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Biomedical subjects

J Bernier

Publications and source records attributed to J Bernier.

At least 19 recordsLinked to original sources
PubMed1992

Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis.

During human immunodeficiency virus (HIV) infection there is a profound and selective decrease in the CD4+ population of T lymphocytes. The mechanism of this depletion is not understood, as only a small fraction of all CD4+ cells appear to be productively infected with HIV-1 in seropositive individuals. In the present study, crosslinking of bound gp120 on human CD4+ T cells followed by signaling through the T cell receptor for antigen was found to result in activation-dependent cell death by a form of cell suicide termed apoptosis, or programmed cell death. The data indicate that even picomolar concentrations of gp120 prime T cells for activation-induced cell death, suggesting a mechanism for CD4+ T cell depletion in acquired immune deficiency syndrome (AIDS), particularly in the face of concurrent infection and antigenic challenge with other organisms. These results also provide an explanation for the enhancement of infection by certain antibodies against HIV, and for the paradox that HIV appears to cause AIDS after the onset of antiviral immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Combined effects of selected insecticides on humoral immune response in mice.

Biological effects data with single insecticides are far more abundant than with mixtures. These data cannot be used directly to predict the effects of insecticide mixtures. Three insecticides of different chemical classes: organochlorine; dieldrin, organophosphate; malathion, and carbamate; carbofuran, previously evaluated for their immunotoxic potential, were selected for studies of combined acute exposure in C57B1/6 inbred mice. The humoral response to sheep red blood cells (SRBC) and the functional activities of peritoneal macrophages, such as phagocytosis of fluorescent beads and presentation of a single protein antigen, avidin, were examined after in vivo exposure of mice to different combinations of the selected pesticides and compared with the vehicle controls. Regarding exposure to single substances, the data confirmed the immunosuppressive potential of dieldrin and carbofuran and the immunopotentiating effect of malathion. Following the acute concomitant exposure to dieldrin/carbofuran mixture, however, values for the parameters of antigen presentation, primary IgM antibody response to SRBC antigen, and macrophage phagocytosis, returned to control or above-control values, indicating a lack of any synergistic or additive effects of the chemicals on the immune response. Thus, it was concluded the dieldrin/carbofuran mixture had an antagonistic effect on the humoral response to SRBC and the macrophage phagocytic activity, in comparison with the action of administration of each of the insecticides alone.

Animals↗
PubMed1991

Evaluation of the immunomodulatory potential of diethyl dithiocarbamate derivatives.

The cytotoxicity, immunotoxicity and immunomodulatory potential of four dithiocarbamate derivatives were assessed and compared with the effects of Immuthiol (diethyl dithiocarbamate, DE-DTC) in mice. Cellular stimulation and cell viability were examined after in vitro exposure of spleen lymphocytes to selected DTC analogues: N-methyl-D-glucamine dithiocarbamate (NMG-DTC), dimethyl dithiocarbamate (DM-DTC), dibuthyl dithiocarbamate (DB-DTC) and diisobuthyl dithiocarbamate (DIB-DTC). Lymphocyte activation by plant and bacterial mitogens: concanavalin A (Con A), phytohaemagglutinin (PHA), lipopolysaccharide (LPS) and allogeneic stimulation of cells in mixed lymphocyte reaction (MLR) were examined in vitro in the presence of 10(-4)-10(-9) g/ml DE-DTC and other selected DTC derivatives. No direct in vitro lymphoproliferative activity of DTC derivatives was observed, although a relatively stronger cytotoxicity with DE-DTC and DM-DTC was noted. In addition, the in vivo effects of DTC derivatives were examined by cytofluorometric profile of splenic and bone marrow cells as well as in mitogenic and allogenic responses, after i.v. exposures of animals to two subsequent (25 mg/kg b.w.) doses of the chemical. Less cytotoxic DIB-DTC, NMG-DTC and DB-DTC expressed weak in vivo immunostimulatory potential when compared with the effect of DE-DTC, whereas the effects of DM-DTC on alloantigenic and mitogenic lymphocyte stimulation were comparable with the known effects of DE-DTC. Cytofluorometric studies showed that the number of cytotoxic/suppressor T-cells (Ts) and helper T-cells (Th) in the cell was increased by DE-DTC and NMG-DTC only. In addition, DM-DTC appeared to affect the Ts/Th ratio. DE-DTC did not affect the B-cell subpopulation, whereas other derivatives induced marked modifications of the pre-B-cell subpopulations in bone marrow. Our data suggest that in vivo the immunostimulatory effect of DM-DTC could be accompanied with major changes in bone marrow B-cell frequency and alteration of spleen Ts/Th ratio.

Adjuvants, Immunologic↗
PubMed1991

Bayesian statistics as applied to hypertension diagnosis.

This paper deals with the following hypertension diagnoses: essential hypertension and five types of secondary hypertension: fibrodysplasic renal artery stenosis, atheromatous renal artery stenosis, Conn's syndrome, renal cystic disease, and pheochromocytoma. Only blood pressures, general information and general biochemical data are taken into account. Nineteen items were finally selected, by statistical investigation of experimental data, as being both discriminative and independent. The marginal density distributions of every item, and then joint density distribution functions were determined within six types of hypertension. The frequency of a given hypertension type within the hypertensive patients was used as prior probability of this state. The loss matrix was established by medical arguments. The expected loss corresponding to six possible decisions could thus be calculated for all cases. Both the ratio of secondary hypertensions that could be inferred from our set of data (not including the results of complementary tests) and that of correct "essential" hypertension diagnosis proved to be satisfactory.

Bayes Theorem↗
PubMed1990

Morphogenesis of endoplasmic reticulum in Xenopus oocytes after microinjection of rat liver smooth microsomes.

We have determined the kinetics of endoplasmic reticulum (ER) reconstitution following insertion of rat-liver smooth microsomes (SM) into Xenopus oocyte cytoplasm using electron microscopy as well as cytochemistry and thick-section 3-dimensional reconstruction. Oocytes were fixed 0, 10, 20, 40, 80, and 120 min after microinjection with SM and processed for thin- and thick-section electron microscopy. At 0 min postinjection, rat liver SM were observed as small vesicles and were loosely dispersed amongst oocyte organelles. At 10 min, tubules were discerned among many elongate vesicles; and these structures comprised large cytoplasmic regions delimited by mitochondria and yolk platelets. By 20 min, segregation of transplanted organelles yielded yolk-platelet-free regions composed of few vesicles but increasingly numerous, long and anastomosing tubules. By 40 min, a network with numerous tubular branches and fenestrations was observed among the few remaining vesicles. By 80 min, transformation of rat liver SM into a complex network of branching and anastomosing tubules was complete. Three-dimensional reconstruction revealed the network to be composed of interconnecting elements consisting of anastomosing tubules. The reconstituted network of anastomosing tubules in Xenopus oocytes was compared to the network of anastomosing tubules in rat liver hepatocytes and was found to be essentially identical. Network formation occurred in oocytes pretreated with either vinblastine (40 microM) or nocodazole (0.166 microM), and network organization was maintained in oocytes treated with the same drugs after microinjection and reconstitution. We conclude that SM retain sufficient molecular information for rapid self-assembly into structures resembling those in the cells from which they were derived. Both the assembly and maintenance of ER structure in oocyte cytoplasm are microtubule-independent. The formation of such structures following microinjection of SM into living cells provides a unique assay for this type of membrane subfraction.

Animals↗
PubMed1990

Further analysis of the time factor in squamous cell carcinoma of the tonsillar region.

Recently, Bataini et al. reported that overall time was the major treatment-related determinant of local control in 465 squamous carcinomas of the tonsillar region. They did not, however, quantify the relationship or relate it to the doubling time of tumorigenic cells, except qualitatively. This note reports an attempt at that quantification.

Carcinoma, Squamous Cell↗
PubMed1990

A new method based on cobalt for histochemical and cytochemical demonstration of glucose-6-phosphatase activity.

We describe a novel technique for the histochemical and cytochemical demonstration of glucose-6-phosphatase activity. In this method, lead is replaced by cobalt. After activity of glucose-6-phosphatase, cobalt phosphate Co3(PO4)2 is formed, and in the presence of ammonium sulfide (NH4)2S, the precipitate is transformed into a sulfide that fixes osmium and provides good electron density. Glucose-6-phosphatase activity was determined mostly in rat kidney cells, but controls were also performed in liver cells. A strong reaction was seen in proximal tubule cells, but the reaction was weak in distal convoluted tubule cells. This technique showed the same endoplasmic reticulum (ER) organization in proximal and distal nephron as that seen with the osmium impregnation technique. In collecting tubules, intercalated cells had irregular reactivity, while principal cells had none. Our results indicate that the cobalt technique is valid, reliable, and sensitive enough to detect low glucose-6-phosphatase activity. Moreover, the technique can be used with 1-mm-thick specimens and obviates the need for use of frozen tissue sections.

Animals↗
PubMed1990

Impact of cervical disease and its definitive radiotherapeutic management on survival: experience in 2013 patients with squamous cell carcinomas of the oropharynx and pharyngolarynx.

Two thousand thirteen patients with squamous cell carcinoma of oropharynx and pharyngolarynx were reviewed with regard to neck disease presentation and disease-free survival after radical radiotherapy. All patients were staged according to both the AJCC 1976 and the UICC 1978 classifications. Causes of failure, disease-free survival, and complication rates were assessed. Sixty percent had a clinically positive neck. The 3-year disease-free survival rates were 58%, 44%, 38%, and 25% for AJCC N0, N1, N2, and N3 cases, respectively. Corresponding UICC figures were 58%, 46%, 26%, and 29%. Analyzed parameters were nodal stage, size, site and fixity, and location of primary. Complications attributed to neck disease did not exceed 3%. A critical appraisal of the nodal staging systems is derived from these sets of data.

Carcinoma, Squamous Cell↗
PubMed1989

Effect of factors unrelated to tissue matching on corneal transplant endothelial rejection.

We examined 348 consecutive adult recipients of a corneal transplant for clinical signs of an endothelial rejection episode in a single-center follow-up study. The variables studied included primary diagnosis, number of previous corneal transplants, previous transplant failures from rejection episodes, transplant size, recipient corneal vascularization, donor age, recipient age and sex, past blood transfusions, and number of pregnancies. Five important risk factors were identified: primary diagnosis of herpetic, interstitial, or traumatic keratitis; transplant size 8 mm and larger; more than one previous corneal transplant; recipients younger than 60 years of age; and the presence of recipient corneal vascularization. This information will serve eventually for analyzing the effect of donor recipient tissue matching on corneal transplant rejection.

Adolescent↗
PubMed1989

A multivariate primary tumour control analysis in 465 patients treated by radical radiotherapy for cancer of the tonsillar region: clinical and treatment parameters as prognostic factors.

Out of a consecutive series of 698 cases of squamous cell carcinomas of the tonsillar region treated by radical megavoltage radiotherapy, a determinate group of 465 cases remained eligible for a multivariate analysis of the pretreatment features of the disease and treatment-related parameters predictive of lasting control of the disease at the primary site. T-stage and initial site within the tonsillar region, were the significant pretreatment factors. Tumours arising from the glossopalatine sulcus which are characterized by involvement of the tongue, do significantly worse than those arising from other sites within the tonsillar region: i.e. the tonsil itself, posterior pillar and to a lesser extent the anterior pillar. As regards treatment-related parameters in the 465 cases which received tumour doses of at least 55 Gy, only the length of overall treatment time was found to be predictive. Combining both pretreatment and treatment variables, T-stage (p less than 0.0001), overall treatment time (p less than 0.0001) were by decreasing order of significance the predicting factors, followed by initial site (p = 0.006). When present, tumour extension to the anatomical structures anterior to the tonsillar region was also found to be significant (p = 0.05). Based on these factors, a multivariate model was constructed and tested by estimating the product-limit survival of the various categories of patients. Four groups are individualized with 3 years local control rates ranging from 90 to 21%. The predictive accuracy of the model was assessed by log-rank test significance levels. The model may help to select patients for whom conventional radical radiotherapy is inadequate, and combined modality or altered fractionation regimes should be tried particularly for advanced tumours of the glossopalatine sulcus, and any case with significant invasion of the oral cavity.

Carcinoma, Squamous Cell↗
PubMed1988

Primary radiotherapy of squamous cell carcinoma of the oropharynx and pharyngolarynx: tentative multivariate modelling system to predict the radiocurability of neck nodes.

In a series of 1251 cases of squamous cell carcinomas of oropharynx and pharyngolarynx with clinically positive neck and treated primarily by radiation therapy a determinate group of 798 cases remained eligible for a multivariate analysis of the prognostic factors related to the regional outcome. Node size (p less than 0.0001), node fixity (p = 0.016) and T stage (p = 0.02) were the significant pretreatment factors independently predictive of neck node control. when regarding the treatment modalities in this determinate group of patients who received tumor doses of at least 55 Gy, only the treatment duration was found to be predictive (p = 0.002). Based on these factors, a multivariate model was constructed and tested by estimating the product-limit survival of the various groups of patients. The predictive accuracy of the equation was assessed by the log-rank test significance levels. The model may help to select, in many clinical situations, the appropriate approach of the management of metastatic neck disease, either by definitive radiation therapy or by combined modalities.

Analysis of Variance↗
PubMed1988

Transient inhibition of mixed lymphocyte reactivity by dieldrin in mice.

Dieldrin, a non-aromatic organochlorinated pesticide, was shown to be a potent modulator of the immune system. We had earlier demonstrated that mice treated with a single sublethal dose of dieldrin showed an impaired antibody response and reduced viral restriction mediated by macrophages. These dieldrin-induced immunosuppressive effects were shown to be dose dependent, when administered by the oral or intraperitoneal (i.p.) route. This study was undertaken to investigate the effect of dieldrin on the T-cell immune response. Lymphoid cells from mice injected i.p. 7 days earlier with 36 mg/kg body weight (0.6 LD50) dieldrin were assessed for their ability to recognize a foreign antigen and to proliferate in a mixed lymphocyte reaction (MLR) at 4, 7, 14 and 24 days post-treatment. We have demonstrated a strong but transient inhibition of MLR at 7 days after pesticide exposure. This effect was reversible and could not be attributed to a direct cell cytotoxicity, nor to the modulation of the T-cell ratio in lymphoid organs. Since the mitogen response was not impaired at this time point, we suggest that T-cell ability to recognize a foreign antigen can be altered by dieldrin, but not the proliferative potential of the cells.

Animals↗
PubMed1988

Abrogation of graft-versus-host reaction by dieldrin in mice.

Sublethal exposure to the organochlorine pesticide, dieldrin, decreased the T-cell immune response in mice. Indeed, a transient inhibition of the mixed lymphocyte reactivity (MLR) was noted at 7 days after intraperitoneal exposure to 0.6 LD50 dieldrin. The present study was undertaken to further investigate the effects of dieldrin on the T-cell immune response, using the graft-versus-host reaction (GVHR) as a model, in order to assess T-cell subset efficiency. Lymphoid cells of A/J mice injected intraperitoneally 7 days earlier with 36 mg/kg body weight dieldrin were transferred into H-2-incompatible F1 hybrids. With this model, known to induce a marked GVHR, we have observed that dieldrin inhibited the potential of parental cells to induce a GVHR in hybrid mice. This effect could not be attributed to a direct cell cytotoxicity, nor to the modulation of major T-cell subsets as shown by thymic and peripheral T-cell subpopulation analysis. Collaboration processes between these cellular subsets seem to represent a potential site for the dieldrin-induced suppression.

Animals↗
PubMed1988

[Contingent negative variation and regional cerebral blood flow in senile dementia and cerebral aging].

Relationships between contingent negative variation (CNV) amplitude, regional cerebral blood flow (CBF), mini mental status examination score (MMSE) and reaction time (RT) have been studied in young subjects, non-demented old subjects and patients with primary degenerative senile dementia. Significant correlations have been found between CNV amplitude and global CBF, MMSE score and reaction time. Factorial analysis has shown 3 factors weighted respectively by MMSE and CNV, antero-posterior ratio fort left hemispheric CBF and age, and antero-posterior ratio for right hemispheric CBF and reaction time. Discriminant analysis has shown 2 discriminant functions differentiating young from old subjects with 90% accuracy and demented from non-demented patients with 75% accuracy.

Adult↗
PubMed1988

[Endoluminal angioplasty of iliac obstruction. Immediate results and cumulative patency at 2 years in 23 patients].

23 patients with obstruction of one or both main iliac arteries underwent one or more transluminal angioplasties by catheterization via the obstructed vessel. 26 iliac arteries were thus reopened. The length of obstructions varied from 1 to 10 cm. The majority of the obstructions were of recent onset whilst in 6 cases the presumed date was more than 6 months previously. In all cases potency was obtained with normal follow-up angiograms in 20 cases, and a residual though not hemodynamically significant stenosis in 6 cases. All patients were followed up by Doppler and in the majority of cases by venous digital angiography, with a follow-up at the present time of 6 months to 2 years. 2 patients underwent surgery because of reobstruction occurring 2 and 13 months after dilatation. Cumulative patency is 79% in 2 years, similar to results obtained by surgery. These results show that iliac angioplasty, a simple procedure, may avoid or delay surgery, and that it should be widely used in this precise anatomical indication.

Adult↗
PubMed1987

In vitro effects of thymopentin on the gamma-interferon production by peripheral blood mononuclear cells from normal subjects and from patients with rheumatoid arthritis.

The in vitro production of gamma-interferon (gamma-IFN) by peripheral blood mononuclear cells (MNC) was measured using a specific radioimmunoassay in 16 patients presenting with active rheumatoid arthritis (RA), in 14 patients with inactive disease, and in 36 control subjects (CS). Unstimulated cultures produced undetectable levels of gamma-IFN and did not incorporate tritiated thymidine. In response to phytohemagglutinin (PHA) 0.2 microgram/ml, MNC from active RA produced 9 times less, and under PHA 2.5 micrograms/ml, 4 times less gamma-IFN than did MNC from inactive RA or from CS. The uptake of tritiated thymidine was, however, similar in the 3 groups. In unstimulated cultures of the 3 groups, thymopentin (TP-5), at all concentrations tested, did not influence either the levels of gamma-IFN or the uptake of tritiated thymidine. In the presence of PHA 0.2 microgram/ml and TP-5, lambda-IFN levels were increased in CS, unchanged in inactive RA and reduced in active RA, whereas no changes were observed in the uptake of tritiated thymidine. Our results show that under our experimental conditions, TP-5 was able to increase the levels of gamma-IFN produced by normal MNC in vitro, but could not reverse the profound defect observed in active RA.

Adult↗
PubMed1987

Impact of neck node radioresponsiveness on the regional control probability in patients with oropharynx and pharyngolarynx cancers managed by definitive radiotherapy.

We reviewed a series of 1,666 patients with squamous cell carcinoma of the oropharynx and pharyngolarynx treated with definitive radiation therapy to determine whether or not radioresponsiveness of the metastatic neck nodes is a reliable indicator of their radiocurability. In a determined group of 708 patients with clinically positive neck nodes, only one third of the adenopathies (247/759) completely regressed at the completion of the treatment. At 6 months, only ten percent of the nodes remained palpable. Lymph node clearance rates and halving diameter times were tumor size-dependent. Node clearance rate was also influenced by the site of the primary lesion. The impact of various parameters, both intrinsic and extrinsic to the tumor behavior, is discussed. Neck control probability was significantly higher for complete responders. In this group, the ultimate node control was as good for adenopathies larger than 6 cm as for the smaller ones. Tumor control probability directly related to clearance rate following radiotherapy. Finally, therapeutic implications are derived for nodal dose adjustments and optimal applicability of radiosurgical combinations.

Carcinoma, Squamous Cell↗