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Biomedical subjects

M Wilson

Publications and source records attributed to M Wilson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Membrane exon sequences of the three Xenopus Ig classes explain the evolutionary origin of mammalian isotypes.

We have cloned and sequenced the genes corresponding to the membrane exons of the three immunoglobulin (Ig) heavy chain isotypes (mu, upsilon and chi) of Xenopus. Among membrane Ig (mIg) polypeptides, the transmembrane domain are the most highly conserved. The transmembrane and cytoplasmic domains of Xenopus mIgM are similar to the corresponding domains of all known vertebrate mIgM molecules, supporting the idea that amphibian mu gene is homologous, not just analogous, to the mu gene of higher vertebrates. The membrane forms of the two other Ig isotypes mIgX and mIgY exhibit the specific structure found in all Ig membrane exons, but are not homologous with any specific mammalian non-mu Ig isotype; they are most similar to Xenopus mIgM. Based on the conserved transmembrane domains of Xenopus mIgX, mIgY, we suggest that first the upsilon and later the chi genes arose by duplication from the original mu gene. The transmembrane and the 37-amino-acid-long cytoplasmic domains of Xenopus mIgY have conserved residues found in avian mIgY and mammalian mIgG and mIgE, suggesting that the modern isotypes might share a common ancestor with amphibian mIgY. However, while the sequence similarity between the membrane exons of avian mIgY and mammalian mIgG and IgE is striking, the overall similarity with Xenopus mIgY is very low. Thus, the genes giving rise to Xenopus mIgY and those eventually leading to avian mIgY and mammalian mIgG and mIgE must have diverged early in evolution, probably at the level of the primitive amphibians or before.

Amino Acid Sequence↗
PubMed1996

Impaired glucose tolerance and mild hyperglycemia in sucrose-fed rats does not impair insulin secretion.

We fed normal rats a high sucrose diet in order to test the hypothesis that mild hyperglycemia can induce defects in pancreatic beta-cell function and impair glucose-stimulated insulin release. Rats provided with free access to a sucrose solution (35%) voluntarily consumed 50% more carbohydrate than control per day. After 7 days of sucrose feeding, glucose tolerance was significantly impaired; the area under the glucose tolerance test curve (GTT) was 683 +/- 61 mmol/120 min compared with 472 +/- 56 mmol/120 min in controls (P < 0.05). Impaired glucose tolerance was still present after a further 12 days (area under the GTT: 749 +/- 99 mmol/120 min). Sucrose-fed rats were significantly (P < 0.05) hyperglycemic by 1.5 mmol/l over controls. When insulin secretion was assessed in vivo and in vitro in control and sucrose-fed rats, no significant differences were apparent in plasma samples collected over a 1-h period or in statically incubated or perifused isolated pancreatic islets. In addition, the rates of glucose utilisation and oxidation were normal in islets from sucrose-fed rats. These data do not support the hypothesis that minimal hyperglycemia is sufficient to impair glucose-stimulated insulin release.

Animals↗
PubMed1996

Picture archiving and communication system training for physicians: lessons learned at the Baltimore VA Medical Center.

Physicians practicing at the "filmless" Baltimore VA Medical Center need to be proficient in the use of the picture archiving and communication system (PACS) to be able to view radiologic images and accompanying reports. PACS training is necessary to assure optimal patient care and to satisfy potential medicolegal requirements. Providing such training is the responsibility of both the Imaging Department and the hospital. Training in the use of the PACS at the Baltimore VA is conducted by an on-site application specialist. Data were collected from interviews with the trainer, training log sheets, and physician surveys. Although 100% of radiologists received formal training, only 22% of nonradiologists were formally trained; 32% of these physicians identified themsleves as having been trained by their peers and 41% stated they were self-trained. We identified two goals of a PACS training program. The first is to teach physicians how to retrieve images and reports from current as well as prior studies and display them on a computer workstation. Secondly, the training should include instruction on the use of the various workstation tools to enhance image interpretation. Imaging requirements and usage by different physician groups vary, and PACS training should be tailored accordingly. Difficulties in the scheduling of training sessions during working hours and the widespread use of a "generic" log-on identification have contributed to the low (22%) compliance of nonradiologists with the formal training program. Although we believe that one-on-one training is most effective and can be best tailored to the needs and computer expertise of an individual particular physician, computer based training (both on and off-line) may provide an acceptable, and in some cases, a preferred alternative.

Baltimore↗
PubMed1996

Tendon shift in hallux valgus: observations at MR imaging.

OBJECTIVE: This study was undertaken to demonstrate a shift in tendon alignment at the first metatarsophalangeal joint in patients with hallux valgus by means of magnetic resonance imaging. DESIGN: Ten normal feet and 20 feet with the hallux valgus deformity conforming to conventional clinical and radiographic criteria were prospectively studied using magnetic resonance imaging. Correlation was made between tendon position at the first metatarsophalangeal joint and the severity of the hallux valgus deformity. RESULTS: There is a significant shift in tendon position at the first metatarsophalangeal joint of patients with hallux valgus. The insertion of the abductor hallucis tendon is markedly plantarward and the flexor and extensor tendons bowstring at the first metatarsophalangeal joint compared with patients without the deformity. The severity of the tendon shift correlates with the hallux valgus angle and clinical severity of the hallux valgus deformity in each case. CONCLUSION: Patients with hallux valgus have a significant tendon shift at the first metatarsophalangeal joint which appears to contribute to development of the deformity.

Case-Control Studies↗
PubMed1996

Adsorption/desorption of amine fluorides to hydroxyapatite.

This study concerned the adsorption and desorption of commercial amine fluoride (AmF) preparations to hydroxyapatite (HA). The influence of pH, ionic strength, temperature, saliva and albumin, the latter as a gingival crevicular fluid analogue, on adsorption/desorption was investigated. AmF levels were determined using a surfactant electrode. AmFs 297 and 335 were found to bind immediately and irreversibly to HA in water over a range of pH values, ionic strengths and temperatures, the amounts increasing with concentration. More monovalent AmF 335 was absorbed than divalent AmF 297. Any AmF desorbed by water from HA was at the lowest end of the minimum inhibitory concentration for oral bacteria. AmF 297 was desorbed by CaCl2, and to a lesser extent by H+, OH-, NH4+, La3+, EDTA, Triton X100 and ethanol, whereas AmF 335 was only slightly desorbed by ethanol. Preadsorption of proteins on HA had little effect on subsequent adsorption or desorption of either AmF. It is postulated that both AmF 297 and AmF 335 are inactivated by an excess of proteins in the surrounding medium, supra- or subgingivally, and not by such proteins preventing or altering the mode or rate of adsorption, or interfering with antibacterial activity, when the AmFs contact a protein-coated tooth surface.

Adsorption↗
PubMed1996

Microbial/host interactions in health and disease: who controls the cytokine network?

The interacting cellular and molecular systems which we classify as immunity and inflammation evolved to protect the organism from exogenous parasites including viruses and bacteria. Cytokines play a pivotal, but paradoxical, role both in immunity and inflammation. These local peptide hormone-like molecules form a major arm of the organisms, defenses against infectious microorganisms but they are also implicated as potent mediators of the pathology of infectious diseases. The apparently lethal effects of interleukin-1 and tumor necrosis factor in experimental septic shock testify to the latter. In the current paradigm, cytokine induction, as a protective or pathological mechanism, is a direct response to the presence of infectious microorganisms. Evidence is now accumulating that cytokines play a much more complex role in the interplay between exogenous microorganisms and the host. For example, it has been established that viruses have evolved pro-active methods of subverting the cytokine network by producing: (i) soluble cytokine receptors which bind and inactivate cytokines, (ii) immunomodulatory cytokine homologues, and (iii) ICE inhibitors. The possibility exists that the major role of these 'viral cytokines' is to neutralize certain host responses. Recent cytokine transgenic knockouts demonstrate that the normal benign response to commensal gut microflora becomes a lethal inflammatory state in the absence of the cytokines interleukin 2 or interleukin 10. The human body contains an enormous number of microorganisms which constitute the normal microflora. It is estimated that the average human contains 10(13) eukaryotic cells but 10(14) bacteria. We propose that the ability of the multicellular organism to live harmoniously with its commensal microflora must depend on mutual signalling involving eukaryotic cytokines and prokaryotic cytokine-like molecules. Such interactive signalling sets up non-inflammatory cytokine networks in tissues which form the background on which responses to infectious microorganisms must be built and related. The capacity of bacteria to induce cytokine synthesis was believed to be due to a small number of components, such as lipopolysaccharide (LPS), which is only active as a complex with host factors (lipopolysaccharide binding protein and CD14). However, it is now clear that bacteria contain and produce a large number of diverse molecules which can selectively induce the synthesis of both pro-inflammatory and immunomodulatory/anti-inflammatory cytokines. Many toxins are potent inducers of cytokine release or synthesis and some can inhibit LPS-induced cell activation. We have introduced the term bacteriokine to describe these bacterial cytokine inducers. The question that has to be addressed therefore is - who controls the cytokine network (eukaryotic or prokaryotic cells) and how is it controlled? It is proposed that an understanding of this question will bring with it an understanding of how to control the pathological inflammatory response and may allow the development of truly effective anti-inflammatory agents.

Animals↗
PubMed1996

Ex-vivo treatment of gastric Helicobacter infection by photodynamic therapy.

Attempts to develop PDT for eradication of Helicobacter infection have only been successful in vitro. We have investigated the effect of topical sensitization (except ALA) of Helicobacter mustelae on explanted ferret gastric mucosa using one of five sensitizers (methylene blue (MB), toluidine blue O (TBO), phthalocyanine, haematoporphyrin derivative and 5-aminolavulinic acid), followed by irradiation with an appropriately tuned copper vapour pumped dye laser. A 90% reduction in counts of bacteria sensitized with 0.75 mg TBO kg-1 were seen after irradiation with 200 J cm-2. Concentrations of MB of 0.75 mg kg-1 and 7.5 mg kg-1 were not toxic to H. mustelae, but the further addition of 20 J cm-2 laser light reduced colony counts by more than 99%. MB at a concentration of 75 mg kg-1 exhibited significant dark toxicity towards H. mustelae, but further addition of 20 J cm-2 laser light resulted in near eradication of all colonies. The remaining three compounds were ineffective. Finally, we studied the microscopic fluorescence distribution of MB (7.5 mg kg-1) on ferret gastric mucosa after topical administration. Fluorescence was greatest in the superficial mucosal layer, upon which lies the bacteria. However, from experiments on rats, the energy required to kill the sensitized bacteria was insufficient to damage the underlying mucosa. We conclude that Helicobacter can be killed on host mucosal epithelium following topical administration of MB and subsequent exposure to laser light.

Aminolevulinic Acid↗
PubMed1996

Effects of variance in mini amplitude on stimulus-evoked release: a comparison of two models.

The strength of synaptic connections between two neurons is characterized by the number of release sites (N) on the presynaptic cell, the probability (p) of transmitter release at those sites in response to a stimulus, and the average size (A) of the postsynaptic response from each site. Quantal analysis can determine N, p, and A, but the large variance in the amplitudes of minis at central synapses is predicted to obscure quantal peaks and render quantal analysis unusable. Recently it has been suggested that the variance in mini amplitude is generated by differences between release sites, rather than by quantum-to-quantum fluctuations at identical sites, and that this form of variance in mini amplitude reduces the amount of variance expected in quantal peaks. Using simulations, we examine the possibility of resolving quantal peaks assuming either form of variance in mini amplitude. We find that individual quantal peaks are resolvable in neither case, provided that the uniquantal distribution is similar to the mini distribution. Because this lack of resolution compromises the utility of quantal analysis, we develop a general description that can solve N and p, given the statistical parameters of the mini distribution and the evoked distribution. We find that this description is relatively insensitive to the source of variance in mini amplitude.

Analysis of Variance↗
PubMed1996

Validation of urine caffeine metabolite ratios with use of stable isotope-labeled caffeine clearance.

OBJECTIVE: A number of caffeine metabolite ratios have been proposed to measure CYP1A2 activity in vivo. The data to validate these ratios are scanty. The objective of this study was to validate urine caffeine metabolite ratios versus stable isotope-labeled caffeine clearance under different caffeine dosing conditions. STUDY DESIGN: Two experiments, one with nine nonsmoking subjects and the other with 12 cigarette smokers, were performed. We explored the relationship between caffeine clearance, measured by means of intravenous infusions of stable isotope-labeled caffeine, and a number of caffeine metabolite ratios during administration of different single or multiple doses of caffeine to smokers and nonsmokers on three different occasions over a 2-week period, using different durations of urine collections, including spot urines. The stable isotope technique allowed simultaneous oral dosing of caffeine and measurement of caffeine metabolite ratios and caffeine clearance, the latter reflecting CYP1A2 activity. RESULTS: The caffeine metabolite ratio of AAMU + 1U +1X/17U (5-acetylamino-6-amino-3-methyluracil + 1-methyluric acid + 1 methylxanthine/1,7-dimethyluric acid) maintained a significant correlation with caffeine clearance for all the above conditions (gamma2 range, 0.4 to 0.9) except for dose. With high doses of caffeine (12 mg/kg), a significant relationship was not observed. AAMU + 1U + 1X/17U also correlated with the formation clearance of paraxanthine (gamma2 = 0.6, p = 0.002). Other reported caffeine metabolite ratios did not display the same robust correlation with caffeine clearance under all these different conditions. CONCLUSIONS: We conclude that AAMU+1U+1X/17U measured from a single spot urine collection is a valid measure of CYP1A2 activity except at very high levels of caffeine dosing. The validity of the other proposed caffeine metabolite ratios is questionable.

Adult↗
PubMed1996

The effect of liver disease on urine caffeine metabolite ratios.

OBJECTIVES: A number of caffeine metabolite ratios (CMRs) have been proposed to measure CYP1A2 activity in vivo. The effect of liver disease on these ratios is not clear. The objective of this study was to determine the influence of liver disease on caffeine metabolite ratios. STUDY DESIGN: Two studies were performed. First, in healthy control subjects and in subjects with cirrhosis, caffeine clearance was measured by intravenous infusion of stable isotope-labeled caffeine while subjects consumed oral caffeine. Second, spot urine samples were collected from control subjects and from subjects with either chronic hepatitis or cirrhosis while they consumed caffeine. RESULTS: In study 1, caffeine clearance was decreased in subjects with cirrhosis (control mean, 0.14 L/hr/kg; cirrhosis mean, 0.04 L/hr/kg; p = 0.003). CMRs were affected by liver disease (e.g., ratio characterizing paraxanthine demethylation [AAMU + 1X + 1U/17U], control median, 8.3; cirrhosis median, 6.2; p = 0.005). AAMU + 1X + 1U/17U correlated significantly with caffeine clearance in the control group (r2 = 0.68; p = 0.0001) and in subjects with cirrhosis (r2 = 0.41; p = 0.05). In study 2, there was a significant difference between control subjects and subjects with cirrhosis for AAMU + 1X + 1U/17U (median for control subjects, 6.2; median for subjects with cirrhosis, 4.3; p = 0.001) but not between control subjects and patients with chronic hepatitis. CONCLUSIONS: We conclude that AAMU + 1X + 1U/17U is affected by liver disease and reflects the decrease in CYP1A2 activity in subjects with cirrhosis. AAMU + 1X + 1U/17U measured from a spot urine sample reflects caffeine clearance in subjects with cirrhosis and may be useful as a hepatic function test. Despite the large interindividual variation observed, the test can be repeated easily in the same patient and an individual patient's decline in CYP1A2 activity, such as in patients with progressively deteriorating liver function, can be monitored.

Adult↗
PubMed1996

Down-regulation of vascular endothelial growth factor in human colon carcinoma cell lines by antisense transfection decreases endothelial cell proliferation.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent paracrine angiogenic factor implicated in human colon cancer angiogenesis. This study determined whether regulation of VEGF expression by human colon cancer cell lines affects endothelial cell proliferation in an in vitro model of angiogenesis. METHODS: Human colon carcinoma cell lines were screened for VEGF mRNA expression. SW480 cells (low VEGF expresser) were transfected with the VEGF sense (VS) vector, and SW620 cells (high VEGF expresser) were transfected with the VEGF antisense (VAS) vector. Cells were transfected with the vector alone as control. Endothelial cells were grown in conditioned, serum-free medium produced from experimental cells, and proliferation was determined. RESULTS: SW480-VS transfectants exhibited a sixfold increase in VEGF secretion. SW620-VAS transfectants exhibited a 50% reduction in VEGF secretion. Endothelial cells grown in conditioned medium from SW480-VS cells exhibited a 1.5- to 2-fold increase in proliferation. Addition of conditioned medium from SW620-VAS cells resulted in a 25% to 50% decrease in endothelial cell proliferation. CONCLUSIONS: VEGF production by human colon cancer cells regulates endothelial cell proliferation. Antisense VEGF transfection can down-regulate VEGF secretion and biologic activity. Therapies to decrease VEGF expression may be a means of inhibiting angiogenesis in primary and metastatic colon cancer.

Alternative Splicing↗
PubMed1996

Fish immunology: the utility of immortalized lymphoid cells--a mini review.

Long term cell lines can be readily established at high frequency with PBLs from normal channel catfish. Depending upon the mode of stimulation, morphologically and functionally distinct catfish lymphoid cell lines resembling B cells, T cells and monocytes have been developed. These fish cell lines appear unique from their putative mammalian counterparts in that they are immortalized without the need for exogenous factors or overt attempts at transformation.

Animals↗
PubMed1996

Saturation of postsynaptic receptors at central synapses?

A fundamental issue in synaptic physiology is whether the postsynaptic response to a quantum of transmitter is limited by the number of receptors available. Fierce debate over the past few years has yielded no consensus. The majority of evidence suggests that the degree of receptor occupancy is likely to be sensitive to a number of factors, including the detailed anatomy of the synaptic cleft and the time course of transmitter clearance, and is probably different from one synapse to the next.

Animals↗
PubMed1996

State anxiety following 20 minutes of bicycle ergometer exercise at selected intensities.

An attempt was made to determine if state anxiety responses following acute exercise are influenced by the intensity of exercise. Fifteen adults (5 female, 10 male) completed 20 minute sessions of bicycle ergometer exercise on separate days at intensities equal to 40, 60, or 70% VO2peak. Expired gas spirometry was employed to determine peak oxygen consumption and to control the workload during the submaximal protocols. State anxiety (STAI-Y1) was assessed prior to and following each exercise session, and 5, 60 and 120 minutes post-exercise. Repeated measures ANOVA revealed that state anxiety decreased (p < 0.05) following each exercise condition. Post hoc analysis indicated that state anxiety was significantly (p < 0.05) reduced at all post-exercise assessments in the 40 and 60% VO2peak conditions. State anxiety was elevated by 3.4 units at 5 minutes following exercise at 70% VO2peak, but decreased (p < 0.05) below baseline at 60 and 120 minutes post-exercise to a degree not different from the other exercise conditions. Further analysis indicated the increase in anxiety 5 minutes following 70% VO2peak exercise was significant only in subjects with low baseline state anxiety values, whereas it was unchanged in subjects with higher baseline values. In conclusion, 20-minute sessions of cycle ergometer exercise at intensities ranging from light to heavy were equally effective in reducing state anxiety in young, healthy adults. However, this reduction is delayed somewhat following exercise at a high intensity (i.e., 70% VO2peak).

Adult↗