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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 325 records · Page 18Linked to original sources

Growth regulation of normal thyroids and thyroid tumors in man.

Our studies using thyrocyte membranes from different human thyroid tissues, monolayer cultures of human thyrocytes, and the permanant cell line FTC-133 demonstrate the stimulatory effect of TSH on metabolism, DNA synthesis, and cell growth in human thyrocytes. Up- and down-regulation of cAMP cell content fails to show direct effects on DNA synthesis and cell growth in primary thyrocyte cultures in man. Increased AC responsiveness to TSH in adenomatous human thyroid tissues, when compared to normal thyroids of the same patient (p less than 0.005), is thus of only questionable importance for thyroid tumor growth. The permanant cell line FTC-133 was established from differentiated follicular human thyroid cancer cells. FTC-133 cells proved to be of particular usefulness in assessing growth regulation of human thyroid tissue. These cells could be propagated in serum free medium, showed thyroglobulin immunoreactivity and EGF receptors, lacked any fibroblast contamination, and responded to TSH and local active growth factors such as EGF and IGF with a stimulated [3H]thymidine incorporation. The latter could be shown in primary cell cultures of normal and pathological human thyrocytes as well. Additional to the stimulatory effect of TSH and IGF on [3H]thymidine incorporation, these substances show an additive effect when incubated simultaneously. Locally active growth factors and endocrine growth stimulation by TSH therefore act synergistically on thyrocyte growth in human thyrocyte cultures. Whether the TSH effect on cell growth is related to its stimulation of AC remains as yet questionable.

Adenylyl Cyclases↗

Effects of oral contraceptives on carbohydrate and lipid metabolisms in a healthy population: the Telecom study.

In a cross-sectional study that aimed to identify risk factors for diabetes, 1290 consecutive, healthy, nonpregnant women of child-bearing age were examined in a center for preventive medicine. An in-depth interview about menses, use of oral contraceptives, and menopause was performed. Plasma glucose at fasting and 2 hours after a 75 gm glucose load, glycated hemoglobin A1c, fasting plasma insulin, total plasma cholesterol, and triglycerides were measured. Compared with nonusers taking no progestogens, oral contraceptive users (n = 431; 33.4%) were younger (p less than 0.001) and leaner (p less than 0.001). After adjustment for age and body mass index, oral contraceptive users had higher 2-hour plasma glucose (p less than 0.001), higher fasting plasma insulin (p less than 0.01), and higher triglycerides levels (p less than 0.01). Fasting plasma glucose, glycated hemoglobin A1c, and total cholesterol did not significantly differ between the two groups. In relation to dosage and types of steroid components, few differences have been found between high-dose and low-dose oral contraceptives or according to the estrogen-progestogen balance of the preparations. Use of oral contraceptives appears to induce an increase of insulin-resistance markers, which have recently been cited as risk factors for ischemic vascular diseases. These markers should be carefully monitored in oral contraceptive users.

Adult↗

Oral contraceptives, insulin resistance and ischemic vascular disease.

From a large prospective study on diabetes risks, 1112 professionally active, non-menopausal, non-pregnant, healthy women were cross-sectionally analysed according to their use of oral contraception. After adjustment for age, weight and diabetes risk factors, those taking the pill, compared to those who did not, had significantly higher fasting serum insulin, triglycerides and 2-h 75 g OGTT blood glucose levels. The insulin-resistance markers which have recently been cited as ischemic vascular disease risk factors should be carefully monitored in pill users.

Adult↗

Chromosomal rearrangements in a primary hepatocellular carcinoma.

Chromosome analysis of cells obtained at biopsy from a 65-year-old man with primary hepatocellular carcinoma revealed characteristic abnormalities of chromosomes 1, 5, 6, 9, 13, 16, and 22 in each cell and maintenance of a pseudodiploid chromosome number (46,XY). Five of the chromosomal sites involved in these rearrangements are either in fragile site regions or in regions containing genes that encode cellular oncogenes. Some of the tumor cells manifest mitotic deviations in the form of asynchronies, spiralization, premature centromere division, and non-sister chromatid associations. The significance of these findings to hepatocellular carcinogenesis is discussed.

Aged↗

[Premedication with intranasal midazolam in pediatric anesthesia].

To evaluate nasally administered midazolam 0.2 mg.kg-1 for preinduction of anaesthesia in paediatric patients the authors studied ASA 1 patients scheduled for elective surgery. Forty-five children, ages 3 to 126 months, were randomized in three groups: group D (n = 16) received diazepam 0.33 mg.kg-1 orally, group P (placebo) (n = 13) 0.04 ml.kg-1 normal saline via the nasal route; in group MDZ (n = 16) the children were given intranasal midazolam 0.3 mg.kg-1. The premedication was assessed on a 5-point sedation scale, modified to include the response to mask placement and the quality of the induction of general anaesthesia. The degree of sedation, heart rate, blood pressure, respiratory rate and oxygen saturation levels were recorded on the arrival in the operating room (0 min) and 3, 6, 9, 12 and 15 min (mask placement) after drug administration. With intranasal midazolam sedation was demonstrable at 6 min and was significant at 9 and 12 min. In this group all the children were calm or drowsy. The induction of anaesthesia was equivalent in group D and MDZ but easier than in those patients receiving normal saline. Vital signs did not change during the study period in any of the three groups. Intranasal midazolam was slightly more effective than oral diazepam. In children, it produces anxiolysis and sedation with rapid onset and is an attractive alternative to other routes for preanaesthetic medication.

Administration, Intranasal↗

Glutamate dehydrogenase in cerebellar mutant mice: gene localization and enzyme activity in different tissues.

Many similarities of both the inheritance pattern and the neuropathology can be observed between olivopontocerebellar atrophies, or so-called multiple system atrophies (MSAs), and murine cerebellar mutations like Purkinje cell degeneration, nervous, staggerer, weaver, and reeler. Our study aimed to test whether the glutamate dehydrogenase (GDH) deficiency observed in some MSA patients could be found also in any of the murine mutants. GDH activity was assayed in several organs of these mutants, and no general deficiency was detected. By contrast, the level was found to be elevated in the cerebellum. The GDH gene was localized on mouse chromosome 14 and does not map close to any known neurological mutation in the mouse. We conclude, for the moment, that none of these cerebellar mutant mice can be considered as an animal model for GDH-deficient MSA.

Animals↗

Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland.

Several mouse genes designated 'Pax genes' contain a highly conserved DNA sequence homologous to the paired box of Drosophila. Here we describe the isolation of Pax8, a novel paired box containing clone from an 8.5 day p.c. mouse embryo cDNA library. An open reading frame of 457 amino acids (aa) contains the 128 aa paired domain near the amino terminus. Another conserved region present in some other paired box genes, the octapeptide Tyr-Ser-Ile-Asn-Gly-Leu-Leu-Gly, is located 43 aa C-terminal to the paired domain. Using an interspecies backcross system, we have mapped the Pax8 gene within the proximal portion of mouse chromosome 2 in a close linkage to the surf locus. Several developmental mutations are located in this region. In situ hybridization was used to determine the pattern of Pax8 expression during mouse embryogenesis. Pax8 is expressed transiently between 11.5 and 12.5 days of gestation along the rostrocaudal axis extending from the myelencephalon throughout the length of the neural tube, predominantly in two parallel regions on either side of the basal plate. We also detected Pax8 expression in the developing thyroid gland beginning at 10.5 days of gestation, during the thyroid evagination. In the mesonephros and metanephros the expression of Pax8 was localized to the mesenchymal condensations, which are induced by the nephric duct and ureter, respectively. These condensations develop to functional units, the nephrons, of the kidney. These data are consistent with a role for Pax8 in the induction of kidney epithelium. The embryonic expression pattern of Pax8 is compared with that of Pax2, another recently described paired box gene expressed in the developing excretory system.

Amino Acid Sequence↗

Extracorporeal shock wave lithotripsy: our experimental and clinical experience with the Direx machine.

The Direx Tripter X-1 is a modular extracorporeal shock wave system that uses underwater spark gaps as its source for lithotripsy. Experience with 712 treatments in 541 patients has given a fragmentation rate of 99%. Of these patients, 27% had stones larger than 2 cm or multiple stones. A stone free situation at 3 months follow-up was achieved in 75% of the cases. Seventeen percent had small fragments less than 4 mm and 8% had fragments greater than 4 mm. Auxiliary procedures following ESWL were required in 7%. No major complications were seen. The advantages of this system are: modularity, mobility, flexibility, and low cost.

Adolescent↗

Potential gastrointestinal uses of somatostain and its synthetic analogue octreotide.

Octreotide is a long-acting analogue of somatostatin which has been FDA approved for symptomatic carcinoid syndrome and for vasoactive intestinal peptide-producing tumors. Somatostatin and octreotide have significant effects on gastrointestinal physiology which may be beneficial for a variety of disorders. This paper will review the currently available literature on the use of somatostatin and octreotide in non-neoplastic disorders of the gastrointestinal tract.

Amino Acid Sequence↗

Early and late peritoneal dialysate leaks in patients on CAPD.

Dialysate leaks, which occurred in 386 CAPD patients over 11 years, were analyzed retrospectively. 18 patients developed 21 early leaks (within 30 days of catheter insertion) and 18 patients developed 28 late leaks (beyond 30 days of catheter insertion). 8 patients had multiple (2-6) leaks. Both early and late leaks, particularly if they were multiple, were associated with conditions that affect adversely tissue healing and tensile strength. Median surgical insertion was apparently associated with a higher incidence of early leaks. Early leaks were manifested externally, usually through the exit site, and did not require imaging. Late leaks were manifested usually by poor dialysate outflow, localized edema and subcutaneous fluid collections. One third of the late leaks required radiological imaging. Hernias caused 42% of the late leaks. Early leaks were managed by temporary discontinuation of CAPD alone (57%) or surgery. Most late leaks (67%) required surgery. Conservative means (change to IPD, observation) were applied for the management of a few late leaks. Both early and late leaks resulted frequently in replacement of peritoneal catheters, but only late leaks resulted in permanent discontinuation of peritoneal dialysis. Paramedian surgical insertion, waiting period of 10-14 days between catheter insertion and initiation of CAPD, and low starting dialysate volumes have resulted in apparent reduction of the incidence of the early, but not of the late leaks. Dialysate leaks have serious consequences on the performance of CAPD. Early leaks differ from late leaks in some clinical manifestations. Preventive measures have decreased the incidence of early, but not of the late leaks.

Catheters, Indwelling↗

[Adrenal gland cancer].

Carcinoma of the adrenal gland is a rare type of tumor disease. Clinical presentation includes the same signs and symptoms as in the equivalent benign disease or otherwise larger palpable tumor masses. Localization is well achieved by ultrasound and CT-scan. 131J-MIBG-Scintican is applied selectively for adreno-medullary tumors and 131J-nor-cholesterol for adreno-cortical tumors. For surgery a transabdominal or sometimes abdomino-thoracic approach is preferred. Sufficiently wide en-bloc resection including lymphnodes and adjacent structures gives hope for local radicality. The experience with 10 adrenal malignancies out of a total of 64 tumors (16%) is presented under various aspects.

Adrenal Gland Neoplasms↗

[Occlusive therapy of psoriasis--comparison of clinical effectiveness of short-term and prolonged use].

In an open clinical trial on stationary psoriatic plaques, we compared the effects of shortime occlusive (SO) dressing (24h) and prolonged occlusion (PO: 5-28 days). IN SO, Weinstein's index decreased from 7.3 +/- 1.7 to 3.3 +/- 1.8 (n = 21), in PO from 6.5 +/- 1.1 to 3.7 +/- 1.7 (n = 15). The results were even better in cases with optimal PO dressing (decrease from 6.8 +/- 1.4 to 2.5 +/- 0.9). The most important side effects were itching and exsudation with ensuing smell. In only one of the cases did the side effects cause a drop-out after 5 days. Regarding stationary psoriatic plaques on the extensor sides of the lower legs and forearms. We recommend continuous occlusive dressing for 8-10 days--either as an alternative mode of therapy, or as an intermediate regimen.

Adolescent↗

[Hyde's nodular prurigo--preference for creases of the skin].

The arrangement of papules in prurigo nodularis Hyde along the cleavage lines of the skin, but not Blaschko's lines, supports the classification of prurigo nodularis Hyde as a traumatic chronic papulosis with cutaneous neural hyperplasia of xerodermal skin.

Depression↗

Non-C-G recognition sequences of DNA cytosine-5-methyltransferase from rat liver.

The eukaryotic DNA cytosine-5-methyltransferase (E.C.2.1.1.37) is known to methylate cytosine in DNA mainly, but not exclusively in C-G. In the present study the minor, non-C-G recognition sequences of a rat DNA methyltransferase were analyzed by Maxam-Gilbert sequencing of in vitro methylated SV40 DNA. The enzyme methylates C-A and C-T at a 50-fold lower initial rate than C-G. Methylation of C-C at the 5'C was not observed in the piece of DNA sequenced. The methylation of C-A is very low in the trinucleotides ACA and CAC, the other C-A containing trinucleotides in DNA are much better methylacceptors. C-T was found methylated predominantly in the sequences CCTAA, ACTAA, and ACTGT. A comparison of the activity with different substrates is in favour of the enzyme making its recognition in the major groove of the DNA.

Animals↗

Aspects of secondary and quaternary structure of surfactant protein A from canine lung.

The results of a large number of studies indicate that pulmonary surfactant contains a unique protein whose principal isoform has a molecular weight of about 30,000, and whose presence in surfactant is associated with important metabolic and physicochemical properties. This protein, SP-A, as isolated from canine surfactant, contains a domain of 24 repeating triplets of Gly-X-Y, similar to that found in collagens. These studies were undertaken to determine whether SP-A forms a collagen-like triple helix when in solution, and to describe certain aspects of its size and shape. Our experiments were done on SP-A extracted by two different methods from canine surfactant, and on SP-A produced by molecular cloning. The results from all three preparations were similar. The circular dichroism of the complete protein was characterized by a relatively large negative ellipticity at 205 nm, with a negative shoulder ranging from 215 to 230 nm. There was no positive ellipticity, and the spectrum was not characteristic of collagen. Trypsin hydrolysis resulted in a fragment with peak negative ellipticity at about 200 nm, without the negative shoulder. Further hydrolysis of this fragment with pepsin resulted in a CD spectrum similar to that of collagen. The spectrum of the collagen-like fragment was reversibly sensitive to heating to 50 degrees C, and was irreversibly lost after treatment with bacterial collagenase. SP-A migrated on molecular sieving gels with an equivalent Stokes radius of 110 to 120 A, and had a sedimentation coefficient of 14 S. Using these data we calculate a molecular weight of about 700,000. The hydrodynamic characteristics can be approximated as a prolate ellipsoid of revolution having an axial ratio of about 20. We conclude that SP-A aggregates into a complex of 18 monomers, which may form six triple-helices. The shape of the complex is considerably more globular than collagen and is not consistent with end-to-end binding of the helices to form fibrous structures.

Animals↗

Epidemiological features of glycated haemoglobin A1c-distribution in a healthy population. The Telecom Study.

HbA1c was measured in 3240 healthy non-diabetic adult individuals in a working population. There was no difference in HbA1c between sexes. The distribution of HbA1c was approximately normal with a slight difference between mean and median values at all ages in both sexes. HbA1c increased with deterioration of glucose tolerance and with all the known risk factors for diabetes (age, obesity, family history of diabetes, history of a large newborn delivery); age but not body mass index appeared as a factor influencing HbA1c independently. In women, HbA1c levels rose particularly at the age of menopause but the use of oral contraceptives or oestrogens made no difference. In both sexes, HbA1c was higher in smokers than in non-smokers. No consistent seasonal variation was observed. Haematologic factors had a negligible influence on HbA1c level. HbA1c was more highly correlated with fasting plasma glucose than with 2 h-plasma/glucose (r = 0.20 vs 0.11). In a stepwise multiple regression analysis, age followed by fasting plasma glucose were the only two significant factors associated with the level of HbA1c. These data indicate that HbA1c is influenced only by factors closely linked to diabetes.

Adult↗