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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 271 records · Page 15Linked to original sources

Escherichia coli expressing a Neisseria gonorrhoeae opacity-associated outer membrane protein invade human cervical and endometrial epithelial cell lines.

Members of the opacity-associated (Opa) outer membrane protein family of Neisseria gonorrhoeae have been proposed to mediate adherence to and invasion of cultured human epithelial cells. We transformed Escherichia coli with a plasmid containing a gonococcal opa gene fused in-frame to the leader sequence of the beta-lactamase gene as described by Palmer et al. [Palmer, L., Brooks, G. F. & Falkow, S. (1989) Mol. Microbiol. 3, 663-671]. These transformed E. coli [E. coli (opa)] expressed the heat-modifiable opa gene product (the Opa protein) in their outer membrane and adhered to and invaded ME-180 human endocervical epithelial cells. In a 2-h adherence assay, an average of 26.7 E. coli (opa) adhered per ME-180 cell, whereas the control E. coli carrying only the expression vector (pKT279) did not adhere at all (less than 0.15 bacterium per cell). We investigated the ability of the adherent E. coli (opa) to invade ME-180 epithelial cells by using a gentamicin selection assay. We recovered up to 1 x 10(6) gentamicin-resistant bacteria per monolayer when ME-180 cells were infected with E. coli (opa) compared to less than 10 bacteria when the epithelial cells were infected with the same number of control E. coli (pKT279). The kinetics and level of invasion by E. coli (opa) were similar to invasion by Opa+ N. gonorrhoeae. Maximum invasion occurred 4 h after infection with 4 x 10(7) bacteria. Transmission electron microscopy studies confirmed that E. coli (opa) invaded ME-180 cells. In comparative studies, the number of E. coli (opa) that invaded HEC-1-B human endometrial epithelial cells was about an order of magnitude less than the number that invaded ME-180 cells, and E. coli (opa) did not invade Chang human conjunctival epithelial cells at all. The observations that early (less than 4 h) invasion by E. coli (opa) was dramatically inhibited, in a dose-responsive manner, by the actin-disrupting reagent cytochalasin D but later invasion (8-24 h) was not suggest that invasion mediated by Opa proteins may occur by two mechanisms, only one of which is dependent upon microfilament function. Transmission electron microscopy also revealed that infected epithelial cells had a dramatically increased amount of cytoplasmic fibrillar material surrounding the nucleus. The function and genesis of this material remain unclear. These studies indicate that at least one gonococcal Opa protein is an invasin.

Adenocarcinoma↗

The influence of aging on plasma sex hormones in men: the Telecom Study.

From April 1985 to July 1987, 1,408 healthy white men aged 20-60 years in Paris, France, recruited on an occupational basis, underwent a physical examination and measurements of plasma sex hormones in a cross-sectional study. Both total testosterone and estradiol showed a significant stepwise decrease with age (p less than 0.001) starting in the early adult years, while estrone did not vary. These relations of testosterone and estradiol with age remained significant after adjustment for body mass index, subscapular skinfold, and tobacco and alcohol consumptions, and they were not modified by exclusion of the men who reported chronic disease. Both the mechanism for the early decrease in testosterone and its clinical significance merit further investigation.

Adult↗

[Rupture of hepatic echinococcal cyst by minimal blunt abdominal trauma].

Hepatic echinococcosis is endemic in Israel, with about 90 new cases diagnosed each year. Although many are asymptomatic for years, 40% develop complications. We describe a man of 37 and women aged 22 and 35, respectively, in whom rupture of an echinococcal cyst followed minimal, blunt abdominal trauma. In each patient the rupture led to complications consisting of massive intra-abdominal bleeding in 1, diffuse peritonitis in another and cystocutaneous fistula with ureteral obstruction due to reactive retroperitoneal fibrosis in the third. All 3 underwent surgery to resolve the immediate complication, with no mortality. A striking feature was the disproportion between the stormy clinical presentation and the relatively innocent nature of the trauma. In only 1 of our cases was the correct preoperative diagnosis made, which in this condition depends primarily on a high index of suspicion.

Abdominal Injuries↗

Interrelation between plasma testosterone and plasma insulin in healthy adult men: the Telecom Study.

Plasma insulin is a risk factor for diabetes mellitus and cardiovascular disease in men. We investigated the association between plasma testosterone and plasma insulin in an occupational sample of 1292 healthy adult men. Total plasma testosterone decreased with each decade of age and insulin increased with each decade of age. In these cross-sectional data, this significant graded inverse association between testosterone and insulin was independent of age. The association was reduced but not explained by the addition of obesity and subscapular skinfold to the model. Adjustment for alcohol consumption, cigarette smoking and plasma glucose did not materially alter the association. These results are the reverse of the positive association of androgens with insulin in women and suggest alternative possible explanations for the effect of hyperinsulinaemia on cardiovascular disease risk. Prospective studies will be necessary to determine the direction and causal nature of this association.

Adult↗

Reliability of glucose measurement by glucose test strips in tropical conditions.

The reliability of glucose test strips and reflectance meters after storage in tropical conditions was assessed. In a first experiment, sealed bottles containing glucose test strips were stored for 1 month in closed sterilising ovens at 40 degrees C, one in dry (0% humidity) and the other in wet (75% humidity) conditions. Results were compared to measurements obtained with glucose test strips stored under standard Western conditions, in non-diabetic and diabetic patients, using the same standard reflectance meter. A second experiment was performed similarly, comparing the values obtained with reflectance meters stored in different conditions, using standard glucose test strips. Reproducibility was assessed on the basis of duplicate measurements for each condition of storage. We observed that temperature and humidity did not significantly affect the glucose test strips (1st experiment), while a slight underestimation of capillary blood glucose was found using reflectance meters stored at 50 degrees C, irrespective of the humidity (2nd experiment). All the correlation coefficients between duplicates were greater than 0.975 irrespective of the conditions of storage for glucose test strips and reflectance meters. Therefore, glucose test strips and reflectance meters appear fairly reliable at the grass-root level in the tropics, if used carefully.

Blood Glucose↗

Unilateral ureteral obstruction secondary to rupture of liver echinococcal cyst.

We report a case of ureteral obstruction by reactive retroperitoneal fibrosis secondary to rupture of a liver echinococcal cyst after minimal blunt flank trauma. The patient presented initially with a cyst-cutaneous fistula and was treated with mebendazole, since surgery was refused. Unilateral ureteral obstruction due to reactive dense retroperitoneal fibrosis developed 2 years later, which presumably was initiated by intense inflammatory reaction to the cyst content. Diagnosis was established by excretory urography, ultrasonography and computerized tomography, and was histologically confirmed. Hydronephrosis and hydroureter resolved following ureterolysis. This complication is anticipated to be encountered more frequently with the use of the new potent anthelmintic agents, which may successfully prevent daughter cyst formation but fail to abolish reactive retroperitonitis.

Aged↗

Homologous chromosomal locations of the four genes for inter-alpha-inhibitor and pre-alpha-inhibitor family in human and mouse: assignment of the ancestral gene for the lipocalin superfamily.

The inter-alpha-inhibitor (I alpha I) and pre-alpha-inhibitor (P alpha I) family is composed of three plasma protease inhibitors, I alpha I, P alpha I, and bikunin, whose chains are encoded by a set of three evolutionarily related heavy (H) chain genes designated H1, H2, and H3 and a fourth gene, the so-called alpha 1-microglobulin/bikunin precursor (AMBP) gene. The latter codes for a precursor that splits into: (i) alpha 1-microglobulin, which belongs to the lipocalin superfamily; and (ii) bikunin, which is made up of two tandemly arranged protease inhibitor domains and belongs to the superfamily of Kunitz-type protease inhibitors. The bikunin chain is found in I alpha I and P alpha I molecules and it is also present as a free molecule in plasma. In human, the AMBP and H2 genes have been mapped to 9q32-q34 and 10p14-p15, respectively, while the H1 and H3 genes are tandemly located at 3p21.1-p21.2. In situ hybridization mappings indicate that the mouse AMBP gene (Intin-4) is located at 4C1----C4, and the H1 (Intin-1) and H3 (Intin-3) genes are colocated at 14A2----C1. In interspecific backcrosses (C57BL/6Pas x Mus spretus) a TaqI restriction variant in (and/or near) the H2 (Intin-2) gene identified a linkage of this gene with other polymorphic loci, which assigns Intin-2 to the centromeric area of chromosome 2. All such assignments are in conserved chromosomal regions between human and mouse. Therefore the genetic events that gave rise to the four I alpha I family genes took place prior to the divergence between human and mouse.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-Globulins↗

G-protein mutations in thyroid tumors.

Tissue specific G-protein mutations have been found in differentiated thyroid cancer with a higher prevalence in tumors from German than from American patients. Since activating mutations of Gs are principally comparable to chronic TSH stimulation of these tumor-thyrocytes such mutations may predict changes in tumor development and patient prognosis. The fundamental background and recent results of studies on mutational activation of G-proteins are presented.

GTP-Binding Proteins↗

Case report: the management of penetrating cardiac trauma with major coronary artery injury--is cardiopulmonary bypass essential?

Major coronary artery injury in penetrating cardiac trauma is relatively uncommon and is associated with a poor prognosis. However, for a variety of reasons, the outcome for such patients has been improving during the last two decades. The main factor responsible for this change is, according to some authors, the use of emergency cardiopulmonary bypass (CPB). We present a case of complete transection of the LAD coronary artery managed by primary ligation of the vessel, but because of progressive signs of extensive myocardial infarction, the patient underwent emergency CPB and an aortocoronary bypass graft. The patient experienced a good cardiac recovery but died 5 days later of irreversible anoxic brain damage. In reviewing the literature concerning the absolute need for emergency CPB in the management of penetrating coronary artery injury (PCAI), we found that the overall outcome for patients treated with emergency CPB was not significantly better than for those treated with ligation alone. We believe that CPB is not always essential in the management of PCAI and should be instituted only when the injury to a main coronary artery is very proximal, whenever associated intracardiac injuries exist, or when the patient develops extensive myocardial infarction or uncontrolled arrhythmias following ligation of the injured coronary vessel.

Adult↗

Chagas' disease.

Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS.

Animals↗

Incidental finding of rectal carcinoma during transrectal US for prostatic diseases.

During transrectal ultrasound (TRUS), rectal carcinoma was an incidental finding in seven patients among a series of 5,000 TRUS examinations. TRUS was performed in seven patients with symptoms characteristic of prostatic diseases. All seven patients underwent examination by at least one physician before TRUS and, except for abnormal prostatic findings, no tumors were detected during digital rectal examination (DRE). The tumors were clearly visualized with TRUS and were easily palpated during DREs performed after TRUS. They were large and were located mainly along the posterior and lateral walls of the rectum. All the tumors were diagnosed by means of proctoscopy; the biopsy findings were positive, and the pathologic staging indicated advanced disease: adenocarcinoma of the rectum with a minimum grade of Dukes C. It is recommended that, in addition to evaluation of scans obtained in the transverse plane, the multiplane transducer be used to evaluate the longitudinal plane of the rectum for detection of possible undiscovered tumors.

Adenocarcinoma↗

Are cysteine-rich and COOH-terminal domains of dystrophin critical for sarcolemmal localization?

It has been hypothesized that the tight localization of dystrophin at the muscle membrane is carried out by its cysteine-rich and/or carboxyl domains. We report the results of biochemical and immunocytochemical investigations of dystrophin in muscle from a 1-yr-old patient with a large deletion that removes the distal part of the dystrophin gene, thus spanning the exons coding for the cysteine-rich and the carboxy-terminal domains, and extends beyond the glycerol kinase and congenital adrenal hypoplasia genes. Immunological analysis of muscle dystrophin shows that the deletion results in the production of a truncated, but stable, polypeptide correctly localized at the sarcolemma. These data indicate that neither the cysteine-rich domain, nor the carboxyl domain, are necessary for the appearance of normal dystrophin sarcolemmal localization.

Cysteine↗

Features of insulin-resistance syndrome in men from French Caribbean Islands. The Telecom Study.

The prevalence of diabetes is known to be high in the West Indies, whereas CVD seems relatively rare. This apparently contradicts the existence of the insulin-resistance syndrome, a cluster of metabolic abnormalities supposedly favoring both diabetes and cardiovascular complications. To address the question of whether this contradiction could be accounted for by specific features of this syndrome, we compared 1505 Caucasian and 181 Afro-Caribbean men, all participants in the French Telecom Study. The Afro-Caribbeans were of the same age and had the same BMI as the Caucasians; they also had significantly higher subscapular skin-fold thickness and fasting insulin level, but similar BP and blood glucose level, and significantly lower plasma triglyceride level. Thus, although some features of the insulin-resistance syndrome were present (central adiposity and high insulin levels), none of the associated metabolic abnormalities were present. However, within the Afro-Caribbean group, subjects with plasma insulin concentrations above the median (> 52 pM) had higher mean BP and glucose and triglyceride levels compared with subjects with insulin concentrations < or = 52 pM (P < 0.001). After adjustment for age and BMI, these differences, though smaller, still were statistically significant. These findings confirm that higher insulin concentrations are associated with higher levels of potentially atherogenic and diabetogenic metabolic parameters. However, depending on ethnic origin, the mean levels of these parameters seem to be different, with the consequence that, even if they are elevated with increasing insulin levels, they may not reach values high enough to determine a substantial risk of disease.

Adult↗

Diagnosis of Encephalitozoon cuniculi infection by western blot and the use of cross-reactive antigens for the possible detection of microsporidiosis in humans.

Microsporidia are very primitive, eukaryotic, obligate, intracellular, protozoan parasites. Encephalitozoon cuniculi, a microsporidian originally described from a rabbit infection, has been described in humans as well as in many species of laboratory animals. We report the detection of E. cuniculi by Western blotting in a rabbit with torticollis that was obtained from an Encephalitozoon-free colony. Cross-reactivity of this serum was observed with antigens prepared from several genera of microsporidia. Identical Western blotting patterns were obtained with sera obtained from a rabbit immunized with E. cuniculi that was purified from tissue culture cells. In addition, we were able to demonstrate cross-reactivity between E. cuniculi rabbit antisera and Enterocytozoon bieneusi antigens by indirect immunofluorescent assay techniques in human intestinal biopsy samples. These cross-reactions between microsporidia may be useful in developing diagnostic tests for non-cultivatable microsporidia such as Enterocytozoon bieneusi.

Animals↗

[Surgical treatment of carcinoid tumors of the intestine].

Carcinoid tumours arise from the neuroendocrine system and present a characteristic morphological picture. They occur in almost every organ, predilected sites are the appendix and the small intestine. Prognosis depends on the primary localization and tumour size. Carcinoids of the appendix and rectum are mostly small and thus have a good prognosis. Growth of bronchial, stomach and small intestinal carcinoids is aggressive and implicates a high percentage of metastatic disease. First choice therapy is the surgical removal of the tumour. Depending on tumour size surgical treatment includes fulguration, local excision and oncologic radical resection up to extended organ extirpation. Reoperation and repeated surgery have good chances to be successful concerning tumour remission and improvement of the carcinoid syndrome. Additive treatment comprises in particular somatostatin therapy and, in some cases, chemotherapy.

Appendiceal Neoplasms↗

Two-site direct immunoassay specific for active renin.

A sensitive immunoradiometric assay, without an enzymatic step and specific for active human renin, was developed with use of two monoclonal antibodies (MAbs). In this assay system, the first MAb was coupled to magnetic beads (Magnogel); the second one, directed against the active form of the enzyme, was radiolabeled with 125I. The specificity of this assay was demonstrated in experiments measuring the active plasma renin concentration in the presence or absence of inactive renin. The assay, performed in two steps, was sensitive enough to detect 0.9 pg of renin per tube (3.5 ng/L). Intra- or interassay CVs were < 10%. Concentrations of active plasma renin measured in normotensive subjects were between 7 and 40 ng/L.

Adult↗