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Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 433 records · Page 24Linked to original sources
PubMed1986

How blind is blind? Assessment of patient and doctor medication guesses in a placebo-controlled trial of imipramine and phenelzine.

The purpose of the double blind is to protect the internal validity of a clinical trial by preventing knowledge of treatment conditions from influencing outcome or its assessment. We studied medication guesses of 137 depressed patients and/or their doctors at the end of a 6-week randomized trial of placebo, imipramine, and phenelzine. Overall, 78% of the patients and 87% of the doctors correctly distinguished between placebo and active medication. Clinical outcome, treatment condition, and their interaction each contributed to guessing accuracy, while medication experience and side effects assessed only in week 6 did not. Accuracy was high, however, even when cases were stratified for clinical outcome, indicating that other cues were available to the patients and doctors. These may include patterns and timing of side effects and clinical response not detectable in this end-point analysis.

Adolescent↗
PubMed1986

Chlorophyllin: a potent antimutagen against environmental and dietary complex mixtures.

Chlorophyllin, the sodium and copper salt of chlorophyll, was tested for its ability to inhibit the mutagenic activity of a variety of complex mixtures--extracts of fried beef, fried shredded pork, red grape juice, red wine, cigarette smoke, tobacco snuff, chewing tobacco, airborne particles, coal dust and diesel emission particles--in strain TA98 of Salmonella typhimurium. Chlorophyllin was highly effective against the mutagenicity (90-100% inhibition) of 8 of these 10 mixtures. The mutagenicity of the other 2 mixtures was inhibited 75-80% at the highest concentration of chlorophyllin studied. Control and reconstruction experiments showed that chlorophyllin was not toxic to Salmonella at the concentrations used. The antimutagenic activity of chlorophyllin was heat-stable. The mechanism of the antimutagenicity of chlorophyllin in these experiments is not known; however, chlorophyllin is an antioxidant. Scavenging of radicals and/or interaction with the active group of mutagenic compounds may be responsible for its antimutagenic activity. The data reported here indicate that chlorophyllin is potentially useful as an antimutagenic agent.

Chlorophyll↗
PubMed1986

Validation of the SOS/Umu test with mutagenic complex mixtures.

The SOS/Umu test, a rapid system for detecting genotoxic agents by monitoring SOS responses, was evaluated with the extracts of 8 mutagenic complex mixtures (airborne particles, coal dust, tobacco snuff, fried beef, fried shredded pork, airborne particles from polyurethane plants). In this system, the SOS function induced by genotoxicants is detected by a colorimetric measurement of beta-galactosidase in tester cells carrying a umuC-lacZ-fused gene on the plasmid. Results from the study show that a higher beta-galactosidase activity was found when the enzyme substrate and treated cells were added simultaneously into the enzyme reaction mixture and post-treatment dilution (10 X dilution with fresh medium) and incubation (for 2 h) were incorporated. The post-treatment dilution is necessary to reduce a possible false positive due to the color of test substances. The extracts of all mutagenic complex mixtures tested were found to induce dose-related SOS responses, indicating that the SOS/Umu test is potentially useful for the detection of mutagenic complex environmental mixtures.

Air Pollutants↗
PubMed1986

The effect of substance P and its fragments on passive avoidance retention and brain monoamine activity.

It has been shown that substance P(SP), as well as its carboxy and amino terminal fragments, affects a wide range of behaviors. In order to test the CNS activity of these fragments, we measured their effects on passive avoidance learning and monoamine activity. Following one-trial passive avoidance training, mice were injected intraventricularly with either a carboxy or amino terminal SP fragment (SP-C or SP-N), SP itself or phosphate-buffered saline (PBS). SP-N enhanced avoidance retention, which was tested 24 h after training. In a second experiment, monoamine activity was measured one hour after intraventricular injection of SP, PBS or SP fragments. SP-C decreased both nigral 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) and, to a lesser extent, 3,4-dihydroxyphenylacetic acid/dopamine, while SP-N increased nigral 5-HIAA/5-HT. It was concluded that SP-N and SP-C can exert behavioral and neurochemical effects that may be independent of the parent SP molecule.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Detection of the c-myc oncogene product in colonic polyps and carcinomas.

The c-myc oncogene has been implicated in the processes of normal cell proliferation and differentiation. Elevated levels of c-myc mRNA and its gene product (p62c-myc), have been detected in a variety of solid tumours and cultured cel lines. Its precise role in normal cell function and in neoplastic transformation and progression has yet to be elucidated. We have used a monoclonal antibody, raised by peptide immunisation, to determine the distribution by immunoperoxidase staining of the c-myc oncogene product in archival specimens of colonic polyps and carcinomas. Samples from 42 patients with colon carcinoma, 24 with benign polyps and 15 normal colon biopsies were examined. Normal colon revealed maximum staining in the mid-zone of the crypts, corresponding to the zone of differentiation and maturation. The staining was predominantly cytoplasmic. Adenomatous polyps revealed the most intense pattern of staining in areas of dysplastic change. Colonic tumours showed a wide range of staining. Well differentiated tumours contained more cytoplasmic p62c-myc than poorly differentiated tumours. These findings suggest that the c-myc oncogene product may play an important role in the evolution of colonic neoplasia.

Adenoma↗
PubMed1986

The clinical significance of flow cytometric c-myc oncoprotein quantitation in testicular cancer.

A sensitive flow cytometric assay has been developed using a monoclonal antibody, Myc 1-6E10, to quantitate c-myc oncoprotein levels in nuclei isolated from wax embedded testicular tumours. The oncoprotein (p62c-myc) level increased significantly with increasing teratoma differentiation. Patients with intermediate and undifferentiated tumours who developed recurrence had lower p62c-myc levels than those who were disease free since their initial treatment. Such quantitative biochemical methods may provide new prognostic indices for cancer patients.

Antibodies, Monoclonal↗
PubMed1986

Neuron specific enolase expression in carcinoma of the lung.

The value of neuron specific enolase (NSE) immunoreactivity as a marker for small cell lung cancer (SLC) has been assessed using a monoclonal antibody (MCAB) against NSE, MCAB specificity was confirmed using purified enolase isoenzymes, sections of human brain, a panel of lung tumours, neuroendocrine and non-neuroendocrine tumours and normal tissues. Using this MCAB in radioimmunoassay and immunohistochemistry, NSE immunoreactivity was detected in all SCLC material examined. However, considerable reactivity was also observed in a number of non-small cell lung cancer cell lines and tumour biopsy specimens. Furthermore, intratumoral heterogeneity with respect to NSE immunostaining was observed in several cases. Factors which may underlie such intratumoral phenotypic diversity were assessed using flow cytometry together with MCABs directed against both NSE and non-neuronal enolase. Such studies revealed that enolase expression in cells which were no longer actively proliferating differed markedly from that of cells in exponential growth. Furthermore, cells grown under conditions of increasing hypoxia exhibited increased enolase expression relative to those grown under oxygenated conditions. It is concluded from these studies that NSE immunoreactivity per se is an unreliable marker for the SCLC phenotype.

Animals↗
PubMed1986

The concentration of latamoxef achieved in the bile and gallbladder wall of patients with cholecystitis.

This study reports the clinical and pharmacokinetic results following an injection of latamoxef (moxalactam disodium) in patients undergoing cholecystectomy for symptomatic cholelithiasis. Two groups were involved in the study. Group A consisted of 22 patients who received 1 g of intramuscular latamoxef at the time of premedication prior to surgery, and group B consisted of 12 patients each of whom received an intravenous dose of 0.5 g of latamoxef at the time of anaesthetic induction. Latamoxef levels were then measured in peripheral blood, gall bladder bile, common bile duct (CBD) bile and gall bladder wall. Despite a significant difference in the sampling times, inhibitory levels were obtained in the majority of samples in both groups, singularly high levels being assayed in CBD bile. We conclude that an intravenous dosage of latamoxef (0.5 g) given with anaesthetic induction is as effective as 1 g intramuscular dosage given with the pre-medication.

Adolescent↗
PubMed1986

Refractory esophageal candidiasis associated with a low molecular weight plasma inhibitor of T-lymphocyte function.

In a patient with chronic esophageal candidiasis due to C. tropicalis that was refractory to mycostatin and ketoconazole, a generalized cell-mediated immunodeficiency state was detected. Samples of plasma from this patient inhibited T-lymphocyte function, suppressing both rosette formation and mitogen responsiveness of T-cells derived from the patient and from normal individuals. Following plasma exchange, the patient's immune defect resolved and her candida infection disappeared. On further analysis, the plasma inhibitory factor was found to be of low molecular weight (less than 10,000) and heat labile. Preliminary studies suggested that this inhibitor was candida-derived, since it was removed from plasma by anti-candida antibodies in solid phase. Immunodeficiency in chronic candidiasis may be improved by removal of circulating inhibitory factors through plasma exchange.

Adult↗
PubMed1986

Gentamicin dosage in foals aged one month and three months.

The absorption and disposition kinetics of gentamicin were compared at two dosage levels (2 and 4 mg/kg bodyweight [bwt]) in one- and three-month-old foals. Following intramuscular (im) injection of single 2 mg/kg bwt doses, the drug was absorbed rapidly and produced peak serum concentration (18.2 mu 5.3 +/- g/ml, n = 8) at 30 mins. Much wider variations were associated with the amount of drug absorbed and the serum gentamicin concentrations after administration at the higher dosage level. The half-life of gentamicin was similar in the one-month-old (3.7 +/- 1.7 h, n = 8) and three-month-old (3.3 +/- 0.8 h, n = 8) foals, and was independent of the dose. One-month-old foals did not appear to have a deficiency in renal excretion of gentamicin. The minimum inhibitory concentration of gentamicin for Corynebacterium equi and certain other equine bacterial isolates was less than 0.195 microgram/ml. It was concluded that 2 mg/kg bwt administered by im injection at 8 to 12 h intervals, depending on the severity of the infection, could be recommended as the dose rate for treatment of systemic infections caused by microorganisms that are susceptible to gentamicin.

Absorption↗
PubMed1986

Sonographic characterization of carotid plaque: detection of hemorrhage.

By careful evaluation of the sonographic characteristics of carotid plaques, two patterns can be identified: a homogeneous pattern containing uniform echoes corresponding to dense fibrous tissue and a heterogeneous pattern containing mixed echoes and anechoic areas that represent intraplaque hemorrhage pathologically. A prospective study was conducted of 50 patients to determine the accuracy of identifying these different forms of plaque. The patients' carotid arteries were examined by a high-resolution duplex scanner before carotid endarterectomy. The plaques were evaluated carefully by vascular surgeons and pathologists for the presence of intraplaque hemorrhage. In this study, the accuracy of identifying the presence or absence of intraplaque hemorrhage with sonography was 90% (48 of 54); sensitivity, 94% (17 of 18); and specificity, 88% (27 of 31). High-resolution sonography appears to be an accurate means of identifying intraplaque hemorrhage and may ultimately be useful in identifying patients at risk for embolic disease.

Aged↗
PubMed1986

Altered immune function in alloxan-induced diabetes in mice.

Macrophage lectin receptors that recognize bacterial cell wall sugars are reduced in alloxan diabetic mice. This is in contrast to the expression of macrophage Fc (IgG2b) receptors which remains unaltered. Peritoneal macrophages, from diabetic and normal mice, were used as a source of accessory cells in an antigen dependent T cell proliferation assay with unopsonized Staph. epidermidis as the antigen. Uptake of this antigen in the absence of serum is via the macrophage lectin receptors. We have shown that diabetic macrophages induce a level of antigen dependent T cell proliferation to Staph. epidermidis. However the T cell response to Con A was similar with both normal and diabetic macrophages. We suggest that the observed defect in antigen presentation by diabetic macrophages is at the level of uptake of antigen. High glucose levels, such as those found in diabetes, down-regulate the lectin receptor, reduce phagocytosis of Staph. epidermidis and affect antigen presentation. This has important consequences in terms of the ability of diabetics to mount an effective immune response.

Animals↗
PubMed1985

Dinitrochlorobenzene skin testing predicts response to hepatitis B vaccine in dialysis patients.

The pattern of seroconversion and anti-HBs titres after 3 doses of hepatitis B vaccine was studied in 40 haemodialysis patients who had been grouped on the basis of their cell-mediated immune (CMI) response into strong or weak reactors. CMI response was determined by means of a dinitrochlorobenzene (DNCB) skin test. Titres of anti-HBs were comparable to those in healthy controls in 13 of 14 (93%) strong reactors but in only 9 of 26 (35%) weak reactors. Strong reactors had an equally satisfactory seroconversion rate with either 20 micrograms or 40 micrograms of vaccine whereas weak reactors had a negligible seroconversion rate with the 20 micrograms dose. In terms of hepatitis B prophylaxis, haemodialysis patients with a well preserved CMI response require only 20 micrograms of vaccine, with a consequent saving in cost. In contrast, it will be necessary to devise more effective immunisation schedules for most patients with a poor CMI response.

Adult↗
PubMed1985

Monoclonal-antibody-defined human lung tumour cell-surface antigens.

A panel of 3 monoclonal antibodies (MAbs) directed against human lung tumour cell-surface antigens has been produced following immunizations with the established small-cell lung cancer (SCLC) cell line, NCI-H69, and with another SCLC cell line, COR-L32, recently derived from clinical material. One MAb, B10/12, reacted strongly with SCLC, immunoprecipitated a protein having an MW of 100kd and failed to react significantly with non-small-cell lung cancer (NSCLC) in radioimmunoassay and in an immunohistochemical assay. MAbs E10/5 and 2G3 reacted extensively with SCLC but also showed significant reactivity with NSCLC. MAb E10/5 immunoprecipitated a protein with an MW of 80kd but no appreciable protein was specifically precipitated by MAb 2G3. Unlike MAb 2G3, both MAbs B10/12 and E10/5 reacted strongly with selected neuroblastomas whereas only MAbs 2G3 and E10/5 reacted significantly with melanoma. All 3 MAbs reacted with breast carcinomas. Other non-pulmonary tumours thus far examined failed to react with the MAbs in radioimmunoassay or immunohistochemical assay. Immunocytochemistry and the use of viable cells in radioimmunoassay confirmed that the antigenic determinants recognized by these MAbs were surface located.

Antibodies, Monoclonal↗
PubMed1985

Hyperthermia induced by morphine administration to the VTA of the rat brain: an effect dissociable from morphine-induced reward and hyperactivity.

Morphine action at opiate receptors in the ventral tegmental area (VTA) of the rat brain has been implicated in the production of increased locomotor activity and in morphine's rewarding properties. In the present experiments, bilateral administration of morphine (18 micrograms tapped into the tips of 28 gauge cannulae) into the VTA resulted in an increase in body temperature in rats. This effect was both reversed and blocked by a systemic injection of the opiate receptor blocker, naloxone, suggesting that it was due to morphine action at opiate receptors. The neuroleptic, pimozide, injected systemically four hours prior to morphine administration completely blocked the increased locomotor activity but had no effect on the hyperthermia. These data demonstrate that the hyperthermia was not brought about by the increased physical activity. Furthermore, these results suggest that while morphine-induced reward and increased locomotor activity may be mediated by an interaction of morphine and the ascending mesolimbic dopamine system, the hyperthermia is not. In an additional experiment, the effect of systemic injections of the central neurotransmitter receptor antagonists, scopolamine, phenoxybenzamine, and methergoline, on the hyperthermia induced by morphine in the VTA was investigated. Only the serotonin antagonist, methergoline, attenuated the hyperthermia.

Animals↗
PubMed1985

Detection of the c-myc oncogene product in testicular cancer.

A set of monoclonal antibodies was constructed by immunising mice with peptide fragments of the c-myc oncogene product. One such antibody, Myc 1-6E10 was shown to bind to a 62,000 dalton protein identifiable with the c-myc product (p62c-myc). The antigen recognised was not destroyed by paraffin wax embedding. Myc 1-6E10 was used to characterise the distribution of p62c-myc in archival testicular tumour material. Normal testes expressed only small amounts of p62c-myc. Seminomas showed increased nuclear and cytoplasmic staining. Undifferentiated teratoma showed little activity, whereas p62c-myc was abundant in the nuclei of differentiating epithelial structures, yolk sacs and embryoid bodies. Only small amounts of p62c-myc were seen in the tumours of 5 patients who subsequently died from their disease.

Antibodies, Monoclonal↗
PubMed1985

Measurement of substance P metabolites in rat CNS.

A procedure based on ion-exchange chromatography for chemical separation and radioimmunoassays for quantitation of substance P (SP), the SP(1-7), and C-terminal fragments, respectively, has been developed. The procedure allows the determination of these fragments in the presence of large (i.e., 50- to 100-fold) excess of parent compound. The chemical identity of isolated SP and fragments was studied with preparative electrophoresis on dilute agarose gel and with HPLC. The activity identified as SP(1-7) comigrated with the authentic standard whereas practically all activity isolated as C-terminal fragments comigrated with SP(5-11). The levels of C-terminal fragments in rat brain areas rich in SP and in spinal cord were 1-2% of those of parent compound. The levels of SP(1-7) were always higher, in the spinal cord markedly higher (three to five times). Postmortem storage of samples from brain and spinal cord indicated that SP(1-7) levels fell more rapidly than those of SP or C-terminal fragments.

Animals↗