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Biomedical subjects

G Mathé

Publications and source records attributed to G Mathé.

At least 199 records · Page 11Linked to original sources
PubMed1985

Circulating CALLA-positive lymphocytes exhibit circadian rhythms in man.

Common acute lymphoblastic leukemia antigen (CALLA) is a polypeptide with a molecular weight of 100,000 daltons (P100). It has been mainly found on the membrane of leukemic lymphoblasts, but not on that of normal circulating lymphocytes. Circadian rhythmicity in circulating CALLA-positive (CALLA+) lymphocytes was investigated in five healthy male subjects. Blood was sampled every 4 h for 24 h in each subject. Seven times series were obtained (three for the same subject). Leukocyte and differential counts were determined, and mononucular cells (greater than 95% lymphocytes) were isolated in Ficoll-Paque gradient. CALLA+ cells were characterized with both J5 and VILA1 monoclonal antibodies. Other T- and B-cell subpopulations were also determined in the same samples. Up to 1160 +/- 498 (mean +/- 1 S.E.M) J5-labelled CALLA+ lymphocytes per mm3 were found in peripheral blood at night. At this time, circulating VILA1-labelled CALLA+ lymphocytes also reached their peak although with a much lower number (66 +/- 14 cells/mm3). A circadian rhythm (with a period identical to 24h) was statistically validated with several methods for the number of J5-labelled cells, that of VILA1-labelled cells and the J5: VILA1 ratio. The count of J5-labelled CALLA+ cells was correlated with that of total lymphocytes, total T (OKT3+) and inducer T (OKT4+) cells (p less than 0.01), but neither with suppressor/cytotoxic cells (OKT8+) nor with B cells (SIg+, B1+, B2+, or HLA-Dr+). No correlation was found between any of these lymphocyte subpopulation and the count of VILA1-labelled CALLA+ cells. Such results further support the hypothesis that VILA1 and J5 monoclonal antibodies do not bind to the same epitope of the CALLA molecule. The large nocturnal increase in circulating J5-labelled CALLA+ lymphocytes may be accounted for by a release of immature presumably T lymphocytes in the peripheral blood.

Adult↗
PubMed1985

Aclacinomycin-A inhibits the development and the expression of suppressor cell activity to contact sensitivity.

Aclacinomycin-A, a cytotoxic antibiotic, is capable of inhibiting the development and expression of suppressor cell activity for the contact sensitivity reaction to picryl chloride elicited by two intravenous injections of 3.5 mg picryl sulfonic acid when given as a single dose of 4 mg/kg 2 or 4 days before the first or 1 or 3 days after the second injection of picryl sulfonic acid. This inhibition may occur because aclacinomycin-A inhibits the development and expression of both suppressor T-cells and their precursors. In addition, it is shown that aclacinomycin-A diminishes the capacity of spleen T-cells from picryl sulfonic acid-injected mice to inhibit upon adoptive transfer the contact sensitivity reaction to picryl chloride of normal and presensitized animals.

Aclarubicin↗
PubMed1985

Immunological effect of cycloheximide in mice.

We evaluated the effects of cycloheximide on two immune responses in the mouse. The data obtained in this series of experiments showed enhancement of the direct splenic plaque-forming cell response to sheep red blood cells when the drug was administered at doses of 25 and 50 mg/kg i.p. and of the delayed type hypersensitivity reaction to oxazolone when cycloheximide was injected at doses of 10, 25 and 50 mg/kg i.p. Depression of these responses was observed when the dose of drug injected was 75 or 100 mg/kg i.p. At a dose of 5 mg/kg cycloheximide had no effect on these immune responses.

Animals↗
PubMed1985

Antitumor activity of l-OHP in mice.

The isomeric mixtures of platinum complexes of diaminocyclohexane (DACH) had been found active on several murine tumors. A recent separation of the oxalato-platinum complex of trans-l-DACH isomer allowed more precise screening studies and permitted the selection of one compound: l-OHP was submitted to our murine tumor screening system. The drug was given: (a) at doses of 1-12 mg/kg i.p. or i.v. on day 1, 5 and 9 compared to identical doses of cis-dichlorodiamine platinum II (CDDP) in L1210 bearing mice and (b) to AkR leukemia, LGC lymphoma, glioma 26, B16 melanoma, MA 16-C mammary carcinoma and Lewis lung carcinoma bearing mice at 2 dosages: 5 mg/kg (minimal effective dose on L1210), and 8 mg/kg (subtoxic dose in L1210). Acute LD10 and LD50 appeared similar to CDDP and l-OHP. l-OHP administered i.p. was more active on L1210 than CDDP. On L1210 grafted intracerebrally and on LGC lymphoma l-OHP increased significantly the lifespan while CDDP was inactive. On AkR leukemia, both drugs were active but l-OHP was less toxic. Both drugs were inactive on murine solid tumors. No renal toxicity was observed with l-OHP as compared to CDDP.

Animals↗
PubMed1985

Phase I pharmacologic study of a new Vinca alkaloid: navelbine.

Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week.

Adolescent↗
PubMed1985

Enhancement of immune responses in tumor-bearing mice after administration of cis-diamino-dichloro-platinum (II).

Following the intraperitoneal injection of cis-diamino-dichloro-platinum (II) (CDDP) into tumor-bearing mice, two immune responses were augmented. The total splenic plaque-forming cells response to sheep red blood cells and the delayed-type hypersensitivity reaction to oxazolone were higher in treated animals than in the control groups. This observation may be relevant in the establishment of clinical protocols associating CDDP and other cytotoxic drugs.

Animals↗
PubMed1985

Establishment and characterization of a new human eosinophilic leukemia cell line.

A human eosinophilic leukemia cell line, designated as EoL, was established from the peripheral blood of a patient with Philadelphia chromosome-negative eosinophilic leukemia (EL). The EoL cell line grows in single cell suspension with a doubling time of 48 hours for about one year. The reactivity of these cells was tested with a panel of monoclonal antibodies; they were found to express surface IA antigen, myeloid antigen (IF10, MY9) and membrane receptors for interleukin 2 (IL-2, Tac antigen). Under standard culture conditions, a small percentage of cells having more typical eosinophilic characteristics was present. These cells had cytoplasmic granules and were positive for Luxol-fast-blue and eosinophil peroxidase. Under culture conditions to induce the maturation of myeloid cells, such as alkaline medium or addition of dimethyl sulfoxide (DMSO), the frequency of cells with typical eosinophilic features increased to about 40%. In addition, cytogenetic studies showed that cultured cells and original leukemic blasts presented similar chromosome abnormalities. EoL seems to be a unique leukemic line committed to the eosinophilic lineage and can provide a useful in vitro model for the study of malignant eosinophilic properties.

Adult↗
PubMed1985

[Prevention of genito-anal and bucco-laryngo-esophageal cancers caused by sexually transmitted viruses].

Whilst some viruses of the Papilloma family cause warts on the skin, others infect mucosal cells. The types called 6 and 11 produce benign papillomas, called condylomata acuminata, visible to the naked eye, not only on the vulva, vagina, penis (cockscomb), but also in the anus, and occasionally the larynx, mouth (tongue) and oesophagus. Types 16 and 18 cause cervical cancer (generally called in situ) and especially very small flat lesions that can only be seen through the colposcope in women and a lens in men. These flat micro-lesions can also be found on the vulva, vaginal walls and on the glans and, balano-preputial area and shaft in males, the distal urethra, anus, larynx (especially the vocal cords), the mouth and oesophagus. These flat micro-lesions are either early cancers (here the deoxyribonucleic acid (DNA) of the virus 16 and/or 18 is integrated into the cell genome), or precancerous lesion in which case the viral DNA is not integrated. Their malignant transformation is much more frequent at the junction of the glandular and squamous parts of the cervix, than in the vulva or vagina. Co-carcinogenic factors appear to have an important role in the malignant transformation;--as for instance sexually transmissible infections including chlamydiae, bacteria that produce carcinogens such as nitrosamines, herpes virus which is known to cause mutations predisposing to the integration of the Papova viruses, chemical substances applied to the genitalia. The role of low hygiene standards in male sexual partners is the major cause (such men can carry simultaneously several sexually transmissible diseases (STD], who are never examined in search for flat lesions, who do not seek medical advice and have multiple sexual contacts with many women among whom some are more dangerous than prostitutes, especially since the wide use of hormone contraceptives and abortion that has multiplied the incidence of cervical cancer by 3 among the 20 year-old females, by 4 among the 25 year-old ones and by 2.5 among the 30 year-old ones, between 1961-65 and 1982-83. These changes in contraception have now made intra-vaginal ejaculation the rule (this not only carries viruses and other micro-organisms into the female genital tract, but also deposits sperm that contains some thirty factors that suppress local immunity). This with the rise of multiple partners, early sexual activity in particular in girls (hardly post-puberty) explains the increase of the frequency of cervical cancer in younger and younger women.(ABSTRACT TRUNCATED AT 400 WORDS)

Anus Neoplasms↗
PubMed1985

Regression of bronchial epidermoid metaplasia in heavy smokers with etretinate treatment.

40 voluntary heavy smokers (over 15 packets-years) were selected for and have completed a six months etretinate treatment on the basis of an index of metaplasia (IM) greater than 15% determined according to the following procedure: bronchoscopy with systematic biopsies in 10 sites of the bronchial tree. Each biopsy was cut into 10 sections and an IM was calculated: (Formula: see text). Etretinate, a retinoid derivative, was given orally at the daily dose of 25 mg, at the end of which they underwent a second fibroscopy protocol. A highly significant reduction of IM (p = 10(-5)) was observed after 6 months of treatment for those of the patients who maintained their smoking habits during treatment. Besides, the 4 patients who stopped smoking while under treatment and are excluded from the statistical analysis, all had a complete regression of metaplasia at the second fibroscopy. No morbidity was due to etretinate or fibroscopy. Etretinate significantly reduces potentially precancerous bronchial epidermoid metaplasia in heavy smokers. Its association with smoking arrest may induce a rapid restoration of bronchial epithelium to normal.

Carcinoma, Bronchogenic↗
PubMed1985

A histological assessment of the four-day subrenal capsule assay (SRCA).

A four-day subrenal capsule assay (SRCA) was developed, since fragments of human tumours implanted under the renal capsule of immunocompetent mice became rejected by the host within six days. The assay requires a histological assessment of both its exploitability and the extent of drug-induced anti-tumour lesions. 45 tumours from 43 patients with solid tumour were submitted to an SRCA in 1410 male B6D2F1 mice. After being biopsied each tumour was dissected by a pathologist, cut into 50 pieces (1.5 mm3), and one piece was implanted under the renal capsule of 35 mice; the mean tumour diameter was measured on day 0. The mice were randomized into groups of 6 to 10 animals each. On days 1, 2 and 3, the mice were treated with either placebo (control group) or with various anticancer agents. On day 4 the animals were sacrificed, the mean tumour diameter measured, the tumour bearing kidney fixed in Bouin's picroformol solution and processed for histological analysis after staining with hematein. Fragments of fresh explants of human tumours retained their proliferative and metabolic capacity: mitoses were observed as well as keratinizing cells in epidermoid carcinomas and melanin-producing cells in melanomas. Proliferation of tumour cells was seen along the renal capsule suggesting their affinity for connective tissue. Capillaries filled with mouse erythrocytes were also seen. No or minimal lymphocytic infiltration was found. Drug oncolytic effects ranged from minor cellular degeneration to almost complete necrosis and were documented by the scoring of histologic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Lymphoid leukemia and non-Hodgkin's lymphoma type continuum, superimposed to lymphocyte differentiation step continuum. A proposition for a revised W. H. O. lympiioid leukemia-lymphoma categorisation.

We have classified 200 cases of lymphoid leukemia and non-Hodgkin lymphoma (LL and L) typed with as many monoclonal antibodies as possible for each case in the WHO Leukemia and Lymphoma categorisation modified according to the today knowledge of normal cell differentiation. We have found that the lymphoid acute leukemias correspond respectively to normal differentiation steps: the [microblastic] to the polyvalent stem cell TdT+, Ia+, B4- or to the lymphoid progenitor TdT+, Ia+, B4-; the [prolymphoblastic T] to the prothymocyte TdT+, OKT11+, OKT10+, 9+, 6-, 4-, 8-; the [prolymphoblastic non T] to the B precursor B4+, B1+, J5+, C mu-, sIg-; the [T-macrolymphoblastic] to the OKT6+ thymocyte; the [B-macrolymphoblastic] to the large pre-B C mu+; the [prolymphocytic T] to the OKT6-, 3+, 4+ and 8+ thymocyte; the [prolymphocytic B] to the small pre-B C mu+; the Burkitt's leukemia to a pre-B cell transformed into a lymphoblastoid cell sIg mu. The B-CLL is constituted of sIg mu+, gamma-, Ia+, B4+, B1+, FC+ virgin lymphocytes and the T-cell either of OKT3+, 4+ or of 8+ peripheral T-lymphocyte, the mantle zone B- lymphoma is constituted of sIg mu+, FC- primary lymphocytes. The B-centro-follicular lymphomas are made of sIg mu+, delta+, gamma+ either small cell cleaved, or large cell. The Burkitt's and non-endemic Burkitt's lymphomas are made of transformed cells into sIg mu+ lymphoblastoid B-cells. We have described a non-blastic, non-Burkitt's, non-follicular, medium cell lymphoma sIg+. The B-immunoblastic lymphoma is sIg mu+, delta-, gamma+, FC+.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1985

Ultrastructural appearance of malignant non-Hodgkin's lymphomas and lymphoid leukemias.

In this report the authors show the main ultrastructural features of malignant non-Hodgkin's lymphomas and lymphoid leukemias, trying to outline the more important findings useful to diagnostic purpose. Since, from an immunologic point of view, lymphoid malignancies reflect the main steps of normal B and T ontogenesis, the various tumours are progressively presented in relation to their stage of phenotypic differentiation. An exact knowledge of the potential information from electron microscopy and its intrinsic limitations, including the high cost and the time expense, permit a correct use of this investigation in diagnostic procedure in lymphoid malignancies.

Antigens, Surface↗
PubMed1985

Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil combined with high-dose folinic acid. An update.

Sixty-six patients with advanced colorectal adenocarcinoma and 24 with advanced gastric adenocarcinoma were treated; all had measurable tumors. The treatment was based on biochemical and cell culture studies which have demonstrated that an excess of intracellular reduced folates is necessary to provide optimal inhibition of thymidylate synthetase and to increase the cytotoxic effect of fluoropyrimidines. The treatment comprised 5-fluorouracil (5-FU) (370-400 mg/m2/day) and high dose folinic acid (200 mg/m2/day) given simultaneously for 5 consecutive days with a 21-day interval between courses. Of the 66 patients with colorectal carcinoma, 44 had not been previously treated with cytostatics and 22 were resistant to previous chemotherapy with 5-FU given either as a single agent or combined with other drugs. The response rates both complete (CR) and partial (PR) were 45% and 18% in the previously untreated and the previously treated patients, respectively. Time to disease progression in the 20 previously untreated patients ranged from 2 to 34.5+ months (median, 10.3 months) and that of the 4 patients previously resistant to 5-FU was 7, 10, 12 and 15 months, respectively. Median survival for the 24 responders was 20.4 months. Survival in responders was significantly superior to that observed in patients with progressive disease (P less than 10(-8)). Of the 24 patients with gastric adenocarcinoma, 23 had not been previously treated with cytostatics and one was resistant to a 5-FU containing regimen. The response rate (CR + PR) was 50% (12 patients). The single previously treated patient failed to respond. Time to disease progression in the 12 responders ranged from 2.1 to 28.9 months (median, 5.6 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1985

Decrease of metastatogenic potential by pregraft treatment of Lewis lung carcinoma cells with proteinase and protein kinase affinity labels.

Three synthetic irreversible enzyme inhibitors (75 microM di-iso-propylphosphorofluoridate (DFP), 310 microM N alpha-p-tosyl-L-lysine (TLCK) and 240 microM L-1-tosylamide-2-phenylethyl (TPCK) chloromethyl ketone), as well as the transition state analogue chymostatin, inhibit the development of Lewis lung adenocarcinoma (3LL) in C57 BI/6 mice, when 3LL cells are treated once and for a limited period (60 min) prior to grafting. These compounds demonstrate divergent protease specificity and, in the case of TLCK and TPCK, convergent reactivity toward the highly conserved protein kinase catalytic subunit. Using 200 microM chymostatin and low doses (25-40 microM) of the irreversible enzyme inhibitors, the antimetastatogenic effect is revealed to be specific, as primary tumor development is not affected. Although no direct experimental evidence can be forwarded, our results fit with the concept that the motile metastatogenic 3LL cells may constitute a phenotype which, in contrast to the resident cells from the primaries, responds to these enzyme inhibitors in a highly sensitive manner.

Affinity Labels↗
PubMed1985

Circadian rhythm in tolerance of mice for etoposide.

Etoposide (40 mg/kg/day X 3 days and 60 mg/kg/day X 3 days) was best tolerated by male B6D2F1 mice when given in the second half of the rest span of their sleep-wake circadian cycle. Such a time-qualified treatment resulted in increased long-term survival rate, highest peripheral leukocyte count at nadir, and lowest body weight loss, as compared to results from drug dosing in the activity span. Assuming that such results may be extrapolated to human beings, the treatment time of etoposide associated with an optimal tolerance would be located in the second half of the sleeping span (usually near 5.00 hrs).

Animals↗
PubMed1985

[Bacteriological study of hygienic conditions in the Department of Blood Diseases and Tumors of the Paul Brousse Hospital at Villejuif. I. The atmospheric flora].

Admission to hospital considerably increases the risk of cross infection. The sources of contamination are of exogenous origin (airborne flora) or endogenous (intestinal flora). Because of the great susceptibility of immunosuppressed patients to microbial agents, it is essential to treat them in a special environment in which there is rigorous attention to hygiene and asepsis. In order to ensure these optimal conditions have been attained, we have made a bacteriological survey for several months in the Service des Maladies Sanguines et Tumorales of the Paul Brousse Hospital, Villejuif. The first part of the survey has given an assessment of the efficiency of the positive pressure air filtration system in one of the units on the Service. Although it should not be neglected, the airborne microbial flora appears to have only a slight effect on the development of infections in our patients. By contrast, the endogenous flora is the main source of infection. Apart from infection via intravenous drips, it is essentially transmitted by direct contact with the nurses' hands or via a variety of instruments. On account of its importance the direct transmission will be described in the second part of this report.

Air Microbiology↗