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Biomedical subjects

G Forget

Publications and source records attributed to G Forget.

At least 19 recordsLinked to original sources
PubMed2001

Role of host phosphotyrosine phosphatase SHP-1 in the development of murine leishmaniasis.

Activation of host phosphotyrosine phosphatase SHP-1 by Leishmania and its subsequent impact on tyrosine phosphorylation-based signaling cascades were shown to represent an important mechanism whereby this pathogen may alter host cell functions. Herein, we report that Leishmania-induced macrophage SHP-1 activity is necessary for its survival within phagocytes through the attenuation of nitric oxide-dependent and -independent microbicidal mechanisms. In vivo, Leishmania major infection, which footpad inflammation is mostly undetectable in SHP-1-deficient viable motheaten mice, was accompanied by increased inducible nitric oxide synthase and activation of neutrophils. These enhanced cellular activities were paralleled by a marked activation of signaling events usually negatively regulated by SHP-1. Overall, this study firmly establishes that modulation of the signaling terminator SHP-1 by Leishmania is essential for its installment and propagation.

Animals↗
PubMed1997

The Impact of upport of Occupational Health Research on National Development in Developing Countries.

This paper assesses the developmental impact of donor-supported occupational health and safety research in developing countries through examining over 40 projects supported by one donor. Based on an analysis of 42 questionnaires completed by principal investigators of 38 international projects in developing countries and an on-site study of five completed projects in Latin America, the results show that donor-supported occupational health and safety research projects have had a significant impact on strengthening the research capacities of recipient scientists and research institutions as well as facilitated changes in the policy environment and the health and safety practices of occupational groups in developing countries. The analysis also suggests that the type of recipient institution has some bearing on the impact of research. Furthermore, effective and broad dissemination of research results and the involvement of stakeholders in the research contributed to the developmental impact.

Journal Article↗
PubMed1991

Pesticides and the Third World.

Many developing countries are importing industrial processes that make use of toxic chemicals. By the same token, pesticides, which are toxic by design, are also used increasingly in agriculture and in public health programs to control pests and vector-borne diseases. Recent estimates suggest that pesticides account for more than 20,000 fatalities yearly, and that most of these will have occurred in developing countries. This may actually be a gross underreporting. Although organophosphate and carbamate insecticides are still responsible for many of those poisoning cases, herbicides such as paraquat are also increasingly being implicated in fatal poisoning cases. Newer pesticides such as the synthetic derivatives of pyrethrin, which were believed to be relatively safe to humans, now appear to be implicated in some serious cases of intoxication. Community-based pest control using locally available botanical pesticides could have severe consequences unless the toxicity of these compounds is carefully assessed relative to nontarget organisms. A high proportion of pesticide intoxications appear to be due to lack of knowledge, unsafe attitudes, and dangerous practices. The technology available to small farmers for pesticide application is often inappropriate: faulty sprayers, lack of protective equipment adapted to tropical conditions, nonexistent first-aid provisions. Agricultural extension is often not oriented to the transfer of information relative to the dangers inherent in the use of pesticides. The lack of information at all levels may be one of the most important causative factors of chemical intoxication in developing countries. Research should at this time concentrate on behaviors leading to chemical intoxication. This should be done concurrently with proper prospective and retrospective surveys of poisonings in developing country communities. More information should be sought relative to the decision processes of import, legislation, and licensing. Research and development efforts in appropriate technology and safety devices are also critically needed.

Animals↗
PubMed1990

Results of neoadjuvant chemotherapy and radiation therapy in the breast-conserving treatment of 250 patients with all stages of infiltrative breast cancer.

Two hundred fifty evaluable patients with breast cancer entered a protocol combining neoadjuvant and consolidation therapy by vinblastine (V), thiotepa (T), methotrexate (M), and 5-fluorouracil (F) (VTMF), with or without Adriamycin (A) (doxorubicin; Adria Laboratories, Columbus, OH), and radiation therapy as exclusive locoregional treatment. Tamoxifen was given to 195 patients (130 postmenopausal and 65 premenopausal) and was omitted in 55 patients (31 postmenopausal and 24 premenopausal). There were 19 Stage I, 86 Stage IIA, 51 Stage IIB, 36 Stage IIIA, and 58 Stage IIIB patients. Primary chemotherapy induced tumor volume regression of more than 75% in 41% of the patients and complete clinical regression in 30% of the patients. The 5-year disease-free survival (DFS) rates were 100% for Stage I, 82% for Stage IIA, 61% for Stage IIB, 46% for Stage IIIA, and 52% for Stage IIIB patients. Among the 72 primary relapses there were 39 distant metastases. The actuarial rate of locoregional recurrence was 13% for T2, 18% for T3, and 19% for T4. At 5 years the rate of breast preservation was 94%. Cosmetic results were excellent or good for most patients. The 5-year overall survival (OS) rates were 95% for Stage I, 94% for Stage IIA, 80% for Stage IIB, 60% for Stage IIIA, and 58% for Stage IIIB. Most patients with breast cancer should be given the option of breast-preserving treatment.

Adult↗
PubMed1990

[Expectations and defeat in the treatment of epithelial cancer of the ovary].

One hundred and thirty-nine patients were treated between 1980 and 1988 for epithelial cancer of the ovary: 35 stage I, 30 stage II, 66 stage III and 8 stage IV (according to the IFGO classification). For stage I and II patients, who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy followed by combination chemotherapy, the 5 year survival rate without relapse was 91%. For those classified as stage III, the 5 year survival rate was 36%. When the tumor was completely removed surgically, the 5 year survival rate was 82%, but the disease-free (without relapse) rate was only 47%. When the malignancy could not be completely excised, the 5 year survival rate was only 15%. The only chance these patients had to survive was if chemotherapy effectively controlled the residual mass (verified during an exploratory laparotomy). In our experience, the combination of cisplatin, doxorubicin and cyclophosphamide, in spite of a 78% response rate, only histologically eliminated the residual tumor in 15% of the patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length.

The effect of glass fibers on rat alveolar macrophages was studied with a new perifusion technique which allows the sequential determination of cell-derived inflammatory mediators as well as estimation of cell viability and aggregation at the end of the incubation period. Our results showed that glass fibers induced dose-dependent release of prostaglandins and beta-glucuronidase from macrophages and the aggregation and death of these cells. These deleterious effects were clearly related to the length of the fibers, with the longer fibers (greater than or equal to 4-5 micron) being more active than the shorter ones (less than 3 micron). Furthermore, a short exposure of 1 hr followed by an 18-hr perifusion induced the same inflammatory and toxic effects on the macrophages as did leaving the fibers undisturbed for the complete 18-hr perifusion. It is concluded that glass fibers produce effects in cultures of rat alveolar macrophages qualitatively similar to those of asbestos, and that fiber length appears to be a critical determinant of toxicity.

Animals↗
PubMed1984

Measurement of beta-glucuronidase in effluent of perifused alveolar macrophages challenged with chemically modified chrysotile asbestos.

Chrysotile asbestos has been implicated with lung disorders, notably fibrotic lesions and cancer. In vitro, chrysotile fibers are cytotoxic to lung macrophages and stimulate the release of inflammatory mediators. Reports to the effect that chemical modifications of asbestos fibers reduce their cytotoxic and inflammatory potential initiated the present study of three fiber modifications. The cytotoxic and inflammatory effects of magnesium-leached chrysotile, POCL3-treated chrysotile, and CaO-treated chrysotile were studied in a perifused rat alveolar macrophage culture system, relative to untreated fibers. Natural Canadian chrysotile (UICC "B") caused dose-dependent cell mortality and clumping. The release of beta-glucuronidase (beta-Glu), a lysosomal enzyme, was also dose dependent. Rhodesian chrysotile (UICC "A") caused similar cytotoxic and inflammatory effects. However, magnesium-leached chrysotile was less cytotoxic (39% less) and had a lesser clumping capacity (31% less) than untreated chrysotile. Total secretion of beta-Glu elicited by magnesium-leached chrysotile was reduced by 43% from the untreated sample, but kinetic monitoring indicates that this reduction in inflammatory potential is only significant during the first 12 h of an 18-h culture period. POCl3 treatment of chrysotile fibers produced differing effects depending on the length of the fibers under study. Treating fibers with a mean length of 8 micron produced a secretion pattern similar to that produced by acid leaching. The total output for the treated sample was 44% lower than with untreated chrysotile; the difference was only significant during the first 12 h of perifusion. Cell mortality and aggregation were not reduced in any important way with POCl3 treatment of these longer fibers. When ultra-short fibers (mean length = 0.8 micron) were treated with POCl3, the total decrease in beta-Glu output was equal to 41%, and the release of enzyme was significantly lower during the whole 18-h experiment. Cell aggregation was not appreciably affected, but cell mortality was significantly lower than for untreated fibers. CaO treatment did not alter the cytotoxic (cell death and aggregation) or inflammatory (beta-Glu release) effects of chrysotile asbestos. These results suggest that chemical modifications affecting the integrity of the surface magnesium and/or the polarity of the surface charge of chrysotile can reduce to some extent the cytotoxic and inflammatory properties of this type of asbestos.

Animals↗
PubMed1983

Development of a radioimmunoassay data analysis pack (RIADAP) in level II basic for microcomputers.

A simple program written in Microsoft BASIC for the analysis of radioimmunoassay data is presented. The program was designed for use by unexperienced operators on a TRS-80 Model III microcomputer. Standard curve data are fitted by linear regression after a logit response/loge dose transformation. Standard errors of individual observations are computed, and confidence intervals are obtained for a critical t of 0.1. Standard observations are eliminated when they lie outside the confidence interval from the calculated response on the fitted curve, and this is accomplished until no datum can be eliminated or until the coefficient of determination reaches an operator defined value. The program then prints the regression parameters and the retained standard values. Unknown sample data can then be entered, and the values are computed relative to the final regression parameters of the standard curve. The values can be modified by operator defined correction/dilution factors. The mean value of the slope for 28 assays is -0.99, while the predicted theoretical slope with a loge transformation is -1. This program finds its greatest use in research laboratories where a number of different RIA are performed and where it is of value to have some control over the computation process.

Computers↗
PubMed1983

An adherent cell perifusion technique to study the overall and sequential response of rat alveolar macrophages to toxic substances.

Essentially pure (97%) alveolar macrophages were isolated by bronchoalveolar lavage of rats with warm (37 degrees C) PBS solution. These cells were allowed to adhere to the inside walls of open-ended glass cylinders which were closed off at each end by three-way stopcocks. The adhering cells were perifused with RPMI-1640 medium supplemented with 5% fetal bovine serum for 18 hr at the rate of 1 mL/hr, and the effluent medium was collected automatically in 2-mL aliquots. Cell recoveries and viabilities did not differ from those found for Petri cultures treated similarly, indicating that the perifusion method under study offered an adequate milieu for short-term primary cultures. The alveolar macrophages in culture were subjected to the presence of particulate (chrysotile asbestos) and soluble (phorbol myristate) toxicants, and their response was monitored in the effluent medium by measuring the release of prostaglandins (PGE) by radioimmunoassay. A significant increase in the sequential release of PGE was observed in the presence of asbestos (100 micrograms/mL) or phorbol myristate (200 ng/mL). Treatment of the cells with indomethacin (20 microM) completely abolished the release of PGE stimulated with phorbol myristate. A cumulative response to the toxicants was also observed when cells were harvested manually from the chambers: asbestos caused a 2-fold increase in cell mortality relative to control, while phorbol myristate brought about a 3-fold increase in the number of dead cells. This effect was not prevented by the presence of indomethacin. Cell aggregation was also observed when cells were perifused in the presence of phorbol myristate, whether indomethacin was present or absent. Our results indicate that the cell perifusion system combines the advantages of conventional adherent cell cultures (viability, aggregation) with those of perifusion techniques (sequential metabolism studies).

Animals↗
PubMed1982

Middle ear pressure variations during nitrous oxide and oxygen anaesthesia.

Many authors have reported middle ear pressure variations during inhalation of high concentrations of nitrous oxide. An on-going study on subjects anaesthetized with nitrous oxide and oxygen supplemented with halogens or narcotics and excluding operations on the ear enables us to register three typical curves of middle ear pressure according to the patency of the Eustachian tube. We recorded significant negative middle ear pressures during the recovery period when there was important obstruction of the Eustachian tube. The presence of a tympanic "neomembrane" due to an old perforation associated with important obstruction of the Eustachian tube could lead to a tympanic perforation that may be unnoticed by the anaesthetist if it is not specifically investigated. In our series, we report one case of tympanic perforation and one case of haemotympanum as examples of such consequences.

Adult↗
PubMed1981

[Gas diffusion in the middle ear during anesthesia for tympanoplasty].

The problems of diffusion of gas into the middle ear during anaesthesia have been described by several authors since 1965. The administration of anaesthetic concentrations of nitrous oxide raises middle ear pressure in the order of 3.43 to 3.92 kPa (350 to 400 mm H2O). This phenomenon disappears spontaneously after cessation of nitrous oxide anaesthesia and causes no trouble except a few cases of deafness and some rare tympanic ruptures. We have tried to solve this problem during anaesthesia for tympanoplasty by substituting air for nitrous oxide and by the use of ethrane as basic anaesthetic agent. Anaesthesia was potentiated by narcotics and the patients were adequately curarized. The results showed that this technique greatly reduced diffusion of gases if we kept the PaO2 under 17.9 kPa (135 mm Hg) and the PaCO2 at 3.9 kPa (30 mm Hg). Controls have shown that diffusion is greater with higher PaCO2. Middle ear pressure, measured with Madsen impedence-meter, was not higher than 0.68 kPa (70 mmn H2O).

Anesthesia↗
PubMed1979

Enzymatic modifications of bovine adrenocortical angiotensin II receptors.

Several classes of proteolytic enzymes were used to gain an insight into the biochemical composition of the antiotensin II (ATII) receptor prepared from bovine adrenal cortices. Exposure of the receptor fractions to trypsin reduced their capacity to bind [3H]ATII. Phospholipases A2 and C similarly inhibited the [3H]ATII binding process, while phospholipase D had no effect. Binding was stimulated following addition of phosphatidylcholine but inhibited by lysophosphatidylcholine. Neuraminidase had no influence on [3H]ATII affinity for binding, while beta-galactosidase reduced binding of the radioligand. Concanavalin A did not displace [3H]ATII bound to receptor fractions. Very little aminopeptidase activity was detected in the receptor fraction, relative to the homogenate. The data suggest that the ATII recognition sites contain protein moieties, while phospholipids may play an essential role in ATII binding. Galactose units may form a part of the ATII receptor not directly associated with the binding site. The peptidase studies indicate that ATII probably cannot be hydrolyzed to its des-Asp1 metabolite at or near the site of binding.

Adrenal Cortex↗
PubMed1979

[Sialoscintimetry in disorders of the facial nerve].

The comparative study of submandibular gland function before and after unilateral section of the chorda tympani, is used to verify the validity of sequential scintigraphy as a method of appraising the function of the salivary glands. Sequential scintigraphy of the submandibular glands was evaluated as a new, simple, and dependable test of the function of the submandibular glands, in topographical and prognostic assessment of 10 patients with unilateral idiopathic facial paralysis. The results of this neurodiagnostic test were compared and were found to be in close agreement with the results obtained by submandibular salivary flow measurement. The use of sequential scintigraphy of the submandibular glands constitutes a valuable tool in the clinical evaluation of patients with peripheral facial nerve disorders.

Chorda Tympani Nerve↗
PubMed1976

Preparation and characterization of adrenocortical plasma membrane angiotensin II receptors.

A bovine adrenocortical particulate fraction prepared by zonal ultracentrifugation and banding between rho20 1.08 and 1.101 in a linear sucrose gradient bound 7.3 times more [3H]angiotensin II (ATII) per milligram protein than the original homogenate. Enzyme marker and electron microscope studies indicated that this fraction was largely devoid of mitochondria while being enriched in smooth membranes of predominantly plasmalemmal origin. The binding of labeled ATII was maximal after 10 min incubation (22degreesC) and remained at equilibrium for at least 20 min thereafter. [3H]ATII binding was completely inhibited by saturating concentrations of nonradioactive ATII. The high-affinity binding site in the preparation had a specific binding capacity of 2.38 pmol-mg-1, with an equilibrium constant of 2.36 x 10(8) M(-1). Inhibition-displacement studies with unlabeled ATI,ATII,ATII fragments, analogs, and antagonists show that the receptor fraction has the highest affinity for the intact native octapeptide. ACTH and bradykinin had no specific effects on [3H]ATII binding. The current study suggests that the receptor fraction may be of use in a highly sensitive ATII radioligand assay.

Adrenal Cortex↗