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Biomedical subjects

G Martin

Publications and source records attributed to G Martin.

At least 271 records · Page 15Linked to original sources

Analysis of the Community Periodontal Index of Treatment Needs--study on adults in France. IV. The significance of gingival recession.

A total of 1005 persons were examined using the CPITN criteria which were recorded for every tooth. All the teeth were also measured on both their buccal and lingual aspects to assess the amount of gingival recession. The combination of pocket depth and gingival recession was computed using a specially written program: 93.8 per cent of the teeth had 1 mm or less gingival recession; 82.5 per cent of the teeth with gingival recession did not present pockets; 26.6 per cent of all subjects had at least one tooth with gingival recession of 2 mm or more but only 9.9 per cent had at least one tooth with 2 mm or more gingival recession and a periodontal pocket.

Adolescent↗

Glutamine synthesis from aspartate in guinea-pig renal cortex.

1. Glutamine was found to be the main carbon and nitrogen product of the metabolism of aspartate in isolated guinea-pig kidney-cortex tubules. Glutamate, ammonia and alanine were only minor products. 2. Carbon-balance calculations and the release of 14CO2 from [U-14C]aspartate indicate that oxidation of the aspartate carbon skeleton occurred. 3. A pathway involving aspartate aminotransferase, glutamate dehydrogenase, glutamine synthetase, phosphoenolpyruvate carboxykinase, pyruvate kinase, pyruvate dehydrogenase and enzymes of the tricarboxylic acid cycle is proposed for the conversion of aspartate into glutamine. 4. Evidence for this pathway was obtained by: (i) inhibiting aspartate removal by amino-oxyacetate, an inhibitor of transaminases, (ii) the use of methionine sulphoximine, an inhibitor of glutamine synthetase, which induced a large increase in ammonia release from aspartate, (iii) the use of quinolinate, an inhibitor of phosphoenolpyruvate carboxykinase, which inhibited glutamine synthesis from aspartate, (iv) the use of alpha-cyano-4-hydroxycinnamate, an inhibitor of the mitochondrial transport of pyruvate, which caused an accumulation of pyruvate from aspartate, and (v) the use of fluoroacetate, an inhibitor of aconitase, which inhibited glutamine synthesis with concomitant accumulation of citrate from aspartate.

Aminooxyacetic Acid↗

Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair.

Adherence of monocytes to endothelial cells or extracellular matrices is likely to play a critical role in triggering monocyte activation in extravascular sites of infection, chronic inflammatory disorders, tissue damage and neoplastic growth. We have constructed a cDNA library from monocytes adhered for 30 min on plastic and have screened it by differential hybridization for mRNA rapidly induced by adherence. Two of the cDNA isolated have been identified as IL-1 beta and superoxide dismutase. Sequence data from three other adherence specific clones demonstrates the presence of ATTTA mRNA instability sequences in their 3' untranslated regions signifying inflammation-associated genes. The deduced amino acid sequences indicate the presence of open reading frames with sequence homologies to a family of host defense cytokines, one of them being identified as IL-8. Of the 14 clones initially identified, 4 have been analyzed for induction of mRNA expression. Although 3 of the 4 clones were equally induced by PMA and LPS under nonadherent conditions, all 4 cDNA showed distinct patterns of induction with adherence to extracellular matrix components or endothelial cells. The deduced amino acid sequence homologies indicate that we have isolated cDNA that code for three unique gene products. These cDNA belong to a gene family of early host defense cytokines involved in inflammation and cell growth, but which are differentially regulated by adherence to different surfaces.

Amino Acid Sequence↗

Antitumor effects of ricin A chain immunotoxins prepared from intact antibodies and Fab' fragments on solid human Hodgkin's disease tumors in mice.

Three monoclonal antibodies which strongly bind to Hodgkin and Reed-Sternberg cells and two corresponding Fab' fragments were linked to deglycosylated ricin A chain (dg A) to evaluate their potential as immunotoxins for the treatment of Hodgkin's disease. Two of the antibodies, Ber-H2 and HRS-3, were shown to bind to the same epitope on the CD30 antigen, whereas the third antibody, IRac, bound to a different antigen. None of the antibodies significantly cross-reacted with normal human tissues as judged by indirect immunofluorescence and immunoperoxidase analyses on frozen sections from 28 normal tissues. All three antibodies formed potent and specific immunotoxins. They inhibited protein synthesis of the L540 Hodgkin's disease cell line in vitro by 50% at concentrations of 1 x 10(-11) M for IRac.dgA, 9 x 10(-11) M for HRS-3.dgA, and 2 x 10(-10) M for Ber-H2.dgA. HRS-3 Fab' and IRac Fab' immunotoxins were 7.8- and 60-fold less cytotoxic, respectively, than their intact counterparts in vitro. In vivo, a single i.v. injection of a dose of Ber-H2.dgA, HRS-3.dgA, or IRac.dgA corresponding to 40% of the LD50 induced lasting complete remissions in 38, 44, and 50%, respectively, of mice with solid s.c. L540 tumors of 60 to 80 mm3 size (0.5-cm diameter). At equivalent dosage (40% of the LD50), the HRS-3 Fab'.dgA and the IRac Fab'.dgA both induced lasting complete remissions in 25% of the mice, although the HRS-3 Fab'.dgA was significantly superior to IRac Fab'.dgA at retarding tumor growth in the remaining animals. The effectiveness of the immunotoxins depended on the size of the tumor at the time of injection, since IRac.dgA treatment induced complete remissions in 100% of mice with small tumors (10 to 20 mm3, approximately 0.3 cm in diameter) but only 13% of mice with larger tumors of 400 to 600 mm3 (approximately 1 cm in diameter). Tumors which regrew after IRac.dgA treatment mainly consisted of antigen-deficient mutants having reduced sensitivity to IRac.dgA but normal sensitivity to HRS-3.dgA. It is concluded that HRS-3.dgA, HRS-3 Fab'.dgA, and IRac.dgA are candidates for the treatment of Hodgkin's disease in humans.

Animals↗

Effect of the antiepileptic drug sodium valproate on glutamine and glutamate metabolism in isolated human kidney tubules.

We studied the effects of sodium valproate, a widely used antiepileptic drug and a hyperammonemic agent, on L-[1-14C]glutamine and L-[1-14C]glutamate metabolism in isolated human kidney-cortex tubules. Valproate markedly stimulated glutamine removal as well as the formation of ammonia, 14CO2, pyruvate, lactate and alanine, but it inhibited glucose synthesis; the increase in ammonia formation was explained by a stimulation by valproate mainly of flux through glutaminase (EC 3.5.1.2) and to a much lesser extent of flux through glutamate dehydrogenase (EC 1.4.1.3). By contrast, valproate did not stimulate glutamate removal or ammonia formation, suggesting that the increase in flux through glutamate dehydrogenase observed with glutamine as substrate was secondary to the increase in flux through glutaminase. Accumulation of pyruvate, alanine and lactate in the presence of valproate was less from glutamate than from glutamine. Inhibition by aminooxyacetate of accumulation of alanine from glutamine caused by valproate did not prevent the acceleration of glutamine utilization and the subsequent stimulation of ammonia formation. It is concluded from these data, which are the first concerning the in vitro metabolism of glutamine and glutamate in human kidney-cortex tubules, that the stimulatory effect of valproate is primarily exerted at the level of glutaminase in human renal cortex.

Adult↗

Single unit activity at ventromedial medulla level in the awake, freely moving rat: effects of noxious heat and light tactile stimuli onto convergent neurons.

In this study, we recorded single unit activity at the ventromedial medulla (VMM) level in the awake, freely moving rat. In agreement with previous work under the same conditions, we found a vast majority of neurons which possess heterosensory and heterosegmental inputs ('convergent'). These units are activated either by auditory or mechanical innocuous and noxious stimuli applied all over the body surface. The activation threshold of these neurons is very low since light stimulation such as air puff produce intense bursts. In addition to this highly represented neuronal class, we also find another consistent VMM group of neurons which fire in relation to precise or generalized body movements. The main result of the present work is that, in addition to auditory and mechanical inputs, a relatively high proportion of VMM convergent neurons are activated by noxious heat pulses between 43 and 51 degrees C. In this range, it was possible to obtain stimulus-response functions with 2 degrees C steps only when a skin twitch reflex produced by the heat was present, also encoding the temperature intensity. In comparison to the VMM activations produced by an intense noxious heat pulse such as 51 degrees C, either auditory or controlled light touch stimuli induced a more robust response in terms of maximum frequency of discharge. Differential properties of VMM neurons in relation to innocuous and noxious information were also found using repetitive stimulation: although a strong and fast habituation of the 51 degrees C responses was observed, this phenomenon was not present for light touch induced activations. We propose that these differential properties might reflect separate pathways reaching the VMM, the one carrying innocuous information possibly relayed through the dorsal column nuclei. Although obtaining stimulus-response functions might implicate the VMM convergent neurons in the sensory-discriminative aspect of pain, their massive heterosensory and heterosegmental inputs favor a role in more general processes such as alertness or stress. Also, due to massive convergent properties, the involvement of this neuronal class in specific bulbospinal descending control systems of nociceptive information is questionable, Finally, our results obtained in the awake, freely moving rat strongly differ from the anesthetized preparation in that we found neither nociceptive specific units nor neurons inhibited by noxious peripheral stimulations largely described in this approach.

Action Potentials↗

The induction of skin graft tolerance in major histocompatibility complex-mismatched or primed recipients: primed T cells can be tolerized in the periphery with anti-CD4 and anti-CD8 antibodies.

Mice given short courses of anti-CD4 and anti-CD8 monoclonal antibodies became tolerant of allogeneic skin grafted at the same time. Tolerance could be obtained without T cell depletion across multiple minor antigen mismatches, both in naive and primed animals, demonstrating that peripheral T cells could be tolerized, even if they had been previously activated. Where donor and recipient were incompatible across the whole major histocompatibility complex, specific tolerance could be achieved by using a combination of depleting followed by non-depleting antibodies, where each alone was unsuccessful. Although mice clearly tolerated their original skin grafts, we observed in some strain combinations that a second fresh, but genotypically identical graft, was slowly rejected. Such mice also possessed T cells which could proliferate to donor-type stimulator cells in vitro. Whatever the mechanisms, we have demonstrated that operational transplantation tolerance can be achieved with simple, non-toxic antibody therapy. The introduction of comparable tolerance-inducing regimens in clinical organ transplantation could obviate the need for long-term immunosuppression and its unfortunate side effects.

Animals↗

Purification and characterization of androgenic hormone from the terrestrial isopod Armadillidium vulgare Latr. (Crustacea, Oniscidea).

Androgenic hormone (AH) was purified from hypertrophied androgenic glands of intersexed Armadillidium vulgare (genetic males feminized by symbiotic endocellular bacteria). Two isohormones labeled AH1 and AH2 with similar molecular weights in the range 17,000-18,000 were isolated. Amino acid analysis showed the absence of cysteine in these two forms. A polyclonal antiserum was raised which recognized AH1 and AH2. The physiological significance of this polymorphism is still not known.

Amino Acids↗

A single-unit recording system, contact thermal probe and electromechanical stimulator for studying cellular mechanisms related to nociception at brain stem level of awake, freely moving rats.

The purpose of this paper is to describe a simple, light-weight (3 g) device bearing a fine platinum-irridium Teflon-coated wire (50 microns) used to record single-unit activity extracellularly at brain stem level in the totally conscious freely moving rat. The up and down movements of the electrode through a guide cannula are insured by a small nut and a spring; the distance between the electrode and the end of the guide cannula is measured with a nut index. The system is directly connected to an amplifier (no FET or preamplifier) and allows for long term recordings necessary for a complete neuronal characterization and pharmacological experiments. The device is easy to make, entirely recoverable, and can be implanted from an animal to another. Further improvements are possible such as tungsten microelectrodes and telemetric or microinjection systems. In order to study some neuronal brain stem mechanisms involved in nociception, we have also designed a contact thermal probe and an electromechanical stimulator. The thermode is stuck to the shaved skin on the back of the rat, allowing heat pulses up to 51 degrees C to be applied. The mechanical stimulator is used manually and delivers reproducible innocuous stimuli to the skin. The fact that both types of stimulations are driven electrically enables the elaboration of cumulated peristimulus histograms which will reflect the neuronal activities in response to the application of noxious and non noxious stimuli.

Action Potentials↗

Identification of three related human GRO genes encoding cytokine functions.

The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. We have identified two additional genes, GRO beta and GRO gamma, that share 90% and 86% identity at the deduced amino acid level with the original GRO alpha isolate. One amino acid substitution of proline in GRO alpha by leucine in GRO beta and GRO gamma leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived from related but different genes. Only one chromosomal locus has been identified, at 4q21, by using a GRO alpha cDNA clone that hybridized to all three genes. Expression studies reveal tissue-specific regulation as well as regulation by specific inducing agents, including interleukin 1, tumor necrosis factor, phorbol 12-myristate 13-acetate, and lipopolysaccharide.

Amino Acid Sequence↗

Phase II trial of carboplatin and tegafur (Ftorafur) as induction therapy in squamous-cell carcinoma of the head and neck.

Cisplatin and 5-fluorouracil by continuous infusion combination produces a high response rate in squamous-cell carcinoma of the head and neck (SCCHN). Carboplatin (CBDCA) is a cisplatin analogue with lower emetic potential and nephrotoxicity, although the myelosuppression potential is higher. Tegafur (ftorafur, FT) is an analogue of 5-fluorouracil. It is absorbed well in its oral form and has moderate gastrointestinal and hematologic toxicity. This clinical trial tested the association of CBDCA i.v. plus FT p.o. in patients with SCCHN who had not been previously treated. Twenty-one patients were evaluable for response; the overall response was 62% (33% complete response, 29% partial response). Toxicity was moderate in most of the patients, although there was a treatment-related death.

Administration, Oral↗

Phase II trial of cisplatin and tegafur (Ftorafur) as initial therapy in squamous-cell carcinoma of the head and neck.

Cisplatin and 5-fluorouracil infusion combination produces a high response rate in squamous-cell carcinoma of the head and neck. Tegafur (Ftorafur) is an analog of 5-fluorouracil, and its oral form is well absorbed. This agent has a moderate toxicity. We report a study to determine the efficacy of the cisplatin (100 mg/m2, day 1) and tegafur (1,000 mg/m2 daily for 21 days) combination. Thirty-nine patients entered the study; 36 were evaluable for response. Overall response was 94%, with a 22% complete response. Toxicity was moderate. We conclude that the cisplatin and tegafur combination is active in untreated patients with head and neck cancer.

Administration, Oral↗