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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 631 records · Page 35Linked to original sources
PubMed1994

T cell recognition of melanoma antigens in association with HLA-A1 on allogeneic melanoma cells.

Previous studies have shown that recognition of melanoma by cytotoxic T lymphocytes may be restricted by HLA-A1, A2 and other HLA antigens. The present study examined the cytotoxic specificity and major histocompatibility complex restriction of cloned cytotoxic T lymphocytes (CTL) isolated from a patient with the HLA phenotype A3,31 who had been immunized with a vaccine prepared from HLA-A1,3 melanoma cells. Cytotoxic assays against HLA-typed allogeneic melanoma cells indicated that cloned CTL from the patient were able to kill allogeneic melanoma cells expressing HLA-A1 but not other HLA-A1-positive cells. Studies on a representative clone indicated that proliferation and cytokine (tumour necrosis factor alpha) production in response to melanoma cells was also associated with HLA-A1 on melanoma cells. Response to the melanoma cells was associated with interleukin-4 (IL-4) rather than IL-2 production. The antigen recognized in the context of HLA-A1 on allogeneic melanoma cells was detected in cytotoxic assays on cells from 9 of 12 HLA-A1+ melanoma cell lines and did not appear to be the product of the MAGE-1 or -3 genes. These findings suggest that T cells can recognize melanoma antigens in the context of alloantigens and that allogeneic vaccines containing "immunodominant" alloantigens may generate CTL that are ineffective against autologous melanoma. The study does not, however, exclude the possibility that CTL with specificity to the latter may be activated by allogeneic vaccines, and further studies are needed to answer this question.

Antibodies, Monoclonal↗
PubMed1994

Effects of ranitidine 150 mg four times a day on 24-hour intragastric acidity and 24-hour plasma gastrin concentration.

Twenty-four-hour integrated intragastric acidity and 24-hr integrated plasma gastrin concentration was measured twice in 23 healthy male volunteers on the seventh day of oral dosing with placebo or ranitidine 150 mg four times a day. The study was a randomized, double-blind, placebo-controlled, two-way crossover investigation. The mean integrated 24-hr intragastric acidity during dosing with ranitidine 150 mg four times a day decreased to 32% of the placebo value (placebo 825 mmol/hr/liter; ranitidine 265 mmol/hr/liter). The mean integrated 24-hr plasma gastrin concentration during dosing with ranitidine 150 mg four times a day was 904 pmol/hr/liter compared with placebo (410 pmol/hr/liter)--an increase of 122%. The median number of hours of pH > 3 during dosing with placebo and with ranitidine 150 mg four times a day were 5 and 11 hr, respectively. Ranitidine 150 mg four times a day caused a significant decrease of mean integrated intragastric acidity for each meal-related interval and also during the night.

Adult↗
PubMed1994

Isolation and characterization of vasoformative endothelial cells from the rat aorta.

We describe here a modified nonenzymatic method for the isolation of rat aortic endothelial cells with vasoformative properties. Aortic rings placed on plastic or gelatin-coated surfaces generated outgrowths primarily composed of endothelial cells. Prompt removal of aortic explants after endothelial migration minimized fibroblast contamination. However, fibroblasts, because of their high proliferative rate tended to overgrow the endothelial cells even when present in small numbers. This potential pitfall was avoided by weeding out fibroblasts with the rounded tip of a bent glass pipette. Primary endothelial colonies free of fibroblasts were segregated in cloning rings, trypsin-treated, and transferred to gelatin-coated dishes. Endothelial cells were cultured in MCDB 131 growth medium containing 10% fetal bovine serum, endothelial cell growth supplement, and heparin. Using this technique, pure endothelial cell strains were obtained from single aortic rings. Confluent endothelial cells formed a contact-inhibited monolayer with typical cobblestone pattern. The endothelial cells were positive for Factor VIII-related antigen, took up DiI-Ac-LDL, and bound the Griffonia Simplicifolia-isolectin-B4. Endothelial cells cultured on collagen gel formed a polarized monolayer, produced basement membrane, displayed Weibel-Palade bodies and caveolae, and were connected by tight junctions. In addition, they reorganized into a network of microvascular cords and tubes when overlaid with a second layer of collagen and formed microvascular sprouts in response to fibroblast-conditioned medium. This isolation procedure yields stable strains of vasoformative endothelial cells, which can be used to study aortic endothelium-related angiogenesis and its mechanisms.

Animals↗
PubMed1994

Advanced radiofrequency catheter ablation in canine myocardium.

Current radiofrequency (RF) ablation technology is limited by small lesion size. To enhance the size of RF-induced left ventricular (LV) endocardial lesions, we evaluated the effects of an enlarged distal electrode tip and increased RF power on lesion volume. Steerable electrode catheters with distal electrode tips of 4 to 12 mm were studied in anesthetized dogs at power settings of 20 to 100 W. Temperature was continuously monitored from a thermistor located at the tip of the catheter. RF energy (500 kHz, unmodulated) was applied between the tip of the catheter and a large skin electrode at four separate LV sites in each animal. Hearts were excised, frozen, sectioned, and stained with nitroblue tetrazolium. Lesion area was planimetered and volume was calculated. Lesion volume increased with increasing electrode size and delivered power. However, a rise in impedance limited maximal lesion size at higher power with each electrode. Maximal lesion size with an 8 mm tip was approximately twice the size of the maximal lesion with a 4 mm tip (914 +/- 362 mm3 vs 460 +/- 150 mm3, p < 0.01). Minimal lesions were seen with large tip electrodes at power < 40 W because of low tip temperature (< 55 degrees C). Average tip temperature correlated with measured lesion volume (r = 0.7). Ventricular fibrillation occurred in approximately one half of the animals studied, and was associated with larger lesion volume (p < 0.01). Catheter ablation of ventricular tachycardia may be enhanced by this technology.

Animals↗
PubMed1994

Analysis of the bimolecular reduction of ferricytochrome c by ferrocytochrome b5 through mutagenesis and molecular modelling.

Site-directed mutagenesis has been used to produce variants of cytochrome c in which selected structural or functional properties of this protein are altered that have been implicated previously in contributing to the rate at which ferricytochrome c is reduced by ferrocytochrome b5. In total, 18 variants have been studied by kinetics and electrochemical methods to assess the contributions of thermodynamic driving force, surface charge and hydrophobic interactions, and redox-linked structural reorganization of the protein to the rate of electron transfer between these two proteins under conditions where the reaction is bimolecular. While some variants (those at position-38) appear to affect primarily the driving force of the reaction, others appear to influence the rearrangement barrier to electron transfer (those at positions-67 and -52) while the interface between electron donor and acceptor centers is the principal effect of substitutions for a conserved aromatic heme contact residue at the surface of the protein (position-82). Interpretation of these results has been facilitated through the use of energy minimization calculations to refine the hypothetical models previously suggested for the cytochrome c- cytochrome b5 precursor complex on the basis of Brownian dynamics simulations of the bimolecular encounter event.

Amino Acid Sequence↗
PubMed1994

Geropsychiatric nursing consultation: a valuable resource in rural long-term care.

Psychiatric and geropsychiatric nurse specialists have the potential to positively influence the day-to-day care provided in rural nursing homes by acting as teachers, resource persons, facilitators, and role models to long-term care (LTC) personnel. The combined approach of training LTC nurses to train their own staff while supporting the application of learning with consultee-focused nursing consultation proved to be an effective and time-efficient method of improving the geropsychiatric nursing care provided in rural nursing homes.

Aged↗
PubMed1994

Successful in vivo immunolocalization of Langerhans cell histiocytosis with use of a monoclonal antibody, NA1/34.

The antibody NA1/34 is a murine monoclonal antibody directed against the CD1a surface antigen expressed on normal Langerhans cells, cortical thymocytes, and on lesional cells in Langerhans cell histiocytosis (LCH). Our hypothesis was that NA1/34 would localize sites of disease activity in patients with multisystem LCH. To test this hypothesis, indium 111-labeled NA1/34 was administered to five patients with multisystem LCH and serial gamma scans were obtained for up to 120 hours. Serial serum samples were obtained from one patient for analysis of anti-mouse Ig antibody and NA1/34 levels. Direct and indirect immunofluorescence staining for CD1a and NA1/34 were performed on a tissue biopsy specimen from one patient after administration of the antibody. The 1- and 4-hour scans showed distribution of antibody in the blood pool, but in later scans localization of the antibody was noted in areas of known disease activity in all five patients. Bony lesions, previously seen on skeletal radiographs, were especially well identified. Serum kinetics studies showed clearance of the antibody from the blood pool within 12 hours of administration. Direct binding of NA1/34 to lesional cells was demonstrated by direct immunofluorescence. The only adverse effect was urticaria in one patient. We conclude that NA1/34 localizes disease activity in vivo in bones of patients with LCH with minimal toxic effects. An evaluation of its role in determining disease extent ("staging") and in treatment is now needed.

Adult↗
PubMed1994

The chest pain emergency department and the outpatient chest pain evaluation center: revolution or evolution?

STUDY OBJECTIVE: To define the chest pain emergency department and the outpatient chest pain evaluation center, and to critically analyze the costs and benefits of modifying or replacing the current system of hospital-based evaluation of chest pain patients with these new systems. DATA SOURCES: Peer-reviewed articles, published letters, book chapters, national health statistics, and personal communications were used. Sources were limited to those describing experiences in the United States. STUDY SELECTION: Relevant sources from the United States were reviewed. DATA SYNTHESIS: The widespread adoption of the chest pain ED as currently configured would result in increased health care expenditures of between $389 million and $3.9 billion. It is estimated that this expenditure might save a maximum of 1,029 additional lives per year, at a cost of between $378,000 and $3.78 million per life saved. CONCLUSION: Current hospital-based systems for evaluating patients presenting with symptoms suggestive of acute ischemic heart disease need improvement. Modification of the system of initial patient evaluation should occur as an evolutionary change to the current ED system. Adoption of a formal system of chest pain EDs represents an inefficient use of resources. Design and implementation of patient education programs about ischemic heart disease should be a public sector responsibility. More research is needed before the proper role of the outpatient chest pain evaluation center can be evaluated.

Adult↗
PubMed1994

A multicenter review of 839 laparoscopic-assisted vaginal hysterectomies.

A multicenter review of 839 cases of laparoscopic-assisted vaginal hysterectomy (LAVH) was conducted to contribute to the clinical decision-making process regarding the procedure, which has been the subject of much debate in recent years. The results suggest that patients undergoing LAVH experience complication rates no higher than those having any other type of hysterectomy, and that efficacy is identical to that of vaginal hysterectomy. Furthermore, the laparoscopic approach affords better visualization of pelvic pathology and better adnexal access for the accomplishment of concurrent pelvic procedures. Mean hospital stay is 1.7 days and mean recovery time 20 days. The notion of a learning curve as described by diminishing procedure time and declining complication rates over time is not supported by this data set. Patients who may traditionally have faced abdominal hysterectomy due to putative or demonstrated pelvic pathology may benefit the most from LAVH.

Adult↗
PubMed1994

Prospective study of verocytotoxin-producing, enteroaggregative and diffusely adherent Escherichia coli in different diarrhoeal states.

One hundred and eighty-one stool specimens from patients with various types of diarrhoea (135 patients) or from non-diarrhoeal controls (23 acute medical patients, 23 inflammatory bowel disease in remission) were investigated using a colony-blot DNA hybridization assay for the presence of Verocytotoxin-producing (VTEC), enteroaggregative (EAggEC) and diffusely adherent (DAEC) Escherichia coli. Twelve patients had probe-positive EAggEC in the stool and 8 of these had diarrhoea, 6 following recent travel. Eight patients had DAEC, 7 of whom had travellers' diarrhoea. Six of 10 (60%) travellers with gastroenteritis, but without a recognized enteric pathogen, were positive for EAggEC (4) or DAEC (2). Five of 10 (50%) travellers with gastroenteritis related to a recognized enteric pathogen also had DAEC identified in their stool. Of the 23 acute medical control patients 11 had been abroad, 4 of these were immigrants and had EAggEC. VTEC were not found and, with one exception, immunoassays for antibodies to E. coli O 157 and O 2 lipopolysaccharides were negative.

Adult↗
PubMed1994

The relations of emotionality and regulation to dispositional and situational empathy-related responding.

The purpose of the present study was to examine the prediction of adults' situational and dispositional empathy-related responses from measures of emotionality (emotional intensity and positive and negative affect) and regulation. A multimethod approach including self-reported, facial, and heart rate (HR) responses was used to assess situational vicarious emotional responding; Ss' (and sometimes friends') reports were used to assess the dispositional characteristics. In general, dispositional sympathy, personal distress, and perspective taking exhibited different, conceptually logical patterns of association with indexes of emotionality and regulation. The relations of situational measures of vicarious emotional responding to dispositional emotionality and regulation varied somewhat by type of measure and gender. Findings for facial and HR (for men) measures were primarily for the more evocative empathy-inducing stimulus. In general, the findings provided support for the role of individual differences in emotionality and regulation in empathy-related responding.

Adolescent↗
PubMed1994

Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients.

Tuberous sclerosis (TSC) is an autosomal dominant condition with characteristic skin lesions, mental handicap, seizures and the development of hamartomas in the brain, heart, kidneys and other organs. Linkage studies have shown locus heterogeneity with a TSC gene mapped to chromosome 9q34 and a second, recently identified on 16p13.3. We have analysed DNA markers in eight hamartomas and one tumour from TSC patients and found allele loss on 16p13.3 in three angiomyolipomas, one cardiac rhabdomyoma, one cortical tuber and one giant cell astrocytoma. We suggest that the TSC gene on 16p13.3 functions like a tumour suppressor gene, in accordance with Knudsen's hypothesis.

Alleles↗
PubMed1994

Growth factor-mediated mechanisms of nicotine-dependent carcinogenesis.

The direct effect of nicotine on the expression of receptors for the tumor necrosis factor alpha (TNF alpha) and transforming growth factor beta (TGF beta) and the internalization, intracellular distribution and stability of these growth factors in cervical cancer cell line SiHa was studied. Nicotine at concentrations in the range 0.05-0.25% inhibited cell growth and it exerted strong apoptotic and cytolytic effects at concentrations above 0.5%. Nicotine at 0.1% stabilized and protected from degradation [125I]TNF alpha and [125I]TGF beta internalized by cervical cancer SiHa cell line. In the absence of nicotine, [125I]TNF alpha and [125I]TGF beta were internalized during the first hour of incubation and localized mainly in the cytoplasm and in smaller amounts in the nucleus. After 1 day of cell exposure to growth factors, only traces of radioactivity were detected inside the cells, which indicated that both growth factors were rapidly degraded. In the presence of nicotine, both [125I]TNF alpha and [125I]TGF beta were detected in high quantities and in a non-degraded form in the cytoplasm and chromatin during 5 days of incubation. In addition to the lack of growth factor degradation, the presence of nicotine induced a nuclear accumulation of growth factors, with up to 37% of the internalized [125I]TGF beta being in the chromatin. An increased intracellular accumulation of [125I]TNF alpha and [125I]TGF beta in cells exposed to nicotine occurred without changes in expression of the cell surface receptors. Nuclear accumulation of TGF beta was followed by increased RNA synthesis and a switch from the growth-promoting action of TGF beta to the strong growth inhibitory effect. Inhibition of the lysosomal degradation of growth factors by nicotine is discussed as a potential mechanism of tobacco-induced carcinogenesis.

Cell Division↗
PubMed1994

Hyperexpression of a synthetic gene encoding a high potential iron sulfur protein.

A gene encoding high potential iron sulfur protein (HiPIP) iso-1 from Ectothiorhodospira halophila was constructed in one step from long synthetic oligonucleotides. The gene was inserted into a phagemid vector from which the HiPIP was expressed as a fusion protein to > 10% of the soluble protein in Escherichia coli, demonstrating that a 4Fe-4S protein can be highly expressed in E. coli. The recombinant HiPIP was purified to apparent homogeneity by affinity chromatography followed by proteolytic removal of the leader sequence and anion exchange chromatography. Approximately 180 mg of HiPIP were purified from 10 l of cell culture. CD spectra of the oxidized and reduced forms of the protein and the 1H NMR spectrum of the oxidized protein are essentially identical to those of the wild type protein, indicating that the environment of the iron sulfur cluster in the two proteins is the same and thus that the recombinant protein is folded correctly. The reduction potential of the recombinant protein was determined to be 120 +/- 6 mV versus NHE (20 mM HEPES, 0.1 M sodium chloride, pH 7.0, 25 degrees C). This efficient heterologous expression of an HiPIP enables a systematic investigation of structure-function relationships in this class of iron sulfur proteins.

Amino Acid Sequence↗
PubMed1994

The pitch of electrically presented sinusoids.

A patient who uses the Ineraid cochlear implant, and who has hearing thresholds less than 50 dB HL for frequencies under 500 Hz in his nonimplanted ear, was asked to match the pitch of low-frequency signals presented to his two ears. The patient produced pitch matches, for frequencies of 125, 200, and 300 Hz presented to his most apical electrode, that were slightly higher than the reference frequency. When signals of fixed frequency were presented to electrodes located in successively more basal cochlear locations, pitch increased in an orderly fashion--an average of 57 Hz (range = 31-87 Hz) for each change in electrode location.

Auditory Threshold↗
PubMed1994

Respiratory morbidity in Merseyside schoolchildren exposed to coal dust and air pollution.

A cross sectional study was carried out to determine whether schoolchildren in a specific locality exposed to pollution from steam coal dust have an excess of respiratory symptoms compared with children in control areas. A total of 1872 primary schoolchildren (aged 5-11 years) from five primary schools in the Bootle dock area of Liverpool (exposed area), five primary schools in South Sefton (control area), and five primary schools in Wallasey (control area) were studied. A questionnaire was distributed through the schools and was completed by the parents of the children. The questionnaire inquired about respiratory symptoms (cough, wheezing, and shortness of breath), allergy, atopy, smoking, and socioeconomic factors. Height, weight, and peak expiratory flow were measured. Compliance was good (92%) and similar in the three study areas. The children in the three areas were of similar mean age (7.5 years), height (1.24 m), sex ratio, and had a similar prevalence of paternal (6.2%) and maternal (7%) asthma. The exposed zone contained more unemployed parents (41, 29, and 29% respectively), more rented housing (64, 45, 34%), and more smoking parents (71, 60, 59%) than the control areas. Respiratory symptoms were significantly more common in the exposed area, including wheeze (25.0, 20.6, and 17.5%), excess cough (40.0, 23.4, and 25.1%), and school absences for respiratory symptoms (47.5, 35.9, and 34.9%). These differences remained significant even if the groups were subdivided according to whether or not parents smoked or were employed. Multiple logistic regression analysis confirmed the exposed zone as a significant risk factor for absenteeism from school due to respiratory symptoms (odds ratio 1.55, 95% confidence interval 1.17 to 2.06) after adjusting for confounding factors. Standard dust deposit gauges on three schools confirmed a significantly higher dust burden in the exposed zone. An increased prevalence of respiratory symptoms in primary schoolchildren exposed to coal dust is confirmed. Although the association with known coal dust pollution is suggestive a cross sectional study cannot confirm a casual relation and further studies are needed.

Absenteeism↗