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Biomedical subjects

A Bosma

Publications and source records attributed to A Bosma.

67 records · Page 4Linked to original sources

Differential expression of pepsinogen isozymogens in a patient with Barrett esophagus.

The pepsinogen A (PGA) isozymogens in the gastric mucosa and Barrett epithelium of a female patient with Barrett esophagus were studied on different occasions during a 3-year period by electrophoretic analysis of in vivo steady-state pepsinogen in biopsies by activity staining in combination with variant specific monoclonal antibodies and of de novo synthesized pepsinogen by autoradiography. In Barrett epithelium only one (Pg3) or two (Pg3 and Pg5) primary PGA gene products were detected, whereas in gastric mucosal biopsies three (Pg3, Pg4 and Pg5) primary gene products were demonstrated on all occasions. These differences strongly suggest differential expression/activation of individual gene numbers in the PGA gene cluster in Barrett esophagus and are in line with the preneoplastic nature of this condition. The mechanism behind this deregulation is currently under investigation by cell biology and molecular genetic techniques.

Aged↗

Gastric proteases in Barrett's esophagus.

Precursors of the gastric proteases pepsinogen A (pepsinogen I) and pepsinogen C (pepsinogen II) and slow-moving protease were demonstrated in biopsy specimens from Barrett's epithelium in 21 of 22 patients with Barrett's esophagus; in 14 of them, in variable combinations at different sites. In 13 of 19 patients (68.4%) with detectable pepsinogen A, different isozymogen patterns were found between the Barrett's epithelium and the gastric corpus mucosa. Discrepancies consisted mainly of a stronger pepsinogen 5 band in the Barrett's epithelium, with a higher incidence in biopsy specimens with features of dysplasia than with no or indefinite dysplasia; the difference was, however, not statistically significant. Zymograms of 69 biopsy specimens from Barrett's epithelium were correlated with the histologic type: pepsinogen A and C were most frequently found in the fundic type, least often in the specialized intestinal type. In control gastric corpus biopsy specimens, pepsinogen A and C as well as slow-moving protease were always detectable. The observed variability of gastric protease patterns, in particular of pepsinogen A isozymograms, may be due to differences in expression within the pepsinogen A cluster, suggesting a deregulation of gene expression or partial deletion of the pepsinogen A gene cluster.

Adult↗

Cartilagenous tumours of the larynx.

A brief review of the literature on cartilagenous tumours of the larynx is presented and their pathology, clinical features and treatment is discussed: Chondromas are rare; Chondrosarcomas can be potentially fatal. Conservative surgical therapy and close follow up is the essential line of treatment for tumours of the cricoid cartilage. Three new cases are presented.

Adult↗

Long-term effects of partial ileal bypass on the health status of rabbits.

Partial ileal bypass (PIB) surgery is a method for the treatment of familial hypercholesterolaemia in man. Since the rabbit is frequently used as an animal model in experimental studies on PIB, we have investigated the long-term effects of this surgical procedure on the health status of rabbits. Forty-eight weeks after surgery plasma and liver cholesterol levels were decreased by about 40%. The inner diameter of the bypassed ileum was drastically reduced, unlike its length. The bypassed segment did not show clear histological abnormalities. The microflora of the caecum was similar in control and PIB rabbits. PIB did not influence liver histology. The bile of the rabbits with PIB was less lithogenic than that of control animals. Blood haemoglobin levels, haematocrit values and plasma concentrations of alkaline phosphatase, alanine aminotransferase, gamma-glutamyl transferase and lactate dehydrogenase were not changed after PIB. Plasma levels of albumin, creatinine, calcium, phosphorus, vitamin B12 and folic acid were not significantly affected by PIB. Rabbits with PIB had significantly higher plasma levels of bilirubin and zinc than control rabbits, but plasma vitamin E concentrations were significantly lower. These results may be of importance for further studies on the effects of PIB in rabbits.

Animals↗

Progressive and fatal course of a patient with a multifocal leiomyomatous tumor.

The case history of a 53-yr-old woman exhibiting the progressive appearance of several hundreds of subcutaneous leiomyomatous tumors in a 15-yr period is presented. The occurrence of multiple tumors in the gastrointestinal tract, mesentery, and retroperitoneum, necessitated several laparotomies because of pain and chronic blood loss. On light microscopy high mitotic activity, which is generally a characteristic of sarcoma, was only encountered in lesions, surgically removed a few months before death. It is argued that our patient suffered from multiple leiomyomatous tumors with progressive growth capacity, which may represent a multifocal origin rather than a metastasized sarcoma.

Duodenum↗

Immunocytochemical localization of pepsinogen I and II in the human stomach.

An immunoperoxidase method using antisera specific for PG I and PG II was developed to assess PG-containing cells in the human stomach. Fundus-chief cells contained abundant PG I and less PG II. Mucus neck cells stained more frequently with anti-PG I, while antral gland cells stained only with anti-PG II. In adenocarcinoma of the corpus, isolated glands faintly staining with anti-PG I or anti-PG II were observed. In dense tumorous tissue no anti-PG I activity could be observed, while PG II sometimes remained present in residual antral glands, even in areas of heavy tumor infiltration. Focal PG II activity was also clearly demonstrated in some antral tumor cells. The immunoperoxidase technique described is suitable for further detailed studies of normal and pathological conditions of the gastric mucosa.

Adenocarcinoma↗

Specific antisera against human blood cells applicable in the indirect immunofluorescence technique.

The preparation of antisera against various cells of the human peripheral blood applicable in the indirect immunofluorescence technique (IIFT) is described. Such antisera will be a great interest for the study of cell-specific membrane antigens, for example during haematopoiesis. Purified erythrocytes, lymphocytes, neutrophils, monocytes, and thrombocytes from healthy donors were injected into rabbits. The antisera thus produced were not spontaneously specific. Only by extensive absorption of the crude antisera with purified cells from healthy donors was it possible to obtain antisera that were specific for erythrocytes, lymphocytes, and thrombocytes. By injection of small doses of leukocyte lysate and by absorption of the resulting antiserum with mononclear cells a specific antineutrophil serum was produced. So far it has not been possible to prepare a specific anti-monocyte antiserum. The specific antisera were applicable in the IIFT on paraformaldehyde-fixed cells in suspension and on cells on slides.

Absorption↗

First-pass elimination of salicylamide in man following oral and rectal administration.

In order to study the avoidance of hepatic first-pass elimination following rectal administration, 500 mg of salicylamide (SAM) were given orally and rectally to man. Plasma SAM concentrations were measurable following oral administration, but following rectal administration SAM concentrations were either very low or not detectable. The mean excretion of SAM sulphate (SAMS) and SAM glucuronide (SAMG) in the urine following oral and rectal administration was 71.3 per cent and 45.6 per cent respectively. Increasing the oral and rectal dose (1500 mg of SAM, solution) showed that the mean AUC values were 911 and 144 micrograms min ml-1, respectively. The mean urinary excretion of SAMS plus SAMG following oral and rectal administration was 82.0 and 75.6 per cent respectively; the mean plasma elimination half-lives were 31 and 40 min, respectively, while the mean urinary elimination half-lives were 63 and 73 min, respectively.

Administration, Oral↗

Significant improvement of survival by intrasplenic hepatocyte transplantation in totally hepatectomized rats.

The effect of intrasplenic hepatocyte transplantation (HTX) was studied in an experimental model of acute liver failure in rats with chronic liver atrophy. Rats underwent a portacaval shunt operation on Day -14 to induce liver atrophy, and underwent total hepatectomy on Day 0 as a start of acute liver failure. Intrasplenic hepatocyte or sham transplantation was performed on Day -7,-3, or -1 (n = 4 to 6 per group). During the period following hepatectomy, mean arterial blood pressure was maintained above 80 mm Hg and hypoglycaemia was prevented. Severity of hepatic encephalopathy was assessed by clinical grading and EEG spectral analysis, together with determination of blood ammonia and plasma amino acid concentrations, and "survival" time. Histological examination of the spleen and lungs was performed after sacrifice. Intrasplenic hepatocyte transplantation resulted in a significant improvement in clinical grading in all transplanted groups (p < 0.05), whereas a significant improvement in EEG left index was seen only in the group with transplantation on Day -1 (p < 0.05). In contrast to hepatocyte transplantation 1 day before total hepatectomy, rats with hepatocyte transplantation 3 and 7 days before total hepatectomy showed a significant 3- and 2-fold increase in "survival" time compared to sham transplanted controls: HTX at Day -1: 7.5 +/- 0.3 h vs. 5.9 +/- 0.6 h (p > 0.05), HTX at Day -3: 19.7 +/- 3.7 h vs. 6.5 +/- 0.3 h (p < 0.05), and HTX at Day -7: 13.8 +/- 3.2 h vs. 6.3 +/- 0.3 h (p < 0.05). Furthermore, rats with hepatocyte transplantation on Day -3 and -7 showed significantly lower blood ammonia concentrations after total hepatectomy (p < 0.0001). Histological examination of the spleens after sacrifice showed clusters of hepatocytes in the red pulp. Hepatocytes present in the spleen for 3 and 7 days showed bile accumulation and spots of beginning necrosis. The present data show that in a hard model of complete liver failure in portacaval shunted rats, intrasplenic hepatocyte transplantation is able to prolong "survival" time significantly 2- to 3-fold. The relevance of this observation for human application is discussed.

Amino Acids↗

Rapid determination of HLA B*07 ligands from the West Nile virus NY99 genome.

Defined T cell epitopes for West Nile (WN) virus may be useful for developing subunit vaccines against WN virus infection and diagnostic reagents to detect WN virus-specific immune response. We applied a bioinformatics (EpiMatrix) approach to search the WN virus NY99 genome for HLA B*07 restricted cytotoxic T cell (CTL) epitopes. Ninety-five of 3,433 WN virus peptides scored above a predetermined cutoff, suggesting that these would be likely to bind to HLA B*07 and would also be likely candidate CTL epitopes. Compared with other methods for genome mapping, derivation of these ligands was rapid and inexpensive. Major histocompatibility complex ligands identified by this method may be used to screen T cells from WN virus-exposed persons for cell-mediated response to WN virus or to develop diagnostic reagents for immunopathogenesis studies and epidemiologic surveillance.

Costs and Cost Analysis↗