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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 451 records · Page 25Linked to original sources

[Dynamic wound healing profile of venous ulcus cruris].

The success of venous leg ulcer treatment can be evaluated by various parameters like wound area reduction in square millimeters, percent reduction of ulcer size, reduction of wound radius, and time of wound closure. Which one is the most reliable parameter if different treatment forms (i.e. various ointments) are to be compared? The best parameter for the evaluation of the speed at which chronic ulcers heal was the daily wound radius reduction, calculated from the wound area by planimetry. Under a standardized treatment (polyvidoniodine ointment, pressure bandaging) the daily ulcer radius fell on the average by 0.24 mm indicating a continuous growth of skin tissue from the wound circumference. Conversely, the daily wound area reduction in mm2 or in percent was difficult to interpret due to the parabolic shape of the area reduction curve. Here the following characteristics were noted: Large wounds displayed a relatively quick reduction of the wound area and at the same time a slow percental wound diminution. Small wounds, on the other hand, displayed a relatively slow reduction of the wound area and at the same time a relatively quick percent wound diminution. The period of time during which a wound became completely closed was equally unsuited for the assessment of therapeutic success because large ulcers healed slower than smaller ones. We conclude from these results that reduction of the wound radius should be used as the most reliable parameter for the evaluation of venous leg ulcer healing.

Adult↗

Cytokine induction of adhesion molecules on synovial type B cells.

OBJECTIVES: To study the role of cytokines on adhesion molecule expression and binding of activated T cells to synovial type B cells. METHODS: Adhesion molecule expression was examined by immunofluorescence and adhesion of 51Cr-labelled T cells to the synovial cells determined. RESULTS: Tumor necrosis factor alpha/interferon gamma (TNF alpha/IFN-gamma) and interleukin 1 alpha (IL-1 alpha)/IFN-gamma enhanced adhesion molecule expression and the adhesion of T cells to synovial cells. Anti-intercellular adhesion molecule 1 blocked adhesion of T cells to TNF alpha/IFN-gamma and IL-1 alpha/IFN-gamma stimulated synovial cells while an antibody to CD61 blocked adhesion to IL-1 alpha/IFN-gamma stimulated cells. CONCLUSIONS: The interaction of leukocytes with adhesion molecules on synovial cells may play a role in recruitment of these cells to an inflammatory site.

Cell Adhesion↗

Cardiac allotransplantation across the ABO-blood group barrier by the neutralization of preformed antibodies: the baboon as a model for the human.

The baboon, like the human, expresses A and/or B blood group antigens on its tissues. Anti-A and anti-B antibodies are directed against these antigens, the epitopes of which are carbohydrate structures. Portions of these carbohydrates have been synthesized (trisaccharides A and B, respectively). When infused intravenously, the synthetic trisaccharides form a complex with the specific antibodies and neutralize their activity preventing them from binding to the antigen targets on a transplanted organ. In nonimmunosuppressed, hyperimmunized baboons, the continuous intravenous infusion of the specific trisaccharide alone (for 6 days) inhibited rejection of ABO-incompatible cardiac allografts, extending survival from a mean of 19 min (n = 3) to 8 days (n = 2), at which time the grafts failed from cellular (not vascular) rejection. The combination of long-term pharmacologic immunosuppression plus trisaccharide infusion (for periods of 8 to 19 days) extended survival to a mean of > 28 days (n = 4) with one heart functioning > 52 days. Accommodation clearly occurred in three of the four cases. This form of therapy may permit cadaveric organ allotransplantation across the ABO blood-group barrier in the human.

ABO Blood-Group System↗

Bacterial translocation following abdominal trauma in humans.

Bacterial translocation in humans has been identified only with small bowel obstruction and in trauma patients. Our aim was to determine whether the occurrence of bacterial translocation correlates with clinical outcome in trauma patients. All patients requiring exploratory celiotomy for abdominal trauma over a 2-month period were considered for the study. Gross fecal contamination of the abdomen was the only exclusion criterion. Five patients with small bowel injuries without obvious contamination were included. Patients received preoperative antibiotics. Once surgical hemostasis and injury repair were complete, two mesenteric lymph nodes were harvested--one for quantitative culture, the other for electron microscopic evaluation. Postoperatively, patients were monitored for infection via temperature, white blood cell (WBC) count, and, when indicated, chest X-ray (CXR) and culture. Statistical analysis utilized ANOVA (P < 0.05 significant) and linear regression. Sixteen patients were included in the study. Fifteen patients sustained penetrating abdominal trauma, one blunt. Six patients presented in Class I hemorrhagic shock, four in Class II, and two in Class III. The remaining four were not in hemorrhagic shock. Thirteen patients demonstrated bacterial translocation: one by culture alone, nine by electron microscopy, and three by both culture and electron microscopy. Statistical analysis of these three groups and patients without evidence of infection failed to reveal significant difference in average age, injury severity, hospital days, or incidence of postoperative infection. Bacterial translocation occurs following abdominal trauma in humans. Electron microscopic evaluation of mesenteric lymph nodes demonstrated that the incidence of translocation is greater than anticipated by culture alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗

Measles vaccine failures: lack of sustained measles-specific immunoglobulin G responses in revaccinated adolescents and young adults.

The measles-specific antibody responses of seronegative adolescents and young adults were evaluated after revaccination. Of 1650 previously vaccinated healthy volunteers between the ages of 10 and 30 years, 4.4% were found to be seronegative for measles antibodies and 9.9% had equivocal titers. Seronegative volunteers were revaccinated to measles and followed serially for development of measles-specific IgG. Of 43 subjects followed for at least 1 year, only 58% developed and maintained positive antibody titers; 12% never developed positive titers and 30% initially developed titers that fell below positive levels within 1 year. The peak titers achieved by those subjects who responded transiently were lower than those achieved by subjects who developed sustained responses. Thus even after the recommended two dose schedule of the current measles vaccine, some adolescents and young adults lack protective titers of measles-specific antibody.

Adolescent↗

Cerebral hemodynamic and metabolic changes in fulminant hepatic failure: a retrospective study.

The purpose of this retrospective study was to determine cerebral hemodynamic and metabolic changes in comatose patients with fulminant hepatic failure. Computerized tomography of the brain and cerebral blood flow measurements by the xenon-computerized tomography scan or intravenous xenon-133 methods were obtained in 33 patients with fulminant hepatic failure. In a subgroup of 22 patients, arteriojugular venous oxygen content difference and cerebral metabolic rate for oxygen were determined. Carbon dioxide reactivity was tested in 17 patients, and intracranial pressure was recorded by an epidural monitor in 8 patients. Cerebral blood flow and arteriojugular venous oxygen content difference were adjusted to the average arterial carbon dioxide pressure of the sample (32 mm Hg). Adjusted cerebral blood flow varied from 16.5 to 94.7 ml/100 gm/min; 52% of the patients had reduced adjusted cerebral blood flows (less than 33 ml/100 gm/min), whereas 24% had hyperemic values (greater than 50 ml/100 gm/min). Patients with higher adjusted cerebral blood flows showed cerebral swelling on computerized tomography scan (p < 0.002), were in deeper coma (p < 0.05) and had greater mortality (p < 0.002). The adjusted arteriojugular venous oxygen content difference was negatively correlated with adjusted cerebral blood flow (r = -0.61, p < 0.002). The majority of patients with reduced adjusted cerebral blood flows had low adjusted arteriojugular venous oxygen content differences (less than 5 vol%), indicating hyperemia rather than ischemia. The average cerebral metabolic rate for oxygen was 50% of normal (1.6 +/- 0.4 ml/100 gm/min); even patients with low cerebral metabolic rates for oxygen recovered neurologically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Computer calculation of multiple binding equilibrium isotherms: application to the binding of bivalent ligands to antibodies interacting with cell surface Fc-receptors.

A method to calculate multiple binding equilibria by looking for a set of complexes satisfying the conservation principle among sets of concentrations of ligands, receptors satisfying the mass action equations is described. The method replaces complex analytical derivations of equations representing the interactions by the minimization of a single function. The method was implemented for use on microcomputers and applied to the calculation of the binding isotherms of the interactions between a bivalent ligand, a bivalent antibody and the cell surface Fc-receptor. The binding parameters were adjusted to experimental data obtained with P388D1 cells, a monoclonal antibody against DTPA-indium complexes and monovalent and bivalent DTPA-indium haptens. The binding of the antibody and of the haptens to P388D1 cells, as a function of antibody or hapten concentration, was satisfactorily represented using a model in which the antibody molecules bind co-operatively to the Fc-receptor in the presence of cross-linking bivalent hapten. The method can thus be used as a general tool for the numeric calculation of complex equilibrium involving simultaneous interactions of multiple receptors and ligands.

Animals↗

The mechanism of action of FK-506 and cyclosporin A.

FK-506 and cyclosporin A (CsA) are potent immunosuppressive agents used clinically to prevent tissue rejection. Interest in the development of more effective immunosuppressive drugs has led to an intense effort toward understanding their biochemical mechanism of action with the result that these compounds have now become powerful tools used in deciphering the signal transduction events in T lymphocyte activation. Although chemically unrelated, FK-506 and CsA exert nearly identical biological effects in cells by inhibiting the same subset of early calcium-associated events involved in lymphokine expression, apoptosis, and degranulation. FK-506 binds to a family of intracellular receptors termed the FK-506 binding proteins (FKBPs). CsA binds to another family of intracellular receptors, the cyclophilins (Cyps), distinct from the FKBPs. The similarities between the mechanisms of action of CsA and FK-506 converge upon the calcium- and calmodulin-dependent serine-threonine protein phosphatase calcineurin (CaN). Both the FKBP/FK-506 complex and the Cyp/CsA complex can bind to calcineurin, thereby inhibiting its phosphatase activity. Calcineurin, a component of the signal transduction pathway resulting in IL-2 expression, catalyzes critical dephosphorylation events required for early lymphokine gene transcription.

Amino Acid Isomerases↗

The maize transposable element system Ac/Ds as a mutagen in Arabidopsis: identification of an albino mutation induced by Ds insertion.

A two-component transposon system based on the Ac element of maize was used as a mutagen in Arabidopsis thaliana. Transposition of a Ds element marked with a hygromycin-resistance gene was activated from four different locations in the Arabidopsis genome. The progeny of 201 plants carrying independent transposition events were screened for mutants with severe, visible phenotypes. Seven mutants were identified and four of them were analyzed genetically. Three mutations were shown to be very closely linked to a transposed copy of the element. Moreover, a mutation (alb3) causing an albino phenotype was conclusively shown to be caused by insertion of the Ds element: somatic and germinal reversion of the mutation occurred in the presence of the transposase gene but not in its absence, and in three revertants the Ds had excised from its position in the mutant line. The DNA adjacent to Ds in the mutant was isolated and it was demonstrated that revertants retained part of the 8-bp duplication caused by insertion of Ds. These experiments indicate that the Ac/Ds system can be used as an insertional mutagen in the heterologous host Arabidopsis, which will permit the isolation of genes from this species by transposon tagging.

Arabidopsis↗

[1-13C]glucose metabolism in rat cerebellar granule cells and astrocytes in primary culture. Evaluation of flux parameters by 13C- and 1H-NMR spectroscopy.

The metabolism of [1-13C]glucose in rat cerebellum astrocytes and granule cells was investigated using 13C- and 1H-NMR spectroscopy. Near homogeneous primary cultures of each cell type were incubated with [1-13C]glucose, under the same conditions. Analysing the relative 13C enrichments of metabolites in spectra of cell perchloric acid extracts, on the one hand, the 13C-1H spin-coupling patterns in 1H-NMR spectra of cell medium lactate and the 13C-13C spin-coupling patterns in 13C-NMR spectra of purified cell glutamate, on the other hand, showed significant differences, between the two cell types, in the activity of various metabolic ways. First, the carbon flux through the oxidative branch of the hexose monophosphate shunt, which leads to unenriched lactate, was found higher in granule cells than in astrocytes. Second, although the specific 13C enrichment of lactate was higher in astrocytes than in granule cells, the fraction of 13C-enriched acetyl-CoA entering the citric acid cycle was more than twice as high in granule cells as in astrocytes. Lactate C3 and acetyl-CoA C2 enrichments were very similar in granule cells, whereas acetyl-CoA C2 enrichment was 60% lower than that of lactate C3 in astrocytes. These results can be explained by the fact that granule cells used almost exclusively the exogenous glucose to fuel the citric acid cycle, whereas astrocytes used concomitantly glucose and other carbon sources. Last, in the case of granule cells, glutamate C2 and C3 enrichments were equivalent; the carbon flux through the pyruvate carboxylase route was evaluated to be around 15% of the carbon flux through the citrate synthetase route. In astrocytes, glutamate C2 enrichment was higher than that of C3, which could be explained by a pyruvate carboxylase activity much more active in these cells than in granule cells.

Animals↗

Place of Iridium 192 implantation in definitive irradiation of faucial arch squamous cell carcinomas.

PURPOSE: We have reviewed the results of 165 T1 and T2 squamous cell carcinomas of the faucial arch treated by definitive irradiation including or not Iridium 192 brachytherapy to ascertain whether a significant relationship existed between Iridium implantation, local control, complications, and survival. METHODS AND MATERIALS: From March 1971 to November 1990, 58 T1 and 107 T2 (NO: 107/165; N1: 30/165; N2: 9/165; N3: 19/165) biopsy proven squamous cell carcinomas of the tonsillar region (104/165) and the soft palate and uvula (61/165) were treated in Henri Mondor Hospital by definitive irradiation with curative intent. From 1971 to 1981 (period 1), only guide gutter technique was available, so that implants were reserved for small tumors: patients were either managed by definitive telecobaltherapy to tumor site and neck node areas (Group 1; n = 48; mean dose: 70 Gy; confidence interval: +/- 5.5; 5 fractions of 1.8 Gy per week) or by exclusive Iridium implant (Group 2; n = 11; all T1NO; 64 Gy +/- 4.8) or by a combination of external beam radiation therapy to tumor site and neck nodes areas and Iridium implant (Group 3; n = 40). In 1981 (Period 2), a new plastic tube technique, which enables implantation of larger areas, was introduced in the department and all patients (Group 4; n = 66) were then managed by external radiation therapy (Group 3 + 4: 47 Gy +/- 4.3) followed by an Iridium implant (31 Gy +/- 10.5). Clinically positive neck nodes either received additional external dose with electrons or were excised. RESULTS: Overall 5-year survival (Kaplan Meier) was 21%, 50.5%, and 60% in groups 1, 2, and 3 + 4, respectively (p < 0.001, log rank). Five-year local control was 58%, 100%, and 91%, respectively (p < 0.001). Five-year necrosis rate was 4.5%, 20.5% and 18%, respectively (N.S.). Comparison of results between the two periods of the study (Group 1 + 2 + 3 vs. group 4) show that these two groups are statistically comparable according to site and size of tumor and N status and that both local control (77% vs. 94% at 5 years; p < 0.01) and disease-free survival (56% vs. 71%; p = 0.03) were improved after 1980, while there was a trend to an increase in overall survival (42% vs. 53% at 5 years; p = 0.08); nodal control (86% vs. 95% at 5 years), and necrosis rate (11% vs. 20% at 5 years) were not modified. Multivariate analysis showed that both local control (p < 0.0001) and overall survival (p < 0.0001) were improved when tumor was implanted. CONCLUSION: We recommend then to treat T1 and T2 squamous cell carcinomas of the faucial arch by external radiation therapy to tumor site and neck areas (45 Gy/25 fractions/5 weeks) followed by a 30 Gy Iridium implant and, for patients with clinically positive nodes, either a further 25-30 Gy electron beam irradiation to the nodes or neck node dissection.

Brachytherapy↗

Glutathione, but not glutamine, is detected in 13C-NMR spectra of perchloric acid extracts from C6 glioma cells.

Glutamine, which is expected to be produced by C6 glioma cells, is not detected in both amino-acid analyses and 13C-NMR spectra of perchloric acid extracts of cells incubated for 4 h with [1-13C]glucose in the absence of extracellular glutamine. However, the resonances of a glutamate-linked product are observed in these spectra. The analysis of the pH dependence of chemical shifts from various glutamate-derived compounds shows that the observed resonances came from glutathione. Glutamine and glutathione signals are in close proximity on the frequency scale, leading to possible misinterpretation of the spectra.

Brain Neoplasms↗

Preferential induction of c-fos versus c-jun protooncogene during the immediate early response of pig skin to gamma-rays.

The involvement of the nuclear protooncogenes c-fos and c-jun in the immediate early response of pig dermis cells was studied after in vivo gamma-irradiation. Following high radiation doses (8 to 48 Gy), the two protooncogenes were concomitantly induced, although c-fos induction was preferential. Both inductions were time and dose dependent. Therefore, the early response of the skin to high doses of radiation might involve heterodimeric activator protein 1 composed of c-Fos and c-Jun proteins. Following low radiation doses (0.5 to 2 Gy), c-jun was not induced. By contrast, dramatic c-fos induction was observed after 0.5 Gy, suggesting a specific role for c-fos at low doses.

Animals↗

Coexpression of type I and type II IL-1 receptors in the murine T helper 2 cell line D10N.

IL-1 receptor heterogeneity in murine lymphocytes was investigated by cross-linking to [125I]IL-1 alpha and competition with IL-1 receptor antagonist, and the molecular identity of the IL-1 receptors was identified with PCR using primers specific for type I and type II IL-1 receptors. The thymoma cell line E14 6.1 exhibits exclusively the 80 kDa receptors which proved to be the type I receptor according to PCR analysis. In the pre-B cell line 70Z/3, predominantly a 60 kDa type II receptor but also a trace of type I receptor can be identified by PCR. The Th2 cell line D10N expresses both types of IL-1 receptors in equivalent amounts according to cross-linking experiments and PCR. The proliferative response of D10N cells to IL-1 is inhibited by IL-1 ra which according to cross-linking affects the binding to the type I receptor only. It is concluded that coexpression of both types of IL-1 receptors might be a characteristic of murine Th2 cells and that their growth-dependence on IL-1 is mediated by the type I receptor.

Amino Acid Sequence↗

A novel population of natural killer progenitor cells isolated from human umbilical cord blood.

In this report, we describe the isolation of a unique subpopulation of CD7+ cells from human fetal blood. Umbilical cord blood was first immuno-rosette-depleted using T cell, B cell, granulocyte, and macrophage markers to isolate a Lin- population. The Lin- cells were further characterized by cell sorting. As expected, the CD34+Lin- population (30%) was homogeneous and highly enriched for hemopoietic progenitors. Somewhat surprisingly, the CD34-Lin- population was also shown to be relatively homogeneous, with over 95% of cells expressing CD7. This CD34-Lin-CD7+ population was shown to be negative for all other T cell markers tested (i.e., CD7+1-2-3-4-8-). However, approximately 30% of these cells were positive for the NK cell surface markers CD16 and CD56 (CD7+NK+). Both CD7+NK+ and CD7+NK- populations proliferated in response to stimulation in vitro with IL-2/PHA/PHA-conditioned medium. After such treatment, approximately 40% of the CD7+NK- acquired CD56 and 20% CD16, whereas about 20% of the CD7+NK+ population became CD2+. The significance of the 60% of CD7+NK- cells that did not acquire other markers remains to be determined. In addition, although neither population was cytotoxic when first isolated, both populations acquired the ability to lyse the NK target cell line K562 while cultured under these conditions. These data suggest that these two populations may represent a developmental sequence among NK cell precursors in human umbilical cord blood. Additional analysis of such precursors may be useful in understanding the ontogeny of NK cells in vivo.

Antigens, CD↗