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Biomedical subjects

M French

Publications and source records attributed to M French.

At least 55 records · Page 3Linked to original sources
PubMed1994

Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)

OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Multicentre study in five European countries and Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed. RESULTS: Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed. CONCLUSIONS: Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

AIDS-Related Complex↗
PubMed1992

Molecular cloning and characterization of v-mos-activated transformation-associated proteins.

Using monoclonal antibodies we previously detected two forms of transformation-associated proteins, a 64-kDa protein and a 68-kDa protein, in temperature-sensitive 110-Moloney murine sarcoma virus-mutant-transformed rat kidney 6m2 cells. The identity and functions of the transformation-associated proteins were previously unknown. By molecular cloning techniques and immunoscreening, we have isolated two cDNA clones (34A and 79B3) that were found by Western blot analysis to code for a monoclonal anti-transformation-associated protein antibody-reactive polypeptide of approximately 58 kDa. Limited restriction enzyme mapping indicated 34A and 79B3 are two different cDNA clones. The nucleotide sequence of 34A cDNA was determined, and a search of GenBank revealed that it is identical to that of rat transin-2. The deduced amino acid sequence of 34A shares 71% sequence identity with rat transin and 41-76% identity with six human metalloproteinases. The limited restriction enzyme mapping and partial nucleotide sequencing data indicated that 79B3 may be the rat transin gene. When either 34A cDNA or 79B3 cDNA was used as a probe in Northern blot analysis, one mRNA band of approximately 1.9 kilobases was detected in 6m2 cells grown at the permissive temperature of 33 degrees C, at which the cells exhibited transformation properties, and a much lower level in 6m2 cells grown at the nonpermissive temperature of 39 degrees C, at which the cells reverted to normal phenotypes. These results suggest that at 39 degrees C, these two genes were not transcribed at the same level as at 33 degrees C. Zymogram and Western blot analysis of 6m2 cells further confirmed that the 64- and 68-kDa proteins have metalloproteinase activities and that the synthesis of metalloproteinases was also temperature-sensitive. Apparently, the two proteins we formerly designated transformation-associated proteins are members of the rat transin gene family. Therefore, within v-mos transformed 6m2 cells, the absence of transformation-associated protein (metalloproteinase) synthesis at the nonpermissive temperature was due to the absence of transcription of two rat transin genes.

Amino Acid Sequence↗
PubMed1992

Pathology of renal transplantation.

Renal transplantation is the most appropriate form of treatment for end-stage renal disease in all age groups. We present the experience of two hospitals in the pathology of kidney allograft. Renal biopsy is the most adequate method for the follow-up of these patients, because it permits the differential diagnosis of acute and chronic rejection, transplant glomerulopathy, recurrent and "de novo" glomerulonephritis and immunosuppression nephrotoxicity, mainly by cyclosporine A. We present the pathology features of all these entities, and study the representativity of the biopsy for diagnosis of rejection. The actuarial survival of the graft is 82% and 71% at 1 and 5 years, respectively.

Biopsy↗
PubMed1991

Echocardiographic determination of aortic and pulmonary valve areas in subjects with normal hearts.

Two-dimensional and Doppler echocardiography were performed in 70 subjects (aged 1 day to 16 years, body surface area from 0.08 to 2.1 m2) to determine aortic and pulmonary valve areas in normal children and adolescents. Valve areas were determined by the continuity equation using echo-determined ventricular outflow tract diameters and Doppler-determined flow velocities from the outflow tracts and corresponding great arteries. Left ventricular outflow tract diameter ranged from 0.3 to 2.2 cm and right ventricular outflow tract diameter from 0.4 to 2.8 cm. Outflow tract diameters were linearly related to the square root of body surface area. Flow velocity increased from a mean of 0.75 m/s in the left ventricular outflow tract to 1.12 m/s in the aorta and from 0.56 m/s in the right ventricular outflow tract to 0.89 m/s in the pulmonary artery. Flow velocities were unrelated to body size. Valve areas were linearly related to body surface area (r = 0.88 and 0.80 for the aortic and pulmonary valves, respectively). Mean aortic and pulmonary valve area indexes were 1.33 cm2/m2 and 1.70 cm2/m2, respectively. The data provide normal values for echocardiographically determined valve areas and validate the practice of indexing valve area for body surface area.

Adolescent↗
PubMed1990

Cyclosporin A-sensitive nephrotic syndrome preceding Hodgkin's disease by 32 months.

A 20-year-old man developed a massive nephrotic syndrome, rapidly complicated by pulmonary embolism and septicemia. Two renal biopsies taken 3 months apart showed minimal change glomerulonephritis. Treatment with prednisolone 1.5 mg/kg/day failed to induce a sustained remission, then monotherapy with cyclosporin A (CsA, 5 mg/kg/day) was started. Complete remission was obtained after 15 weeks. CsA was gradually tapered to 3 mg/kg/day. Twenty-two months after starting CsA, a routine examination disclosed a right sub-clavicular lymph node, of which histological examination showed a class 4 large cell Hodgkin's lymphoma. CsA was abruptly withdrawn and a polychemotherapy resulted in lymphoma remission after four courses. Ten months later, Hodgkin's disease is currently in remission and there is no relapse of proteinuria.

Adult↗
PubMed1989

Phase II trial of plicamycin and hydroxyurea in acute myelogenous leukemia.

A total of 23 patients with high-risk acute myelogenous leukemia (AML) at diagnosis (2 patients), relapsing AML (14) or resistant AML (6) were treated with 25 micrograms/kg i.v. plicamycin every other day for 3 weeks and 500-4,000 mg hydroxyurea per day p. o. according to the WBC count. Aplasia was observed in only two patients. Severe extrahematologic toxicity included sepsis (four cases), vomiting (four patients), toxic hepatitis (three cases), and fibrinopenia (one patient). No partial or complete responses were observed. The 95% confidence interval limit of the overall response rate (CR + PR) was 0-14%.

Bone Marrow↗
PubMed1989

Pressure ejection of acetylcholinesterase within the guinea-pig substantia nigra has non-classical actions on the pars compacta cells independent of selective receptor and ion channel blockade.

In the substantia nigra, acetylcholinesterase may have a non-classical function unrelated to cholinergic transmission. Acetylcholinesterase is released from the dendrites of dopamine-containing nigrostriatal neurons and has a subsequent action on these cells, independent of hydrolysis of acetylcholine. The aim of this study was to explore further the precise nature of this "non-cholinergic" action of acetylcholinesterase. Acetylcholinesterase was pressure-ejected in the vicinity of the dendrites of putative nigrostriatal neurons in vitro, in near-physiological amounts, and the effects of this treatment on neuronal membrane properties were investigated. It was found that acetylcholinesterase reversibly hyperpolarized the nigrostriatal cell membrane independent of sodium and calcium channel blockade. Acetylcholinesterase pretreated with an irreversible inhibitor (Soman) of its classical catalytic site produced the same hyperpolarizing effect: however, butyrylcholinesterase, which hydrolyses acetylcholine, was inefficacious. These effects persisted in the presence of the dopamine receptor antagonist sulpiride. It is suggested the acetylcholinesterase can facilitate the generation of a long-duration conductance, which enhances the firing of nigrostriatal cells if the neuron is first hyperpolarized. Hence the action of acetylcholinesterase would be to modulate inputs. These actions are independent of direct interaction with acetylcholine and dopamine systems. Hence, in the substantia nigra, acetylcholinesterase might serve as a "neuromodulatory" secretory protein.

Acetylcholinesterase↗
PubMed1989

Comparison between image and flow DNA cytometry in non-Hodgkin's lymphomas.

To assess the reliability of DNA estimation in cytological material, Feulgen lymph node imprints from 22 cases of malignant non-Hodgkin's lymphomas were examined by image cytometry (ICM) for both ploidy and cell kinetics, and the results obtained were compared with flow cytometry (FCM). The DNA distribution pattern was less accurate with ICM than with FCM; however, a high correlation was found between proliferative indices (r = 0.91) and between aneuploidy rates (agreement in about 86% of the cases) determined by FCM and ICM. Moreover, DNA tetraploid (or near-tetraploid) stem lines were more easily detected by ICM, due to the morphological selection of lymphomatous cells. The proliferation rate and the aneuploidy frequency according to morphological classification were in agreement with larger, previously reported studies with FCM. Therefore, ICM appears to supply additional complementary information to that obtained with FCM, particularly for the study of heterogeneous cell populations, which may be usefully applied to refine the large cell lymphoma subclassification.

DNA, Neoplasm↗
PubMed1989

Growth hormone-releasing factor-sensitive adenylate cyclase system of purified somatotrophs: effects of guanine nucleotides, somatostatin, calcium, and magnesium.

The purpose of this study was to characterize the adenylate cyclase system in a purified population of normal somatotrophs derived from rat pituitary and to determine the responses of this system to GRF, somatostatin, guanine nucleotides, and cations. Additionally, experiments were performed to evaluate the interrelationships among changes in adenylate cyclase activity, cellular cAMP levels, and GH release induced by GRF and somatostatin. The results obtained using homogenates and membrane preparations from somatotrophs included the following. 1) GRF caused guanine nucleotide-dependent concentration-related (Ka, approximately 10(-8) M) stimulation of adenylate cyclase activity. 2) Guanine nucleotides were effective in stimulating cyclase in the absence of GRF; the concentration of guanine nucleotide required for half-maximal stimulation was decreased more than 10-fold in the presence of GRF. 3) Adenylate cyclase activity increased with increasing concentrations of free Mg2+ (0.25-20 mM); activation by GRF and guanine nucleotide resulted in an approximately 7-fold increase in the enzyme's affinity for free Mg2+. 4) Somatostatin, up to 10(-6) M, did not alter basal or GRF-stimulated adenylate cyclase activity. 5) Ca2+ (0.5-11.9 microM) produced concentration-dependent inhibition of basal (up to 28%) and GRF-stimulated (up to 47%) cyclase activities; the inhibitory effect of Ca2+ was accompanied by a decrement (2- to 3-fold) in the apparent affinities of the enzyme for both GRF and guanine nucleotide. In intact somatotrophs, GRF produced concentration-dependent stimulation of GH release (Ka, approximately 6 x 10(-11) M), preceded by a marked elevation of cAMP levels. While somatostatin blocked GRF-induced GH release, the augmented cAMP levels were only slightly reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1988

An electrophysiological action of acetylcholinesterase independent of its catalytic site.

Acetylcholinesterase (AChE) is released from the cell bodies and/or dendrites of dopaminergic neurones in the substantia nigra. Extracellular AChE can modify both the electrical activity of dopaminergic nigral neurones and the associated motor behaviour of the animal. These effects seem to be unrelated to hydrolysis of acetylcholine, but the underlying cellular mechanisms of these actions of AChE are unknown. The possible non-cholinergic action of AChE on the membrane properties of dopaminergic neurones was thus investigated by intracellular recording from midbrain slices in vitro. Application of AChE resulted in a marked hyperpolarization of the membrane accompanied by a decrease in input resistance, sometimes preceded by a period of spontaneous firing. Butyrylcholinesterase (BuChE) was without effect. AChE pre-treated with an irreversible inhibitor (Soman) of its enzymic activity caused similar changes to those seen following administration of untreated AChE. It is concluded that AChE can modify the membrane properties of nigrostriatal neurones in a way that is independent of its ability to hydrolyse acetylcholine. This novel biological property of AChE provides a possible mechanism by which this neurosecretory protein could modulate the functioning of the neurones from which it is secreted and suggests that other 'non-cholinergic' actions of AChE might exist.

Acetylcholinesterase↗
PubMed1988

Differential stimulation of sea urchin early and late H2B histone gene expression by a gastrula nuclear extract after injection into Xenopus laevis oocytes.

Sea urchin early histone genes are active in preblastula embryos; late histone genes are maximally expressed during subsequent stages of embryogenesis. We used the Xenopus laevis oocyte to assay for trans-acting factors involved in this differential regulation. Sea urchin nuclear proteins were prepared by extracting gastrula-stage chromatin successively with 0.45, 1, and 2 M NaCl. We injected three fractions into oocytes along with plasmids bearing sea urchin early and late H2b histone genes. While neither the 0 to 0.45 M nor the 1 to 2 M salt fraction affected H2b gene expression, the 0.45 to 1 M salt fraction stimulated early and late H2b mRNA levels significantly. Late H2b gene expression was stimulated preferentially when the early and late genes were coinjected into the same oocytes. This extract did not stimulate the accumulation of transcripts of injected herpesvirus thymidine kinase genes or of the sea urchin Spec 1 gene, suggesting that the stimulatory activity is not a general transcription factor. We localized the DNA sequence required for the stimulatory effect to a region of the late H2b gene located between -43 and +62 relative to the transcription start site. A component of the 0.45 to 1 M salt wash fraction specifically bound to the 105-base-pair late gene DNA sequence and to the corresponding early gene fragment. The abundance of this binding activity decreased on a per genome basis during early development of the sea urchin.

Animals↗
PubMed1987

Preliminary observations on lactoferrin secretion in human vaginal mucus: variation during the menstrual cycle, evidence of hormonal regulation, and implications for infection with Neisseria gonorrhoeae.

The concentration of the iron-binding protein lactoferrin was measured in vaginal mucus of women throughout the menstrual cycle. Lactoferrin is proposed to limit growth of mucosal pathogens such as Neisseria gonorrhoeae. Lactoferrin concentration in mucus was highest just after menses (62.9 to 218 micrograms/mg of protein) and lowest (3.8 to 11.4 micrograms/mg of protein) just before menses. Overall concentration of mucus protein showed no variation with menstrual cycle, and little lactoferrin was detectable in cell debris. Plasma lactoferrin did not show the variation seen in vaginal mucus. Because of the suggestion of hormonal influence on vaginal lactoferrin, its concentration was determined in women receiving oral contraceptive therapy. Mean lactoferrin concentration in women taking oral contraceptives was significantly lower than in the control group (never exceeding 19.8 micrograms/mg of protein) and showed no monthly variation. Vaginal lactoferrin appears to be under hormonal control. Variation in vaginal lactoferrin concentration may result in alterations in susceptibility to bacterial pathogens such as Neisseriae gonorrhoeae.

Cervix Mucus↗
PubMed1986

Hepatitis delta virus infection in Kenya. Its geographic and tribal distribution.

In 1982-1984, an epidemiologic survey of the prevalence of hepatitis B virus surface antigen (HBsAg) in circulating blood (HBs-antigenemia) and of hepatitis delta virus infection was performed in Kenya. The distributions of hepatitis B virus and the delta virus were shown to be very variable. In southern Kenya, only two of 202 sera from HBsAg-positive individuals with no known liver disease and none from 123 HBsAg-positive patients with hepatitis B-related liver disease were positive for delta antibody. In contrast, in northern Kenya, there was an overall prevalence of delta antibody in healthy individuals of 31%. The distribution of delta infection is discussed in relation to lifestyle, ethnic group, and geographic area.

Adult↗
PubMed1985

[Phosphatidylethanolamine methylase and cyclic nucleotide phosphodiesterase activities in human B lymphoid hemopathies].

Phospholipid methylase and cyclic nucleotide phosphodiesterase activities were studied in human B lymphoïd hemopathies (51 patients: acute lymphoblastic leukemia, B lymphoma, chronic lymphocytic leukemia, hairy cell leukemia) and compared with activities in lymphoblastïd and Burkitt lymphoma cell lines and with normal B lymphocytes: methylase activity proved to be lower in ALL and high grade lymphoma and inversely related to the percent of cells in S phase state; the A/G ratio of phosphodiesterases was low in ALL and CLL and high in hairy cell leukemia and it was related to the percent of cells in S phase state.

3',5'-Cyclic-AMP Phosphodiesterases↗