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Biomedical subjects

M Younes

Publications and source records attributed to M Younes.

At least 271 records · Page 15Linked to original sources
PubMed1975

A method for the assessment of phasic vagal influence on tidal volume.

Vagal influence related to lung volume changes results in reduction in tidal volume during spontaneous breathing due primarily to premature termination of inspiration. The strength of this vagal influence was traditionally assessed by the duration of apnea following lung inflation, a method recently shown to be inadequate and potentially misleading. An alternate method is described utilizing analysis of the volume tracing of spontaneous breaths and the tracheal pressure tracing during the first breath following airway occlusion at FRC. A formula was devised which, on the basis of previous observations, should predict the tidal volume to be obtained in the absence of phasic vagal influence. The formula was tested in four pentobarbital-anesthetized rabbits using a technique of vagal cooling which rapidly eliminated the vagal influence under study. It was found that the tidal volume obtained following vagal block could be accurately predicted provided allowances were made for the vagally mediated terminal inhibition during spontaneous breathing and the relative stiffness of the respiratory system at high lung volumes.

Action Potentials↗
PubMedDate not supplied

Dioxins: WHO's tolerable daily intake (TDI) revisited.

In December 1990, the World Health Organization (WHO) established a tolerable daily intake (TDI) of 10 pg/kg b.w. (body weight) for TCDD, based on liver toxicity, reproductive effects and immunotoxicity in experimental animals, and making use of kinetic data in humans and experimental animals. Since then new epidemiological and toxicological data have emerged, in particular with respect to neurodevelopmental and endocrine effects of dioxin. Therefore, the European Centre for Environment and Health of the World Health Organization (WHO-ECEH) and the International Programme on Chemical Safety (IPCS) jointly organized a consultation on the "Assessment of the health risk of dioxins: re-evaluation of the TDI", May 1998, Geneva, Switzerland. The participants discussed the health risks for infants, cancer and non-cancer endpoints in humans and animals, mechanistic aspects, kinetic behaviour, modelling, exposure, and the applicability of the toxic equivalency (TEQ) concept. For the health risk assessment of dioxin-like compounds, the WHO Consultation focused on the most sensitive effects that are considered adverse (hormonal, reproductive and developmental effects) seen at low doses in animal studies (rats and monkeys). Human daily intakes corresponding with body burdens similar to those associated with adverse effects in animals could be estimated to be in the range of 14-37 pg/kg b.w./day. To arrive at a TDI expressed as TEQ, a composite uncertainty factor of 10 was recommended. By applying this uncertainty factor a TDI range of 1-4 pg TEQs/kg body weight was established. An extensive executive summary of the results of this WHO Consultation with all the underlying background documents will be published in Food Additives and Contaminants (in press).

Animals↗
PubMedDate not supplied

Hazard characterisation of chemicals in food and diet. dose response, mechanisms and extrapolation issues.

Hazard characterisation of low molecular weight chemicals in food and diet generally use a no-observed-adverse-effect level (NOAEL) or a benchmark dose as the starting point. For hazards that are considered not to have thresholds for their mode of action, low-dose extrapolation and other modelling approaches may be applied. The default position is that rodents are good models for humans. However, some chemicals cause species-specific toxicity syndromes. Information on quantitative species differences is used to modify the default uncertainty factors applied to extrapolate from experimental animals to humans. A central theme for extrapolation is unravelling the mode of action for the critical effects observed. Food can be considered as an extremely complex and variable chemical mixture. Interactions among low molecular weight chemicals are expected to be rare given that the exposure levels generally are far below their NOAELs. Hazard characterisation of micronutrients must consider that adverse effects may arise from intakes that are too low (deficiency) as well as too high (toxicity). Interactions between different nutrients may complicate such hazard characterisations. The principle of substantial equivalence can be applied to guide the hazard identification and hazard characterisation of macronutrients and whole foods. Macronutrients and whole foods must be evaluated on a case-by-case basis and cannot follow a routine assessment protocol.

Animals↗
PubMedDate not supplied

Harmonisation of rat fetal skeletal terminology and classification. Report of the Third Workshop on the Terminology in Developmental Toxicology. Berlin, 14-16 September 2000.

The initial efforts of the Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV) and the Free University of Berlin to standardise terminology in the field of developmental toxicology began in 1995. Procedures were undertaken to harmonise the terminology used by the International Federation of Teratology Societies (IFTS) and the International Programme on Chemical Safety (IPCS). This article reflects these activities and is a report on the Third Workshop on the Terminology in Developmental Toxicology held in September 2000. This Workshop served as a forum to discuss the results of a survey on the classification of skeletal anomalies that had been previously sent to scientists active in the field. Although high agreement was reached among the evaluators for several terms, the use of a number of terms was rather variable. Therefore, the discussions at the workshop among the experts from research institutions, regulatory agencies, and industry were mainly focussed on those terms for which there was disagreement and/or uncertainties and the possible reasons. Pictures provided by the participants for the illustration of "grey zone" anomalies constituted the basis for detailed discussions. In many of the cases with lower agreement, decisions were facilitated by the provision of the corresponding picture. The main reasons for lower agreement were imprecise terms, insufficient knowledge on postnatal consequences, theoretical terms that are unlikely to occur in isolation, and the possibility of observing a range of severity that might be decisive for the classification of either a malformation or variation. The attendees concluded that "grey-zone" anomalies will never disappear completely and that for the assessment, the grade of severity and/or the frequency of the observation can be decisive for the terminology chosen. A Joint IPCS/IFTS Project was proposed to further consensus of terminology and classification and to link these anomalies to pictures at different skeletal sites. In order to support the harmonisation of regulatory decisions, it was proposed to establish a "Clearinghouse" System under the umbrella of the IPCS. The Clearinghouse could be contacted either by the regulatory authorities or by any company to clarify their queries, particularly with regard to registration or authorisation processes. Finally, it was recommended to also carry out a similar survey on "soft tissue anomalies" and "external findings." The results of this survey will be discussed at a Joint IPCS/IFTS Workshop in Berlin in 2002.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Detection of p53 protein accumulation in sputum and lung adenocarcinoma associated with indoor exposure to unvented coal smoke in China.

Lung cancer in Xuan Wei (XW), China has been linked to exposure to unvented coal smoke and adenocarcinoma, especially bronchioloalveolar carcinoma, is most common. p53 mutations occur commonly in lung cancers and usually generate detectable levels of p53 protein accumulation. Sputum is noninvasive to collect and ideal for screening p53 abnormalities. p53 protein accumulation was detected by immunohistochemistry in lung tumors and sputa from XW lung cancer patients to determine (1) the role of p53 in lung pathogenesis, and (2) feasibility of detecting p53 protein accumulation in sputum, p53 protein accumulation was detected in 73% (22/30) of lung adenocarcinomas from XW females exposed to coal emissions and significantly higher than the control cases (33%, p < 0.05). In sputum, we detected p53 overexpression in tumor cells in 54% (13/24) of XW cases and also in dysplastic cells (50% or 4/8). These findings suggest that p53 abnormalities is important in XW lung cancer etiology.

Adenocarcinoma↗
PubMedDate not supplied

Expression of the neutral amino acids transporter ASCT1 in esophageal carcinomas.

Cancers cells utilize more glucose and amino acids than their benign counterparts. Overexpression of the facilitative glucose transporter Glut1 in human cancers was found to correlate with aggressive biologic behavior. The aim of this work was to determine whether the neutral amino acid transporter ASCT1 is expressed in human esophageal carcinomas, and to correlate the findings with Glut1 expression. Sections of formalin-fixed and paraffin-embedded tissue from 42 cases of esophageal carcinomas were entered in the study. Immunohistochemical staining was performed using a rabbit anti-ASCT1 IgG developed in our laboratory, and anti-Glut1 antibody, using standard avidin-streptavidine immunoperoxidase method. Sections of formalin-fixed and paraffin-embedded HepG2 cells were used as positive controls. The percent of ASCT1-positive cells was scored. Statistical analysis was performed using Fisher's exact test. ASCT1 immunoreactivity was cytoplasmic, whereas Glut1 was membranous. Significantly more adenocarcinomas expressed ASCT1 than squamous cell carcinomas (p < 0.0001), whereas Glut1 expression was similar in both tumor types. There was no association between the expression of either transporter and lymph node metastasis. Glut1 was expressed more often in the better differentiated than the poorly differentiated squamous carcinomas (p = 0.003). These results suggest that unlike in squamous cell carcinoma, ASCT1 plays a significant role in the recruitment of amino acids in adenocarcinoma of the esophagus, and suggest that the metabolic needs, and uptake of nutrients, are regulated differently in these two tumor types. Additional studies with larger number of patients are needed to determine the biological significance of ASCT1 expression in esophageal carcinomas.

Adenocarcinoma↗
PubMedDate not supplied

Glut 1 expression in transitional cell carcinoma of the urinary bladder is associated with poor patient survival.

Cancer cells show increased glucose uptake compared to normal cells. Glut1 has been shown to be expressed in many human cancers, including transitional cell carcinoma of the urinary bladder (TCCB). The aim of this study was to determine the biologic significance of Glut1 expression, as determined by immunohistochemistry, in TCCB. Using the polyclonal anti-Glut1 antibody MYM, microwave-aided antigen retrieval, and standard immunoperoxidase ABC technique, we immunostained sections of formalin-fixed and paraffin-embedded tissue from cystectomy specimens from 40 patients with TCCB, who received no adjuvant therapy. The percent of positive cancer cells was scored on a semiquantitative scale as 1) 0%, 2) 1-10%, 3) 11-25%, 4) 26-50%, 5) 5.1-75%, and 6) > 75%. Statistical analysis was performed using the Kaplan-Meier survival method, the Log rank test, and Fisher's exact test. Glut1 immunoreactivity was detected in 58% of the cases. Glut1 expression in > 10% of cancer cells was associated with worse patient survival than expression in < 10% of the cancer cells (p = 0.0064). Tumors with > 10% Glut1-positive cancer cells were more likely to be of pT2 stage or higher than tumors with < 10% Glut1-positive cells (100% vs 68%, respectively, p = 0.0109), but showed no significant difference in the incidence of nodal metastasis (p = 0.4258). Our results suggest that Glut1 expression in TCCB is a marker of aggressive biologic potential in patients undergoing cystectomy.

Adult↗
PubMedDate not supplied

Protection by diethyldithiocarbamate, a CS2-liberating agent, against different models of experimentally-induced liver injury.

In experimental animals, diethyldithiocarbamate as well as carbon disulfide exert antihepatotoxic effects in different models of chemically-induced liver injury like carbon tetrachloride, chloroform, bromobenzene, dimethyl nitrosamine, furosemide, D-galactosamine, paracetamol, thioacetamide and trichloroethylene. On the other hand, both dithiocarb and CS2 are strong inhibitors of the microsomal mixed-function oxidase system which is involved in the bioactivation of these hepatotoxic agents. It is concluded that CS2 and CS2-producing agents as dithiocarb and disulfiram may inhibit metabolism of other xenobiotics and, thereby, not only protect against various hepatotoxic compounds that require bioactivation but also affect efficacy and duration of action of many drugs.

Animals↗
PubMedDate not supplied

GLUT1 expression in human breast carcinoma: correlation with known prognostic markers.

BACKGROUND: Breast cancers have been shown to have increased glucose uptake and utilization, and to express the facilitative glucose transporter Glut1. The aim of this study was to determine the biological significance of Glut1 expression in breast cancer. METHODS: Paraffin sections of 118 breast cancers were immunostained with antibody to Glut1. The percent of Glut1-positive cancer cells in each tumor was correlated with known prognostic markers, and with patient outcome. RESULTS: Glut1 was expressed in 42% of the tumors. Glut1 immunoreactivity correlated positively with the proliferative activity as determined by Ki-67 immunostaining, and with the total histologic score, and showed negative correlation with bcl-2 immunostaining. There was no correlation between the percent of Glut1-immunoreactive cancer cells and estrogen receptor status, tumor size, or lymph node status. CONCLUSIONS: 1) Glut1 expression is increased in breast cancers with higher grade and proliferative activity, and 2) glucose transport in the majority of breast cancers may be mediated by a glucose transporters other than Glut1.

Breast Neoplasms↗
PubMedDate not supplied

Transforming growth factor alpha (TGF-alpha) expression in biopsies of colorectal carcinoma is a significant prognostic indicator.

BACKGROUND: Predicting the outcome of patients with colorectal adenocarcinoma (CRCA) prior to surgery would be valuable in selecting high-risk individuals who may benefit from pre-operative adjuvant therapy. The aim of this study is to determine whether the expression of TGF-alpha in preoperative biopsies of patients with CRCA constitutes a significant prognostic indicator. METHODS: We studied the expression of TGF-alpha in preoperative biopsies of 106 patients with CRCA, who had at least 5 years follow-up, using an anti-TGF-alpha monoclonal antibody and utilizing the ABC immunoperoxidase technique. For survival analysis, we used the actuarial survival method, and the Log Rank test for statistical significance. RESULTS: CRCAs with low TGF-alpha expression (less than 25% of the tumor cells immunoreactive for TGF-alpha) had a significantly poorer survival than those with high TGF-alpha expression (more than 25%). After excluding from analysis biopsies showing mucinous or poorly differentiated CRCA, known predictors of poor prognosis, the results remained significant (p = 0.0289). CONCLUSION: It is concluded, therefore, that low or absent expression of TGF-alpha in pre-operative biopsies of patients with CRCA, as detected by immunohistochemistry, is a significant predictor of an unfavorable outcome.

Actuarial Analysis↗