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Biomedical subjects

M Polak

Publications and source records attributed to M Polak.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Basedow's disease in an adolescent with histiocytosis X].

BACKGROUND: Immunological dysfunction is known to be present in Langerhans cell histiocytosis; some autoimmune diseases with autoantibodies associated with this condition have already been described. This immunological dysfunction could play a role in the Langerhans cell histiocytosis pathogenesis. CASE REPORT: A 13 year-old boy presented a multifocal bone Langerhans cell histiocytosis associated with Graves' syndrome. This last condition was successfully treated with carbimazole while the focal lesions of histiocytosis did not require any treatment. CONCLUSION: This unique association could be explained by the immunological dysfunction seen in Langerhans cell histiocytosis with secondary appearance of thyreo-stimulating antibodies.

Adolescent↗
PubMed1997

[Severe ketoacidosis because of delayed diagnosis of diabetes in children. 4 cases to alert physicians].

BACKGROUND: In France, 48% of children with insulin-dependent diabetes mellitus (IDDM) are seen for the first time at the stage of keto-acidosis (DKA), a figure far higher than in other countries. The four consecutive cases reported in this paper suggest that severity at presentation is directly related to the delay of diagnosis. CASE REPORTS: All children, aged 6 to 11, presented with severe clinical and metabolic conditions: coma, hemodynamic failure, severe dehydration and acidosis (pH = 6.86 to 7.06). However, clinical symptoms were a present from 2 to 4 months, parents did not worry about them. Family practitioners visited 2-21 days before admission failed to immediately make the diagnosis of IDDM. True DKA was however present in all cases 48 hours prior to admission. CONCLUSIONS: Earlier diagnosis of IDDM in children is necessary to reduce morbidity and mortality of DKA. General practitioners, pediatricians and emergency care practitioners must be made fully aware to consider diabetes in children and to use more extensively glucose-tests based on urine and blood strips.

Child↗
PubMed1997

Fetal cord blood sampling in the diagnosis and the treatment of fetal hyperthyroidism in the offsprings of a euthyroid mother, producing thyroid stimulating immunoglobulins.

We described here three individual pregnancies in a euthyroid mother with a past history of Graves disease and high levels of thyrotropin receptor stimulating antibodies. Ten years prior to her first pregnancy the mother underwent a partial thyroidectomy for Graves disease and remained euthyroid since, but still produced high levels of thyrotropin receptor stimulating antibodies. Fetal and postnatal hyperthyroidism was not recognized for the first child who was referred to us at one year of age for craniostenosis. During the two next pregnancies fetal hyperthyroidism was suspected on the basis of fetal tachycardia, growth retardation, fetal goiter and fetal cord blood sampling confirmed high levels of free T3, free T4, suppressed fetal TSH levels, and high levels of fetal TRAb. The mother received propylthiouracil to control fetal hyperthyroidism. Neither baby was premature and each had a more favorable outcome than the first. Fetal cord blood sampling proved to be useful during these two pregnancies to ascertain the diagnosis of fetal hyperthyroidism and to monitor the dose of PTU administered to this euthyroid mother.

Adult↗
PubMed1996

Clinical and pathological associations with p53 tumour-suppressor gene mutations and expression of p21WAF1/Cip1 in colorectal carcinoma.

Inactivation of the p53 tumour-suppressor gene is common in a wide variety of human neoplasms. In the majority of cases, single point mutations in the protein-encoding sequence of p53 lead to positive immunohistochemistry (IHC) for the p53 protein, and are accompanied by loss of the wild-type allele. Recently, the WAF1/Cip1 gene was identified as one of the genes induced by wild-type p53, and increased expression of p21WAF1/Cip1 has been found to reflect the status of the p53 tumour-suppressor pathway. We investigated the inactivation of p53 in a relatively small, but well-characterised, group of 46 colorectal carcinomas that were previously studied for allelic alterations, ras oncogene mutations and DNA aneuploidy. Alterations in p53 were identified by IHC, loss of 17p and DNA sequence analysis of exons 5-8, whereas p21WAF1/Cip1 protein expression was determined by IHC. p53 mutations were identified in 19 of the 46 tumours (41%), whereas positive IHC for p53 was found in 21 of the 46 tumours (46%). Positive IHC for p21WAF1/Cip1 was detected in 16 of 42 cases (38%). We found no relationship between p21WAF1/Cip1 staining and p53 protein expression or p53 mutational status. Inactivating mutations in the p53 gene correlated with LOH at 17p but not with LOH at 5q or 18q, Dukes' stage, tumour grade or DNA ploidy. There was a higher survival rate independent of Dukes' stage in the group with no alterations in p53 compared with those with evidence of dysfunction of p53, but the difference was not statistically significant. We conclude that inactivation of p53 and altered expression of p21WAF1/Cip1 are common in colorectal carcinoma but do not correlate with each other or with the clinical or pathological parameters investigated.

Adenocarcinoma↗
PubMed1996

A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism.

Until recently, neonatal hyperthyroidism has been considered to be related to the transplacental passage of thyroid-stimulating Ig present in the serum of the mother. We report here the case of a newborn who presented with severe hyperthyroidism, diffuse goiter, and important ocular signs (eyelid retraction and possibly proptosis). However, the absence of thyroid pathology in the parents and the lack of antithyroid antibodies in the mother and in the patient led us to suspect a nonimmune aetiology. Direct genomic sequencing of the last exon of the TSH receptor in the patient revealed a T-->C transversion yielding to a Met453-->Thr heterozygous substitution in the second transmembrane domain of the receptor. The mutation was absent in both parents. Eukaryotic expression analysis in COS-7 cells yielded a mutated receptor that produced constitutive activation of adenylate cyclase without enhancement of phospholipase C activity.

Amino Acid Sequence↗
PubMed1996

Subcutaneous or intramuscular injections of insulin in children. Are we injecting where we think we are?

OBJECTIVE: This study was designed to assess the insulin injection location in a group of children who had their injection according to their daily practice, thought to lead to subcutaneous injections. RESEARCH DESIGN AND METHODS: The location of the insulin deposit at the injection site was visualized using an ultrasound device. RESULTS: The exact insulin injection location could be localized, and 18 of 59 injections (30.5%) (one injection for each child) were in the intramuscular tissue. Of the children who had intramuscular injection, 15 of 18 were boys. The children who had an intramuscular injection had a significantly lower percentile of BMI (mean +/- SE: 47 +/- 8 vs. 72 +/- 4, P = 0.004), lower distance from skin surface to muscle fascia without a skinfold (5.6 +/- 0.6 vs. 11 +/- 0.7 mm, P < 0.0001), and a lower distance from skin surface to muscle fascia with a skinfold (8.1 +/- 0.9 vs. 15.9 +/- 0.8 mm, P < 0.0001) than children who had a subcutaneous insulin injection. CONCLUSIONS: We identified a group of children at risk for intramuscular insulin injections and that may deserve specific injection technique and advice.

Analysis of Variance↗
PubMed1996

Case report: insulin-dependent diabetes mellitus in childhood associated with scleroderma.

A 14-year-old boy presented with Type I diabetes mellitus and subsequently developed pancreatic exocrine insufficiency and systemic sclerosis (SSc). His diabetes had been diagnosed when he was about 5 years old, after the onset of ketoacidosis. Insulin treatment was provided from then until the time he was treated in our department. Exocrine pancreatic insufficiency, which occurred at age 9, was treated with pancreatic extracts. Cystic fibrosis was excluded after a chloride sweat test. The diagnosis of SSc was confirmed at age 14 on the basis of skin sclerosis, sclerodactyly and oesophageal and pulmonary involvement and then at age 18 by the occurrence of Raynaud's disease. Thus, this patient demonstrated a rare and previously unreported association of Type I diabetes mellitus and systemic scleroderma. Limited joint mobility and skin abnormalities are frequent in childhood diabetes mellitus but should not be misdiagnosed as systemic scleroderma.

Adolescent↗
PubMed1995

Dexamethasone regulates the expression of neuronal properties of a rat insulinoma cell line.

Insulin producing cells of the pancreas (beta cells) and neuronal cells share a large number of similarities. For example, different molecules, thought to be specific of neuronal cells, are expressed by beta cells. The factors regulating the expression of these molecules in beta cells are poorly understood. In the present work, we have studied the effect of dexamethasone, a synthetic glucocorticoid, on the expression of three different neuronal traits expressed by INS-1 cells, a highly differentiated beta cell line. We demonstrate that dexamethasone treatment decreases the steady state levels of mRNAs coding for both the low- and the high-affinity NGF receptors and of mRNA coding for NF-H, an intermediate neurofilament specific of neurons. This effect was time-dependent, the decrease being detectable after 4-8 h treatment. The decrease in NGF receptors mRNAs steady state levels was paralleled by a decrease in the number of NGF binding sites as demonstrated after Scatchard analysis. We further focused on the mechanisms by which dexamethasone affects the expression of the low affinity NGF receptor. The effect is countered by the glucocorticoid antagonist RU486, indicating that it is mediated by the glucocorticoid receptor. Finally, the decrease in the low-affinity nerve growth factor receptor mRNA steady state level after dexamethasone treatment is not due to mRNA destabilization but can be rather explained through a change in gene transcription.

Animals↗
PubMed1994

Overexpression of p53 protein in adenocarcinoma of the pancreas.

Mutations in the p53 tumor suppressor gene are frequently identified in human neoplasms. These mutations may be associated with stabilization and, therefore, with overexpression of the p53 protein product as determined by immunohistochemical staining. Using a new antigen retrieval method and a polyclonal antibody to p53 (CM-1), the authors examined 48 formalin-fixed paraffin-embedded adenocarcinomas of the pancreas for overexpression of the p53 gene product. These 48 carcinomas were obtained from a series of patients with well-documented clinical histories and extensive follow-up. The carcinomas had been analyzed previously for K-ras gene mutations, tumor ploidy, and tumor proliferating index. Specific diffuse nuclear staining for the p53 protein was identified in 19 of the 48 (40%) infiltrating carcinomas examined. Focal or negative staining was seen in the remaining 29 cases (60%). In addition, 17 of the neoplasms contained synchronous in situ carcinomas; two (12%) of these displayed diffuse nuclear staining for the p53 protein. Overexpression of p53 was associated with aneuploidy (P = .05), which had been a poor prognosticator in this series of adenocarcinomas of the pancreas. Although overexpression of p53 appeared to be associated with poor prognosis (hazard ratio, 1.8; P = .07), this was not statistically significant. Overexpression of p53 was not significantly associated with K-ras oncogene mutations or tumor proliferating index. The authors conclude that overexpression of the p53 protein occurs frequently in invasive adenocarcinomas of the pancreas and in some in situ carcinomas, as well.

Adenocarcinoma↗
PubMed1993

Nerve growth factor induces neuron-like differentiation of an insulin-secreting pancreatic beta cell line.

Nerve growth factor (NGF) is the best understood of a class of trophic proteins that are important for the survival of neurons and the elaboration of their characteristic processes. Here we demonstrate that RINm5F, a rat insulinoma cell line representing an early stage in pancreatic beta cell differentiation, expresses both the Trk and p75 NGF receptors and responds to NGF by extending neurite-like (neurofilament-containing) processes. NGF treatment of RINm5F cells also induces the expression of genes normally responsive to NGF in neurons, including the NGF-1A gene. Inasmuch as pancreatic beta cells arise from the embryonic endoderm, these results suggest that NGF may play a wider role during development than previously thought-a role not restricted to cells of neuroectodermal origin--and that endocrine and neuronal cells share a developmental pathway. The specific effect of NGF on an early pancreatic beta cell line also suggests that this neurotrophic factor might form the basis of a therapeutic treatment for some types of diabetes by inducing the proliferative differentiation of islet cells.

Animals↗
PubMed1993

Genetic mapping of human heart-skeletal muscle adenine nucleotide translocator and its relationship to the facioscapulohumeral muscular dystrophy locus.

The mitochondrial heart-skeletal muscle adenine nucleotide translocator (ANT1) was regionally mapped to 4q35-qter using somatic cell hybrids containing deleted chromosome 4. The regional location was further refined through family studies using ANT1 intron and promoter nucleotide polymorphisms recognized by the restriction endonucleases MboII, NdeI, and HaeIII. Two alleles were found, each at a frequency of 0.5. The ANT1 locus was found to be closely linked to D4S139, D4S171, and the dominant skeletal muscle disease locus facioscapulohumeral muscular dystrophy (FSHD). A crossover that separated D4S171 and ANT1 from D4S139 was found. Since previous studies have established the chromosome 4 map order as centromere-D4S171-D4S139-FSHD, it was concluded that ANT1 is located on the side of D4S139, that is opposite from FSHD. This conclusion was confirmed by sequencing the exons and analyzing the transcripts of ANT1 from several FSHD patients and finding no evidence of aberration.

Alleles↗
PubMed1993

Overexpression of the p53 tumor suppressor gene product in primary lung adenocarcinomas is associated with cigarette smoking.

Mutations in the p53 tumor suppressor gene are frequently observed in primary lung adenocarcinomas, suggesting that these mutations are critical events in the malignant transformation of airway cells. These mutations are often associated with stabilization of the p53 gene product, resulting in the accumulation of p53 protein. In this study, 70 formalin-fixed, paraffin-embedded primary lung adenocarcinomas resected for potential cure were examined for p53 overexpression. These 70 lung adenocarcinomas were obtained from a series of patients with well-documented clinical histories, and all 70 carcinomas had been previously evaluated for point mutations in codon 12 of the K-ras oncogene. Overexpression of the p53 protein was detected using an antigen retrieval system (Target Unmasking Fluid) and the anti-p53 antibody CM-1. CM-1 is a polyclonal antibody directed against the wild-type p53 protein. Overexpression of the p53 protein was found in 23 (33%) of the 70 lung adenocarcinomas. In all 23 cases, overexpression was confined to neoplastic cells. Overexpression of the p53 protein correlated with cigarette smoking: 10 (56%) of the 18 adenocarcinomas from patients who were current smokers overexpressed p53 compared with 13 (33%) of the 40 adenocarcinomas from patients who had quit smoking and 0 (0%) of the 12 adenocarcinomas from patients who had never smoked (p = 0.002, trend test). Overexpression of the p53 protein was also related to the degree of histologic differentiation: 48% of the p53 negative carcinomas were well differentiated, whereas only 13% (p = 0.003) of the carcinomas in which p53 was overexpressed were well differentiated. Overexpression of the p53 protein did not correlate with point mutations in codon 12 of the K-ras oncogene, nor did it correlate with tumor stage or patient survival. These findings indicate that p53 protein is frequently overexpressed in primary lung adenocarcinomas. Furthermore, the association of tobacco smoking with this overexpression suggests that the p53 gene is a target of specific mutagens in tobacco smoke.

Adenocarcinoma↗
PubMed1993

Decreased risk of type I diabetes in offspring of mothers who acquire diabetes during adrenarchy.

Fathers with type I diabetes transmit diabetes to their offspring 2-3 times more frequently than mothers with type I diabetes. This phenomenon has provoked both genetic and nongenetic hypotheses, but the mechanism remains obscure. We find that mothers who develop diabetes before age 8 transmit diabetes at the same rate as diabetic fathers, and that the sex difference in diabetes transmission is explained by a decreased transmission rate in mothers who acquired diabetes after age 8. We constructed a data base containing 2156 nondiabetic and diabetic offspring of parents with type I diabetes. Families were selected from our main data base, which contains demographic information and diabetes autoantibody test results on > 8000 first-degree relatives of patients with type I diabetes and diabetic probands. Identification of offspring was made through diabetic parents who had participated in our autoantibody screening program at the Joslin Diabetes Center between 1983 and 1990. Questionnaires were sent to all other family members to determine the number of diabetic and nondiabetic offspring in each family. The 20-yr life-table risk of diabetes in offspring of diabetic fathers and mothers is 8.9 +/- 1.0 and 3.4 +/- 0.6%, respectively. For mothers acquiring diabetes before or after age 8, the risk of diabetes in offspring is 13.9 +/- 4.4 and 2.4 +/- 0.6% at 20 yr of age, respectively. Furthermore, we find that duration of diabetes in mothers before pregnancy has no effect on the risk of diabetes in their offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗