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Biomedical subjects

L David

Publications and source records attributed to L David.

At least 19 recordsLinked to original sources

Mutation rate and pattern of microsatellites in common carp (Cyprinus carpio L.).

Microsatellites are popular molecular markers in genetic and evolutionary studies. Their mutational dynamics have been extensively studied in humans and fruit flies, but few data were available in fish. By genotyping 55 individuals of a F1 pedigree, we investigated the mutation rates and patterns of 49 microsatellites in one of the most important fresh water fish species, the common carp (Cyprinus carpio L.). The overall mutation rate of the 49 loci was 5.56 x 10(-4)/locus/generation (95% confidence interval 1.52 x 10(-4) and 1.63 x 10(-3)). The change of allele size was between +2 to -5 repeat units, assuming that the mutation allele arose from the parental allele most similar in size to the mutant.

Animals↗

Two-stage hepatectomy: an analysis of a single center's experience.

Hepatic resection remains the only potential curative treatment for either primary or secondary liver tumors. In order to increase the resectability of initially unresectable tumors and to decrease the posthepatectomy morbidity and mortality, ligation and section of a portal branch with consecutive hepatic resection is recommended. Between September 1st 1999 and January 1st 2006, in the Department of General Surgery and Liver Transplantation of Clinical Institute Fundeni (Bucharest), the ligation of a portal branch was performed in 15 patients with gross hepatic tumors: hepatocellular carcinoma (2 cases), peripheral cholangiocarcinoma (6 cases) and hepatic metastases for colorectal cancer (7 cases). Two-stage hepatectomy was performed in 8 cases. The interval between the two operations ranged between 4 weeks and 2 months (except one case that returned to us only after 6 months, when was reevaluated and resected). Hepatic resection could not be performed in 7 cases due to the local and regional progression of the disease (4 cases) or to the absence of the hypertrophy-atrophy process (3 cases). In the 8 resected cases, hepatic failure occurred posthepatectomy in 2 patients, resulting in the death of one patient; that means a mortality of 12.5%. Other two patients died at 4 and 10 months respectively, as a result of distant metastases. The rest of 5 patients are alive, free of recurrence; two of them have more than 5 years from the operation. CONCLUDING: portal vein ligation can be performed in selected cases of unresectable gross hepatic tumors. Two-staged hepatectomy is not always feasible. Moreover, the hypertrophy of the contralateral lobe does not always prevent the postoperative hepatic failure. For the cases that can be resected, both survival and quality of life are significantly improved.

Female↗

Evidence for a major gene affecting the transition from normoglycaemia to hyperglycaemia in Psammomys obesus.

We investigated the mode of inheritance of nutritionally induced diabetes in the desert gerbil Psammomys obesus (sand rat), following transfer from low-energy (LE) to high-energy (HE) diet which induces hyperglycaemia. Psammomys selected for high or low blood glucose level were used as two parental lines. A first backcross generation (BC(1)) was formed by crossing F(1) males with females of the diabetes-prone line. The resulting 232 BC(1) progeny were assessed for blood glucose. All progeny were weaned at 3 weeks of age (week 0), and their weekly assessment of blood glucose levels proceeded until week 9 after weaning, with all progeny maintained on HE diet. At weeks 1 to 9 post weaning, a clear bimodal distribution statistically different from unimodal distribution of blood glucose was observed, normoglycaemic and hyperglycaemic at a 1:1 ratio. This ratio is expected at the first backcross generation for traits controlled by a single dominant gene. From week 0 (prior to the transfer to HE diet) till week 8, the hyperglycaemic individuals were significantly heavier (4--17%) than the normoglycaemic ones. The bimodal blood glucose distribution in BC(1) generation, with about equal frequencies in each mode, strongly suggests that a single major gene affects the transition from normo- to hyperglycaemia. The wide range of blood glucose values among the hyperglycaemic individuals (180 to 500 mg/dl) indicates that several genes and environmental factors influence the extent of hyperglycaemia. The diabetes-resistant allele appears to be dominant; the estimate for dominance ratio is 0.97.

Animals↗

Distribution of HPV infection and tumour markers in cervical intraepithelial neoplasia from cone biopsies of Mozambican women.

AIMS: To evaluate human papillomavirus (HPV) infection in whole cervical cone specimens with cervical intraepithelial neoplasia (CIN). In addition, to evaluate the relation between the presence of CIN lesions and HPV infection and the expression of Ki-67, p53, cytokeratins, Gp230 glycoprotein, and simple mucin-type carbohydrates. METHODS: Cervical cone specimens from five patients with CIN were studied. For each specimen, serial sections encompassing the whole cone were collected (52 samples). HPV infection and HPV types were detected by the polymerase chain reaction and enzyme immunoassay. The expression of Ki-67, p53, cytokeratins, Gp230, and simple mucin-type carbohydrates was examined immunohistochemically. RESULTS: All cases showed high risk HPV types, namely types 16, 33, 35, and 58. Four of the five patients were infected by multiple viral types. HPV-58 was always seen in CIN III, whereas HPV-35 was more frequent in CIN I. The expression of Ki-67 and p53 was higher in CIN III lesions. The expression of cytokeratins 8 and 17 showed complete or almost complete overlap with CIN III. Altered expression of Gp230, Tn, and sialyl-T was often seen in all grades of CIN. CONCLUSIONS: When whole cervical cone specimens are evaluated the rate of multiple HPV infection is very high. The expression of cytokeratins 8 and 17 is a useful marker of CIN III.

Biomarkers, Tumor↗

Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism.

Aberrant glycosylation of mucins is a common phenomenon associated with oncogenic transformation. We investigated the association between expression of the tumor-associated antigens T, Tn, and sialyl-Tn and polymorphism in the length of the MUC1 mucin tandem repeat in a series of gastric carcinomas. We further evaluated the relevance of MUC1 tandem repeat length on the expression of these tumor-associated carbohydrate antigens (TACAs) using a gastric carcinoma cell line model expressing recombinant MUC1 constructs carrying 0, 3, 9, and 42 repeats. Gastric carcinomas showed a high prevalence of Tn and sialyl-Tn antigens, whereas T antigen was less frequently expressed. The expression of T antigen was significantly higher in gastric carcinomas from patients homozygous for MUC1 large tandem repeat alleles. No significant associations were found for Tn and sialyl-Tn antigens. This novel association was reinforced by the gastric carcinoma cell line model experiments, where de novo expression of T antigen was detected in clones transfected with larger VNTR regions. Our results indicate that polymorphism in the MUC1 tandem repeat influences the expression of TACAs in gastric cancer cells and may therefore allow the identification of subgroups of patients that develop more aggressive tumors expressing T antigen.

Antigens, Tumor-Associated, Carbohydrate↗

MUC5B expression in gastric carcinoma: relationship with clinico-pathological parameters and with expression of mucins MUC1, MUC2, MUC5AC and MUC6.

Previous studies have shown that mucin expression can be used to evaluate differentiation patterns of gastric carcinoma: MUC5AC expression is associated with diffuse type and early gastric carcinomas, and MUC2 expression is associated with mucinous gastric carcinomas. The role played by MUC5B in the evaluation of differentiation and biological behaviour of gastric carcinoma is largely unknown. Our aim was to characterise the pattern of expression of mucins MUC1, MUC2, MUC5AC, MUC5B and MUC6 in a series of 50 gastric carcinomas to evaluate whether MUC5B expression was associated with the clinico-pathological characteristics of the cases and/or with the co-expression of other mucins. A panel of six monoclonal antibodies (HMFG1, SM3, PMH1, CLH2, EU-MUC5Ba and CLH5) was used to determine the expression of mucins (MUC1, MUC1 underglycosylated form, MUC2, MUC5B, MUC5AC and MUC6, respectively) using immunohistochemistry. Cases were considered positive if more than 5% of the cells expressed immunoreactivity for the several mucins evaluated. Our results showed that: (a) expression of MUC5B was observed in 11 cases (22.0%) and was associated with the "unclassified" histological type of gastric carcinoma according to Laurén ( P = 0.03) and with the absence of venous invasion ( P = 0.02); (b) in this series, MUC5B expression had no impact on survival of patients with gastric carcinoma; (c) the expression of MUC5B was associated with the co-expression of MUC5AC ( P = 0.02) and (d) none of the cases with the so-called complete intestinal phenotype of mucin expression expressed MUC5B.

Antibodies, Monoclonal↗

The use of chondrogide membrane in autologous chondrocyte implantation.

UNLABELLED: Autologous chondrocyte implantation is a new technique for the treatment of chondral defects in the knee. The exact procedure involved is continuously being developed with the ultimate aim of achieving hyaline cartilage regeneration. We present the outcome of our series of 31 patients, focussing on the use of the chondrogide membrane in the implantation process. Assessment is presented both in the form of arthroscopic appearance at approximately 1 year, and in the form of clinical outcome measures at 1 year and at 2 years after the second stage of the procedure. CONCLUSION: the use of chondrogide membrane in the fixation of cells during the implantation process is associated with satisfactory clinical outcome and does not appear to show evidence of hypertrophy at one-year arthroscopy, as compared to periosteum.

Adolescent↗

Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma.

AIMS: Mutations in the gene coding for p53 protein are among the most frequent genetic alterations observed in human cancers. The relevance and biological significance of p53 expression in gastric carcinoma are far from being fully established. The aim of our study was to evaluate the influence of p53 detected by immunohistochemistry in the clinicopathological behaviour of a series of gastric carcinoma cases. METHODS AND RESULTS: Samples from 163 patients treated by gastric resection for gastric carcinoma between 1988 and 1995 were used. Surgical specimens were evaluated for the presence of p53 protein detected by immunohistochemistry with a monoclonal antibody. Cases were classified as positive or negative for p53. Several clinicopathological parameters and c-erb B-2 expression were analysed in the same series and compared with the expression of p53. Cumulative survival was evaluated using univariate analysis and Cox model regression. p53 expression was identified in 41 carcinomas (25.2%) and was significantly associated with venous invasion (P = 0.049), lymph node metastases (P = 0.01) and c-erb B-2 expression (P = 0.003). All the parameters except gender, tumour size and Laurén's classification influenced survival on univariate analysis. p53 expression correlated with overall survival (P = 0.006) and survival in the subgroup of patients with intestinal type carcinoma (P = 0.04). In the subgroup of patients with carcinomas not expressing c-erb B-2, p53 expression significantly influenced cumulative survival (P = 0.02). CONCLUSIONS: p53 expression is associated with the aggressive biological behaviour of gastric carcinomas and is related to cumulative survival.

Adult↗

[Usher's syndrome].

PURPOSE: to show the manner of diagnose of this syndrome and to evaluate the possibilities of treatment MATERIAL AND METHOD--there are shown: --ophthalmological and ENT clinical examination --visual field test--adaptometry--audiometry --impedance--auditive evoked potentials--cataract extraction (phacoemulsification). RESULTS: After cataract extraction the visual acuity increase. CONCLUSIONS: For the diagnosis we need both the diagnosis of retinitis pigmentosa and neurosensorial deafness. For the certainty of the diagnosis genetic tests are required. The treatment of associate ocular pathology may increase the visual status.

Hearing Loss↗

Peptide mimotopes of oncoproteins as therapeutic agents in breast cancer.

Generation of an immune response to oncoproteins can lead to a cancer specific protective immunity. Several such oncoproteins are being examined as tumor targets with mixed results. We are evaluating the clinical utility of synthetic peptides that would mimic the antigen immunologically and elicit a tumor specific immune response. HER-2/neu, an oncoprotein whose expression in breast cancer is associated with poor prognosis, lower disease free-survival and a propensity for metastases was chosen as a model. Antibodies, Ab2, Ab4 and Ab5 directed towards the extracellular domain of HER-2/neu were reacted to peptides from two synthetic phage display peptide libraries, LX-8 (12-mer peptide library containing disulfide bridge) and X-15 (linear 15-mer). The isolated peptides were sequenced and characterized for ability to produce high titer antibodies and cross-reactivity. The peptides isolated did not show any sequence homology to protein databases but did show a hierarchy of immunogenic epitopes. Antibodies generated against peptides selected against the same antibody Ab2 or Ab4 showed affinity variation. Phages selected against Ab2 were also able to compete with binding of Ab2 to HER-2/neu. These results validate our hypothesis that synthetic peptides that mimic the antigenic epitope of oncoprotein can be generated and their clinical utility rests on devising a screening mechanism to identify peptides that can elicit an immune response directed to the oncoprotein and if possible its antigenic variants.

Animals↗

[Neurologic signs revealing a Behçet's disease: two pediatric case reports].

UNLABELLED: Behçet's disease can be revealed by neurologic signs. CASE REPORTS: We report two pediatric cases of Behçet's disease which initially presented with cerebral venous thrombosis. Glucocorticoïds, associated with anticoagulant treatment allowed a rapid recovery. One of the children presented three years later a thrombotic recurrence. CONCLUSION: A cerebral venous thrombosis may reveal Behçet's disease.

Adolescent↗

[Feeding jejunostomy and protective ileostomy in acute necrotizing pancreatitis].

The authors emphasize the complexity of the problem of treating acute necrotizing pancreatitis. On their own group of 52 operated patients during 1995-2000 they present the gradual, in 2000 dramatic, improvement of results in which participate in addition to modern therapeutic procedures also the concentrated interest in the problem and the personal experience of the surgeons.

Enteral Nutrition↗

Polymorphism in ornamental and common carp strains (Cyprinus carpio L.) as revealed by AFLP analysis and a new set of microsatellite markers.

Forty-seven new microsatellite markers were generated and applied, together with the AFLP (Amplified Fragment Length Polymorphism) technique using two different enzyme combinations, to the genetic analysis of two carp species, Cyprinus carpio L. and Ctenopharyngodon idella. The extent of polymorphism and the genetic relationships between nine carp populations were studied. The incidence of microsatellites containing CA and CT motifs was estimated to be one every 17.4 and one every 126.3 kb, respectively, and their average allele numbers were four and five, respectively. Across populations, the average proportion of individuals that were heterozygous for microsatellite markers was 44.2% and the average allele number was 4.02. The EcoRI/TaqI combination generated more analyzable AFLP bands than the EcoRI/MseI pair, making the former preferable for the analysis of carp populations. The proportion of polymorphic AFLP bands within populations ranged from 6.7% in grass carp to 59.9% in Kohaku strain (Koi) of the ornamental carp. The fixation index (FST) for microsatellites in these populations was estimated to be 0.37, and for AFLP markers the value was 0.39. Genetic distance matrices derived from microsatellites and from two AFLP analyses were positively correlated. Grass carp showed fewer AFLP bands than other populations and was genotyped by only half of the microsatellite markers. These findings agree with genetic distance estimates in suggesting that the grass carp is phylogenetically quite remote from all the other populations examined.

Animals↗

Role of cytomegalovirus infection in the incidence of viral acute respiratory infections in children attending day-care centers.

In a prospective study carried out in Lyon, France, the association between the excretion of cytomegalovirus (CMV) and the increasing frequency and severity of viral respiratory infections in children attending day-care centers was evaluated. Urine samples were collected in November 1992 (S1) and 4 months later in February 1993 (S4). A total of 246 children aged 6-12 months attending 29 day-care centers from 1 November to 28 February were screened for the excretion of CMV in urine. The diagnosis of viral acute respiratory infection was performed in the case of outbreaks only. Forty-eight (19.5%) children were both S1 and S4 positive for CMV, 30 (12.4%) became CMV positive (S1-/S4+), 4 (1.6%) became negative (S1+/S4-) and 164 (66.7%) remained negative. The percentage of children becoming CMV positive was significantly (P<0.001) higher in day-care centers where more than 40 children were enrolled. Nine outbreaks due to respiratory syncytial virus, rhinovirus and enterovirus were recorded in 8 of 29 (27.6%) day-care centers. Viral acute respiratory infections were significantly (P<0.05) more frequently recorded in day-care centers in which CMV and respiratory viruses cocirculated and were significantly (P<0.001) more frequently reported in CMV-infected children. These findings suggest that viral acute respiratory infections are significantly more likely to occur in CMV-infected children.

Acute Disease↗

Leadzyme.

Explore the source record for details and available documents.

Base Sequence↗

[Eccrine neutrophilic hidradenitis: idiopathic plantar form in children].

UNLABELLED: In this study, two cases have been reported of idiopathic plantar hidradenitis, an uncommon dermatological pathology with a spontaneous favorable outcome. OBSERVATIONS: Two children aged 12 and 14 years presented with a painful papulo-nodular plantar rash with major functional impairment. The diagnosis of idiopathic plantar hidradenitis was considered, and then confirmed in one case by plantar biopsy. Non-steroidal antiinflammatory drugs, associated with paracetamol in one case were administered. The symptoms disappeared spontaneously within a few days in both cases, without any recurrence. CONCLUSION: A knowledge of the symptoms connected with plantar hidradenitis in the child allows a rapid diagnosis to be made without hospitalization or further medical examination. Analgesic treatment and rest seem to be the only useful approaches. Biopsy to investigate eccrine gland infiltration by neutrophils can only be proposed in the case of an abnormally prolonged duration or an atypical presentation of this pathology.

Acetaminophen↗

[Pigmented villonodular synovitis. Diffuse and localized forms in children].

UNLABELLED: Pigmented villonodular synovitis (PVS) is characterized by a locally aggressive synovial proliferation that engenders progressive destruction of cartilage and bone. Two cases, a diffuse and a localized form, are reported. CASE REPORT: 1) A 9.9-year-old boy followed up for a popliteal cyst presented with chronic arthritis of the left knee. Aspiration yielded a bloody synovial fluid. MRI showed a heterogeneous synovial process with decreased signal in both T1- and T2-weighted images. The diagnosis of PVS was made on histology of an excisional biopsy. A complete open synovectomy was then performed. 2) A 13.8-year-old boy had a palpable mass on the internal side of the right patellofemoral joint. MRI showed a heterogenous mass with areas of hypointensity on all spin echo sequences corresponding to hemosiderin deposits suggestive of PVS. Surgical excision of a reddish-brown circumscribed lesion was performed. Diagnosis of PVS was made at surgery and confirmed by histologic examination. CONCLUSION: PVS diagnosis is frequently delayed due to nonspecific symptoms. Bloody fluid aspiration and MRI are valuable tools for early diagnosis. Treatment is surgical: extensive synovectomy for the diffuse form, excision of the lesion for the localized form.

Adolescent↗