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Biomedical subjects

J Murray

Publications and source records attributed to J Murray.

At least 235 records · Page 13Linked to original sources
PubMed1995

Effects of recombinant human hemoglobin on motor functions of the opossum esophagus.

Chemically altered hemoglobins are being investigated as blood substitutes. They may affect numerous biological processes since free hemoglobin binds nitric oxide (NO). Nitric oxide is a neural mediator of relaxation of the lower esophageal sphincter (LES) and esophageal peristalsis. We hypothesize that recombinant human hemoglobin (rHb1.1) alters esophageal motor function by scavenging NO. Contraction of transverse muscle strips from the opossum esophagus and LES was monitored. Transmembrane potential differences of circular smooth muscle from the esophagus were recorded using glass microelectrodes. Intrinsic esophageal nerves were stimulated electrically. Esophageal manometries were performed with a low-compliance perfused-catheter system. The activity of the enzyme NO synthase was determined with the citrulline assay. Recombinant hemoglobin diminished nerve-induced relaxation of LES muscle but did not alter LES tone. Circular esophageal muscle responded to nerve stimulation with an inhibitory junction potential and a mechanical off response. Recombinant hemoglobin diminished the inhibitory junction potential and shortened the latency of the off response. It increased the velocity of esophageal peristalsis, decreased the amplitudes of these contractions and diminished LES relaxation. Cyanomethemoglobin had little effect on nerve- or swallow-induced responses. Hemoglobin did not inhibit the activity of NO synthase. Recombinant human hemoglobin appears to alter esophageal motor function by scavenging NO.

Amino Acid Oxidoreductases↗
PubMed1995

Epidemic dysentery caused by Shigella dysenteriae type 1: a sentinel site surveillance of antimicrobial resistance patterns in Burundi.

Annual epidemics of bacillary dysentery have been a public health problem in Burundi for the last 14 years. Recent civil unrest, resulting in the displacement of large numbers of people into refugee settlements, has aggravated the situation. We report the results of a nationwide, health-centre based, sentinel site survey to check the drug resistance of Shigella dysenteriae type 1 (Sd1), the causal organism of such epidemics. Shigella spp. (of which 97% were Sd1) were isolated from 73% of the 126 specimens collected from six main sites around the country. There was no difference in culture results from fresh and frozen stool specimens. Overall Sd1 resistance to commonly available antibiotics (sulfamethoxazole + trimethoprim, ampicillin, tetracycline, and chloramphenicol) varied from 77% to 99% and was fairly uniformly distributed over the country. All Sd1 isolates were susceptible to newer drugs, such as ciprofloxacin and ceftriaxone. Resistance to nalidixic acid, the current first line of treatment for bacillary dysentery in Burundi, varied from 8% to 83% in the different sentinel sites; global resistance was 57%.

Anti-Infective Agents↗
PubMed1994

Tumor activity confirmation and isodose curve display for patients receiving iodine-131-labeled 16.88 human monoclonal antibody.

A study was performed to correlate activity quantitation derived from external imaging with surgical tumor specimens in patients who received radiolabeled monoclonal antibody. Patients were given I-131 labeled 16.88 human antibody and scanned 3-5 times by planar and/or single photon emission computed tomography imaging methods to acquire time-dependent activity data in tumor and normal tissues. A method also was developed to assess the heterogeneous activity distributions in tumor samples. Postsurgical tumor and normal tissue samples were subdivided into volume elements (voxels) of 0.5 cm x 0.5 cm x 0.05 cm thick, which were used to verify the activity quantitation computed by the conjugate view method and to appraise the heterogeneity of radiolabeled antibody uptake. Through the use of the measured voxel activities, along with the time-dependent activity curves available for the entire tumor specimen derived from imaging, the cumulated activity and absorbed dose for each voxel were uniquely determined. The calculated total absorbed dose values were color-coded as isodose curves and overlaid on a correlated computed tomographic image. In two patients, activity quantitation derived from external imaging correlated with surgical tumor resection specimens within +/- 11%. The tumor-absorbed dose heterogeneity ratio was found to be as high as 10:1, with an average tumor to whole body absorbed dose ratio of 4:1. The mapping of activity with a histologic overlay showed a good correlation among activity uptake, the presence of tumor, and antigen expression on a microscopic scale. The resultant isodose curves overlaid on correlative computed tomographic scans represent the first images obtained with actual radiolabeled antibody biodistribution data in patients.

Absorption↗
PubMed1994

Three-dimensional dynamics of pseudopod formation and the regulation of turning during the motility cycle of Dictyostelium.

Employing a newly developed computer-assisted system for visualizing and quantitating cell motility in three dimensions, we have examined the 3-dimensional changes in cell shape and the dynamics of pseudopod extension during translocation of Dictyostelium amoebae. Amoebae exhibit a 3-dimensional behavior cycle with an average period of 1.5 min. The cycle includes a transient pseudopod extension phase in the x,y axis followed by a z-axis expansion phase. Anterior pseudopod extension in the x,y axis is accompanied by a decrease in height, not by uropod retraction. The increase in height is accompanied by uropod retraction. In the pseudopod extension phase in the x,y axes, pseudopods form either anteriorly or laterally, and either on or above the substratum. Pseudopods which initially form on the substratum in almost all cases continue to expand as the anterior end of the cell. In the case of lateral pseudopods, anteriorization leads to a turn. Approximately half of anterior pseudopod and two-thirds of lateral pseudopods which initially form above the substratum are retracted. These results suggest that pseudopod-substratum interaction plays a fundamental role in the regulation of directionality and turning in the translocation phase of the 3-dimensional behavior cycle.

Animals↗
PubMed1994

Structure-activity studies of the s-echistatin inhibition of bone resorption.

Synthetic Arg-Gly-Asp (RGD)-containing peptides were examined in bone resorption or attachment and detachment assays with isolated mammalian osteoclasts in an effort to elucidate the mechanistic and structural basis for the inhibition of bone resorption by s-echistatin. Bone resorption was the process most sensitive to inhibition by s-echistatin, with IC50 = 0.3 nM; inhibition of attachment to bone or detachment (lamellipodial retraction) was 30- to 70-fold less sensitive, with IC50 = 10 or 20 nM, respectively. Single amino acid substitutions within the 49-residue sequence of s-echistatin showed that although the efficacy of s-echistatin is dependent on the Arg24-Gly25-Asp26 sequence, additional residues, including Asp27, Met28, and Cys39, are also critical for potent inhibition of the resorbing activity of isolated rat osteoclasts. Because of the identification of the av beta 3 as the primary integrin on rat osteoclasts interacting the RGD peptides (Helfrich et al.), we examined the possibility of modeling bone resorption with other beta 3-mediated processes. Specifically, av beta 3 endothelial cell (human or rat) attachment to vitronectin and aIIb beta 3 platelet aggregation were compared with bone resorption for sensitivity to s-echistatin analogs, linear RGD peptides, and cyclic RGD peptides. Essentially no similarity in sensitivity to RGD peptides were observed between bone resorption, platelet aggregation, or endothelial cell attachment. Because rat osteoclasts and human giant cell tumors (osteoclastomas) shared similar sensitivity to s-echistatin and rat and human endothelial cells showed a similar sensitivity profile to RGD peptides, the dissimilarity of bone resorption to other beta 3-mediated processes cannot be explained in terms of species differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Nerve-mediated nitric oxide production by opossum lower esophageal sphincter.

Antagonists of nitric oxide synthesis inhibit nerve-induced hyperpolarization and relaxation of muscle from the opossum lower esophageal sphincter. These studies test the hypothesis that nitric oxide is released during stimulation of intrinsic esophageal nerves. The intrinsic nerves were stimulated with an electrical field (10-sec trains of 1-msec, 30-V pulses delivered at 10 Hz). Nitric oxide production was measured with a DASIBI model 2108 Chemiluminescence NO Analyzer. NG-Nitro-L-arginine, an inhibitor of NO synthase, antagonized nerve-induced relaxation the lower esophageal sphincter. Nerve stimulation increased NO production from 0.50 +/- 0.04 nmol/min/100 mg tissue to 0.87 +/- 0.07 nmol/min/100 mg tissue (P < 0.01). NG-nitro-L-arginine inhibited both basal (0.030 +/- 0.09 nmol/min/100 mg tissue, P < 0.05 vs baseline) and stimulated (0.38 +/- 0.10 nmol/min/100 mg tissue, P < 0.01 vs stimulated). These studies support the hypothesis that nerve stimulation releases nitric oxide from the lower esophageal sphincter.

Amino Acid Oxidoreductases↗
PubMed1994

Ingestion of host immunoglobulin by three non-blood-feeding nematode parasites of ruminants.

Host immunoglobulin was detected in homogenates of adult worms or fourth stage larvae of Haemonchus contortus, Ostertagia ostertagi, O circumcincta and Dictyocaulus viviparus, but not in preparasitic third stage larvae of H contortus. All the worms had been washed in detergent before being homogenised to remove any immunoglobulin adhering to the cuticle. This procedure, the concentrations of immunoglobulin detected and observations on sections of the worms stained with fluorescent anti-sheep immunoglobulin, all suggested that the immunoglobulin had been ingested, even by the non-blood-feeding species. This finding suggests that the Ostertagia species and D viviparus may be susceptible to vaccination by the gut antigen approach, a method with considerable promise for blood-feeding parasites like H contortus and Boophilus microplus.

Animals↗
PubMed1994

Evidence for a microdeletion in 1q32-41 involving the gene responsible for Van der Woude syndrome.

Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder representing the most frequent form of syndromic cleft lip and palate. Other characteristic features are pits of the lower lip and hypodontia. The gene shows high penetrance and seems to play an important role in orofacial development determined by the tissues involved and their formation during different periods of craniofacial development. Although most individuals affected with VWS show Mendelian inheritance, one patient with a macroscopic deletion and multiple malformations including two primary features of VWS has been described in the literature, indicating hemizygosity is compatible with the VWS phenotype. We report here the allelic loss of a stable and highly polymorphic microsatellite (D1S205) from region 1q32-41 in one family with VWS. Classical manifestations of the syndrome superimposed on developmental delay in all affected members of the family, the absence of cytogenetic abnormalities, the reproducibility of the null allele with a new set of primers and close linkage of this marker in a total of 15 VWS families provide strong evidence that the first microdeletion involving the gene for VWS has been identified. Assuming 1 Mb of DNA per cM of genetic distance, the upper bound of the deletion size would amount to 4 Mb.

Abnormalities, Multiple↗
PubMed1994

Identification of structural domains within the large subunit of herpes simplex virus ribonucleotide reductase.

The large subunit (R1) of herpes simplex virus (HSV) ribonucleotide reductase is a bifunctional protein consisting of a unique N-terminal protein kinase domain and a ribonucleotide reductase domain. Previous studies showed that the two functional domains are linked by a protease sensitive site. Here we provide evidence for two subdomains, of 30K and 53K, within the reductase domain. The two fragments, which were produced by limited proteolysis and were resistant to further degradation, remained tightly associated in a complex containing two molecules of each. They were capable of binding the R2 subunit of HSV ribonucleotide reductase with approximately the same affinity as the intact protein but the complex did not complement the small subunit (R2) to give an active enzyme. At low concentrations (0.4 micrograms/ml) of trypsin or V8 protease, cleavage between the subdomains was prevented by the presence of the N-terminal protein kinase domain. At higher protease concentrations (1 micrograms/ml) the N-terminal domain is extensively proteolysed and the 30K and 53K domains were generated. Identical results were obtained using purified R1 isolated from infected cell extracts or following expression in Escherichia coli. The origin of the two domains was investigated by N-terminal sequencing of the 53K fragment and by examining their reactivity with a panel of R1-specific monoclonal antibodies which we isolated and epitope mapped for that purpose. The trypsin cleavage site was found to lie between arginine 575 and asparagine 576, and proteolysis in this region was not prevented by the presence of R2 or the nonapeptide YAGAVVNDL. We propose that the ribonucleotide reductase region of HSV R1 exists in a two domain structure, and that the interdomain linking region is protected by the unique N terminus.

Amino Acid Sequence↗
PubMed1994

EMACO in high risk gestational trophoblast disease--the Australian experience. Gestational Trophoblast Subcommittee, Clinical Oncological Society of Australia.

Sixty-five patients with high-risk trophoblast disease have been treated with the EMACO combination split regimen therapy in the 10 year period, 1981 to 1990. Four patients died but the remaining 61 (94%) remain free of disease up to 10 years later. Toxicity was manageable in most cases with minimal delay in treatment from myelosuppression. EMACO is a well tolerated regimen with a high cure rate in patients with high-risk gestational trophoblast disease (GTD).

Adolescent↗
PubMed1994

Emphysema and airway obstruction in non-smoking South African gold miners with long exposure to silica dust.

OBJECTIVE: Occupational exposure to silica dust is associated with significant impairment of lung function. The present study investigates which pathological changes in the lung are associated with impairment of lung function in silica dust exposed workers who were life-long non-smokers. METHODS: 242 South African white gold miners who were lifelong non-smokers and who had a necropsy at death were studied. The pathological features identified at necropsy were the degree and type of emphysema, the presence of airway disease, and the degree of silicosis in the lung parenchyma and pleura. These features were related to lung function tests done a few years before death, to type of impairment (obstructive or restrictive), and to cumulative silica dust exposure. RESULTS: The degree of emphysema found at necropsy was not associated with a statistically significant impairment of lung function or with dust exposure. The degree of silicosis in the lung parenchyma and the large airways disease (based on mucus gland hyperplasia) were associated with a statistically significant impairment of lung function. The large airway disease was, however, not positively associated with dust exposure or silicosis. In miners with a moderate or a higher degree of limitation of airflow the main findings were silicosis, heart disease, and obesity. The presence of small airways disease could not be established from the necropsy material. CONCLUSION: The results indicate that the level of exposure to silica dust to which these miners were exposed, without a confounding effect of tobacco smoking, is not associated with a degree of emphysema that would cause a statistically significant impairment of lung function. Silicosis of the lung parenchyma was associated with loss of lung function. Other factors that may play a part in impairment of lung function in these miners are obesity and heart disease.

Adult↗
PubMed1994

Craniofacial morphogenesis workshop report.

The following report highlights the discussions and interaction at the workshop on craniofacial morphogenesis, sponsored by The Human Frontier Science Program, held in April 1993 at the University of Iowa. A brief summary of selected sessions is included to exemplify the benefits of bringing together individuals from various disciplines and backgrounds in order to establish a unified theory of craniofacial morphogenesis. The synthesis of information and experience of a wide range of approaches made the 4-day period an invaluable experience for the participants from nine different countries.

Cleft Lip↗
PubMed1994

Repeatability of insulin sensitivity and glucose effectiveness from the minimal model. Implications for study design.

To determine the repeatability of insulin sensitivity measurements generated by the minimal model, we subjected 11 normal men to 3 frequently sampled intravenous glucose tolerance tests (FSIGTs) over the course of 12 days under conditions of fixed diet and limited physical activity. FSIGTs were analyzed by the minimal model using a full, 30-sample data set, as well as a reduced, 12-sample data set that has been proposed for population studies. Minimal model insulin sensitivity index (SI) calculated from the 30-sample data set averaged 0.8 +/- 0.083 x 10(-4) min-1.(pmol/l)-1 (range 0.10-1.64 x 10(-4) min-1.(pmol/l)-1 with an average interday coefficient of variation (CV) of 20.2 +/- 3.2% (range 6-44%). Glucose effectiveness (SG) was slightly less repeatable, with an average interday variability of 25.1 +/- 8.8%. The mean CVs for first-phase insulin secretion (20.1 +/- 3.5%) and total insulin secretion (21.4 +/- 3.2%) were similar to the CV for SI. Mean insulin sensitivity calculated from the 12-sample data set (0.82 +/- 0.08 x 10(-4) min-1.(pmol/l)-1 was not significantly different from the mean calculated from the full data set (P = 0.37, paired Student's t test). However, the mean CV of SI calculated from the reduced data set tended to be greater than that calculated from the full data set (27.7 +/- 5.4% vs. 20.2 +/- 3.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The standard answer.

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Comprehensive Health Care↗