Immunization survey of non-institutionalized adults--Quebec (as of May 30, 1996).
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Biomedical subjects
Publications and source records attributed to A Fortin.
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PURPOSE: To study the predictive value of pretreatment potential doubling time and labeling index, as measured by flow cytometry in patients with head and neck squamous cell carcinoma treated with conventional radiotherapy. METHODS AND MATERIALS: 70 patients with a squamous cell carcinoma of the oropharynx and 4 patients with another involved head and neck site were entered in this prospective study. The duration of the S phase (TS), the labeling index (LI), and the potential doubling time (Tpot) were obtained by flow cytometry measurements of a tumor biopsy obtained after i.v. injection of 200 mg bromodeoxyuridine to the patient. The treatment consisted of 70 Gy in 7 weeks, 2 Gy per fraction and five fractions per week. RESULTS: The mean and median LI were 7.7% (standard deviation, SD: 5.0) and 6.3%, respectively. The mean and median TS were 9.3 h (SD: 3.6) and 8.3 h, respectively. The mean and median Tpot were 5.6 days (SD: 5.4) and 4.6 days, respectively. No significant relationship was found between the Tpot or LI and the tumor stage (T), nodal status (N), histological grade, and the site of the primary within the oropharynx. The only parameter significantly associated with an increased risk of local relapse was the tumor stage (p < 0.001). The mean Tpot for the group of tumors that relapsed locally was 5.3 days (SD: 3.3), compared to 6.1 days (SD: 4.08) for those who did not relapse locally (NS). Two parameters were significantly associated with a decrease in disease-free (DFS) and overall survival, namely the tumor stage (p < 0.005, and p < 0.001, respectively, for DFS and overall survival) and nodal involvement (p = 0.02 and (p < 0.005, respectively, for DFS and overall survival). The TS, LI, DNA index, and Tpot were not significantly associated with local relapse, DFS, and survival, either in the univariate or in the multivariate analysis. CONCLUSIONS: The method used to evaluate tumor cell kinetics did not provide clinically relevant kinetic parameters for this type of cancer. The classic prognostic factors (tumor stage and nodal status) were strongly associated with clinical outcome.
Liposomes act as powerful adjuvants if physically associated with a protein antigen. Their effect on the immune response, however, varies with the nature of this linkage, surface-linked and encapsulated antigens having different properties. Cytometric analysis and cytokine measurements indicate that this difference may be due to the differential activation of T lymphocyte populations. Surface-linked antigen appears to preferentially stimulate CD4+ T cells to proliferate and mature into a typical Th1 phenotype; this is indicated by a positive shift in the CD4+/CD8+ ratio of sensitized splenocytes, a massive production of interferon-gamma, and the absence of interleukin-4 secretion. In contrast, encapsulated antigen, while stimulating spleen cell proliferation, does not significantly affect the CD4+/CD8+ ratio and induces only low levels of interferon-gamma production in the absence of interleukin-4 secretion. These results suggest that CD4+ and CD8+ populations are both expanded in response to encapsulated antigen but that neither typical Th1 nor Th2 phenotypes are induced. High-resolution immunocytochemical investigations show that this differential activation of T cell populations may be related to a different intracellular trafficking of antigens into professional antigen-presenting cells. Whereas surface-linked antigen remains predominantly in endosomal compartments where it may be associated with major histocompatibility (MHC) class II products for presentation to CD4+ T cells, encapsulated antigen escapes into the cytosol, reaching the MHC class I pathway for presentation to CD8+ T cells. The results therefore suggest that both liposomal antigens stimulate cell-mediated immunity albeit differently. This behavioral difference may be of practical importance in the design of adjuvants for the preferential potentiation of specific cytotoxic effector functions.
As a tumour suppressor gene, the inactivation of p53 induces the development of numerous human cancers. Mutations of p53 have been implicated in the pathogenesis of head and neck squamous cell carcinoma (HN-SCC) at a high incidence. In premalignant lesions and in situ carcinomas, p53 overexpression is not exclusively restricted to neoplastic cells, but frequently affects the normal appearing keratinocytes adjacent to p53 positive neoplasms or present in dysplastic areas. These results suggest that as contributors to the early phases of HN-SCC development, p53 alterations may be excellent biomarkers that indicate the predisposition of a particular oral cavity premalignant lesion toward malignancy. In most cases, the p53 overexpression status of a tumour metastasis is identical to that of a primary tumour, indicating that a p53 mutation precedes metastatic spread. In patients with multiple primary tumours, multiple foci of p53 overexpression are observed in epithelia distant from the tumour. So the expression of p53 in normal epithelium would indicate an increased risk for transformation to second or third primary cancers. Distinct p53 mutations in different primary tumours of the same patient indicate that these cancers arise as independent events; these results support the existence of multifocal polyclonal processes. Regardless of the aforementioned results that support p53 as a valid tumour biomarker, most studies have shown no relationship between the expression of p53 and clinical and histopathological parameters. The role played by p53 mutations in the progression and vital prognosis of HN-SCC has not yet been demonstrated.
PURPOSE: To report preliminary results of a very accelerated radiation therapy Phase I/II trial in locally advanced head and squamous cell carcinomas (HNSCC). METHODS AND MATERIALS: Between 01/92 and 06/93, 35 patients with an unresectable HNSCC were entered in this study. Thirty-two (91%) had Stage IV, and 3 had Stage III disease. The mean nodal diameter, in patients with clinically involved nodes (83%), was 6.3 cm. The median Karnovsky performance status was 70. The treatment consisted of a twice daily schedule (BID) giving 62 Gy in 20 days. RESULTS: In all cases, confluent mucositis was observed, which started about day 15 and resolved within 6 to 10 weeks. Eighty percent of patients had enteral nutritional support. The nasogastric tube or gastrostomy was maintained in these patients for a mean duration of 51.8 days. Eighteen patients (53%) were hospitalized during the course of treatment due to a poor medical status or because they lived far from the center (mean 25 days). Nineteen patients (56%) (some of whom were initially in-patients) were hospitalized posttreatment for toxicity (mean 13 days). Five patients (15%) were never hospitalized. During the follow-up period, 12 local and/or regional failures were observed. The actuarial 18-month loco-regional control rate was 59% (95% confidence interval, 45-73%). CONCLUSIONS: The dramatic shortening of radiation therapy compared to conventional schedules in our series of very advanced HNSCC resulted in: (a) severe acute mucosal toxicity, which was manageable but required intensive nutritional support in all cases; and (b) high loco-regional response rates, strongly suggesting that the time factor is likely to be critical for tumor control in this type of cancer.
The fragile X syndrome is an X-linked inherited disease and is the result of transcriptional inactivation of the FMR1 gene and the absence of its encoded FMR protein (FMRP). Using a specific monoclonal antibody directed against human FMRP, we have studied the steady-state levels of its murine homolog in several tissues and organs of adult and young mice. In immunoblot analyses, the antibody recognizes a heterogeneous subset of proteins with apparent molecular weights ranging from 80 to 70 kDa. These proteins are detected in all the 27 tissues tested; however, the relative proportion of each polypeptide recognized varies between tissues, and a significantly higher expression is observed in young animals. Northern blot analysis of RNA extracted from selected tissues from adult mouse shows that these tissues express the major 4.8 kb mRNA, although at different levels, and contain several additional shorter transcripts, particularly in muscular tissues. We also report that expression of the FMR1 gene is modulated in proliferating and quiescent primary mouse kidney cell cultures with an inverse relationship between levels of FMR1 mRNA and of its encoded proteins. This suggests that FMRPs are highly stable in quiescent cells and that FMR1 expression is likely post-transcriptionally controlled. Our results document the widespread expression of the FMR1 gene, and suggest that it is controlled by different mechanisms implicated in cell growth and differentiation.
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The reputation of liposomes as adjuvant of the immune response is now firmly established despite the lack of information on the mechanisms involved in their immunopotentiating properties. The rapid targeting of massive doses of antigenic material to antigen-presenting cells, especially macrophages has, however, often been invoked as the principal source of liposomal adjuvanticity. In order to test this hypothesis, we analyzed the humoral response to antigen encapsulated in liposomes containing increasing amounts of surface-exposed mannose residues, ligand specific of an exclusive macrophagic receptor. Using BSA as a model antigen, we demonstrated that the humoral response is profoundly affected by mannosylation, being of prolonged duration and either inhibited or activated depending on the immunizing doses. These results suggest that the rapidity of antigen targeting is not the sole reason to liposome adjuvanticity and that the role of liposomes as antigenic depot is probably important to sustain substantial activation through successive restimulations. In this context, the increased rapidity in antigen targeting which favors the concentration of activation signals in time, results in an under-optimization of the response at high immunizing doses and in an optimization of this response at doses that would otherwise give rise to signal of sub-threshold intensity albeit during a longer period of time.
The humoral response to bovine serum albumin either encapsulated in or surface-linked to liposomes was studied as a function of dose and protein:lipid ratio. Total immunoglobulin, total IgG, IgM, and the G isotypes, IgG1, IgG2a, and IgG3 were measured during the plateau phase of production after a boosting injection. Although the adjuvant character of liposomes was confirmed regardless of the mode of antigen association, important differences in the response to the two types of liposomal formulations were observed. Our results suggest that surface-linked antigen stimulates the immune system at lower doses than its encapsulated counterpart, is more sensitive to the protein:lipid ratios, and can stimulate the production of particular immunoglobulin isotypes in controlled conditions. Our data support the idea that different pathways of processing are utilized by the two forms of liposomal antigen.
The dental care of handicapped person is often neglected and many reasons can explain this situation. The purpose of this article is to show factors causing dental deterioration of this particular group and to highlight the special role of the dentist. A new approach to dental care for the handicapped person is proposed.
Experimental control Strains 30, representative of commercial broiler dam stocks in the late 1970's, and K, representative of commercial broiler stocks of 20 years earlier, were compared. Development of carcass fatness and related traits and physiological traits from 3 to 17 weeks of age were studied. About 12 chickens of mixed sex of each strain were bled and killed at 2-week intervals beginning at 3 weeks of age for measurement of traits. From 3 to 17 weeks of age, percentage abdominal fat of carcass, carcass fat (ether extract) and plasma very low density lipoproteins (VLDL) increased with age. Percentage carcass nitrogen, ash, and water, lipase activity of abdominal fat expressed per mg protein or per g of fat (LIP/g F), and protein concentration of the abdominal fat enzyme preparation (P/ml EPrep) decreased with age. Strain 30 had a higher percentage of abdominal fat and carcass fat, but less carcass nitrogen, ash, and water than Strain K, although there were interactions with sex and age. For physiological traits, Strain 30 had more LIP/g F and less P/ml EPrep than Strain K. Males had lower percentages of abdominal fat, carcass fat, and plasma VLDL, and higher percentages of carcass nitrogen, ash, and water than females. There were no significant differences between sexes for the other physiological traits. There were significant (P less than .01) partial correlations between plasma VLDL and percentage abdominal fat (.22), and between P/ml EPrep and percentages of abdominal fat (-.25), carcass fat (-.29), carcass nitrogen (.30), and carcass water (.30). These observations in conjunction with multiple regression analyses indicated that, in addition to plasma VLDL, protein concentration of adipose tissue expressed as P/ml EPrep might be a useful predictor of fatness in chickens.
Genetic variation for more than 40 traits was assessed in 26 stocks of mature chickens reared together and fed ad libitum from hatching to slaughter at 507 days of age. There was greater genetic variation among males than among females. The intraclass correlation, t, was high (greater than .75) for measures of size and weight and moderate (.20 to .60) for most other traits (P less than .05) including a measure of lean distribution (.37). Three main categories of stocks were studied, viz. outbred Leghorns, medium-sized stocks, and contemporary heavy meat chickens. Differences in lean distribution were not associated with category, but differences of 40 to 50 g/kg lean in the breast of some stocks may be caused by a single gene. Lean:bone ratios were similar in medium and heavy stocks but were greater (P less than .05) in heavy meat-types compared with outbred Leghorns. Bone density was higher (P less than .01) in females compared with males and in outbred Leghorns compared with heavier stocks (P less than .01). Heavy meat-type males were leaner (P less than .01) and had proportionately less fat in the abdominal cavity than outbred Leghorns. Carcass fatness was similar among stocks of females, but abdominal fat was lower in Leghorns selected for high egg production compared with unselected Leghorns (P less than .05) and heavy stocks (P less than .001). One resistant and two Marek's disease-susceptible stocks were replicated in a specific pathogen-free (SPF) environment. Spleen weight was larger (P less than .001) in the conventional environment. Females were relatively smaller (P less than .05) than males in the conventional environment. Body temperature (t = .25, P less than .05) and feed intake were assessed in males. Heavy meat birds had a lower (P less than .01) body temperature than outbred Leghorns and medium-sized stocks. Differences among stocks for feed intake (t = .77) were significant (P less than .05); however, they were greatly reduced when feed intake was expressed as g/kg liveweight (LW) (t = .49) or g/kg LW.75 (t = .25). Outbred Leghorns ate less in absolute terms but significantly more (P less than .01) as a proportion of LW or LW.75 than the medium and heavy lines.
The possible role of calmodulin in exocytotic secretion is supported by the presence of this calcium-binding protein in secretory cells, and by the antisecretory effects in intact secretory cells of substances which can antagonize calmodulin-stimulated enzymes in broken cell preparations. In this study, two in vitro calmodulin antagonists, W-7 and chlorpromazine, were found to produce both similar and different pharmacological effects on the secretory process in rat exocrine pancreas. Both substances blocked amylase secretion in response to carbachol or cholecystokinin octapeptide, but only chlorpromazine inhibited the ability of carbachol to stimulate 45Ca efflux from isotope-preloaded cells. Only W-7 could inhibit the secretory response to vasoactive intestinal peptide (VIP); but both W-7 and chlorpromazine were equipotent partial antagonists of VIP-stimulated cyclic AMP synthesis. Chlorpromazine increased the secretory response to melittin but W-7 did not. The divergence in biological responsiveness to W-7 and chlorpromazine makes it difficult to extrapolate the in vitro effects of these agents to similar actions in intact cell systems.
Chemical composition of the empty body was determined in 159 animals slaughtered at weights ranging from 121 to 706 kilograms. Holstein and Angus bulls, steers and heifers were fed at two energy levels: ad libitum and 65 to 70% ad libitum. The allometric equation, Y = aXb, was used to determine the effect of energy intake and the influence of breed and sex on the accretion rates of the chemical components relative to the growth of the empty body or fat-free empty body. Group comparisons for chemical composition were made after adjustment by regression to a common empty body weight. The expression of the sex influence on the accretion rates of water, protein and ash relative to the empty body depended on the breed and the energy intake level considered. The accretion rate of chemical fat was not influenced by sex. Genetic differences in the accretion rate relative to the empty body were detected only among animals in the high energy intake group. Regardless of sex, the accretion rates of protein and ash were more rapid (P < .05) in Holsteins than in Angus. However, a breed influence on the accretion rate of chemical fat was detected only among bulls, where Angus had a more rapid accretion rate. Feeding animals at two energy levels resulted in different accretion rates relative to the empty body. In the Angus breed, regardless of sex, the accretion rates of water, protein and ash were more rapid (P < .05) in the low intake group, whereas the accretion rate of chemical fat was slower (P < .05). Among Holsteins, the low energy intake level had a less definite effect; for bulls, the accretion rates of water and chemical fat were more rapid (P < .05) and slower (P < .05), respectively; for steers, and accretion rate of protein was more rapid (P < .05), and for heifers, none of the accretion rates was altered.
Growth and distribution of muscle in the trunk, and thoracic and pelvic limbs were studied in 141 cattle ranging in slaughter weight from 121 to 706 kilograms. Holstein and Angus bulls, steers and heifers were fed at two levels of energy: ad libitum and 65 to 70% of ad libitum. The allometric equation Y = aXb was used to examine the effects of energy intake and of breed and sex on the rate of muscle growth of the three joints relative to the carcass side or to total muscle in the carcass side. Group comparisons of muscle distribution in the three joints were made after adjustment by regression to a total muscle weight of 53.1 kilograms. In both breeds, and irrespective of the level of energy intake, sex did not influence (P greater than .05) growth rate of muscle in the thoracic and pelvic limbs relative to the carcass side or to total muscle. However, sex was found to affect growth rate of muscle in the trunk relative to the carcass side. Generally, neither level of energy intake nor breed altered (P greater than .05) growth rate of muscle in the three joints relative to the carcass side or total muscle. The distribution of muscle in the three joints adjusted to a total muscle weight of 53.1 kg was generally not influenced (P greater than .05) by sex or altered (P greater than .05) by the level of energy intake. Breed influenced (P less than .05) the distribution of muscle in the trunk and pelvic limb; however, the commercial importance of this difference is questionable.
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OBJECTIVE: Ovulation induction, the usual resort of Assisted Reproductive Technologies (ART), has been suspected of carrying a responsibility in the genesis of ovarian tumours. For patients with a borderline or invasive ovarian tumour, treated by conservative surgery and desiring to become pregnant, the problem is thus of a possible resort to the Assisted Reproductive Technologies. PATIENTS AND METHODS: This is a multicenter, national and retrospective study. 40 operated patients between January 1971 and January 2001 have been included. 27 patients (67.5%) had a borderline tumour, 10 (25%) a non-epithelial tumour (germinal or stromal) and 3 (7.5%) an epithelial invasive carcinoma. All these patients have benefited from a conservative surgical management of fertility. The Assisted Reproductive Technologies were simple stimulation for 5 women and IVF for the 35 others. The effectiveness and the risks of Assisted Reproductive Technologies have been estimated respectively by the number of pregnancies obtained and the recurrence rates. RESULTS: With a global follow-up of 372 months (January 1971: date of the primary surgical procedure--June 2002: closing of the study), 17 patients have obtained 17 pregnancies with the Assisted Reproductive Technologies, rate of 42.5% (17/40): 1 spontaneous abortion, 16 delivery with 23 children (triple pregnancies and 3 twin pregnancies). 3 patients treated for a borderline tumour have had a recurrence after induction of ovulation. Among the 40 patients, no one presented an evolved disease at the last news. The patients who had a recurrence had a delay to begin the Assisted Reproductive Technologies significantly lower than the patients who had no recurrence. DISCUSSION AND CONCLUSION: The assisted reproductive technologies for patients who had been treated for a borderline or invasive ovarian tumour, and who were infertile in spite of conservative management, have allowed 42.5% of these women to obtain a pregnancy and does not seem to increase significantly the risk of recurrence.
The major advantages of the horseradish peroxidase chemiluminescence (HRP-CL) immunodetection method in Western blot analysis are its high sensitivity, nonradioactive detection, economy of the primary antibody, and speed of detecting the signal. However, we observed a strong and reproducible signal that was detected regardless of the primary antibody and of the cell type used. This signal, present at 56-54 kilodaltons (kDa), is generated in absence of any primary antibody and seems to be an intrinsic reaction of the HRP-labeled second antibody anti-immunoglobulin with an unidentified cellular protein. The use of dry milk throughout all the steps of the procedure abolishes this signal. For those interested in one of the numerous proteins migrating at or close to 56-54 kDa, the question therefore arises as to which signals generated by the HRP-CL in this region are bona fide and which are non grata pseudo signals.