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Biomedical subjects

B Martin

Publications and source records attributed to B Martin.

At least 235 records · Page 13Linked to original sources

In vivo interaction of neuropeptide Y and peptide YY with sigma receptor sites in the mouse brain.

Neuropeptide Y (NPY-(1-36)), peptide YY (PYY) and various other peptides were investigated for their interaction with the binding of [3H](+)-SKF10,047 to sigma binding sites in mouse hippocampus in vivo. NPY-(1-36), PYY-(1-36), [Leu31,Pro34]NPY, NPY-(2-36), and NPY-(3-36) inhibited the labelling of a population of haloperidol-sensitive binding sites corresponding to 35% of the specific binding. These in vivo binding results confirm the previous interaction already reported between NPY peptides and sigma binding sites.

Animals↗

Sequence, expression pattern, intracellular localization, and targeted disruption of the Dictyostelium myosin ID heavy chain isoform.

The complete sequence of the Dictyostelium myosin ID (DMID) heavy chain isoform has been determined from cDNA and genomic clones. Like the DMIB isoform characterized previously, the DMID isoform is up-regulated during starvation-induced chemotactic aggregation, and its 124-kDa heavy chain contains the tail domain sequences that correspond to both the membrane and second actin-binding sites. An antibody that is specific for the DMID isoform was found to stain the actin-rich pseudopods at the leading edge of migrating cells. Protein microsequencing data reveals that the myosin I isoform localized to leading edge pseudopods in a previous study (Fukui, Y., Lynch, T. J., Brzeska, H., and Korn, E. D. (1989) Nature 341, 328-331) was DMIB, indicating that DMID and DMIB also colocalize and that both should influence the dynamics of actin-rich cortical structures. This and other data indicate that the DMID and DMIB isoforms are closely related and are distinct from the DMIA and DMIE isoforms, which possess truncated tail domains and are not up-regulated during chemotactic aggregation. Cells in which the DMID gene was rendered nonfunctional by targeted gene disruption do not show obvious behavioral defects, suggesting that another myosin I isoform(s) (possibly DMIB) might compensate for DMID. Finally, Southern blot data indicate that Dictyostelium may contain as many as nine myosin I isoforms.

Amino Acid Sequence↗

Stifling the media.

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Acquired Immunodeficiency Syndrome↗

Aging and strength of bone as a structural material.

There is a general, age-related reduction in the material strength and stiffness of bone in both men and women. Between the ages of 35 and 70, cortical bone strength in bending is diminished by about 15-20%, and cancellous bone strength in compression is reduced about 50%. In addition, bone becomes increasingly brittle and fractures with less energy. It is hypothesized that this tendency is driven by the need for remodeling to repair fatigue damage, and the fact that most osteonal and endotrabecular remodeling events fail to replace all the bone that they remove. Each remodeling event also introduces cement line interfaces, which although affording protection against fatigue failure, weaken bone for monotonic loading. Remodeling also affects collagen fiber orientation, mineralization, and the amount of unrepaired fatigue damage, which are additional determinants of bone strength and stiffness. Mechanical factors apparently inhibit age-related bone loss where stresses are higher by reducing remodeling rates and/or the deficit at each remodeling site. They may also stimulate modeling responses, primarily in the form of periosteal bone formation, which, in men more than women, alter bone size and shape to effectively compensate for loss of material strength. Suggested directions for future research include elucidation of the relationships between (1) histologically observable microcracks and bone fragility, (2) remodeling and the repair of fatigue damage, and (3) estrogen and other hormones and mechanically adaptive responses.

Adult↗

Transmural redistribution of myocardial blood flow during isoflurane anesthesia and its effects on regional myocardial function in a canine model of fixed coronary stenosis.

BACKGROUND: The effects of isoflurane on the transmural distribution of myocardial blood flow distal to an acute critical coronary stenosis and the relationship between the changes in regional blood flow and function were studied to determine whether isoflurane can produce a transmural "steal" phenomenon and to assess the role of this phenomenon in producing changes in regional myocardial function. METHODS: After production of acute critical coronary stenosis under baseline chloralose and fentanyl anesthesia, the animals were exposed to increasing end-tidal concentrations of isoflurane (0.7%, 1.4%, and 2.1%) without control of the hemodynamic parameters. At 2.1% isoflurane, the blood pressure then was restored to the baseline level by administration of phenylephrine. Changes in the following parameters were assessed: global contractility (measured by changes in pressure with time), regional myocardial function (assessed by systolic wall thickening and measured by sonomicrometers), transmural distribution of myocardial perfusion (measured by the radioactive microsphere method), and regional oxygen consumption and extraction. RESULTS: Distal to the critical stenosis, a transmural redistribution of myocardial blood flow (endocardial-epicardial ratio < 1) occurred with all concentrations of isoflurane. With higher concentrations (1.4% and 2.1%), a significant decrease in subendocardial blood flow occurred only in the presence of hemodynamic changes and was restored by phenylephrine. In this area, changes in regional myocardial function correlated most strongly with changes in subendocardial perfusion (y = -0.17 + 1.70x -0.58x2, r2 = 0.90). In the stenotic region, oxygen extraction remained stable, but oxygen consumption decreased in parallel with reductions in regional myocardial function. In the normal region, oxygen consumption did not change, but oxygen extraction decreased with increasing isoflurane concentrations. CONCLUSIONS: These results show that isoflurane is a coronary vasodilator able to induce a transmural redistribution of myocardial blood flow distal to an acute critical coronary stenosis. A true transmural steal, however, was not produced reliably in the absence of hemodynamic changes, suggesting that isoflurane either is only a moderate vasodilator, or that the decrease in subendocardial blood flow is offset by the negative inotropic action of the drug. When regional myocardial dysfunction distal to a severe coronary stenosis occurs, this correlates with decreasing subendocardial blood flow during isoflurane anesthesia, suggesting ischemia as the cause.

Anesthesia, Inhalation↗

Docosahexaenoic acid--a new therapeutic approach to peroxisomal-disorder patients: experience with two cases.

Docosahexaenoic acid (DHA, 22:6 omega 3) is a major constituent of brain membrane phospholipids and photoreceptor cells. Patients with generalized peroxisomal disorders have extremely low levels of DHA in the brain and other tissues. Since a DHA deficiency could explain some basic symptoms in peroxisomal-disorder patients, we tested the possible beneficial effects of DHA in two patients with neonatal adrenoleukodystrophy (NALD). Before the treatment, both patients had very low DHA levels in plasma and erythrocytes. We first gave DHA in the form of fish oil and, in both patients, the rapid increase in red-cell DHA levels indicated that this fatty acid was being absorbed and incorporated into membrane phospholipids very fast. However, a low ratio 22:6 omega 3/22:5 omega 3 was still present in erythrocyte membranes, and the content of 20:5 omega 3 (eicosapentaenoic acid) was too high with the fish oil diet. We then began treatment with pure DHA ethyl ester and, after a few weeks, erythrocyte omega 3 polyunsaturated fatty acids were normal. There was an increase in the 18:0 molecular species of plasmalogens in both patients, most significantly in the child with affected plasmalogen biosynthesis in cultured fibroblasts. In the less severely affected NALD patient, treatment with DHA produced a very significant decrease in the ratios 24:1/22:0 and 26:1/22:0, and this child improved neurologically. The present data suggest that DHA deficiency may be the cause for some of the most characteristic abnormalities in peroxisomal-disorder patients and open new therapeutic possibilities for these patients.

Child↗

Limited proteolysis reveals a structural difference in the globular head domains of dephosphorylated and phosphorylated Acanthamoeba myosin II.

Phosphorylation at three sites at the tip of the tail of myosin II from Acanthamoeba castellanii inactivates the actin-activated Mg(2+)-ATPase activity of filamentous myosin and the in vitro motility activity of both monomeric and filamentous myosin. To seek a structural explanation for these effects, we examined the susceptibilities of dephosphorylated and phosphorylated myosins II to endoproteinases. Endoproteinase Arg-C cleaved myosin II preferentially at two sites in the globular head, Lys-621 and Arg-638, producing an NH2-terminal fragment of about 67,000 Da and a COOH-terminal fragment of about 112,000 Da. Dephosphorylated monomers and filaments were cleaved about 3 times more rapidly than their phosphorylated counterparts principally because of a much greater rate of cleavage at Arg-638; the ratio of cleavage at Arg-638:Lys-621 was about 3 for dephosphorylated myosins and about 0.5 for phosphorylated myosins. These data demonstrate that phosphorylation at the tip of the tail of Acanthamoeba myosin II causes a conformational change in the globular head that contains the catalytic sites; therefore, this conformational change may be related to the different catalytic and motile activities of the dephosphorylated and phosphorylated enzymes.

Acanthamoeba↗

Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma.

The action of retinoids on gene regulation is mediated by three distinct nuclear retinoic acid receptor (RAR) subtypes called RAR alpha, beta and gamma. Since RAR gamma is predominantly expressed in adult skin, specific ligands for this subtype could (i) represent valuable tools to evaluate the biological role of RAR gamma in skin and (ii) provide therapeutic entities with a higher therapeutic index at lower teratogenic risk. Using in vitro binding studies and a functional transactivation assay, we have identified three compounds with high RAR gamma selectivity.

Animals↗

A highly conserved repeated DNA element located in the chromosome of Streptococcus pneumoniae.

We report the discovery of a group of highly conserved DNA sequences located, in those cases studied, within intergenic regions of the chromosome of the Gram positive Streptococcus pneumoniae. The S. pneumoniae genome contains about 25 of these elements called BOX. From 5' to 3', BOX elements are composed of three subunits (boxA, boxB, and boxC) which are 59, 45 and 50 nucleotides long, respectively. BOX elements containing one, two and four copies of boxB have been observed; boxB alone was also detected in one instance. These elements are unrelated to the two most thoroughly documented families of repetitive DNA sequences present in the genomes of enterobacteria. BOX sequences have the potential to form stable stem-loop structures and one of these, at least, is transcribed. Most of these elements are located in the immediate vicinity of genes whose product has been implicated at some stage in the process of genetic transformation or in virulence of S. pneumoniae. This location raises the intriguing possibility that BOX sequences are regulatory elements shared by several coordinately controlled genes, including competence-specific and virulence-related genes.

Base Sequence↗

Preparation of a phospholipid-insensitive, autophosphorylation-activated catalytic fragment of Acanthamoeba myosin I heavy chain kinase.

The actin-activated Mg(2+)-ATPase activity of Acanthamoeba myosin I depends on phosphorylation of its single heavy chain. The activity of the myosin I heavy chain kinase is increased about 50-fold by autophosphorylation, and the rate of kinase autophosphorylation is enhanced about 20-fold by acidic phospholipids independent of the presence of Ca2+ (Brzeska, H., Lynch, T. J., and Korn, E. D. (1990) J. Biol. Chem. 265, 3591-3594). In this paper, we show that chymotryptic digestion of the kinase produces a 54-kDa fragment which contains three to four of the approximately 11 original phosphorylation sites and whose activity is greatly stimulated by autophosphorylation. However, both the rate of autophosphorylation and the kinase activity of the 54-kDa fragment are independent of phospholipid and comparable to those of intact kinase in the presence of phospholipid. These data imply that the (probably NH2-terminal) region(s) removed by proteolysis is necessary for phospholipid-sensitive inhibition of autophosphorylation of sites residing within the (probably COOH-terminal) 54-kDa fragment. The 54-kDa fragment contains the catalytic site of the kinase as well as three to four sites whose phosphorylation is necessary for full expression of kinase activity. The middle region of the kinase molecule contains proline-rich regions that are similar to the COOH-terminal tail of the kinase substrate, Acanthamoeba myosin I.

Acanthamoeba↗

A theory of fatigue damage accumulation and repair in cortical bone.

An analysis is presented of the balance between the accumulation and repair of fatigue damage in osteonal bone. Fatigue damage is defined in terms of cracks seen histologically when precautions are taken to avoid preparation artifact. The rate of occurrence of such damage is assumed to be proportional to the product of applied peak-to-peak stress, raised to a power, and the loading frequency. The rate of damage repair is assumed to be proportional to the activation rate for osteonal remodeling, and to the mean cross-sectional area of the resulting osteons. An additional factor is introduced to account for the possibility that damage provokes nearby remodeling. The theory is used to compare data from previous experiments of two types: fatigue-to-failure, and studies in which histologically observable cracks are made more numerous by repetitive loading. The analysis shows that there is a measure of agreement between the results of the two kinds of experiments, but the current data are too limited, and the results are too dependent on the mode of loading, to adequately test the theory. However, the analysis provides a framework for designing experiments to more efficiently clarify the relationships between fatigue failure, cracks seen in histologic sections, and the rate at which such cracks are repaired by osteonal remodeling.

Biomechanical Phenomena↗

Recombinant congenic strains of mice from B10.D2 and DBA/2: their contribution to behavior genetic research and application to audiogenic seizures.

Recombinant congenic strains (RCS) represent a series of related strains, each of which carries a small fraction of the genome of one strain ("donor" strain) on the genetic background of another strain ("background" strain). Recombinant inbred strains (RIS) are commonly used to identify major gene segregation and linkage and associations between behavior and quantitative trait loci, whereas recombinant congenic strains (RCS) open other complementary leads. The variability in the reactivity of RCS to a trait is thus the expression of few minor-effect genes originating from the donor strain, because the probability that major genes are present in any one RCS is low. Unlike RIS in which minor-effect genes are often masked by major genes, RCS enable the effects of minor genes to be studied. With our method, for a given trait, an estimate can be made of the gene strength distribution as well as an estimate of the minimal number of genes involved having a certain strength.

Acoustic Stimulation↗

Binding of estrogen-3-sulfates to stallion plasma and equine serum albumin.

The binding of estrone-3-sulfate (E1-3-S) and estradiol-3-sulfate (E2-3-S) to adult stallion plasma was determined and compared with the binding to equine serum albumin (ESA). On the ESA molecule, two binding sites for E1-3-S with an association constant of 1.3 x 10(5) M-1 and several sites of weaker affinity were found; the data for E2-3-S showed the existence of four binding sites of moderate affinity (1 x 10(5) M-1) and several sites of weaker affinity. The removal of albumin from the stallion plasma resulted in the absence of binding of E1-3-S or E2-3-S, whereas the removal of glycoproteins resulted in binding parameters similar to those obtained with whole plasma. These results indicate that ESA is the only estrogen sulfate binder in horse plasma. Under physiological conditions, 95% of E1-3-S was bound to ESA.

Animals↗

Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily.

Fluticasone propionate was compared with beclomethasone dipropionate for the treatment of allergic rhinitis in a multicenter, double-blind, randomized, placebo-controlled study during the mountain cedar (Juniperus ashei) pollination season in central Texas. Adults (n = 313) with moderate to severe symptoms were treated with fluticasone propionate aqueous nasal spray 200 micrograms once a day or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice a day or placebo for 2 weeks. Fluticasone propionate administered once daily and beclomethasone dipropionate administered twice daily were equally effective as assessed by clinician- and patient-rated scores for nasal obstruction, rhinorrhea, sneezing, and nasal itching throughout the treatment and follow-up periods. Both regimens were more effective than placebo. Adverse events were related to topical administration and were similar in frequency and nature in all three treatment groups. Fluticasone propionate and beclomethasone dipropionate displayed a similar safety profile that did not differ from placebo. We conclude that fluticasone propionate aqueous nasal spray administered as 200 micrograms once daily in the morning is as safe and effective as beclomethasone dipropionate aqueous nasal spray administered as 168 micrograms twice daily for seasonal allergic rhinitis.

Administration, Topical↗

Iron status in exercising women: the effect of oral iron therapy vs increased consumption of muscle foods.

Forty-seven previously sedentary women participating in a 12-wk moderate aerobic-exercise program were randomly assigned to one of four dietary groups: 50-mg/d iron supplement and a low food-iron diet (50 FE + EX), 10-mg/d iron supplement and a low food-iron diet (10 FE + EX), placebo and unrestricted diet (P + EX), and meat supplement and high food-iron diet (M + EX). A sedentary control group (n = 13) received no dietary interventions. Hematocrit, total iron-binding capacity, and hemoglobin, serum iron, serum ferritin, and serum albumin concentrations were measured every 4 wk. Hemoglobin values decreased at the end of 4 wk in all exercising groups compared with the control group. Iron status in the 50 FE + EX and M + EX groups improved after week 4 as indicated by an increase in serum ferritin, serum iron, and hemoglobin concentrations, and a decline in total iron-binding capacity. Thus, short-term, moderate aerobic exercise resulted in compromised iron status that was offset to varying degrees by ingesting iron or meat supplements. However, meat supplements were more effective in protecting hemoglobin and ferritin status than were iron supplements.

Adolescent↗