/S from 0.32 to 0.97). One year after these dietary changes, cholesterol and triglycerides decreased by approximately 10%, platelet aggregation to thrombin by 81%, and their clotting activity by 30%. However, ADP aggregation was enhanced by 54%. At 2 yr the P/S was decreased to 0.7 and diet also modified in controls, with 18:2 being increased mostly in one group (P/S = 0.81) and 18:3 in another (P/S = 0.59). In both groups, the main platelet function tests were significantly depressed 1 yr later. Considering the whole study, the intake of saturated fat was mostly correlated (group and individual) with platelet aggregation to thrombin, platelet clotting activity, and 20:3 (n-9) in plasma and platelet lipids.

Adenosine Diphosphate↗

Induction of acyclovir-resistant mutants of herpes simplex virus type I in athymic nude mice.

Induction of acyclovir resistance was studied in the immune compromised host by multiple passage of plaque-purified herpes simplex type I strains in athymic nude mice receiving suboptimal antiviral therapy. Mice infected with a highly pathogenic clinical isolate rapidly developed infections that were resistant to therapy. Viruses isolated from these mice had decreased in-vitro sensitivities to acyclovir, as well as altered characteristics when assayed by [125I]plaque autoradiography. In contrast, less virulent laboratory strains, or a genetically stable clinical isolate, showed no indication of mutation to resistance after extended passage in this mouse model. Highly pathogenic viruses may increase the probability of mutation to resistance because of the large amount of infectious virus they produce, while viruses of equivalent virulence may produce different amounts of drug-resistant progeny because of alterations in the replication fidelity of the viral DNA polymerase.

Acyclovir↗

Relationship between inotropy and relaxation in rat myocardium.

Myocardial mechanics of 56 rat papillary muscles were investigated in various inotropic states, i.e., early postpartum (1st day, 1st mo) and, in adult, by altering external calcium concentration, [Ca2+]0, stimulation frequency (F), and initial muscle length (L). In all these protocols, the decrease of the inotropic level paralleled a progressive diminution in load sensitivity of relaxation. In such protocols modifying cardiac contractility, peak shortening velocity of the twitch with preload only at Lmax (Vcmax) was always less depressed than peak lengthening velocity (Vrmax), and the ratio R1 = Vcmax/Vrmax always increased. This increase of R1 was linearly related with the decrease of the maximum unloaded shortening velocity (Vmax). The ratio R2 (positive over negative peak force derivatives of the isometric twich at Lmax) was significantly lowered in newborn and was lowered in adult for [Ca2+]0 less than or equal to 1 mM and L less than or equal to 94% Lmax. For a given change in Vmax, each of the experimental protocols gave rise to specific changes in contraction-relaxation coupling tested at low load (R1) and at heavy load (R2).

Aging↗

Radioimmunoassay of growth hormone-dependent insulinlike growth factor binding protein in human plasma.

A specific radioimmunoassay has been established for a growth hormone-dependent insulinlike growth factor (IGF) binding protein (BP) from human plasma. Although the assay was directed against a 53-kD, acid-stable BP subunit, the main immunoreactive BP in the circulation had an apparent molecular mass of approximately 125 kD. Only higher primate species showed cross-reactivity, and IGF-I, IGF-II, and other peptides were without effect. Circulating BP levels in healthy subjects rose threefold from early childhood to puberty. In 65 adults aged 18 to 65, the mean level (+/- SD) was 6.12 +/- 1.43 micrograms/ml, and declined with age. Strong growth hormone-dependence of BP was also seen; there was a 2.2-fold increase in active acromegaly and a 50-80% reduction in growth hormone deficiency. Poorly controlled diabetic subjects had BP levels 40% below normal, whereas in renal failure and third-term pregnancy a mild elevation was seen. Measurement of BP may provide a useful adjunct to IGF assays in growth disorders.

Adolescent↗

AIDS risk reduction recommendations and sexual behavior patterns among gay men: a multifactorial categorical approach to assessing change.

A sample of 745 New York City gay men, aged 20-65, were interviewed in 1985 as part of a longitudinal effort to determine the behavioral, psychological, and social impact of the AIDS epidemic on the non-ill but at-risk community. Detailed sexual behavior histories were taken for the year prior to the interview (1984-1985) and the year prior to when respondents first heard about AIDS (mode = July 1981). Parallel questions were asked for each annual time period allowing pre-AIDS/post-AIDS comparisons to be conducted. A multifactorial index of sexual behavior was constructed from three categorical variables: number of different sexual partners, (0, 1, and 2 or more); engaging in sexual contact outside a private home, (0, vs. 1); and engaging in sexual acts considered to be of higher risk for exposure to disease pathogens (0 vs. 1). These three factors, representing aspects of sexual behavior targeted for change by authors of risk reduction educational materials, were combined to form a seven-level typological index of sexual behavior. Analyses are based on comparisons between pre- and post-AIDS time periods on this index. Results indicate that both substantial change and substantial lack of change have occurred in gay male sexual behavior patterns, when sexual behavior measures are scaled to reflect complete abstinence from a particular type of sexual activity, as they are here. Results are discussed in light of previously reported findings on sexual behavior changes and the ambiguity surrounding the question of how much change is needed for significant risk reduction of AIDS.

Acquired Immunodeficiency Syndrome↗

Adenosine stimulates glycogenolysis in mouse cerebral cortex: a possible coupling mechanism between neuronal activity and energy metabolism.

Adenosine promotes a concentration-dependent hydrolysis of 3H-glycogen newly synthesized from 3H-glucose by mouse cerebral cortical slices. The EC50 for this effect is 7 microM. Theophylline antagonizes the glycogenolysis induced by adenosine with an EC50 of 80 microM. The rank-order of potencies of adenosine agonists is adenosine 5'-cyclopropyl-carboxamide greater than 2-chloroadenosine much greater than N6-cyclohexyladenosine = adenosine, suggesting that adenosine promotes glycogenolysis via receptors of the A2 type. This contention is substantiated by the weak stereospecificity observed for the glycogenolytic action of D- and L-(phenylisopropyl)-adenosine. The glycogenolysis elicited by adenosine at 10 and 100 microM is inhibited by ouabain at 10 microM, a concentration of the cardiac glycoside not significantly affecting 3H-glycogen levels per se. Interestingly, the previously demonstrated glycogenolytic action of vasoactive intestinal peptide (Magistretti et al., 1981, 1984) and of norepinephrine (Quach et al., 1978) is also antagonized by ouabain. These results demonstrate the existence of a metabolic action of adenosine, which is sensitive to ouabain and appears to be mediated by A2 receptors. The concentrations at which adenosine promotes glycogenolysis are of the same order of magnitude as those reached extracellularly by the nucleoside during neuronal depolarization (Pull and McIlwain, 1972). This set of observations therefore supports the notion that adenosine plays a modulatory role in the coupling between neuronal activity and energy metabolism in the CNS.

Adenosine↗

[The mechanics of sarcomeres studied using laser diffraction. A study of relaxation].

Myocardial tissues act as an optical filter to light. This is due to their regular striation--periodically alternating clear and dark anisotropic bands. When a narrow band of rat right ventricle is illuminated with a Helium-Neon laser (lambda = 633 nm) diffraction bands are observed, the spacing of which is inversely proportional to the sarcomere length. After muscular stimulation, the displacement of the diffraction bands allows measurement in real time of the contraction and relaxation of the sarcomeres. Sarcomere relaxation comprises two successive experimental phases, one rapid and the other one slow. The time constant of the rapid phase (tau 1) increases linearly with the total load; that of the slow phase (tau 2) decreases. The end of the rapid phase and tau 1 depend on the conditions of load. Our results suggest that the recaptation of calcium by the sarcoplasma reticulum and the affinity of troponine C for calcium depend on the level and changes of load. The affinity of TnC for calcium increases with high load and/or low amplitude of sarcomere shortening: it decreases with low loads and/or high amplitudes of sarcomere shortening.

Animals↗

[Variations in birth weight as a function of various fetal and maternal characteristics. The application to the diagnosis of hypotrophy].

The known variations in weight for gestational age as well as compounding maternal and/or fetal factors, puts into question the usual definition of small for gestational age (SGA) which is based on gestational age alone. On the basis of more than 20,000 births studied in 4 maternity hospitals from 3 separate regions in France, the authors propose a new definition for growth retardation in full-term babies, taking into account 4 factors: gestational age, sex, birth rank, height and usual weight of mothers. This definition allows constitutionally SGA newborns to be considered normal, while some babies previously classified as normal would now lead one to suspect intra-uterine growth retardation (IUGR). This approach tries to take constitutional and environmental risk factors into account in fetal growth hopefully allowing for help better detection of IUGR.

Adult↗

Sulfonic acid enkephalin: binding specificity to rat brain opiate receptors.

We tested sulfonic-acid enkephalin, a SO3H-Tyr derivative of the Leu-enkephalin, for its binding capacity to rat brain opiate receptors, by competition against several tritiated enkephalins. Using [3H]DADLE as the competitor, we demonstrated that sulfonic-acid enkephalin binds to rat brain opiate receptors, and using [3H]DSLET and [3H]DAGO as the competitors, we demonstrated that sulfonic-acid enkephalin binds preferentially to delta-opiate receptors. The affinity ratio of sulfonic-acid enkephalin for delta-opiate receptors versus mu-opiate receptors, is considerably higher than that of the parent compound, Leu-enkephalin, and of DADLE and is similar to the affinity ratio of DSLET for the same receptors.

Animals↗

Effect of high dose aspirin on coronary hemodynamics during pacing-induced myocardial ischemia.

The effects of aspirin on coronary hemodynamics and transcardiac concentrations of thromboxane B2 (the stable metabolite of thromboxane A2) were determined at rest and during pacing-induced myocardial ischemia in 11 patients with coronary disease. Control coronary sinus pacing increased both arterial thromboxane B2 (331 +/- 70 to 623 +/- 132 pg/ml, p less than 0.02) and coronary sinus thromboxane B2 (184 +/- 3 to 403 +/- 156 pg/ml, p less than 0.05), but positive transmyocardial gradients developed in only three patients. After 650 mg of oral aspirin, more than 90% inhibition of in vitro thromboxane B2 production was demonstrated and circulating thromboxane B2 was undetectable at rest and during pacing in all patients. Despite these changes in thromboxane B2 concentrations, coronary blood flow was unchanged by aspirin at rest (107 +/- 14 versus 112 +/- 13 ml/min, p = NS) and during pacing (189 +/- 29 versus 181 +/- 25 ml/min, p = NS). Myocardial lactate extraction was also unchanged at rest (24 +/- 7 versus 19 +/- 5%, p = NS) and during pacing (5 +/- 6 versus 9 +/- 5%, p = NS). No change occurred in the anginal threshold. Thus, aspirin does not have the vasoconstrictive properties that have been reported with another cyclo-oxygenase inhibitor, indomethacin. These findings also suggest that thromboxane A2 production does not play a major role in the pathogenesis of stress-induced ischemia. Nonetheless, intracoronary thromboxane A2 production in some patients may potentiate platelet activation and coronary thrombosis. Such patients may benefit from long-term aspirin therapy and can be treated with aspirin without risk of adverse coronary hemodynamic effects.

Administration, Oral↗

Analysis of isoenzymes in normal and carcinogen-treated human endometrial stromal cells in culture.

The isoenzyme patterns of lactate dehydrogenase (LDH), hexokinase, phosphofructokinase, and aldolase were investigated in cultured normal and carcinogen-treated human endometrial stromal cells. Both normal and carcinogen-treated cells had similar phosphofructokinase and aldolase isoenzymes. Distinctive changes in hexokinase and LDH isoenzyme patterns were found in the carcinogen-treated stromal cells. The LDH isoenzyme patterns of the carcinogen-treated stromal cells were shifted toward the muscle LDH forms. This is comparable to the alteration of LDH isoenzyme profiles observed in cell lines established from human uterine sarcomas. The two tissue culture media used affected the LDH isoenzyme patterns of endometrial stromal cells but differences between the LDH isoenzyme patterns of control and carcinogen-treated cells were detected regardless of the growth medium used. Total LDH activity was not significantly different in control and carcinogen-treated stromal cells. The hexokinase isoenzyme patterns expressed by the carcinogen-treated stromal cells were distinctly different from the normal hexokinase patterns. The treated stromal cells contained both hexokinase I and II, whereas the normal cells contained only hexokinase I. Hexokinase and LDH isoenzyme patterns may serve as markers with which to evaluate carcinogen-induced neoplastic changes in cultured endometrial stromal cells.

Cell Line↗