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Biomedical subjects

K Simon

Publications and source records attributed to K Simon.

At least 109 records · Page 6Linked to original sources
PubMed1989

Intestinal mast cells and neutrophil chemotactic activity of serum following a single challenge with gluten in celiac children on a gluten-free diet.

The number of one subtype of mast cells (formalin fixation, toluidine blue staining), cells of the lamina propria, and intraepithelial lymphocytes were counted in the intestinal biopsy specimens of 14 children with treated celiac disease following a single challenge with gluten. The serum neutrophil chemotactic activity was measured at 0, 1, 3, 5, and 24 h after challenge. There was no significant change in the number of intraepithelial lymphocytes, but the biopsy samples obtained at 5 h showed a marked increase in the inflammatory cells of the lamina propria and a significant decrease in the number of mast cells. A pronounced decrease was present at 3-5 h in the number of eosinophil cells in the blood. The neutrophil chemotactic activity of sera showed a significant increment in 10 of 14 patients. The intestinal permeability of patients became abnormal, as detected by the increased absorption of lactulose. These findings suggest that degranulation of mast cells may be involved in the pathogenesis of the small intestinal mucosal injury in children with celiac disease.

Adolescent↗
PubMed1989

[Incidence of markers of HBV and HAV infections in workers of the departments and clinics of anesthesiology and intensive care at the medical academy in Wrocław].

The frequency of markers of infection by hepatitis virus A and B was studied among the workers (physicians, nurses, auxiliary personnel) of the Chair and Department of Anaesthesiology and Intensive Therapy, Medical Academy in Wroclaw. Serological tests were done by the immunoenzymatic method using kits of Abbott Diagnostics Division. IgG anti-HAV antibodies were found in 62.8% of the tested subjects. HBV markers were present in 44.3% of the subjects, that is several times more frequently than in the general population. HBsAg carriers accounted for 4.3% of the whole group, while in 40% of the group anti-HBV antibodies were present in various combinations suggesting an immunity against HBV infection.

Adult↗
PubMed1988

Phase I clinical trial of a combination of dipyridamole and acivicin based upon inhibition of nucleoside salvage.

A Phase I clinical trial of simultaneous 72-h infusions of dipyridamole and acivicin was carried out in patients with advanced malignancies. The objective of this trial was to determine the maximum tolerated dose of dipyridamole when administered as a 72-h infusion in combination with acivicin. The development of this combination is of interest because of in vitro observations which demonstrate that dipyridamole potentiates the cytotoxic action of acivicin by blocking nucleoside salvage. Patients were treated with concomitant i.v. infusions of dipyridamole and acivicin for 72 h. The acivicin dose infused remained constant during the trial at 60 mg/m2/72 h. The maximum tolerated dose (MTD) of dipyridamole was 23.1 mg/kg/72 h. Limiting toxicities at the MTD of dipyridamole with acivicin were severe gastrointestinal and constitutional symptoms which appeared to be caused by the high doses of dipyridamole administered. Escalation of dipyridamole did not potentiate the mild myelosuppression or the neurotoxicity which occurs with acivicin alone. At a dose of dipyridamole which was well below the MTD, one patient experienced symptomatic orthostatic hypotension, and another patient with coronary artery disease developed dizziness and transient electrocardiogram abnormalities. However, no other hypotensive or cardiovascular events occurred as dipyridamole was escalated to the MTD. Phlebitis occurred at the site of infusion when the dose of dipyridamole exceeded 13.5 mg/kg/72 h. Because of this local toxicity, it was necessary to administer dipyridamole through a central venous catheter to achieve maximum plasma levels. At the MTD of dipyridamole, steady-state total and free plasma levels of 11.9 microM and 27.8 nM, respectively, were attained by 24 h. These are free dipyridamole levels which in vitro were sufficient to block cytidine salvage and to potentiate the biochemical and cytotoxic effects of acivicin against human colon cancer cells (P.H. Fischer et al., Cancer Res., 44:3355-3359, 1984).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

A block to the intracellular transport and assembly of hepatitis B surface antigen polypeptides in Xenopus oocytes.

Hepatitis B surface antigen is the major protein of the virion envelope, and is also independently secreted from infected cells as a subviral particle composed exclusively of HBsAg and host-derived lipid. Similar particles are efficiently assembled and secreted by cultured mammalian cells transfected with the gene for HBsAg. In contrast to such cultured cells, Xenopus oocytes microinjected with HBsAg mRNA secrete less than 5% of newly synthesized HBsAg polypeptides. We have examined the HBsAg biosynthetic intermediates in such oocytes and provide evidence that the impaired secretion of HBsAg is due to a discrete block in the assembly of lipoprotein particles.

Animals↗
PubMed1988

Secreted hepatitis B surface antigen polypeptides are derived from a transmembrane precursor.

Hepatitis B surface antigen (HBsAg), the major coat protein of hepatitis B virus, is also independently secreted from infected cells as a lipoprotein particle. Secretion proceeds without signal sequence removal or cleavage of other segments of the polypeptide. We have examined the synthesis and transport of HBsAg in cultured cells expressing the cloned surface antigen gene. Our results show that HBsAg is initially synthesized as a integral membrane protein. This transmembrane form is slowly converted to a secreted lipoprotein complex in the lumen of the endoplasmic reticulum via a series of definable intermediates, after which it is secreted from the cell. This unusual export process shares many features with the assembly and budding reactions of conventional enveloped animal viruses. However, it differs importantly in its absence of a requirement for the participation of nucleocapsid or other viral proteins.

Animals↗
PubMed1988

HLA antigens and the antibody response after vaccination to hepatitis B.

The aim of our work was the search for immunogenetic factors that influence the antibody response to HBs antigen. We analyzed the HLA-A, -B, and -DR antigen frequencies in 19 seropositive to HBs and 28 seronegative to HBs healthy persons finding an elevated frequency of B5 in the seropositive group (p value 0.037). After vaccination with Hevac B Pasteur vaccine of the seronegative persons, the low antibody response was associated with B13 (p value 0.041). An association between local side reactions to the vaccine and HLA A3 and B35 were also found (p values 0.042 and 0.022 respectively). The presented p values are not significant after correction for the number of antigens tested and for this reason our findings require confirmation in an independent study.

Adult↗
PubMed1988

Glycosaminoglycan containing fat-storing cells in hepatic fibrogenesis.

Male F-344 rats were treated for 10 weeks either with CCl4 (0.2 ml/kg, per os, twice a week) or with CCl4 (same as above) and phenobarbital (0.2 g/l in drinking water). Liver fibrosis and cirrhosis developed in both treated groups, and was confirmed histologically. Cirrhosis was more frequent after the CCl4 + phenobarbital treatment. The collagen content of the liver, measured by morphometry and biochemically, was significantly higher in the animals of the group treated with CCl4 + phenobarbital than in the animals treated only with CCl4. Specially altered fat-storing cells (Ito cells) were found in the periportal and septal fibrotic areas in direct proportion to the amount of fibrosis and cirrhosis. They were identified as altered fat-storing cells by their desmin content and Vitamin A storing capability. This study demonstrated that these cells were enlarged and contained neutral fat, lipofuscin and PAS-positive material. The potential role of GAG-containing FSC in fibrogenesis is discussed.

Animals↗
PubMed1987

Phase I clinical trial and pharmacokinetic evaluation of acodazole (NSC 305884), an imidazoquinoline derivative with electrophysiological effects on the heart.

Acodazole (NSC 305884) is a synthetic imidazoquinoline which has antimicrobial as well as antineoplastic properties. A Phase I trial of acodazole administered as a 1-h i.v. infusion once weekly X 4 was conducted. Mild to moderate nausea and vomiting and moderate burning and erythema at the infusion site were the only toxicities seen among 33 patients treated over 51 courses at doses between 20 mg/m2/week and 888 mg/m2. The first patient treated at 1184 mg/m2 developed an irregular pulse and was found to have a prolonged cardiac output interval (Q-Ti) on electrocardiogram and polymorphic ventricular tachycardia ("torsades des pointes"). Careful study of five additional patients treated according to a modified schedule (340 mg/m2 week one, 500 mg/m2 week 2, 666 mg/m2 week 3, and 888 mg/m2 week 4) revealed 20% or greater Q-Ti prolongation after 20 of 27 treatments; Q-Ti prolongation had resolved 24-36 h after each infusion. Q-Ti prolongation occurred at all dose levels; no ventricular arrhythmias occurred. Acodazole was cleared with a long t1/2 (20.7 h) primarily by nonrenal mechanisms. No alterations in peak plasma levels or excretion were seen in the patients in whom Q-Ti prolongation was detected. No antitumor activity was seen. Further development of acodazole will require delineation of pharmacological means of surppressing this Q-Ti prolongation.

Adult↗
PubMed1987

Translocation of globin fusion proteins across the endoplasmic reticulum membrane in Xenopus laevis oocytes.

We have studied the translocation of a normally cytoplasmic protein domain across the membrane of the endoplasmic reticulum in cell-free systems and in Xenopus laevis oocytes. Coding regions for the normally cytoplasmic protein globin were engineered in frame either 3' or 5' to the coding region for the signal sequence of either Escherichia coli b-lactamase or bovine preprolactin, respectively, in SP6 expression plasmids. RNA transcribed from these plasmids was microinjected into oocytes as well as translated in cell-free systems. We demonstrate that both in vivo and in vitro, a previously amino-terminal signal sequence can direct translocation of domains engineered to either side. Moreover, the domain preceding the signal sequence can be as large as that which follows it. While, in general, cell-free systems were found to faithfully reflect translocation events in vivo, our results suggest that a mechanism for clearance of signal peptides after cleavage is present in intact cells that is not reconstituted in cell-free systems.

Animals↗
PubMed1987

Hydrogen breath test in small intestinal malabsorption.

Jejunal biopsy and hydrogen breath test were performed in 57 children, 34 having coeliac disease and 23 with other forms of malabsorption. In children affected by coeliac disease there was a gradually increasing incidence of positive findings with the H2 breath test as villous damage progressed. In the group of subtotal villous atrophy age dependence was also observed, the majority of positive results occurring below three years of age. In the non-coeliac group the most frequent cause of the positive finding was Giardia lamblia infestation. Among 27 cases with lactose malabsorption confirmed by a positive hydrogen breath test only 11 had diarrhoea. The test proved to be useful in differentiating between the contaminated intestine syndrome and malabsorption due to reduced absorptive surface.

Adolescent↗
PubMed1987

Efficient recognition of adverse drug reactions.

The author discusses the possibility of detection of adverse drug effects. Two methods of data collection are compared: the "side effect oriented" and the "change oriented" method. Well-known and new adverse effect may be detected with greater probability by the described "change-oriented" method. The important role of ward doctors in data collection is emphasized. The method is considered suitable for carrying out both drug trials and intensive drug monitoring.

Data Collection↗