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Biomedical subjects

G Mathé

Publications and source records attributed to G Mathé.

At least 55 records · Page 3Linked to original sources
PubMed1997

Apoptosis: an identical central or collateral mechanism in the development, function and death of neurons.

The author shows that the previously known and recently re-described and explained process called apoptosis, or program cell death, applies not only to the morphologic and functional development of the embryo and the organism at any age, but as well to the induction and/or promotion of many major diseases. The death of cells which do not disappear mitotically being replaced by two daughter cells, the neurons, serves as an example of the extremely important role of apoptosis in the mechanisms of neuro-psychiatric diseases, which merits to create as much research interest as mitosis has generated.

Apoptosis↗
PubMed1997

Is the study of human cancer-associated factors, the best or the only model for human carcinogenesis research? I. The question of Helicobacter pylori infection as an accused human gastric carcinogen.

Experimental carcinogenesis has discovered and analyzed the inductive effect for one type of cancer, of single factors in given animal strains. Human carcinogenesis analyses the effect of associated factors on one cancer type incidence. It does not find any direct correlation and finds a lot of intermediary effects and mechanism between the factor and established carcinogenesis. Regarding Helicobacter pylori (HP), one realizes there is no statistical correlation between gastric infection and carcinoma. The only data which sustain its role is its possible effect in promoting atrophic gastritis with intestinal metaplasia, via the serum pepsinogen 1 reduction due to anti-HP immunoglobulin A (IgA) antibody. Intestinal metaplasia of the stomach is a condition increasing cell proliferation.

Biomarkers, Tumor↗
PubMed1997

Immunity aging. I. The chronic perduration of the thymus acute involution at puberty? Or the participation of the lymphoid organs and cells in fatal physiologic decline?

The author has focused the subject on the perduration of puberty thymus involution as a cause of immunity aging, a term in which he does not include senescence. The decrease between immune reactions against HIV1 at 25 years of age and those at 35 is considerable; the decrease is also indirectly revealed by spontaneous tumor exponentially growing incidence after 40 years in man and its equivalent, 16 months in mice: the immunity parameters indicate a regression correlated with this incidence growth. He regrets the neglect of suppressor cell and anti-idiotype problems by the basic immunologic research. Given the role of cofactors non specifically related to the antigen, such as that CD28 and its ligands, he suggests the interest to approach immunology via the science of chaos and fractals, which would be more appropriate than classical methodology to study highly complex phenomena on which apparently minimal interventions may induce considerable effects.

Adult↗
PubMed1996

Lysosomal exocytosis induced by hyperthermia: a new model of cancer death. III. Effect on liver metastasis.

The purpose of the present study was to evaluate by morphological approaches (light and electron microscopy), the effect of hyperthermic treatment in one case of human liver metastasis. The results demonstrate that hyperthermia causes a significant reduction of the metastatic cells circulating into sinusoids and the "normalization" of the hepatocytes substructure. The data are consistent with a direct and/or indirect action of the temperature on the presence of infiltrating tumor cells. Particular importance is attributed to a general activation of lysosomes present in neoplastic cells, Kupffer cells and hepatocytes.

Cell Death↗
PubMed1996

The last revised "Euro-American classification" of lymphoid leukemias and non-Hodgkin's lymphomas: the same inaccuracies and inconsistencies in a chaotic complexity.

After a review of the recent physiologic, cellular genetic and molecular genetic acquisitions, a critical comment of the proposed classification is presented concerning especially a) the inclusion in the so-called "precursor B-lymphoblastic leukemias", which are pre-B neoplasias, of Burkitt's leukemic lymphoma, the cells of which are sIg+, hence B and not pre B; b) the inclusion in the chronic B lymphocytic leukemia of the so-called Galton's "prolymphocytic" leukemia, the cells of which are also sIg+, thus B and not pro B. In fact, the transformed blastoid medium size cells of this leukemia present the markers of the plasmablasts, which are the precursors of the long-lived plasma cells and migrate from the lymphoid tissue T-zone to bone marrow, where they secrete IgD, or G, or E, or to the mucosae, where they secrete IgA. Thus the so called "B-prolymphocytic leukemia" is the leukemic conversion of the (blastoid medium size cell) plasmablast lymphoma. There is in the new classification, a "large cell lymphoma" entity, which makes redundance with the "large cell follicle centre lymphoma". This large cell lymphoma representes a heterogen complex, as it includes the B-immunoblastic lymphoma which is not presented as an entity. As far as T lymphomas are concerned, it is not indicated that the CD8 cells may be CD57 + or - , and CD28 + or -. It could be mentioned that the cytotoxic T-cells are CD8+ C57- CD28+, while the suppressor T-cells are CD8+ CD57+ CD28-.

Humans↗
PubMed1996

Will killing the last HIV1 particle cure AIDS patients? Doesn't CMV activation and/or a graft-versus-host component of the disease, also have to be considered? I. First of two parts.

Before the discovery of HIV1 and HIV2, I proposed as the mechanism of HIV1-AIDS complex, a graft versus host reaction (GvH) induced by transfusion or seringe or sexual act blood transferred lymphocytes: this was based on the clinical, pathological and biological, and especially immunological similarities. I have treated ten HIV1-AIDS complex patients in the last phase with five virostatics, distributed in three week sequence combinations of 3 or 4, each differing from the preceeding and following ones. After follow-up between one and three and a half years, the results can be summarized as such: when the viral loads fall below the detectable level, the CD8+ CD57+ suppressor T-cell and CD8+ CD57- cytotoxic T-cell numbers tend towards normal levels (approximately 200/mL), but the CD4 counts go up to a maximum of only 394, far from the normal level (800). Moreover, none of these subsets present a significant coefficient of correlation with the HIV1 load, which indicates that these immunologic markers and the viral one provide different information. I suggest the hypothesis according to which HIV1-AIDS complex comprises other components than HIV1 infection, such as a) the evoked GvH, which would occur early enough and might explain this CD4 incomplete restoration by virostatics, and b) cytomegalovirus (CMV) activation which occurs later. The second part of this editorial review will be published in a part II of the "Dossier" on AIDS. It will be devoted to the discussion of GvH and CMV infection systematic treatments.

AIDS-Related Opportunistic Infections↗
PubMed1996

AIDS therapy with two, three or four agent combinations, applied in short sequences, differing from each other by drug rotation. I. First of two parts: a phase I trial equivalent, concerning five virostatics: AZT, ddI, ddC, acriflavine and an ellipticine analogue.

We have individually treated ten AIDS patients whose CD4 numbers were inferior to 200/mm3, with the five following HIV1 virostatics: a) azido-deoxythymidine (AZT), dideoxyinosine (ddI) and dideoxycytidine (ddC), which affect the same viral target, retrotranscriptase, b) acriflavine (ACF) and methyl-hydroxy-ellipticine (MHE) which we have discovered to be strong virostatics in vivo, in mice, against Friend's virus, and in man, against AZT resistant HIV1. We have shown that their combinations with AZT, hitting three viral targets, reduces in mice, the blood Friend's virus load below detectable level. Due to the short doubling time of HIV1, AIDS therapy must be continuous, and to allow the best tolerance, the five virostatic combinations were applied in short, three-week sequences, each differing as much as possible from the former and from the following one, due to drug rotation [1]. Among the ten patients, a) three received the two-drug combinations for 15 to 30 months, followed by the three-drug combinations, b) three received the three-drug combinations from the beginning, c) four received the four-drug combinations also from the beginning, two having less than 10 CD4/mm3 at initiation of treatment, and two having more than 100. The tolerance was remarkable: the only side-effect being macrocytosis. The application of the two-drug combination sequences maintained stable CD4 levels in two subjects whose viral load (the evaluation of which had became available) was, at the end of this period, of 4,486 and 39,238 RNA copies. The third subject who had received, an intensive UV irradiation for a psoriasis, presented an irreversible decrease in his CD4 count and a high viral load (1,352,495 RNA copies/mL) at the end of the two-drug period. Fifteen to 25 months after the shift to the three-drug combinations, the viral load decreased, from 39,328 to 13,291 in one of the non-UV irradiated subjects, and from 1,352,495 to 314,387 in the irradiated one. No subject had an increase in CD4 number. In the three patients having initially received the three-drug combinations, a very strong decrease of viral load was registered after periods of observation varying from 77 to 40 months, while the CD4 counts increased moderately in two subjects, and noticeably in the third (from 126 to 266). Out of the four subjects initially treated with four-drug combinations, the two with less than 10 CD4/mm3 had a moderate decrease in viral load in about three months, and the CD4 increased from 9 to 34/mm3 in one. But the two subjects, because of opportunistic infections and psychological reasons, abandoned their treatments. In the two subjects who had more than 100 CD4/mm2 at initiation of the four-drug combination treatment, the viral load decreased to undetectable levels after four months: but their CD4 counts, after some oscillations, had very moderately increased at the end of the observation period (respectively, from 200 to 222, and from 129 to 134). In practice, these results suggest the interest of conducting phase II or III studies of AIDS treatment protocols, starting with the four-drug combination model, and attempting to maintain the effect with the three-drug combination one. As for theoretical considerations, one must underline the contrast between the remarkable reduction of the viral load and the usually moderate increase of the CD4 counts. The study but not the trial has been interrupted, due to the unavailability of three antiproteases, saquinavir, ritonavir and indinavir, which are now introduced in the same type of combinations, one by one, in replacement of one of the studied agents as shown in figure 1. The effect of increasing the total number of virostatics from five to eight will be published in the second part of this article series.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The medium cell sIg+, proplasmocytic lymphoma/leukemia. Positive and differential diagnosis with other B-lymphoblastoid neoplasias.

The authors describe the neoplasia of the only cell of the B-lymphocytic differentiation step, of which no lymphoma has yet been described: the cell intermediary between the memory B cell of the mantle zone, and the long-lived, marrow migrating and IgD or IgG secreting plasma cell, or mucosae migrating IgA secreting plasma-cell: they describe its neoplasia under the name of "medium cell cmu- sIg+ proplasmocytic lymphoma". It is defined by four characters: a) the homogeneous medium sized lymphoblastoid cells with one nucleolus per cell; b) the cmu- sIg+ marker as well as the CD38 and CD22; c) the t(11;14) translocation; and d) the poor prognosis and rapidly fatal evolution with a rapid conversion to the leukemic phase. The latter has probably been described, when the diagnosis is only made at this stage, as "B-prolymphocytic leukemia", which is nonsense, as the pre B-cells are cmu+ sIg-.

Aged↗
PubMed1996

Will killing the last HIV1 particle cure AIDS patients? II: Second Part. Decrease of viral load and of T-suppressor cells, and increase of the cytotoxic cells, without effect on CD4, after the use of 10 virostatics applied in 3 or 4 drug combinations of different sequences. The time for CD4 immunotherapy?

We reported in the first part of this editorial and in an article AIDS therapy with five HIV1 virostatics applied in two then three, or initially three, or initially four agent combinations, given in 3 week sequences differing from each other due to drug rotation, the contrast between: a) the decrease of viral load, possible below the detectable level, b) the absence of effect on the helper CD4+, the CD8+ C57- cytotoxics and the CD8+ C57+ suppressor cells. We proposed a thesis according to which the HIV1-AIDS complex might have another pathogenic component other than HIV1, ie, a microchimerism graft-versus host reaction (GvH) or an autologous GvH-like reaction. Shifting from five to 10 virostatics owing to the availability of lamivudine or 3TC, stavudine or d4T and three HIV1 protease inhibitors, saquinavir, ritonavir and indinavir, applied according to the same modality, we have enhanced the reduction of viral load, and significantly decreased the CD8+ C57+ suppressor cell counts, and increased those of the CD8+ C57- cytotoxic cells. This result which indirectly shows the role of HIV1 in the increase of suppressor CD8+ cells, hence in the late loss of immune memory and of opportunistic infections, reinforces the thesis of a role, in AIDS pathogenesis, of a latent GvH reaction activated by HIV1 primo-infection, and its evolution from the hyperplastic phase to the hypoplastic one, which, inducing severe immune suppression, is responsible for HIV1 active infection relapse after the so-called latent phase. Hence the proposition we make, of an indication of CD4 modulation with non specific immunotherapy by bestatin, of which we showed the effect in another population of HIV1-AIDS complex patients. Its effect can be potentiated by tuftsin. When the suppressor cell number goes up over that of the cytotoxic one after the HIV1 active infection relapse, interferon gamma could be added, which, by amplifying the CD28 pathway on CD8+ cytotoxics, while suppressor cells lack CD28, which might reestablish a ratio of suppressor over cytotoxic cells nearer to normal. It remains that the role of the five secondarily included agents in the decrease of suppressor cells will only be attributed with certainty and entirely to their virostatic effect, if it is shown that none of them exerts a selective anti-suppressor cell action.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration.

PURPOSE: To determine the long-term impact on disease-free survival (DFS) and overall survival (OS) of adjuvant anthracycline-based chemotherapy, when prospectively compared by random allocation with standard cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive (N+) breast cancer patients. PATIENTS AND METHODS: Two hundred forty-nine patients with N+ breast cancer, recruited from eight French cancer centers, were randomized to receive 12 monthly cycles of adjuvant chemotherapy, either CMF (n = 112) or doxorubicin, vincristine, cyclophosphamide, and fluorouracil (AVCF) (n = 136). All had a negative metastatic work-up before inclusion, which was stratified by accrual center, tumor stage (International Union Against Cancer [UICC]), and menopausal status. RESULTS: No severe adverse effect related to grade 4 (World Health Organization [WHO]) toxicity was observed. There was no difference in second primary tumor incidence between the two arms. The treatment given was 88% of planned for AVCF and 75% for CMF in both premenopausal and menopausal patients. With a median follow-up time of 16 years (range, 13 to 17), the OS and DFS rates are significantly longer in the AVCF arm (56% v 41% [P = .01] for OS, and 53% v 36% [P = .006] for DFS). These differences are significant, irrespective of tumor stage (T1 to T2 v T3 to T4), and remain positive in patients with or without postoperative locoregional radiotherapy (55% of cohort). When analyzed according to menopausal status, the differences remain significant only for premenopausal patients. CONCLUSION: This set of mature controlled data confirms the added value of anthracycline-based combination adjuvant therapy for N+ breast cancer patients when compared with CMF, with both regimens given for 1 year.

Adult↗
PubMed1995

Can an adjuvant treatment or a pharmacologic prevention be common to several diseases? The case of those associated to neuromediator defects.

The author has tried to extrapolate on several neurological diseases of the ageing, Knoll's proposition to treat Parkinson's disease chronically for relapse prevention, by MAO-B. At this occasion, the author makes a critical review of the clinical trial results concerning the new different series of depression treatments, as most authors propose today to use some new ones not only in depression, but in Parkinson's and Alzheimer's diseases and in ageing.

Aging↗