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Biomedical subjects

D Martin

Publications and source records attributed to D Martin.

At least 19 recordsLinked to original sources
PubMed1992

Ethanol inhibits release of excitatory amino acids from slices of hippocampal area CA1.

Slices of hippocampal area CA1 were employed to test the hypothesis that release of excitatory amino acids glutamate and aspartate is regulated by ethanol. K(+)-evoked release of glutamate and aspartate was inhibited by ethanol (25-100 mM) in a dose-dependent manner. Ethanol (100 mM) also inhibited K(+)-evoked gamma-aminobutyric acid release. This selective inhibition of excitatory amino acid release by ethanol may contribute to some of the learning and memory deficits associated with ethanol abuse, since excitatory amino acid receptors play an important role in synaptic plasticity processes.

Animals↗
PubMed1992

NMDA receptor-mediated depolarizing action of proline on CA1 pyramidal cells.

This study investigated the actions of proline on CA1 hippocampal pyramidal cells with use of slice preparations. Bath-applied L-proline first induced these cells to fire multiple orthodromic population spikes in response to a single stimulus and then blocked their response to both orthodromic and antidromic stimulation. These effects could be explained by postsynaptic depolarization followed by depolarization block. Grease-gap studies confirmed that L-proline depolarizes CA1 pyramidal cells. D-Proline was inactive in these tests. Excitatory amino acid antagonists reduced depolarizing responses to proline and N-methyl-D-aspartate (NMDA) in parallel. Mn2+ failed to attenuate proline-evoked depolarizations at concentrations that substantially inhibited synaptic transmission, but at a higher concentration it reduced responses to both proline and NMDA. These results suggest that proline depolarized CA1 pyramidal cells mainly by activating postsynaptic NMDA receptors. The neuroexcitatory and neurotoxic actions of proline in the hippocampus may contribute to the seizures and mental retardation associated with hyperprolinemia.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Isolation of eastern equine encephalitis virus from Aedes albopictus in Florida.

Fourteen strains of eastern equine encephalitis (EEE) virus were isolated from Aedes albopictus mosquitoes collected in Polk County, Florida. These are the first isolations of an arbovirus of proven public health and veterinary importance from naturally infected Ae. albopictus in the United States since established populations of this introduced mosquito were first discovered in 1985. The widespread distribution of Ae. albopictus in Florida and in other areas of the United States where EEE is endemic raises concern that this species may become an epizootic and epidemic vector of EEE virus.

Aedes↗
PubMed1992

Streptococcal infection and renal disease markers in Australian aboriginal children.

OBJECTIVE: To demonstrate an association between markers of streptococcal infection and markers of glomerulonephritis in Aboriginal children. DESIGN: A cross-sectional study of Aboriginal children of school age. SETTING: Three Aboriginal communities in the Northern Territory--two, coastal and one, desert. PARTICIPANTS: Sixty children, randomly selected from the school roll, were studied in each community; thus there were 180 children in total, aged 5-17 years. Midstream urine and venous blood was collected and swabs were taken from the pharynx and from impetiginous skin lesions or axillary skin in the absence of impetigo. Clinical records were examined for evidence of past glomerulonephritis. MAIN OUTCOME MEASURES: Swabs were cultured for beta-haemolytic streptococci and isolates were grouped; serum was tested for titres of antistreptolysin O (ASO) and antideoxyribonuclease B (anti-DNaseB). Protein and creatinine levels were measured in urine, and a ratio of protein to creatinine (UPC) of more than 50 mg protein per mmol creatinine was taken as a measure of significant proteinuria. Urine was examined microscopically for glomerular haematuria (greater than 10 red blood cells per microL with at least 20% dysmorphic red cells). RESULTS: Group A beta-haemolytic streptococci were isolated from the throat swabs of two children and from skin swabs of 25 (13.9%) children; 20 of these were from impetiginous lesions and five from normal axillary skin. beta-Haemolytic streptococci of group C or G were grown from the throat swabs of 13 (8.1%) children. The median titre of ASO (256 IU) was raised compared with a reference level, and the median titre of anti-DNaseB (3172 IU) was particularly high; ASO titres were significantly higher in 31 children with impetigo than in 149 children without impetigo. Significant proteinuria was present in 7 (3.9%) children and glomerular haematuria in 16 (8.9%). Glomerular haematuria was present in 2/7 (28%) children with proteinuria, 4/21 (19%) children with a past history of post-streptococcal glomerulonephritis, in 5/31 (16%) of those with impetigo and in 4/25 (16%) of those with positive skin cultures. However, none of these prevalences was significantly greater than the prevalence of glomerular haematuria among the other children. The prevalence of proteinuria differed significantly between communities and increased significantly with age. Furthermore, the differences in childhood proteinuria observed between communities in this study were parallel with community differences in the prevalence of proteinuria in a related study of adults. CONCLUSIONS: Group A streptococci are important causes of impetigo in Aboriginal children. Streptococcal skin infection may contribute to glomerular haematuria, proteinuria and persistent glomerulonephritis in Aboriginal children, and possibly to chronic glomerulonephritis in adult life. Public health programs are needed to reduce the prevalence of impetigo and group A streptococcal infections in Aboriginal communities; longitudinal studies are needed to test the relationship between streptococcal skin infection in Aboriginal children and chronic renal disease in later life.

Adolescent↗
PubMed1992

Early predictors of career achievement in academic medicine.

OBJECTIVE: To identify early personal and scholastic factors that predict academic career choice and long-term career achievement among academic physicians. DESIGN: A longitudinal cohort study. PARTICIPANTS: Nine hundred forty-four male physicians who graduated from The Johns Hopkins University School of Medicine, Baltimore, MD, from 1948 through 1964. OUTCOME MEASURES: Career achievement outcomes included attained faculty rank in 1990 and the number of citations (20 to 24 years after graduation) to published work. RESULTS: Of the 944 physicians, 424 (45%) had chosen academic careers. Scholastic performance and research experience in medical school were independently associated with having chosen an academic career (P less than .001). Among academicians, higher attained rank in 1990 was independently associated with the following: (1) membership in Alpha Omega Alpha (relative risk [RR] = 4.94, P = .0001); (2) rank in the top third of the graduating class (RR = 2.68, P = .01); and (3) research experience in medical school (RR = 3.11, P = .0001). These three factors were also independently associated with more citations to participants' published work (P less than .05). CONCLUSION: These data suggest that scholastic performance and research experience during medical school predict career achievement in academic medicine over 20 years in the future.

Achievement↗
PubMed1992

Experimental acute traumatic injury of the adult rat spinal cord by a subdural inflatable balloon: methodology, behavioral analysis, and histopathology.

We describe an experimental model to produce closed traumatic injuries to the spinal cord of adult rats. This model uses an inflatable balloon that is introduced in the dorsal subdural space and moved to a location rostral to the laminectomy site. The spinal cord trauma can be graded by varying either the duration of compression or the volume of saline used to inflate the balloon. The locomotor deficit of animals with various degrees of injury has been assessed at increasing delays after trauma. The parameters generating transient or definitive deficits of varying intensity were defined. Some injured animals underwent nuclear magnetic resonance imaging. Detailed histopathological studies demonstrated that the extent of the spinal lesion was significantly correlated with the physical parameters of compression and with the severity of the behavioral deficit.

Animals↗
PubMed1992

Bone blood flow and in vitro proliferation of bone marrow and trabecular bone osteoblast-like cells in ovariectomized rats.

Ovariectomy in the rat induces a rapid osteopenia associated with an elevated bone turnover. One hundred and twenty-day-old rats were ovariectomized (OVX) or sham-operated (n = 6-8 per group and per time period studied). 45Ca accretion rate and bone blood flow (microspheres trapping technique) in the femurs were determined at 28, 42, 84, and 119 days after ovariectomy. Both parameters were markedly increased by 84 days and subsided thereafter. At the 42nd day, when bone turnover was maximal, bone marrow and trabecular bone cultures were obtained from sham-operated and ovariectomized animals (n = 10/group). Proliferation rate of bone marrow cells and trabecular osteoblast-like cells estimated by fibroblast colony-forming units (FCFU) efficiency and cell counting was markedly increased in primary and secondary cultures in ovariectomy. These data fitted well with the enhanced number of osteoblasts observed in situ in the long bone metaphyses of estrogen-depleted animals. As estrogens were shown in the literature to inhibit proliferation of the red cell line and of other hemopoietic lines, it is possible that estrogens, through a general mechanism, inhibit hemopoietic and stromal lines and also the proliferation of bone marrow-derived trabecular bone cells.

Animals↗
PubMed1992

MRI-pathological correlations in acute traumatic central cord syndrome: case report.

Ante- and post-mortem MRI and detailed pathological examination were performed in a patient with a typical acute traumatic central cord syndrome (ATCCS) after a minor hyperextension injury to the neck who died 60 h later from heart failure. T2-weighted MRI showed a central hyperintense area at C3-4. There were disc protrusions, but no vertebral fracture or displacement. Histopathology disclosed severe axonal swelling and oedema in the dorsolateral fasciculi and, to a lesser degree, in the dorsal columns. In addition, an area of recent necrosis was found in the right anterior horn at C4-5. These findings suggest that the pathological hallmark of typical ATCCS is mechanical axonal disruption at a segmental level, but that more severe trauma may be accompanied by tissue destruction.

Axons↗
PubMed1992

Exercise-induced hypoxemia in athletes: role of inadequate hyperventilation.

These experiments examined the exercise-induced changes in pulmonary gas exchange in elite endurance athletes and tested the hypothesis that an inadequate hyperventilatory response might explain the large intersubject variability in arterial partial pressure of oxygen (PaO2) during heavy exercise in this population. Twelve highly trained endurance cyclists [maximum oxygen consumption (VO2max) range = 65-77 ml.kg-1.min-1] performed a normoxic graded exercise test on a cycle ergometer to VO2max at sea level. During incremental exercise at VO2max, 5 of the 12 subjects had ideal alveolar to arterial PO2 gradients (PA-aO2) of above 5 kPa (range 5-5.7) and a decline from resting PaO2 (delta PaO2) 2.4 kPa or above (range 2.4-2.7). In contrast, 4 subjects had a maximal exercise PA-aO2 of 4.0-4.3 kPa with delta PaO2 of 0.4-1.3 kPa while the remaining 3 subjects had PA-aO2 of 4.3-5 kPa with delta PaO2 between 1.7 and 2.0 kPa. The correlation between PAO2 and PaO2 at VO2max was 0.17. Further, the correlation between the ratio of ventilation to oxygen consumption vs PaO2 and arterial partial pressure of carbon dioxide vs PaO2 at VO2max was 0.17 and 0.34, respectively. These experiments demonstrate that heavy exercise results in significantly compromised pulmonary gas exchange in approximately 40% of the elite endurance athletes studied. These data do not support the hypothesis that the principal mechanism to explain this gas exchange failure is an inadequate hyperventilatory response.

Adult↗
PubMed1992

In vitro and in vivo modulation of 5-hydroxytryptamine-, thyrotropin-releasing hormone- and calcitonin-gene related peptide-like immunoreactivities in adult rat sensory neurons.

In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not found in situ, while several other transmitters are expressed in a much higher percentage of neurons in culture than in situ [Schoenen J. et al. (1989) J. Neurosci. Res. 22, 473-487]. The aim of the present study was to investigate the origin and the nature of the relevant environmental signals that allow this plasticity to be expressed, focusing on three neurotransmitters: 5-hydroxytryptamine, thyrotropin-releasing hormone and calcitonin-gene related peptide. The main results can be summarized as follows: (1) culturing cells in fetal calf serum or on feeder layers of astrocytes, Schwann cells or fibroblasts partially inhibits the serotoninergic phenotype of dorsal root ganglia neurons; (2) in vivo disconnection of dorsal root ganglia from their spinal targets but not from their peripheral or supraspinal targets induces a significant increase of the percentage of 5-hydroxytryptamine- and thyrotropin-releasing hormone-positive neurons in disconnected ganglia; (3) growth factors such as ciliary neuronotrophic factor or basic fibroblast growth factor but not nerve growth factor repress 5-hydroxytryptamine and calcitonin gene-related peptide immunoreactivity in cultured sensory neurons. In conclusion, neurotransmitter gene expression of adult dorsal root ganglia neurons is controlled by complex influences. Our data suggest that thyrotropin-releasing hormone and 5-hydroxytryptamine gene expression are tonically repressed in vivo by factors originating from the spinal segmental level and that growth factors such as ciliary neurotrophic factor or basic fibroblast growth factor could be potential vectors of this repressing effect.

Animals↗
PubMed1992

Epitope analysis of an immunodominant domain on the P1 protein of Haemophilus influenzae type b using synthetic peptides and anti-idiotypic antibodies.

Synthetic peptides, anti-idiotypic antibodies (anti-Id) and human and murine monoclonal antibodies (mAbs) were used to further define a major antigenic domain on the outer membrane P1 protein (OMP) of Haemophilus influenzae type b (Hib). Synthetic peptides were elaborated from the known primary sequences of the P1 protein of prototype Hib strains MinnA (OMP subtype 1H) and 8358 (OMP subtype 6U). By peptide mapping, antibodies are categorized into three groups: A, B and C. A first epitope on the P1 from strain MinnA was identified by the reactivity of one set of murine anti-P1 mAbs with the two overlapping peptides 11H and 13H, corresponding to amino acid residues 384-412 and 400-437, respectively. On the basis of their reactivity with both peptides, these mAbs were designated as group A. Anti-Id obtained from mice immunized with two group A mAbs reacted specifically with all group A mAbs. A second epitope on the same P1 protein was identified by the reactivity of the peptide 13H with another distinct set of murine anti-P1 mAbs assigned to group B. This group of mAbs did not recognize the peptide 11H. Murine anti-Id which were prepared against one group B mAb inhibited the attachment of this mAb to outer membrane preparations, whereas the binding of the other group B mAbs was not affected, suggesting that these mAbs represent a heterologous group of mAbs. The epitope(s) recognized by two human anti-P1 mAbs was (were) distinct from the ones recognized by murine mAbs since no reactivity with the peptides was observed. Similarly, the binding of the two human mAbs to the P1 antigen was not inhibited by anti-Id raised against group A or B mAbs. Interestingly, an epitope on a different P1 protein recovered from strain 8358 was identified by the reactivity of group C murine mAbs with the peptide 13U, which occupies the same position on the P1 protein as 13H but differs from the latter by 10 amino acid residues. Our studies demonstrated the presence of several distinct surface-exposed B-cell epitopes within the antigenic domain which was defined previously on the P1 protein of Hib MinnA. Furthermore, we showed the immunodominance of this region on two different P1 proteins. None of the mAbs, however, had a bacteriolytic or protective activity against Hib strains. We suggest that the surface-exposed immunodominant region on the OMP P1 of Hib do not induce protective antibodies against Hib infection.

Amino Acid Sequence↗
PubMed1992

Laparoscopic feeding jejunostomy tube in oncology patients.

Laparoscopic-guided feeding jejunostomy tubes are being utilized in two specific groups of patients: (i) patients with resectable or locally advanced adenocarcinoma of the pancreas treated on a protocol of preoperative chemoradiation, who may require nutritional support, and (ii) patients with metastatic or obstructing foregut tumours who require a route for delivery of fluid and medication. The technique, rationale and results for our first 17 patients who underwent laparoscopic placement of a tube jejunostomy are described. Laparoscopic feeding tube placement is a safe and cost-effective method to gain enteral access and stage the oncology patient's disease. This procedure is less invasive than standard surgery for tumour staging and feeding tube placement, and facilitates formula advancement and the patient's early hospital release without morbidity or mortality.

Aged↗
PubMed1992

The number of fibroblastic colonies formed from bone marrow is decreased and the in vitro proliferation rate of trabecular bone cells increased in aged rats.

Four- and 21-month old female Sprague-Dawley rats were sacrificed and their tibiae and femurs isolated for histology and initiation of bone marrow and trabecular bone cultures. The bone loss observed in 21-month old rats was associated with a markedly decreased osteoblastic index. The percentages of mineralizing trabecular surfaces were only slightly decreased in aged rats, whereas the percentages of mineralizing endocortical surfaces were strikingly decreased. Diaphyseal femoral marrows from 21-month old rats were less cellular than those from four-month old rats, and developed in culture fewer fibroblast colony forming units (FCFU) and fewer adherent cells with phenotypic characteristics of osteoblast-like cells. Trabecular bone cultures from 21-month old rats produced as many cells as cultures from four-month old rats, whereas the amount of trabeculae put into culture was much less in aged rats. Moreover, the proliferation rate in secondary culture was significantly increased in 21-month old rats. Similar responses to calcitriol were observed in bone marrow and trabecular bone cells from aged and younger mature rats, while cAMP responses to PTH were decreased in cells from aged rats. Our data confirm the age-related decrease in the FCFU efficiency of the bone marrow and show a stimulated proliferation of trabecular bone cultures from 21-month old rats that could be seen either as the result of the inhibition in vivo of the response to a signal to proliferate, or as a rebound response to factors present in the serum-enriched medium and lacking in vivo.

Aging↗
PubMed1992

EDRF role in renal function and blood pressure of normal rats and rats with obstructive uropathy.

There is a decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) and an increase in mean arterial pressure (MAP) and renal vascular resistance (RVR) after release of bilateral ureteral obstruction (BUO) of 24 hours duration. The present studies examine the role of endothelium-derived relaxing factor (EDRF) in the renal hemodynamics of sham-operated rats (SOR) and rats in which BUO of 24 hours duration was unilaterally released. In both groups of rats, renal function and blood pressure were measured in the awake state under basal conditions and after administration of L-arginine (L-arg), the substrate for EDRF synthesis, followed by NwNAME, an L-arg antagonist, or after administration of NwNAME followed by L-arg. Administration of L-arg alone to SOR did not affect renal function, MAP or RVR. In SOR given L-arg and then NwNAME, there was significantly decreased GFR and ERPF and increased MAP and RVR. When NwNAME was given initially, similar changes were obtained, and these were reversed by the administration of L-arg. Rats given L-arginine immediately after unilateral release of BUO of 24 hours duration had significantly greater GFR and ERPF values and lower MAP and RVR than temporal controls. NwNAME given to BUO rats decreased renal function further and increased MAP and RVR. We found a dose-dependent increase in GFR and ERPF and a dose-dependent decrease in MAP and RVR in both SOR and rats with BUO given increasing amounts of L-arg. There was also a dose-dependent decrease in GFR and ERPF and an increase in MAP and RVR in SOR and rats with BUO given increasing amounts of NwNAME or NGNMA, the two different antagonists of L-arg. In another set of experiments, SOR and rats with BUO were given L-arg preoperatively (that is, 24 hr prior to study). Both groups of rats had significantly higher GFR and ERPF values and lower MAP and RVR than control rats. Sham-operated rats given NwNAME 24 hours prior to study had significantly lower GFR and ERPF and higher MAP and RVR than untreated rats. Rats with BUO given NwNAME prior to obstruction had no measurable renal function and had significantly higher values for MAP after release of obstruction. These studies confirm the role of L-arg administration, and presumably EDRF, in the regulation of MAP and renal function in sham-operated rats. The results of this study also suggest decreased availability of arginine for EDRF synthesis in rats with BUO.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Exercise training-induced alterations in skeletal muscle oxidative and antioxidant enzyme activity in senescent rats.

Limited data exist concerning exercise training-induced alterations in skeletal muscle oxidative and antioxidant enzyme activity in senescent animals. Therefore, the purpose of this study was twofold: 1) to examine the exercise training-induced changes in oxidative and antioxidant enzyme activity in skeletal muscle of old rats; and 2) to critically analyze the relationship between oxidative and antioxidant enzyme activities in skeletal muscle in both trained and untrained senescent rats. Female Fischer-344 rats (approximately 24-mo-old) were divided into 1) exercised trained (ET; n = 10) and 2) sedentary (S; n = 6) groups. The ET rats performed a 10-week training program of treadmill exercise (approximately 60 min, 5 days/wk). Training significantly (p less than 0.05) improved VO2max (delta 22.8%) in the ET rats above their age-matched controls. Further, the ET group had significantly elevated (p less than 0.05) activities of succinate dehydrogenase (SDH) in the soleus and red gastrocnemius (RG) muscles as well as greater (p less than 0.05) 3-hydroxyacyl-CoA dehydrogenase (HADH) activity in the RG when compared to the S group. However, training did not alter (p greater than 0.05) HADH activity within the white gastrocnemius (WG) or soleus muscles. Activity of the antioxidant enzyme, glutathione peroxidase (GPX) was higher (p less than 0.05) in the soleus and RG in ET rats when compared to the S rats; in contrast, training did not alter (p less than 0.05) GPX activity in the WG. Finally, the correlation coefficients between SDH and GPX activities (combined ET and S groups) for the RG, WG, and soleus muscles were r = .73, .17 and .36, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1992

Outer membrane proteins P1 and P2 of Haemophilus influenzae type b: structure and identification of surface-exposed epitopes.

The outer membrane proteins (OMPs) P1 and P2 of Haemophilus influenzae type b exhibit molecular size and antigenic variation. Their structural genes have been cloned from prototype isolates of the most common disease-producing clonal groups. The derived amino acid sequences of P1 from strains of OMP subtypes 1H, 3L, and 6U have three variable regions between highly conserved regions. An immunodominant surface-exposed epitope was identified near the carboxyl terminus of P1 proteins from subtype 1H and 3L strains. The P2 genes from subtype 1H, 1L, and 3L isolates were identical. The P2 gene sequence from a subtype 6U isolate differs from the subtype 1H P2 gene by 13 nucleotides, resulting in 10 amino acid changes. The P2 gene from a subtype 2L isolate differs by 1 nucleotide from the subtype 1H P2 gene, resulting in 1 amino acid change at position 166. Two surface-exposed epitopes of OMP P2 were identified, one each between residues 158 and 174 and residues 319 and 341.

Animals↗
PubMed1992

TGF beta 1 expression is initiated in adult auditory neurons by sectioning of the auditory nerve.

Neuronotrophic factors (e.g. basic fibroblast growth factor, bFGF and nerve growth factor, NGF) have been demonstrated to respectively promote survival and neuritogenesis in cultures of dissociated adult rat spiral ganglia. Transforming growth factor beta (TGF beta 1) has been shown to modulate the response of cultured auditory neurons to bFGF through the induction of high affinity receptors for bFGF in the neurons. In this study, we show that TGF beta is expressed in situ by adult auditory neurons in response to traumatic injury (i.e. transection of the eighth cranial nerve). Based on these in vivo results and on the results from our previous in vitro studies, we propose that TFG beta 1 acts as an early autocrine signal involved in the response to injury by neurons of the peripheral auditor system.

Animals↗