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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 235 records · Page 13Linked to original sources

Analysis of a primer-independent GTF-I from Streptococcus salivarius.

A glucosyltransferase (GTF) gene, designated gtfL, from Streptococcus salivarius was cloned and expressed in Escherichia coli and its nucleotide sequence determined. The GTF-L enzyme catalysed the synthesis of water-insoluble glucan in a primer-independent manner. The nucleotide sequence and derived amino acid sequence of GTF-L were similar in size and domain structure to previously sequenced glucosyltransferases. However, a 464-bp region of high variability was identified which could be selectively amplified from strains of S. salivarius by the polymerase chain reaction and could therefore form the basis for species identification. No sequence-specific motifs related to the solubility and linkage of the glucan product or its need for a dextran primer could be ascertained.

Amino Acid Sequence↗

Interaction of pathogenic Neisseria with host defenses. What happens in vivo?

N. gonorrhoeae initiates infection by adhering to and invading columnar epithelial cells. Over time these activities often induce inflammation, with the influx of neutrophils and serum into the urethral lumen, cervical os, conjunctiva, and the like. At least some of these infected niches contain CMP-NANA (cytidine monophospho-N-acetyl neuraminic acid, also called CMP-sialic), contain sialylated gonococci, and are relatively or strictly anaerobic due to neutrophil and gonococcal metabolism and to the site of disease, that is, the peritoneal cavity. Gonococci thus encounter environmental conditions, reagents, and substrates in the human body that are not normally present in vitro. Knapp and Clark were the first to successfully grow gonococci anaerobically in an easily reproducible system, allowing researchers to begin to investigate in vitro the effects of anaerobiosis on gonococcal virulence traits. As a result of a series of elegant and in depth studies, Smith and Parsons and their colleagues showed that growth in CMP-NANA confers on the gonococcus a high degree of phenotypic (readily reversible) serum resistance and that CMP-NANA is available in vivo at sites of gonococcal infection and disease; gonococci become covalently coated with sialic acid and they become serum resistant (reviewed in refs. 8-10). Given that gonococci growing in the absence of oxygen or in the presence of CMP-NANA probably more closely resemble gonococci growing inside the human host, we studied several possible virulence traits of gonococci cultivated under these conditions. We first observed that anaerobic growth (in the absence of CMP-NANA) increases gonococcal resistance to killing by low (but not high) concentrations of normal human serum. We also asked whether anaerobic growth affected gonococcal association with host cells. Contrary to the effects on serum killing, anaerobic growth (in the absence of CMP-NANA) does not appear to affect the ability of gonococci (expressing certain adhesive outer membrane proteins called Opa proteins) to bind to and enter human epithelial cell lines or to bind to or resist killing by human neutrophils. The results from studies investigating the modulatory role of CMP-NANA were more striking. Growth in CMP-NANA dramatically inhibits the adherence of Opa+ gonococci to human neutrophils. It does not, however, appear to significantly decrease their sensitivity to phagocytic killing or to in vitro killing by lysosomal contents (aqueous extracts of human neutrophil granules).(ABSTRACT TRUNCATED AT 400 WORDS)

Anaerobiosis↗

Blood glucose distribution and prevalence of diabetes in Hanoi (Vietnam).

Few epidemiologic surveys have been performed to assess the prevalence of diabetes in representative samples, and few data are available on the epidemiologic features of diabetes in Southeast Asia. We report the results of a 1990 study performed in the Hanoi area (Vietnam) on 4,912 subjects (95.0% of the eligible population), aged 15 years or over, selected by a stratified random cluster procedure using the 1989 census list. A two-step design was used: 1) screening for diabetes by measuring capillary blood glucose (CBG) before dinner with a Glucometer II device; and 2) for subjects with a CBG measurement of > or = 105 mg/dl, a diagnostic test on the following morning, using a 75-g oral glucose tolerance test and World Health Organization criteria (93.9% of the positive screenees took this test). CBG values before dinner were unimodally distributed and skewed to the right, increasing with age in both sexes. Women had a significantly higher level of age-adjusted CBG than did men before dinner (p < 0.0001) as well as when fasting (p < 0.0001) and 2 hours after the oral glucose tolerance test (p = 0.013). The prevalence of diabetes was 1.2% (95% confidence interval (CI) 0.9-1.5) and of impaired glucose tolerance, 1.6% (95% CI 1.3-2.0). Women had a significantly higher age-adjusted prevalence of diabetes than did men (relative risk = 2.3; 95% CI 1.3-4.1). Of the 63 diabetic subjects, nine (14.3%) had been diagnosed before the study, only one was obviously insulin dependent, and only one was obese with a body mass index of > or = 27 kg/m2. The subjects living in the urban areas had higher levels of fasting and 2-hour CBG and a higher diabetes prevalence than did the rural inhabitants (relative risk = 1.3; 95% CI 1.04-3.23). Diabetes appears to be a rare disease in the Hanoi area (1.4% for subjects aged 30-64 years, after age standardization using the Segi distribution), affecting women two times as often as men. Typical insulin-dependent (type I) or obese non-insulin-dependent (type II) diabetes mellitus patients are uncommon.

Adolescent↗

Metachronous bladder tumors in patients with upper urinary tract transitional cell carcinoma.

Sixty-nine patients who underwent nephroureterectomy for upper urinary tract transitional cell carcinoma were included in the study. The following data were collected for each patient: grade and stage of renal/ureteral tumor, tumor location, timing of tumor appearance and recurrence in the bladder, grade and stage of each of the recurrent tumors, and number of recurrences. Follow-up ranged between 2 and 15 years. Thirty-three patients (47.8%) developed metachronous bladder tumors. The appearance of the bladder tumors was related to tumor grade and multifocality of the upper urinary tract TCC. Of the 33 patients, 19 had 1 tumor appearance in the bladder, 6 had 2 recurrences, and 8 had 3 recurrences. The 5-year survival rate for patients with no subsequent bladder tumors was 57% compared to 22% for those who had subsequent tumors. It is concluded that the appearance of bladder tumors following nephroureterectomy characterizes a group of patients with biologically more active disease with unfavorable prognosis.

Adult↗

Non-Hodgkin's lymphoma related eosinophilic endomyocardial disease.

Two patients with eosinophilic endomyocardial disease related to peripheral T-cell lymphomas are reported. Both patients were free of cardiac symptoms at presentation and during follow-up. Routine two dimensional echocardiography revealed bi-apical ventricular obliteration, which was also seen on MR imaging. On the T1-weighted sequence, the thickened endocardium appeared with an isointense signal. Gadolinium DOTA provided an enhanced contrast of the internal part of the left ventricular wall. On T2-weighted sequence, a thin hypointense curvilinear structure drew a dividing line between the internal, endocardial, and the external, myocardial area. Left-ventricular systolic and diastolic functions remained unaltered during subsequent follow-up.

Adult↗

Inhibition of human T cell leukaemia virus type I long terminal repeat expression by DNA methylation: implications for latency.

Human T cell leukaemia virus type I (HTLV-I) provirus DNA was found to be methylated in patients with adult T cell leukaemia. We have therefore examined the possibility that DNA methylation might contribute to HTLV-I latency. In vitro methylation of HTLV-I long terminal repeat (LTR)-chloramphenicol acetyltransferase or LTR-Luciferase constructs at eight HpaII sites, a subset of the eukaryotic methylation site CpG, resulted in a three- to fourfold inhibition of transcription in transfected cells. Inhibition of transcription by methylation of all CpG methylation sites using SssI methylase was much more pronounced (50- to 80-fold). As partial methylation of the LTR showed, methylation of the promoter region was responsible for most of the effect. Whereas cellular stimulation by a combination of phorbol 12-myristate 13-acetate and Tax was able to reverse the HpaII methylation effect, the inhibition by SssI methylation was not suppressible under these conditions. The results are in line with a possible function of DNA methylation in HTLV-I latency.

Adult↗

Feminist method and qualitative research about midlife.

This paper identifies criteria seen as essential to feminist research. In light of these criteria, issues which have arisen during our current research on women and their experiences of midlife and menopause are discussed. Issues considered include the researchers' responsibilities to participants when exploring sensitive and highly personal issues relating to participants' life experiences, and less clear cut issues such as knowledge construction, power and control. In relation to the latter the balance of power in the research-participant relationship, and the role and responsibilities of the researcher in knowledge construction, are explored. Foucault's notions of knowledge construction and power and control and the feminist researcher's position, are considered in terms of rigour in feminist research and dissemination of research reports. Issues which are seen as problematic and worthy of further debate are: the relations between interviewer and interviewee; the intellectual (the researcher) as the bearer of universal values and as truth teller; and the level of critical activism possible in research studies of this nature.

Age Factors↗

Longitudinal study of brainstem auditory evoked responses in 87 normal human subjects.

We evaluated the reproducibility of brainstem auditory evoked responses (BAERs) in 87 normal individuals in a longitudinal study by estimating the correlation coefficients and variability of the interpeak intervals and the V/I amplitude ratio between trials on the same day and between sessions spaced 2 years apart. The highest correlation coefficients occur for the I-V interpeak interval between trials on the same day. The coefficients for the I-III and III-V intervals are lower, due to the variability of wave III. The correlations between ears done on the same day are lower still and are similar to measures obtained from the same ear at a 2-year interval. BAERs are more variable than previously believed between ears and over time, but not in a manner that is clinically significant and can be used longitudinally as a measure of neurologic disease. Finally, we provide the sample size required to detect a significant change in interpeak intervals.

Acoustic Stimulation↗

Negative correlation between plasma GHRH values and growth velocity in short prepubertal children.

Numerous data suggest that impaired growth hormone secretion in short children is usually related to abnormal regulation of the hormone at the hypothalamic level. In order to improve our understanding of neurohypothalamic dysfunction in short children, we measured basal and peak (after L-dopa stimulation) plasma growth hormone-releasing hormone levels in 43 prepubertal children. Among them, in 23 children suspected of having hypothalamic growth hormone dysregulation, growth hormone-releasing hormone values were significantly higher than those observed in normal short stature children (n = 20), no longer correlated with peak growth hormone following L-dopa, and negatively correlated with growth velocity. This suggests that a predominant inhibitor of growth hormone secretion, such as an increase in somatostatin tone, might be prevalent in a large number of children with partial growth hormone deficiency and suspected hypothalamic growth hormone dysregulation.

Adolescent↗

[Minor aplasia of the ear: anatomical findings and results of functional surgery].

We report a retrospective study of 57 cases of minor aplasia of the ear. Each case was analyzed according to the clinical presentation, audiometric results and preoperative radiography. Intra-operative classification of the malformation was obtained in 56 of the 57 cases. The post-operative anatomic and functional results were analyzed. Stapedectomy in type II malformations (stapedo-vestibular ankylosis) gave the best results but this procedure also carries the highest risk for the inner ear. Globally, functional results were good or average in 48% of the patients. These results may appear unsatisfactory but must be appreciated in light of the fact that half of the patients benefited from the operation (particularly in eliminating further use of an external hearing aid). Nevertheless, the long-term stability of these audition results is unknown.

Adolescent↗

Esophageal motility in AIDS patients with symptomatic opportunistic infections of the esophagus.

OBJECTIVES: In patients with AIDS, esophageal symptoms are commonly due to opportunistic esophageal infection with Candida, cytomegalovirus (CMV), herpes simplex virus (HSV), and HIV. Despite apparently appropriate therapy against these pathogens, some patients continue to complain of dysphagia or odynophagia. This study was designed to determine whether such complaints were associated with a motility disorder of the esophagus. METHODS: Sixteen patients underwent esophagoscopy and biopsy followed by esophageal manometry, performed using a 5-channel water perfused system (Synectics Medical, Inc., Irving, Texas). All patients had odynophagia, and eight had dysphagia. RESULTS: Identified infections included: Candida (11), HSV and Candida (1), CMV (3), and a giant ulcer presumably caused by HIV (1); one patient also had lymphoma. Seven patients had normal esophageal motility, and in nine patients, a nonspecific motility disorder was found. After therapy, one of 10 patients had persistent odynophagia and dysphagia, and two had odynophagia only. At follow-up endoscopy, complete healing was demonstrated in six of eight patients with Candida. One of two patients with CMV and the patient with HSV also showed complete healing of the esophagus. Repeat esophageal motility studies were performed after therapy in 10 patients. Five had a persisting abnormality despite eradication of the pathogen (three Candida, one HSV, one CMV); in four, the previously identified motor abnormalities resolved after eradication of the infection (three Candida, one CMV). CONCLUSIONS: These findings suggest that a nonspecific motility disorder exists in AIDS patients with esophageal symptoms and may contribute to the persistence of symptoms despite appropriate therapy of esophageal opportunistic infections.

AIDS-Related Opportunistic Infections↗

Pharmacokinetics and bioavailability of bemoradan, a long-acting inodilator in healthy males.

Bemoradan is a potent, long-acting orally active inodilator. The pharmacokinetics and bioavailability of bemoradan were studied in twelve normal males following oral administration of single, ascending doses of the bemoradan HCL salt in capsules. Plasma and urine levels of bemoradan were determined by HPLC (detection limits: approximately 0.5 ng/ml for plasma and 5 ng/ml for urine). Bemoradan was rapidly absorbed from the capsule formulation at all doses (Cmax occurred at 2.1-2.4 hours). Bemoradan was slowly eliminated from the body (harmonic mean t1/2 16-23 hours). There was a dose-proportional increase in the AUC (0-48) values of bemoradan in humans following the administration of 0.5, 1, 1.5 and 2 mg of bemoradan. The AUC (0-48) values increased to 2.3, 3.4 and 4.0 times when the dose was increased to 2, 3 and 4 times. Urinary excretion of unchanged bemoradan accounted for approximately 5-12% of the dose. Results from this study and previous studies in rats and dogs indicate that bemoradan is well and rapidly absorbed after oral dosing, has linear pharmacokinetics and long elimination half-lives across species.

Administration, Oral↗