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Biomedical subjects

D Martin

Publications and source records attributed to D Martin.

At least 559 records · Page 31Linked to original sources
PubMed1991

Induced rearrangement of kappa genes in the BLIN-1 human pre-B cell line correlates with germline J-C kappa and V kappa transcription.

The human pre-B acute lymphoblastic leukemia cell line, BLIN-1, has been previously shown to undergo kappa light chain rearrangement in vitro, making it a valuable resource for analyzing pre-B to B cell differentiation. We have examined the recombination potential of BLIN-1 by characterizing several independently derived kappa-expressing subclones for DNA rearrangement and V kappa gene usage. Analysis of five kappa-expressing subclones (all having the same heavy chain rearrangement) demonstrated independent kappa light chain rearrangement events by DNA hybridization analysis. Northern blot analysis using probes recognizing the four different V kappa families revealed that two subclones used the most proximal V kappa (V kappa IV), one subclone used a V kappa I, and one subclone used a V kappa II. By polymerase chain reaction analyses, we detected transcripts from rearranged V-J-C kappa genes as well as transcripts from germline J-C kappa and V kappa in BLIN-1 cells induced to rearrange the kappa locus. kappa germline transcripts were also detected in normal developing B cell populations in fetal liver and bone marrow. Our collective results indicate that: (a) BLIN-1 can be induced to rearrange the kappa locus, and this correlates with the expression of germline kappa locus transcripts that may play a role in activating or targeting gene rearrangement; and (b) active rearrangement and usage of V genes representing different kappa families suggest that, like in the mouse, repertoire diversification in humans occurs in the presence of a fixed heavy chain rearrangement.

B-Lymphocytes↗
PubMed1991

N-(fluorenyl-9-methoxycarbonyl) amino acids, a class of antiinflammatory agents with a different mechanism of action.

Several members of a series of N-(fluorenyl-9-methoxycarbonyl) amino acids were found to possess a broad spectrum of antiinflammatory activity. The compounds were active against oxazolone dermatitis in mice and adjuvant arthritis in rats, models in which activated T lymphocytes are implicated. The compounds also inhibited T-lymphocyte activation in vitro, assessed by using the mixed lymphocyte reaction. The compounds inhibited the reversed passive Arthus reaction in rats and arachidonic acid-induced dermatitis in mice, models in which leukocyte infiltration is responsible for the inflammatory reaction. More complete evaluation was made of one compound, N-(fluorenyl-9-methoxycarbonyl)leucine (NPC 15199). On histologic examination after arachidonic acid administration, NPC 15199 was found to block recruitment of neutrophils into the inflammatory site. The compound was not a general myelotoxin. Prolonged treatment of animals did not alter bone-marrow progenitor number or the numbers of circulating white blood cells. Further, several white cell functions were not inhibited in vitro, including neutrophil respiratory burst and macrophage phagocytosis. NPC 15199 was effective in blocking antigen arthritis in rabbits and was effective in a therapeutic protocol, reversing oxazolone edema. These studies suggest that N-(fluorenyl-9-methoxycarbonyl) amino acids may be valuable therapeutic agents for inflammatory diseases.

Amino Acids↗
PubMed1991

Estrogen therapy and variable-resistance weight training increase bone mineral in surgically menopausal women.

This study was undertaken to examine the effect of estrogen replacement therapy alone and estrogen replacement therapy plus variable-resistance weight training on the bone mineral content of surgically menopausal women. A total of 20 surgically menopausal women were randomized and treated with either 0.625 mg conjugated estrogen daily or the same dose of estrogen plus a closely monitored exercise program involving the use of Nautilus muscle strengthening/endurance equipment. After 1 year's observation, the bone mineral density (BMD) of the spine determined by dual-photon absorptiometry increased in the exercising subjects by 8.3 +/- 5.3% (p = 0.004), 95% confidence limits (CL) 3.9-12.8%; the group with estrogen replacement therapy alone maintained their BMD: 1.5 +/- 12.4% (p = 0.36; 95% CL = -6.9-9.8%). The total body BMD of the exercising group increased by 2.1 +/- 1.5% (p = 0.003; 95% CL = 0.8-3.3%); the nonexercising women had a nonsignificant 0.6 +/- 2.9% change (p = 0.30; 95% CL = -1.4-2.5%). A significant increase of 4.1 +/- 4.3% (p = 0.01; 95% CL = 0.8-7.4%) in the radial midshaft BMD of the exercising group was found; the estrogen alone group recorded a nonsignificant change of -0.3 +/- 3.1% (p = 0.33; 95% CL = -1.7-2.4%). The results of this study suggest that variable-resistance training in estrogen-replete women adds bone to both the axial and appendicular skeleton.

Absorptiometry, Photon↗
PubMed1991

Additional mapping of mouse chromosome 2 genes.

The purpose of this work was to elucidate the genetic fine structure of the central portion of mouse chromosome (Chr) 2. Seven Chr 2 congenic mouse strains [B10.PA(L)-pa we un at, B10.PA(L)-pa Aw, B10.PA(L)-we un at, B10.PA(J)-pa a, B10.FS-we Aw, B10.C-we Aw, and B10.YBR-a] were produced. Breeding studies were carried out using strains B10.PA(L)-pa we un at and B10.LP-H-13b to accurately determine the recombination frequencies between marker genes pa and we (1.9% +/- 0.3), we and un (8.8% +/- 0.5), and un and at (4.5% +/- 0.4) of strain B10.PA(L)-pa we un at. These strains and other Chr 2 congenic strains were typed for immunologically defined loci using monoclonal antibody (mAb) C23 reactive with the gene product of B2mb T-lymphocyte clone C1 reactive with the gene product of H-3a and H-3c, and lymphocyte clone H1.8 reactive with the gene product of Hd-1a. B2m and H-3 typing located a recombinational event separating [pa B2m H-3] from we (the order of bracketed genes is not known). Hd-1 typing indicated that Hd-1 maps distal to [H-42, H-44] and proximal to un. The gene order [pa, B2m, H-3], we, [H-42, H-45], Hd-1, un, H-13, at, with H-44 mapping centromeric to Hd-1, is indicated by the data.

Animals↗
PubMed1991

Enzyme levels in cultured astrocytes, oligodendrocytes and Schwann cells, and neurons from the cerebral cortex and superior cervical ganglia of the rat.

Data are presented for 16 enzymes from 8 metabolic systems in cell cultures consisting of approximately 95% astrocytes and 5% oligodendrocytes. Nine of these enzymes were also measured in cultures of oligodendrocytes, Schwann cells, and neurons prepared from both cerebral cortex and superior cervical ganglia. Activities, in mature astrocyte cultures, expressed as percentage of their activity in brain, ranged from 9% for glycerol-3-phosphate dehydrogenase to over 300% for glucose-6-phosphate dehydrogenase. Creatine phosphokinase activity in astrocytes was about the same as in brain, half as high in oligodendrocytes, but 7% or less of the brain level in Schwann cells and superior cervical ganglion neurons and only 16% of brain in cortical neurons. Three enzymes which generate NADPH, the dehydrogenases for glucose-6-phosphate and 6-phosphogluconate, and the NADP-requiring isocitrate dehydrogenase, were present in astrocytes at levels at least twice that of brain. Oligodendrocytes had enzyme levels only 30% to 70% of those of astrocytes. Schwann cells had much higher lactate dehydrogenase and 6-phosphogluconate dehydrogenase activities than oligodendrocytes, but showed a remarkable similarity in enzyme pattern to those of cortical and superior cervical ganglion neurons.

Animals↗
PubMed1991

Thrombotic thrombocytopenic purpura first seen as massive vaginal necrosis.

Thrombotic thrombocytopenic purpura is a hematologic disorder that affects the microcirculation. A 38-year-old woman was first seen with fever, thrombocytopenia, and vaginal bleeding. Pelvic examination revealed massive vaginal necrosis. Hematology consultation resulted in agreement with the diagnosis of thrombotic thrombocytopenic purpura. This is the first reported case of thrombotic thrombocytopenic purpura first seen as vaginal necrosis of which we are aware.

Adult↗
PubMed1991

Ethanol and magnesium ions inhibit N-methyl-D-aspartate-mediated synaptic potentials in an interactive manner.

The role of magnesium ions in the inhibitory effect of ethanol on NMDA receptor-mediated population synaptic potentials (pEPSPs) in area CA1 of the hippocampus of the adult rat, was studied. The excitatory amino acid (non-NMDA) receptor antagonist, DNQX and the GABAA channel antagonist, picrotoxin, were used to pharmacologically isolate NMDA-mediated pEPSPs. In the presence of a physiological concentration of magnesium (1.0 mM), ethanol (25-100 mM) inhibited NMDA-mediated pEPSPs, with an apparent EC50 of approximately 50 mM. The ability of ethanol to inhibit NMDA-mediated pEPSPs was reduced when the slices were incubated in the absence of magnesium. Concentrations of ethanol, in the range of 50-200 mM (apparent EC50 100 mM), were required to inhibit NMDA-mediated pEPSPs, in the absence of added magnesium. Combination studies of these two antagonists indicated that the sensitivity of NMDA-mediated pEPSPs to one antagonist was not altered by the presence of the other. This finding suggests that the affinity of each antagonist binding site is not affected by the presence of the other antagonist. In the case of ethanol, its low maximum antagonist efficacy may require larger concentrations of ethanol to inhibit NMDA-mediated pEPSPs, in the absence of other non-competitive antagonists such as magnesium.

Animals↗
PubMed1991

Revascularization of a finger with a thenar mini-free flap.

A devascularized index finger with a soft tissue defect on its palmar side was managed by using a small free flap raised at the level of the metacarpophalangeal joint of the thumb. The radial digital artery was included in the flap and used to revascularize the index finger, and a palmar vein was used to drain the flap. This resulted in minimal donor side morbidity.

Adult↗
PubMed1991

The effect of moderate aerobic exercise on physical fitness among women 70 years and older.

This study investigated benefits of 26 weeks of moderate aerobic exercise for women 70 years or older. Sixteen healthy women with a mean age of 72.0 years were randomized into exercise (n = 10) and control groups (n = 6). The exercise group walked on a treadmill 3 times per week for 20 min, at 70% of maximum heart rate. Oxygen uptake VO2max expressed in l/min and ml.kg-1.min-1, total exercise time on the treadmill (TET), maximum heart rate (HRmax) and body mass index (BMI) were measured at baseline and 6 months. Two-way repeated measures analysis of variance (ANOVA) determined the effect of exercise intervention. Both measures of VO2max in addition to TET were significantly improved by the moderate training program, compared to the control group. VO2max in the exercise group increased by +/- 6.6% (S.E. 2.9) measured in l/min and 8.4% (S.E. 3.2) measured in ml.kg-1.min-1. TET increased by 25.4% (S.E. 4.9) in the exercise group. The ANOVA was unable to detect significance between the exercise and control groups for HRmax or BMI. All exercising subjects finished the program, apparently tolerating the intervention. The results indicate that healthy women over the age of 70 years can increase fitness measures with a moderate training program.

Age Factors↗
PubMed1991

Therapy of human ovarian cancer xenografts with intraperitoneal liposome encapsulated muramyl-tripeptide phosphoethanolamine (MTP-PE) and recombinant GM-CSF.

Three intraperitoneal human ovarian cancer xenografts (OS, HU, and LA) were used to assess the antitumour activity of intraperitoneal therapy with liposome encapsulated MTP-PE. MTP-PE led to significant prolongation of survival in all three xenograft models, but with varying efficacy. In one tumour model (OS), 80% of mice were cured of tumour by twice weekly therapy for 4 weeks, whereas in another xenograft model (LA), the median survival time was approximately doubled compared to PBS injected and placebo liposome injected controls (median survivals: 30 vs 62.5 days respectively). The antitumor efficacy of MTP-PE did not correlate with the extent of peritoneal neutrophil infiltration after intraperitoneal therapy. Combined therapy with liposome encapsulated MTP-PE and recombinant murine granulocyte-macrophage colony stimulating factor led to increased survival of mice bearing the LA and HU xenografts, compared to tumour bearing mice treated with either agent singly.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Evidence for an alveolar-arterial PO2 gradient threshold during incremental exercise.

Examination of the alveolar-to-arterial O2 tension (A-a PO2 difference) provides a method of examining the efficiency of pulmonary gas exchange during exercise. At present, considerable confusion exists as to the exact pattern of the A-a PO2 difference during incremental exercise. We tested the hypothesis that the A-a PO2 difference during incremental exercise is alinear with respect to metabolic rate. Measurements of the A-a PO2 difference were made on six healthy male subjects during incremental exercise under sea level conditions (PIO2 = 149 torr). An alinear model best described the relationship between the A-a PO2 difference and metabolic rate; only small increases in the A-a PO2 difference occurred at low work rates followed by a rapid increase at higher work rates. The existence of a "A-a PO2 difference threshold" was mathematically confirmed by the use of a computer algorithm to define inflection points. These data provide evidence that the relationship between the A-a PO2 difference and metabolic rate is alinear and that a metabolic threshold exists for a rapid increase in the A-a PO2 difference. We conclude that the efficiency of pulmonary gas exchange during exercise is unaltered from rest during low-to-moderate power outputs, however, high intensity exercise compromises pulmonary gas exchange efficiency as evidenced by a significant widening of the A-a PO2 difference.

Adult↗
PubMed1991

An efficient program for computing conditional maximum likelihood estimates and exact confidence limits for a common odds ratio.

This paper describes a method and associated computer program for calculating exact confidence limits and P values, along with the conditional maximum likelihood estimate of the common odds ratio for a series of 2 x 2 tables. The program can be used to calculate exact estimates for matched data and is considerably faster than others currently available.

Algorithms↗
PubMed1991

Limitations of analysis of covariance designs in aging research.

Control of peripheral hearing loss represents a significant design problem in research examining age-related changes in central auditory processing. Statistical control procedures (e.g., partial correlation or analysis of covariance) represent one means of achieving such experimental control. Although these techniques have been advocated for this purpose by some researchers, potential confounding of the data due to statistical dependence between age and peripheral hearing loss may introduce significant bias into the data distorting the reported results.

Age Factors↗
PubMed1991

Immunohistochemical demonstration of sensory nerve fibers and endings in lumbar intervertebral discs of the rat.

Although it is accepted that the intervertebral disc has a sensory component, it has not been previously shown by any specific method. Immunoreactivity of the physiologically active neuropeptide, calcitonin gene-related peptide (CGRP), was used as a specific marker of sensory nerve fibers and their endings in the intervertebral disc of the rat. In this study, positive fiber immunoreactivity was taken as an indication that those fibers were of sensory, and not sympathetic, origin. Immunoreactivity was found in the outer annulus fibrosus of all intervertebral discs studied. The CGRP-like immunoreactivity was also found in structures that resembled nerve endings. To the authors' knowledge, this is the first report presenting detailed positive evidence of sensory fibers and their endings in the lumbar intervertebral disc of any mammalian species.

Animals↗
PubMed1991

Characterization and comparative bactericidal activity of monoclonal antibodies to Bordetella pertussis lipo-oligosaccharide A.

Spleen cells from mice immunized with a Bordetella pertussis N-lauroyl sarcosine membrane extract (SME) were used to generate hybridoma cells lines producing monoclonal antibodies (mAbs). Seven mAbs were shown to be specific to B. pertussis lipo-oligosaccharide (LOS) by immunoblotting of SME or purified LOS following SDS-PAGE. All mAbs reacted with the B. pertussis Tohama I strain of the LOS AB phenotype, and did not react with the atypical variant strain 134 of the LOS B phenotype. The immune reactivity of the mAbs was retained after treatment of SME with proteinase K and was lost after sodium periodate treatment. No cross-reactivity was observed with the mAbs when tested against B. parapertussis and other Gram-negative bacteria. However, all mAbs reacted with B. bronchiseptica. Binding assays with live B. pertussis cells demonstrated that mAbs strongly reacted with cell surface exposed antigenic determinants. High bacterial cell lytic capability was observed for five of these mAbs. Concentrations between 0.22 and 2.2 micrograms mAb ml-1 (0.1 and 1 microgram per 450 microliter assay) purified by protein A were required to kill at least 50% of the bacteria. Competition immunoassays with biotinylated antibodies showed that the bacteriolytic and non-bacteriolytic mAbs were directed to different epitopes of the B. pertussis LOS A.

Animals↗