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B Simon

Publications and source records attributed to B Simon.

522 records · Page 29Linked to original sources

Analysis of beta-catenin gene mutations in pancreatic tumors.

BACKGROUND/AIM: Mutations of the adenomatous polyposis coli (APC) tumor suppressor gene have been described in a subset of pancreatic carcinomas. The APC gene modulates the beta-catenin-Tcf pathway. The major player in this pathway is the beta-catenin protein encoded by the beta-catenin gene. A variety of different tumors, including colon, prostate, endometrial, and hepatocellular carcinomas, carry mutations in exon 3 of the beta-catenin gene. The aim of this study was to determine the role of the beta-catenin gene in the genesis of exocrine and endocrine tumors of the pancreas. METHODS: 78 ductal pancreatic adenocarcinomas, 14 ductal pancreatic cancer cell lines, and 33 endocrine pancreatic tumors were evaluated for mutations in exon 3 of the beta-catenin gene by single-strand conformation polymorphism analysis and direct DNA sequencing. In addition, 40 ductal pancreatic adenocarcinomas were analyzed for intracellular beta-catenin accumulation by immunohistochemistry, indicating alterations of the beta-catenin gene. RESULTS: Neither the 111 exocrine and endocrine pancreatic tumors nor the 14 pancreatic cancer cell lines carried mutations in exon 3 of the beta-catenin gene. Intracellular beta-catenin accumulation was not identified in any of the 40 pancreatic adenocarcinomas. CONCLUSION: These data suggest that the beta-catenin gene as the major player of the beta-catenin-Tcf pathway does not play an important role in the genesis of pancreatic tumors.

Adenocarcinoma↗

Enolases are highly conserved fungal allergens.

BACKGROUND: Lack of knowledge of the identity of fungal allergens still is a major obstacle for improvement of diagnosis and therapy of allergies to moulds. We have therefore further analyzed the allergens of the two moulds, Alternaria alternata and Cladosporium herbarum and found that enolases (EC 4.2.1.11) are major allergens, at least of the two fungal species just mentioned. METHODS: The enolases of Alternaria and Cladosporium were cloned from cDNA libraries constructed from vegetative cells of the two moulds by immunological screening with sera from selected patients allergic to the moulds. The two enolases were expressed as recombinant nonfusion proteins and used for determination of the incidence of allergy to enolase among a cohort of patients. RESULTS: Sequencing of the two enolases showed very close relationships with other known fungal enolase sequences. Competition experiments using immunoblots of the recombinant nonfusion proteins showed nearly complete identity of the epitopes on both enolases. Serum from a patient reactive to Cladosporium enolase reacted equally well with the enolases of Alternaria, Saccharomyces and Candida. About 50% each of the sera from patients reactive to Cladosporium and Alternaria were strongly reactive to the recombinant enolases. CONCLUSIONS: Enolases are therefore considered to be highly conserved major fungal allergens.

Allergens↗

Dynamics of P. falciparum gametocytemia in symptomatic patients in an area of intense perennial transmission in Tanzania.

We investigated the dynamics of Plasmodium falciparum gametocytemia in symptomatic patients attending a local dispensary in the Kilombero district, Tanzania. Consenting individuals aged one and above, with varying asexual and sexual parasitemias were treated appropriately and asked to return weekly for 28 days. Gametocyte prevalence was highest on Day 7 of follow-up in all age groups (overall 30.5%). Multifactorial analysis showed that young age (chi2 = 18.4; P = 0.004), high asexual parasitemia on presentation (chi2 = 19.4; P = 0.0007) and gametocyte positivity on presentation (chi2 = 29.4; P = 0.001) were all significantly associated with the presence of gametocytes on Days 7 and 14 of follow-up. High presentation of asexual parasitemia alone was positively correlated with higher gametocyte densities on both days of follow-up (F4, 297 = 2.0; P = 0.049). Gametocyte incidence rates decreased significantly with age (chi2 = 7.6, P < 0.005). In summary, in this group of chloroquine-treated individuals, gametocyte prevalence and incidence rates decreased with age, while densities remained relatively constant.

Adolescent↗

[Inhibition of uterine contractions: new in vitro pharmacological approaches on the pregnant human myometrium].

The aim of this study was to evaluate the in vitro effects of phosphodiesterase 4 inhibitors (PDE4I) and their combination with salbutamol (beta 2-adrenoceptor agonist) on spontaneous contractions and to investigate by in vitro and biochemical studies and analysis of mRNA expression the presence of beta 3-adrenoceptor in human near-term myometrium. Rolipram, RP 73401 and Ro 20-1724 (PDE4I) inhibited spontaneous myometrial contractions (Emax approximately 100 per cent; pD2 approximately 6.80 for the two first and 6.31 for Ro 20-1724). Rolipram 10(-8) M potentiated the response to salbutamol (Emax = 88 per cent vs. 40 per cent and pD2 = 6.93 and 6.36 with or without rolipram respectively). SR 59119A, a beta 3-adrenoceptor agonist, was more efficient than salbutamol in inhibiting the contractions (Emax 52 per cent and 27 per cent respectively, p < 0.05) but they both induced a significant increase of cAMP production. In both functional and biochemical studies, SR 59119A was only antagonized by the beta 3-adrenoceptor antagonist SR 59230A. The beta 3-AR mRNA was positively expressed in myometrium preparations in a reverse transcription polymerase chain assay. In conclusion, phosphodiesterase 4 inhibitors alone or combined with beta 2-adrenoceptor agonists and beta 3-adrenoceptor agonists might have potential interest as tocolytic agents.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

[Gastroduodenal tolerance of tenoxicam versus diclofenac-Na: an endoscopy double-blind controlled study in healthy probands].

The gastroduodenal tolerability of tenoxicam vs diclofenac-Na was evaluated in a double-blind, parallel group study in 36 healthy male volunteers. The doses used were 20 mg tenoxicam vs 100 mg diclofenac-Na in a retard formulation daily over a period of 14 days. Gastric tolerability was assessed by using upper endoscopy. Gastroscopy was performed at base-line after the dosing period of 14 days and again after a follow-up period of 14 days without any treatment. The mucosal lesions were scored using modified Lanza criteria. In comparison to diclofenac-Na, tenoxicam was significantly better tolerated after a 14-day dosing period (mean gastric score: tenoxicam: 1.3 +/- 0.7; diclofenac-Na: 2.2 +/- 1.1 p = 0.0143). Both treatment groups had comparable scores at base-line and post-study assessments. Tenoxicam and diclofenac-Na were generally well tolerated. Only two volunteers reported intermittent lack of appetite, heartburn, and a feeling of pressure in the stomach. In summary, tenoxicam given as a 20 mg single oral morning dose over a 14-day period was significantly better tolerated than diclofenac 100 mg with regard to gastroduodenal mucosal damage.

Adolescent↗

[Endoscopic studies of the stomach tolerance of ibuprofen: comparison of 2 galenically different preparations].

In randomised crossover fashion, the gastric and duodenal tolerability of two different ibuprofen galenic formulations were directly compared in ten healthy volunteers. An endoscopic evaluation was performed after 7 and 14 days treatment. 300 mg Ibuprofen q.i.d. as pellets, as well as 600 mg Ibuprofen b.i.d. as dragees, evoked a lesion score of 1.6 +/- 0.3 and 1.7 +/- 0.4 after 7 days of treatment (n.s.). After 14 days, the lesion score under ibuprofen dragees was slightly higher (1.9 +/- 0.3) when compared with the pellet formulation (1.6 +/- 0.3). This difference did not reach statistical significance. Both ibuprofen preparations were well tolerated.

Adult↗

[Stomach tolerance of indomethacin derivatives: an endoscopic comparative study in healthy probands].

The effect of 5 days' treatment with indomethacin, acemethacin and proglumethacin on the gastroduodenal mucosa was endoscopically evaluated in healthy volunteers. In a randomised double-blind crossover system 16 subjects received 50 mg t.i.d. indomethacin and 60 mg t.i.d. acemethacin, and a further 16 volunteers received 50 mg t.i.d. indomethacin and 150 mg t.i.d. proglumethacin. After 5 days both proglumethacin and acemethacin caused significantly less gastroduodenal lesions than indomethacin. Possible reasons for the apparently better gastro-duodenal tolerability of both indomethacin derivatives are discussed.

Adult↗

[Does simultaneous administration of a PGE1 analog prevent indomethacin damage to human gastric mucosa? An endoscopic double-blind study].

The influence on gastroduodenal mucosa of indomethacin (50 mg t.i.d.) administration for 6 days was investigated in 7 healthy volunteers in a double-blind randomized crossover study with and without concomitant administration of MDL 646, 400 micrograms q.i.d. and 800 micrograms q.i.d. Indomethacin induced a gastroduodenal lesion index of 2.4 +/- 0.1. Neither of the prostaglandin E1-analogue dosages afforded significant protection of gastric and duodenal mucosa (2.1 +/- 0.4 in the presence of 400 micrograms q.i.d. and 1.9 +/- 0.4 in the presence of 800 micrograms q.i.d.). Major side effects were not observed.

Adult↗

[Philosophy of the treatment of intermittent claudication].

Everything points to the prime importance of good health habits and the prevention of risk factors. Long-term medication has only a limited and still questionable impact. Surgery will never be proposed straight off, but only if the claudication is persistent and troublesome in an active individual. Lumbar sympathectomy always provides a degree of improvement and entails a minimal risk. There is no secondary deterioration. Yet in cases of associated phlebites, it can aggravate trophic skin problems. Reconstructive surgery gives far better immediate results but at the price of increased risk and a secondary deterioration that makes difficult repeat operations necessary. It is thus necessary to be very careful in using surgery to deal with intermittent claudications.

Humans↗

[Circadian aspects of diclofenac gastroduodenopathy and the protective effect of roxatidine].

The gastrointestinal side-effect profile of non-steroidal anti-inflammatory drugs should follow a circadian rhythm. In a randomized, parallel, double-blind study the gastric duodenal effects of 100 mg diclofenac retard daily in the presence and absence of 150 mg roxatidine was evaluated in 20 healthy volunteers undergoing upper GI-endoscopy. Drugs were taken over a period of 14 days either at 8 a.m. (n = 10) or at 8 p.m. (n = 10). Endoscopic controls were performed at entry and repeated after 14 days of treatment. A damaging score according to Lanza et al. was used. At entry both groups showed comparable mucosal damages: 8 a.m.-group: placebo 0.9 +/- 0.1 (+SEM), roxatidine 0.9 +/- 0.1; 8 p.m.-group: placebo 1.0 +/- 0.0, roxatidine 0.9 +/- 0.1. After 14 days of treatment the lesion score increased in the diclofenac retard/placebo-group in the 8 a.m.-group to 7.6 +/- 1.9 and in the 8 p.m.-group to 7.2 +/- 1.1. The corresponding values in the diclofenac/roxatidine-group were 2.1 +/- 0.9 (8 a.m.-group) and 1.4 +/- 0.4 (8 p.m.-group). This protection afforded by roxatidine was significant when compared with placebo (p < 0.05). Our data suggest that the gastrolesive effects of diclofenac retard are independent of the time of drug ingestion; in addition protection by roxatidine was also time-independent.

Adult↗

The prognostic significance of arterial blood pressure in liver cirrhosis.

A decrease of the blood pressure (BP) due to the changes in the regulatory mechanisms of blood pressures homeostasis is frequently observed in cirrhosis. The present work studied the blood pressure profile of the cirrhotic patients and estimated the influence it might have on the survival prognosis at one year. A lower mean blood pressure: 8.25 +/- 1.5 cm Hg is observed versus a control group: 9.8 + 2.0 cm Hg (p < 0.001). The decrease is due to the patients with severe liver impairment (Child class C). The survival is poor in cirrhosis with hypotension (systolic blood pressure < 9 cm Hg): 75 +/- 10%, than in patients with systolic blood pressure between 9 and 11 cm Hg (survival rate 91 +/- 6%) and patients with systolic blood pressure over 11 cm Hg (survival rate 88 +/- 6%) (p < 0.001).

Adult↗