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Biomedical subjects

M J Smith

Publications and source records attributed to M J Smith.

At least 289 records · Page 16Linked to original sources
PubMed1987

Isolation and identification of partial cDNA clones for endoplasmin, the major glycoprotein of mammalian endoplasmic reticulum.

The amino acid sequences of peptides isolated from murine endoplasmin showed significant homology (approximately 50%) with sequences in the heat-shock proteins 90 and 83 of yeast and Drosophila, respectively, indicating that they are related proteins. Mixed oligonucleotide probes, deduced from the peptide sequences, were used to isolate cDNAs from a murine liver cDNA library. DNA sequencing confirmed the presence of a coding sequence for one of the endoplasmin peptides, formally establishing the authenticity of the cDNA. The identity of the murine and hamster endoplasmin sequences suggests a level of sequence conservation associated with proteins that perform a structural role in cells.

Amino Acid Sequence↗
PubMed1987

Oral ciprofloxacin compared with conventional intravenous treatment for Pseudomonas aeruginosa infection in adults with cystic fibrosis.

40 adult patients with cystic fibrosis (CF) were admitted to hospital with acute exacerbations of infection associated with isolation of Pseudomonas aeruginosa from sputum. The patients were randomly allocated (20 per group) to receive intravenous azlocillin 5 g and gentamicin 80 mg, or oral ciprofloxacin 500 mg. Both treatments were given three times a day for 10 days. The patients were assessed on days 1 and 10, and at 6 weeks. There was a significant improvement in lung function between days 1 and 10 in both groups (p less than 0.001). Significant improvement was maintained at 6 weeks after ciprofloxacin but not in the intravenous group. Improvement after ciprofloxacin was superior at day 10. Sputum weight decreased in both groups (p less than 0.001). Patient-recorded symptoms also improved in both groups. There was no serious toxicity or side-effects. Drug resistant organisms were isolated no more frequently after ciprofloxacin than after intravenous therapy. 17 of the ciprofloxacin-treated patients said they preferred oral treatment to intravenous therapy. Oral ciprofloxacin is a useful short-term treatment for patients with CF who are infected with Ps aeruginosa.

Acute Disease↗
PubMed1987

Intraoperative Polaroid roentgenograms.

The introduction of a new Polaroid film (TPX) prompted an evaluation of all Polaroid films that are available, and a comparison with Kodak Xomat film was done both in the experimental mode and the clinical situation. Type TPX shows excellent definition but is still an experimental film. All the other Polaroid films (Types 52, 57, and TPX 10 x 8) produce images in twenty seconds. This is really the only advantage over the conventional Kodak X-Omat KS film processed as an x-ray film.

Humans↗
PubMed1987

Mechanism of attenuated hydrochlorothiazide response during indomethacin administration.

Indomethacin antagonizes the natriuretic and chloruretic response to hydrochlorothiazide in most studies. Neither the mechanism nor nephron site of this antagonism has been determined. To identify sites and potential mechanisms, cortical micropuncture was performed during hydrochlorothiazide treatment in control and indomethacin rats. Indomethacin reduced (P less than 0.005) FeCl from 5.20 +/- 0.49% to 2.26 +/- 0.49% (mean +/- SE). MAP, CIn, and plasma volume were not different between groups. SNGFR and fractional proximal fluid and chloride delivery were not different between groups. Fractional chloride delivery to early distal tubules was 10.8 +/- 0.4% in control but 6.2 +/- 0.3% in indomethacin rats (P less than 0.001). Calculated loop chloride reabsorption was greater in indomethacin than control rats during hydrochlorothiazide administration (41.0 +/- 1.6% vs. 34.3 +/- 2.3%; P less than 0.05). Fractional chloride delivery to late distal tubules was 7.8 +/- 0.7% in control and 4.6 +/- 0.3% in indomethacin rats (P less than 0.005), but distal tubule chloride reabsorption was not different between groups. Papillary tissue chloride was less in control than indomethacin rats during hydrochlorothiazide (P less than 0.05). Urinary PGE2 excretion was reduced (P less than 0.001) by indomethacin during hydrochlorothiazide. Thus indomethacin induced reductions in hydrochlorothiazide response result in part from increased chloride reabsorption in the loop segment. This suggests indomethacin antagonizes hydrochlorothiazide by reducing chloride delivery to hydrochlorothiazide's site of action in the distal tubule rather than by effects of indomethacin on hydrochlorothiazide pharmacokinetics.

Animals↗
PubMed1987

A monocyte function test (complement receptor enhancement) to assess the extent of bronchial carcinoma.

A monocyte function test (complement receptor enhancement) was undertaken on 45 patients with suspected bronchial carcinoma in whom this diagnosis was subsequently substantiated. In 38 (84%) complement receptor enhancement was below a range of values previously established for monocytes from 48 healthy control subjects and from 12 patients with non-malignant respiratory diseases. It was found that all 38 patients with reduced complement receptor enhancement had either local or widespread metastases, as determined by the chest radiograph and a variable combination of chest tomography, liver, bone and brain scanning, computed tomography, fibreoptic bronchoscopy, bone marrow aspiration, liver function tests, mediastinoscopy, and surgical assessment, where appropriate. By contrast, at the time of presentation there was no clear relationship between abnormal values in several conventional screening haematological or biochemical tests and the stage of the tumour. These results suggest that complement receptor enhancement might serve as a useful pointer to the extent of the disease, since low values were associated with extension within the chest and very low values were found with widespread metastases.

Adult↗
PubMed1987

Norepinephrine metabolism in humans. Kinetic analysis and model.

The present study was undertaken to quantify more precisely and to begin to address the problem of heterogeneity of the kinetics of distribution and metabolism of norepinephrine (NE) in humans, by using compartmental analysis. Steady-state NE specific activity in arterialized plasma during [3H]NE infusion and postinfusion plasma disappearance of [3H]NE were measured in eight healthy subjects in the supine and upright positions. Two exponentials were clearly identified in the plasma [3H]NE disappearance curves of each subject studied in the supine (r = 0.94-1.00, all P less than 0.01) and upright (r = 0.90-0.98, all P less than 0.01) positions. A two-compartment model was the minimal model necessary to simultaneously describe the kinetics of NE in the supine and upright positions. The NE input rate into the extravascular compartment 2, estimated with the minimal model, increased with upright posture (1.87 +/- 0.08 vs. 3.25 +/- 0.2 micrograms/min per m2, P less than 0.001). Upright posture was associated with a fall in the volume of distribution of NE in compartment 1 (7.5 +/- 0.6 vs. 4.7 +/- 0.3 liters, P less than 0.001), and as a result of that, there was a fall in the metabolic clearance rate of NE from compartment 1 (1.80 +/- 0.11 vs. 1.21 +/- 0.08 liters/min per m2, P less than 0.001). We conclude that a two-compartment model is the minimal model that can accurately describe the kinetics of distribution and metabolism of NE in humans.

Adult↗
PubMed1987

Differential expression of murine macrophage surface glycoprotein antigens in intracellular membranes.

A monoclonal antibody recognizing a novel murine macrophage glycoprotein antigen (MAG) was prepared by the hybridoma technique. Using live and permeabilized macrophages to estimate surface and total MAG, respectively, it was found that at least 50% of the total antigen was intracellular. In contrast, another macrophage surface glycoprotein antigen, Mac-1, was undetectable in the intracellular pool. Immunofluorescence studies confirmed the existence of a substantial intracellular pool of MAG antigen. Similar results were obtained with a panel of cultured tumour cell lines. In one such cell line, it was shown that surface MAG existed in a distinct punctate pattern indicative of microdomains, whereas surface Mac-1 antigen gave a uniform distribution. The possible role of the surface microdomains in the differential expression of the two surface glycoproteins in intracellular membranes is discussed.

Animals↗
PubMed1987

Visualization of the intact endoplasmic reticulum by immunofluorescence with antibodies to the major ER glycoprotein, endoplasmin.

Antibodies to endoplasmin were used to examine the morphology of the endoplasmic reticulum (ER) by immunofluorescence on permeabilized plasmacytoma and fibroblastoid cells. In unfixed cells, permeabilization led to a pronounced vesiculation of the ER. Therefore cells were first fixed lightly prior to permeabilization with detergent. Fibroblastoid cells gave a characteristic reticular pattern surrounding the nucleus with clear staining of the nuclear membrane. Plasmacytoma cells, in the conventional fluorescence microscope, gave a cisternae-like pattern. Optical sectioning with a confocal scanning laser microscope gave a distinct pattern of concentric cisternae similar to those obtained with transmission electron microscopy on cell sections. The overall morphology of the ER in such cells could be revealed by serial optical sectioning. Evidence was obtained that the ER does not undergo extensive vesiculation during mitosis in plasmacytoma cells. Using anti-endoplasmin immunofluorescence monitoring, conditions were developed for the retention of ER morphology in unfixed, permeabilized cells. These studies illustrate the value of endoplasmin as a general marker for the analysis of ER morphology in different types of cells by immunofluorescence microscopy.

Antibodies, Monoclonal↗
PubMed1987

Lymphocyte subpopulations and function in cystic fibrosis.

Circulating lymphocytes subpopulations and their function have been studied in 25 young adults with cystic fibrosis (CF) and 25 normal controls. Mean absolute numbers of all lymphocyte subsets in the CF group were not significantly different from the controls. Antibody-dependent cell cytotoxicity was significantly higher in the CF patients who had Pseudomonas aeruginosa in their sputum compared with those who had not and compared with the normal controls. Within the CF group the numbers of B cells, total T cells and OKT4+ helper cells fell as percent predicted peak expiratory flow (PEF) declined and similar significant positive correlations were found between lymphocyte subsets and percent predicted body weight. Serum albumin levels also showed a positive correlation with total T lymphocyte numbers (p less than 0.05). In vitro lymphocyte proliferative responses to mitogen were not significantly different from the control group, but again correlated positively with body weight in the CF patients. This provides further evidence that immune function in CF patients may become impaired as pulmonary disease and nutritional status deteriorate.

Adolescent↗
PubMed1986

Hypercalciuria associated with long-term administration of calcitriol (1,25-dihydroxyvitamin D3). Action of hydrochlorothiazide.

Urine calcium excretion was evaluated in 19 patients before and after calcitriol (1,25-dihydroxyvitamin D3) treatment that was followed up for a five- to seven-year period. The effects of increases of calcitriol dosage and modifications of calciuria with hydrochlorothiazide were systematically examined. The urine calcium excretion before calcitriol therapy was 2.3 +/- 0.8 mg/kg/day (mean- +/- SEM) and the urine calcium-creatinine concentration ratio was 0.12 +/- 0.04. With the dose of calcitriol at 23 ng/kg/day, these values increased to 3.2 +/- 0.8 mg/kg/day and 0.19 +/- 0.04, respectively. Following double dose of calcitriol (44 ng/kg/day), increments in calciuria and urinary calcium/creatinine concentration of 1.4 +/- 0.6 mg/kg/day and 0.10 +/- 0.03, respectively, were observed. With concomitant administration of hydrochlorothiazide (1 to 2 mg/kg/day) therapy at maintenance dose and calcitriol (31 ng/kg/day), the urine calcium excretion effectively decreased by 1.3 +/- 0.6 mg/kg/day and the urine calcium-creatinine concentration ratio by 0.05 +/- 0.02. The results suggest that children with calcium-phosphate disorders who require long-term treatment with calcitriol must be carefully monitored in terms of urine calcium excretion, especially when the dosages are increased to achieve maximal therapeutic efficacy. Calciuria induced by calcitriol administration is effectively reversed by addition of hydrochlorothiazide to the treatment regimen.

Adolescent↗
PubMed1986

Arthroscopic treatment of the septic knee.

Pyarthrosis of the knee was treated in 30 patients by arthroscopic decompression and lavage, coupled with parenteral and oral antibiotics. There were 21 men and nine women patients whose ages ranged from 6 months to 65 years of age. Twenty-two patients were considered to have a hematogenous origin as a cause of their pyarthrosis, and eight were caused by penetrating trauma. Twenty-eight of these patients had the onset of symptoms within 72 h prior to arthroscopy. Two adults had the onset of their symptoms 1 week prior to treatment. Follow-up has ranged from 6 months to 5 years. Staphylococcus aureus was cultured in 20 knees, Streptococcus pneumonia in three knees, Haemophilus influenzae in four knees, and Neisseria gonorrhoeae in one knee. The average hospital stay among 22 children aged 12 years or younger was 3.50 days. The other eight patients had an average hospital stay of 9.50 days. Three adults with diabetes and other medical problems, such as renal failure, had an average hospital stay of 17.33 days. Excellent results were obtained in 28 (93.3%) of 30 patients and good results were obtained in two (6.7%) of 30 patients. There were no poor results or recurrences, and no cases of osteomyelitis occurred. This method of treatment markedly reduces the morbidity and hospital stay of patients with a septic knee.

Acute Disease↗
PubMed1986

Specificity of antibodies to the purified Con A acceptor glycoproteins of cultured tumour cells.

Con A acceptor glycoproteins from the human Molt 4 (T cell leukaemia) and HeLa (endocervical adenocarcinoma) cell lines were purified by affinity chromatography and used for the preparation of rat antisera. Cross-absorption analysis showed that each antiserum contained antibodies which recognised cell surface antigens preferentially expressed by the donor cell line. Molt 4-associated antigens were fully expressed on T cell tumour lines and normal thymocytes, but not on non T cell tumour lines, peripheral blood lymphocytes or other blood cells. Immunofluorescence studies showed that the antigens were preferentially expressed on a sub-population of immature thymocytes. HeLa-associated antigens were only fully expressed on one other epithelial tumour cell in a panel of 17 cell lines. Immunofluorescence studies showed that the HeLa-associated antigens were expressed on normal endocervical adenoepithelium but not on ectocervical, endometrial or intestinal epithelia. Thus purified Con A acceptor glycoproteins of cultured tumour cell lines are potent immunogens for the generation of antibodies recognising lineage-associated differentiation antigens. These antigens should be useful in tumour classification and in the study of normal differentiation.

Adenocarcinoma↗
PubMed1986

Effective and reliable behavioral control technology.

The fiberglass-reinforced plastics industry and the literature on controlling exposures to toxic substances were surveyed to select work practices and housekeeping conditions that might be useful in reducing workers' exposures to styrene. A training program was developed to teach the selected behaviors to workers, and a behavior maintenance program was developed to encourage their continued use after training. These behavioral controls were introduced to appropriate workers in three different plants and were effective in changing all selected behaviors and conditions. Statistically reliable reductions in workers' exposures to styrene accompanied the changes in behaviors. All improvements were maintained throughout the course of data collection. The research provides a clear demonstration that behavioral controls can be used reliably to reduce workers' exposures to toxic substances.

Behavior Therapy↗