Does body growth impair immune function in a large herbivore?

According to the principle of allocation, trade-offs are inevitable when resources allocated to one biological function are no longer available for other functions. Growth, and to a lesser extent, immunity are energetically costly functions that may compete with allocation to reproductive success and survival. However, whether high allocation to growth impairs immune system development during the growing period or immune system performance during adulthood is currently unknown in wild mammals. Using three roe deer (Capreolus capreolus) populations experiencing contrasting environmental conditions, we tested for potential costs of growth on immune phenotype over both the short-term (during growth), and the long-term (during adulthood) over the course of an individuals' life. We investigated potential costs on a set of 12 immune traits that reflect both innate and adaptive responses, and compared them between sexes and populations. Although fast growth tended to be associated with low levels of some humoral traits (globulins) during the growing period and some cellular immune traits (i.e. eosinophil and neutrophil counts) during adulthood, evidence for a trade-off between growth and other immune components was limited. Unexpectedly, no detectable growth costs on immunity were found in females from the population experiencing the least favourable environment. We discuss our findings in the light of the complex interplay between resource allocation strategies among reproduction, maintenance and immunity, in relation to local environmental conditions experienced by roe deer.

Influence of cigarette smoking on P53 gene mutations in bladder carcinomas.

BACKGROUND: The aim of this study was to analyse the influence of cigarette smoking on bladder carcinomas. PATIENTS AND METHODS: 98 cases of bladder cancers were examined by single strand conformation polymorphism analysis of exons 5 to 9, followed by DNA direct sequencing. RESULTS: The incidence of p53 gene mutations was not significantly influenced by habitual smoking. However, the p53 mutation spectrum of current smokers differed significantly from the pattern for non-smokers and ex-smokers. Differences between the two populations included multiple mutations in the current-smokers and an absence in non- and ex-smokers (p<0.01), with the predominance of G:C to A:T transitions at CpG sites in non-smokers (60.0%) in comparison with current smokers (7.6%) (p<0.02). Moreover, G:C to T:A and G:C to C:G transversions were found solely in current smokers. CONCLUSION: It would appear that, in current-smokers, the spectrum of p53 gene mutations is related to tobacco-smoke carcinogens and that the habit of smoking increases the extent of DNA damage.

Pattern of chromosomal imbalances in non-B virus related hepatocellular carcinoma detected by comparative genomic hybridization.

Only limited data are available on comparative genomic hybridization (CGH) in hepatocellular carcinoma (HCC). They concern mainly B virus related HCC. Therefore, we used CGH to detect chromosomal imbalances in 16 non-B virus related HCC in alcoholic cirrhosis in 7 cases (HA1 to HA7), in C virus cirrhosis in 7 cases (HC1 to HC7), in non-cirrhotic liver in 2 cases (NC1, NC2), and in 9 non-malignant cirrhotic tissues. The most frequent imbalances in HCC were gains of whole chromosomes or chromosomal regions 7 or 7q (10/16, 62%), 1q (9/16, 56%), 5 or 5q (9/16, 56%), 8q (8/16, 50%), 6p (6/16, 37%), 15q (5/16, 31%), 20 or 20q (5/16, 31%), and losses of 17p (6/16, 37%), and 8p (5/16, 31%). High-level gains were identified in HCC on 1q (2/16), 3q (1/16), 7q (1/16), and 8q (3/16). No chromosomal imbalances were detected in any of the cirrhotic tissues. Most of the gains, losses, and amplifications detected in this CGH study corresponded well to those identified in previous studies, except for gains of whole chromosome 5 or 7 and/or of chromosome arms 5q or 7q and losses on 4q. Our results suggest that other chromosomal regions are involved in hepatocarcinogenesis.

Treatment of mild chronic hepatitis C with interferon alpha-2b: results of a multi-centre randomized study in 80 patients.

OBJECTIVE: The natural history of mild chronic hepatitis C is not well-known and the benefit of treating this form of the disease is not well-defined. We conducted a pilot study to answer this question. DESIGN: Mild chronic hepatitis C was defined by positivity for anti-HCV antibodies, detectable serum HCV RNA by PCR, and a Knodell score < or = 5 on a liver biopsy performed within the previous 6 months. Eighty patients from six centres were randomized into two groups receiving interferon alpha-2b, 3 MU three times a week for 6 months (group 1, n = 39) or no treatment (group 2, n = 41). Sustained response was defined by the loss of detectable serum HCV RNA at 6 months after therapy. RESULTS: The two groups were not different at entry with respect to age, sex ratio, source of infection, disease duration, genotype, viral load and Knodell score. One patient (group 1) was excluded from the study, while two patients in group 1 (5%) and seven in group 2 (17.1 %) did not complete the trial. A sustained response was observed in seven patients (18%) in group 1 versus none in group 2 (P < 0.01). The difference in mean Knodell score remained non-statistically significant between the two groups at the end of the study. Reduction or interruption of interferon was necessary in eight patients (24.2%). CONCLUSIONS: This first randomized controlled study in mild chronic hepatitis C shows a proportion of sustained responders to interferon alpha-2b similar to that observed in active chronic hepatitis C.

Cervical cancer screening in France.

In France, as in other European countries the incidence and mortality rates of carcinoma of the cervix uteri indicate a clear decrease in invasive cancers. Opportunistic screening has spread and, presently, approximately 60% of the female population undergo a regular cytological test. This rate increases up to 80% in the younger age groups and decreases to 20% after the age of 60 years. In 1990, intervention procedures were defined at a consensus conference; the major recommendations were to screen all women exclusively by cervical smears, for ages 25-65 years over a 3-year period. Guidelines on the quality control of cervical smear taking and reading were published by the national agency of evaluation of health intervention (ANAES). Since 1990, four population-based, organised pilot programmes, have been implemented in Isère. Doubs, Bas-Rhin and Martinique. These programmes evaluate the participation rate (from approximately 20-80% depending upon the age and the geographical area), the rate of abnormal tests (0.2-3%), according to the laboratories, the cancer detection rate (0.04%-0.15%) and some other quality indicators. Recently (November 1998) a law was passed stipulating that the screening test will be free of charge when performed in agreement with the national recommendations. A specific organisation for cytological quality control will be implemented. An effort to better identify and to include the screening process the women in the population who are not yet participating has to be made.

[Solid cell nests and thyroid pathologies. Retrospective study of 1,390 thyroids]. / <> et pathologies thyroïdiennes. Etude retrospective de 1,390 thyroïdes.

Solid Cell Nests (SCN) of the thyroid gland were considered as embryonic remnants or as squamous metaplasia of follicular epithelium. In a retrospective study of 1 390 thyroids, SCN were found in 9.7 % of thyroids (16 % men and 8 % women, chi(2) : p <0, 01). The number of SCN rises with increasing number of sections examined. No statistical differences were found with age or thyroid disorders and presence of SCN, excluding the metaplastic theory. SCN contained in 38 % of cases, neuroendocrine cells (calcitonin and/or calcitonin gene related peptide, chromogranin A) and thyroglobulin cells was observed in 78.3 % of SCN. The different cell types of SCN fitted with the ultimobranchial remnant theory. Thus, some rare carcinomas (like mixed medullary and vesicular carcinoma or mucoepidermoid carcinoma) might originate from SCN.

Ultrastructural features of "solid cell nest" of the human thyroid gland: a study of 8 cases.

The ultrastructural features of solid cell nests (SCN), made of squamous cells, and associated calcitonin cells (C cells), of the thyroid gland were studied in only a few cases in humans. A study was performed on 8 paraffin-embedded SCN, postembedded in Epon, to look for their ultrastructural features. Immunohistochemical analysis using calcitonin antibody was performed on semithin sections of SCN to explore the presence of C cells. Three cases (37.5%) of SCN were positive for calcitonin, and electron-dense secretory granules were observed in the cytoplasm. In two of these cases, an increased number of C cells in the adjacent thyroid parenchyma was observed. The presence of ciliated and lymphoid cells, in addition to intracytoplasmic microvacuolar and microfollicular (microglandular) structures, was noticed. Ciliated cells have already been reported in embryonic rests of human and animals, but ultrastructurally for the first time in human SCN. The presence of microfollicular structures, intracytoplasmic microvacuolar, secretory granules features, and ciliated cells, in addition to lymphoid cell, suggests the existence of a common ultimobranchial stem cell for C cells or for one or more cell types of the thyroid gland.

[Participation of women in cervical cancer screening. Results of the first 5 years of a pilot program in the province of Doubs]. / Participation féminine au dépistage des cancers du col de l'utérus. Résultats des 5 premières années du programme pilote du département du Doubs.

OBJECTIVE: To analyze women participation and test results during the 1993 to 1997 screening cycle. METHODS: The program was managed by a multidisciplinary health professional committee who determined the screening policy according to the recommendations of the French consensus (Lille 1990). All smears and cervical histological tests taken from women living in the area were collected by centralizing data from cytopathological laboratories. RESULTS: Within five years, 71% of women in the 20-65 years age group had at least one smear. After the age of 29, participation rate decreased with age. The prevalence of unsatisfactory smears was 1.4/1000 and 3% of screened women had an abnormal smear (squamous intraepithelial lesion or carcinoma). A follow-up test was registered for 83% of women with an abnormal smear. Lesions were confirmed by histology in 77% of women with a histological test. CONCLUSION: In the context of initiating a national screening program, our study shows that implementing women invitation and follow-up and quality control procedures are necessary to improve the results of ongoing cervical cancer screening.

Genital human papillomavirus infection among women recruited for routine cervical cancer screening or for colposcopy determined by Hybrid Capture II and polymerase chain reaction.

The purpose of this study was to evaluate the clinical use of the Hybrid Capture (HC)-II system for the detection of human papillomavirus (HPV) DNA to identify women at risk of progression to high grade squamous intraepithelial lesions (HGSIL) and carcinomas by differentiating low risk (LR) HPV types (6, 11, 42, 43, 44) and high/intermediate risk (HR) HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68). Five hundred and ninety-six women were enrolled in the study. Among them, 466 attended the hospital for routine cytologic screening and 130 were referred for colposcopy because of an abnormal Pap smear. The presence of HPV DNA was tested in cervical samples collected with the Digene Cervical Sampler in Digene Specimen Transport Medium (Digene Corporation, Silver Spring, MD, U.S.A.) using the HC-II assay. Results were compared with those obtained by polymerase chain reaction (PCR) using the MY09-MY11 primers followed by several hybridizations with specific probes. The overall HPV positivity was 32.9% by HC-II and 37.8% by PCR. Among cytologically normal smears, 19.5% were positive by HC-II (14.3% HR) and 25.1% by PCR. Of the atypical squamous cells of undetermined significance samples, 52.9% were positive by HC-II (41.1% HR) and 55.9% by PCR. Of the low grade SIL, 64.5% were positive by HC-II (59.4% HR) and 68.7% by PCR. The HPV positivity rate was found identical by both techniques in high grade smears (81.6%) and squamous cervical carcinomas (100%). By using PCR as the reference method, the sensitivity of HC-II was higher among women with abnormal cytology than with normal cytology (87.3% vs. 70%). Specificity was 80.8% and 97.5%, respectively. In summary, these results indicate that the HC-II method and MY-PCR identified nearly equivalent prevalences of HPV in cervical smear specimens.

Immunohistochemical detection of p53 protein overexpression versus gene sequencing in urinary bladder carcinomas.

PURPOSE: Mutations of p53 tumor suppressor gene and nuclear accumulation of p53 protein are common in bladder tumors. The prognostic significance of p53 alterations in bladder tumors has not been established. The aim of the present study was to evaluate an immunohistochemical (IHC) method for the routine determination of p53 protein overexpression in human bladder tumors and to determine the relation between nuclear accumulation of p53 with the traditional prognostic indicators and patient survival. MATERIALS AND METHODS: 104 transitional cell carcinomas of the bladder were analyzed simultaneously by immunohistochemistry for p53 protein overexpression and direct DNA sequencing for p53 gene mutations. RESULTS: The overexpression of p53 protein was reported in 30.8% of the cases and mutations of p53 gene in 23.0%. A significant association was observed between p53 alterations established either by IHC or direct DNA sequencing and stage (p<0.0001), grade (p<0.001), vascular invasion (p = 0.0005), DNA ploidy (p = 0.0002) and carcinoma in situ (p<0.0001). The correlation between the p53 gene mutations and p53 nuclear reactivity as detected by IHC was highly significant (p<0.0001). Univariate statistical analysis showed that the expression of p53 was significantly correlated to poor prognosis (p<0.0001). However, in multivariate analysis, only stage was significantly correlated to prognosis (p<0.0001). CONCLUSIONS: The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does not appear to have a better predictive prognostic value than stage in bladder tumors.

[Value of histologic examination of the interamniotic membrane in the twin placenta for confirmation of chorionicity diagnosis]. / Intérêt de l'examen histologique de la membrane interamniotique du placenta gémellaire pour confirmation du diagnostic de chorionicité.

The interest of twin chorionocity and zygosity diagnosis is unquestioned. Indeed, in many medical situations, the knowledge of zygosity is an important fact for management of twins. Prenatal echographia is not a perfect tool to characterize chorionicity, and so postnatal examination of the placenta is always necessary. But macroscopic examination is also not relevant, and competent midwives can make many mistakes. Considering that biological postnatal diagnosis of twin zygosity is difficult and costly, we believe that microscopic chorionicity confirmation is required for identical twins.

[Antigenicity of fresh, cryopreserved, or liquid-medium-preserved human parathyroid adenomas]. / Antigénicité des adénomes parathyroïdiens humains frais, cryopréservés et conservés en milieu liquide.

We have studied the ability of the cryopreservation and culture techniques to reduce the antigenicity of human parathyroid tissue by suppressing HLA DR bearing cells. Antigenicity was studied with an immunoperoxidase technique applied on frozen sections. Antibody against HLA DR, CD1a, CD3, CD22, CD45RA, CD68 and H et Y antigens were used. In fresh parathyroid tissue, endothelial cells, histiocytes and interstitial dendritic cells expressed HLA DR antigens. Antigenicity of cryopreserved tissue were not altered. In cultured tissue, interstitial HLA DR bearing cells have disappeared but antigenicity of endothelial cells were not modified.

The level of the collagen cross-link pyridinoline reflects the improvement of cutaneous lesions in one case of skin alveolar echinococcosis.

Cutaneous parasitic lesions, associated with a dense fibrous reaction, markedly improved under albendazole treatment in one case of supraumbilical skin localization of alveolar echinococcosis. Since collagen cross-linking increases during fibrogenesis and contributes to the stability of fibrotic lesions, we monitored the level of the cross-links pyridinoline and pentosidine in skin lesions from this patient to determine if they would reflect the changes occurring during treatment. We looked at the deposition of cross-linked type I collagen by immunohistochemistry and also measured the serum concentrations of pentosidine and of a fragment of type I collagen (ICTP), which contains a site of pyridinoline formation. Albendazole treatment did not affect either the collagen content of skin lesions or the serum concentrations of ICTP and pentosidine, but it led to a pronounced decrease in pyridinoline level concomitant with the disappearance, observed by immunohistochemistry, of extensively cross-linked fibrotic type I collagen. The follow-up of collagen cross-linking by pyridinoline in skin tissue thus appears to be useful in reflecting the improvement of fibrotic skin diseases during therapy.

Echinococcus multilocularis: relationship between susceptibility/resistance and liver fibrogenesis in experimental mice.

To analyze collagen and other matrix protein deposits in experimental alveolar echinococcosis as well as the expression of lysyl oxidase, the enzyme that initiates the first steps in the pyridinoline cross-linking of collagen, and to establish a relationship between resistance/susceptibility to Echinococcus multilocularis larval growth and fibrogenesis, we compared AKR/J mice (susceptible to E. multilocularis infection) with NMRI mice (resistant hosts) in this study. Collagen deposits in the lesions were evaluated using a colorimetric method; the nature of matrix proteins involved in the periparasitic fibrosis and lysyl oxidase expression were assessed using immunostaining on tissue sections. The results obtained in this sequential study confirm that fibrogenesis is an important aspect of the host immune reaction against parasitic development and that both the extent and the course of matrix protein deposition differ in the liver of susceptible and resistant mice, respectively. The long-lasting expression of alpha-actin and lysyl oxidase by host cells in NMRI mice suggests that in this resistant strain, fibrosis was not only more developed but also more highly cross-linked and, thus, less sensitive to collagenases than in susceptible mice. A very strong expression of lysyl oxidase by parasitic cells was observed in both strains of mice; the observation that E. multilocularis itself has a role in lysyl oxidase cross-linking of host collagens can be hypothesized and would be a new example of parasite-host interplay.

Intestinal and systemic humoral immunological events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs.

The aim of the study was to investigate the systemic and, for the first time, the intestinal humoral events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs. Thirty-one mice were divided into three groups; W-2, W-8 and control group. Each mouse of the W-2 and W-8 groups was orally infected with 1,500 E. multilocularis eggs, two weeks and eight weeks before sacrifice respectively. Control group mice received phosphate buffer saline. Measurement of anti-E. multilocularis and non-specific IgG, IgA and IgM, and of a transudation marker, albumin, were performed in serum and intestinal washings by a time-resolved immunofluorometric assay. These results were complemented by microscopic examination of the intestinal mucosa. This infection model is well-suited to the study of mucosal immunity during alveolar echinococcosis. It showed a major specific intestinal response in the early stage of the disease whereas the systemic response predominated later in the disease. Histopathological studies and calculation of the relative coefficient of excretion of Ig also confirmed that the presence of the parasite, even during a short period, was responsible for a local immunological and inflammatory response and for a change in mucosal permeability. Mucosal immunity could thus play a role in tolerance induction against E. multilocularis that could be a prerequisite for the subsequent development of the larvae in the liver, and for the occurrence of the parasitic disease, alveolar echinococcosis.

[Acute cytolytic hepatitis caused by coumarin. 2 cases]. / Hépatite aiguë cytolytique à la coumarine. Deux cas.

Coumarin is a drug which is extensively used to treat lymphedema. We report two cases of acute hepatitis probably due to coumarin. Two women, 40 year and 45 year-old, were treated with 90 mg/d of coumarin for 5 months. Clinical features included jaundice, pruritus, and diarrhea. A marked increase in serum aminotransferases was observed (ALT: 30 and 100 times the upper limit of normal, respectively). Coumarin withdrawal was rapidly followed by a favorable outcome in both cases. Rechallenge in one case induced a relapse of symptoms and liver test abnormalities. Coumarin can induce acute cytolytic hepatitis.

[Obliterative arteriopathy in chronic rejection after hepatic transplantation. Search of cytomegalovirus genome by in situ hybridization and viral antigens by immunohistochemistry]. / Artériopathie oblitérante du rejet chronique après transplantation hépatique. Recherche du génome du cytomégalovirus par hybridation in situ et des antigènes viraux par immunohistochimie.

OBJECTIVES: This study was performed to assess the role of cytomegalovirus in the parietal infection of intrahepatic arteries in the pathogenesis of obliterative arteriopathy from chronic rejection after orthotopic liver transplantation. METHODS: We studied two groups of liver transplants by in situ hybridization and immunohistochemistry: group 1, including 10 liver grafts with obliterating arteriopathy, and group 2 including 7 liver grafts without any arterial disorders. The results were correlated with clinical data (cytomegalovirus infection and acute rejection). RESULTS: By in situ hybridization, cytomegalovirus DNA was identified in the media in 70% of transplants in group 1 and 42% in group 2. Detection of immediate early and late antigens by immunohistochemistry was negative. Cytomegalovirus infections were often associated with acute rejection. CONCLUSION: These results suggest that cytomegalovirus detected in arteries is latent, and that cytomegalovirus probably does not play a role in the pathogenesis of chronic rejection obliterative arteriopathy.

[Amyloid goiter. Report of two cases]. / Le goitre amyloïde. A propos de deux observations.

We report two cases of amyloid goiter which clinical appearance had evoked a neoplastic lesion. The diagnosis was made by histologic examination. The nature of the amyloid precursor, determined by immunohistochemistry, has allowed to evoke primitive amyloidosis in one case and to attribute amyloid goiter to renal insufficiency in the second case.