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Biomedical subjects

W Fischbach

Publications and source records attributed to W Fischbach.

At least 109 records · Page 6Linked to original sources
PubMed1991

Structural heterogeneity of faecal alpha 1 antitrypsin shown by immunoblot analysis in patients with Crohn's disease.

Faecal alpha 1 antitrypsin was determined in 34 patients with Crohn's disease and in 19 healthy subjects by immune nephelometry. A structural analysis of faecal alpha 1 antitrypsin was carried out using immunoblot analysis under non-reducing conditions. Native serum alpha 1 antitrypsin migrated with an apparent molecular weight of 45 kDa. Proteolytic alpha 1 antitrypsin fragments (5-42 kDa) were specifically immunostained in 13/19 and 22/34 stool samples from control subjects and from patients with Crohn's disease respectively. There was a weak correlation (r = 0.47; p less than 0.02) between the molecular weight of fragmented alpha 1 antitrypsin and the faecal concentration in both groups, indicating that alpha 1 antitrypsin inhibits its own proteolysis by intestinal proteases in a dose dependent way. The incidence of polymeric forms (greater than 45 kDa) was similar in patients (10/34) and control subjects (5/19). In only one case in each group was the native serum form of alpha 1 antitrypsin found in faeces. We conclude that faecal alpha 1 antitrypsin differs structurally from the native serum form. Immunochemical measurements, therefore, reflect rather than represent faecal concentrations of alpha 1 antitrypsin. The controversial results in published reports may be partly explained by these findings. The molecular heterogeneity of faecal alpha 1 antitrypsin is not specifically associated with Crohn's disease.

Adult↗
PubMed1991

Prostaglandin E2 inhibits secretagogue-induced enzyme secretion from rat pancreatic acini.

Prostaglandins of the E type may have a potential role in pancreatic physiology and pathophysiology. Because prostaglandins of the E type inhibit HCl secretion in parietal cells via a specific receptor by inhibition of adenylylcyclase, we studied whether a similar mechanism exists in the exocrine pancreas. Isolated rat pancreatic acini were incubated with various concentrations of secretagogues, such as cholecystokinin-octapeptide (CCK-8), bombesin, carbachol, and vasoactive intestinal peptide (VIP), in the absence or presence of prostaglandin E2 (PGE2), and amylase secretion was measured. For receptor binding studies, acini and pancreatic membranes were incubated with [3H]PGE2 and either unlabeled PGE2 or other types of prostaglandins. PGE2 (10(-13) to 10(-5) M) did not inhibit basal amylase secretion. However, CCK-8-stimulated secretion was significantly inhibited. Stimulation of secretion by bombesin, carbachol, VIP, and secretin was also inhibited by PGE2, but not as pronounced as CCK-8-stimulated secretion. The formation of inositol 1,4,5-trisphosphate induced by CCK-8 was markedly inhibited by simultaneous incubation with PGE2. Furthermore, PGE2 slightly but significantly reduced the CCK-8-induced efflux of 45Ca2+ from prelabeled acini. Intact acini and a membrane fraction bound [3H]PGE2 and this function could be equally competed by either unlabeled PGE2 or PGE1 in contrast to less-related prostaglandins such as PGF2 alpha, PGD2, and prostacyclin. We conclude that prostaglandins of the E type inhibit pancreatic enzyme secretion stimulated by various secretagogues. This function is mediated via specific receptors for PGE. With regard to CCK-8-stimulated secretion this function may be mediated by an inhibition of formation of inositol 1,4,5-trisphosphate.

Amylases↗
PubMed1991

Clinical relevance of activity parameters in Crohn's disease estimated by the faecal excretion of 111In-labeled granulocytes.

The fecal excretion of 111In-oxine-labeled autologous granulocytes was determined in 58 patients with Crohn's disease. A representative analysis of the total amount of excreted cells requires a 4-day stool sampling at least in those patients suffering from Crohn's ileitis or ileocolitis. Various laboratory tests (Orosomucoid, alpha 1-antitrypsin, C-reactive protein, erythrocyte sedimentation rate, leukocytes, thrombocytes, albumin, Fe, alpha 1-globulin and alpha 2-globulin) and the van Hees index significantly correlated with this specific estimate of intestinal inflammation, indicating that it is of little importance which one is clinically used for the assessment of inflammatory activity in Crohn's disease.

Adult↗
PubMed1991

Comparison between the synthetic cholecystokinin analogues caerulein and Thr28NlE31CCK25-33(CCK9) with regards to plasma bioactivity, degradation rate and stimulation of pancreatic exocrine function.

A new synthetic analogue of cholecystokinin, Thr28Nle31CCK25-33(CCK9) is compared with caerulein with regards to plasma bioactivity, degradation rate, side effects, and stimulation of pancreatic secretion. 24 healthy male volunteers were intubated with a double lumen Lagerlöf-tube. 30 min after correct positioning of the tube subjects received a continuous intravenous infusion of synthetic secretin (1 U/kg) together with either ceruletide (61.5 pM/kg) or CCK9 (30 pM/kg) both for 45 min. 30 pM/kg of CCK9 have been shown by others to cause maximal enzyme secretion (1). 61.5 pM/kg (= 100 ng) of caerulein are probably supramaximal but used by many centers for direct pancreatic function tests. Plasma CCK was measured by bioassay which compares amylase release of isolated rat pancreatic acini stimulated by plasma extracts with known standards of CCK8. Lipase, amylase, trypsin, chymotrypsin, and bicarbonate were measured in 15 min fractions after the onset of CCK infusion. Both drugs caused a similar stimulation of pancreatic enzyme secretion during infusion of the respective analogue which declined after termination. After the onset of CCK9 infusion plasma bioactivity reached a plateau around 20 pM at 15 min. Values declined after 30 min. After termination of infusion bioactivity rapidly declined within 3 min but still remained slightly elevated after further 15 min as compared to basal values (3.9 vs 0.6 pM). Plasma kinetics of caerulein were quite similar. However, despite a dose which was only twice as high as compared to CCK9, plasma bioactivity was six times higher with plateau values of about 120 pM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Initial clinical experiences with a simplified analytic method for fecal alpha-1-antitrypsin].

A new assay for the determination of faecal alpha-1-antitrypsin including a simplified extraction of native stool and nephelometric measurement was studied. Its validity was established by a comparison with standardized methods and with well-known activity parameters. Excellent correlations were found, comparing this method with radial immuno-diffusion carried out on lyophilized (R = 0.96; p less than 0.05) and native (R = 0.97; p less than 0.05) stool samples. Faecal alpha-1-antitrypsin concentrations as measured with this method were significantly (p less than 0.001) higher in patients with inflammatory bowel diseases (Crohn's disease = 40, ulcerative colitis = 15) than in 25 normal controls (0.51 +/- 0.06 mg/g vs. 0.13 +/- 0.02 mg/g; x +/- SEM). There was a significant correlation of faecal alpha-1-antitrypsin with CDAI, activity index van Hees, and with various laboratory parameters (ESR, CRP, serum alpha-1-antitrypsin, orosomucoid, albumin, iron, haematocrit, haemoglobin, leucocytes, and thrombocytes). The presented method is equivalent to standard techniques in measuring faecal alpha-1-antitrypsin concentrations. It is highly useful for clinical routine and for follow-up studies in patients with inflammatory bowel disease.

Adult↗
PubMed1991

DNA aneuploidy and proliferation in spontaneous human and dimethylhydrazine-induced murine colorectal carcinogenesis.

DNA aneuploidy and proliferative abnormalities were studied by flow cytometry in 169 colorectal specimens from 162 patients. Of 37 adenomas, three showed aneuploidy and another seventeen revealed a "near diploid" DNA pattern. The rate of aneuploid and "near diploid" DNA changes in 92 carcinomas was 53.3% and 23.9%, respectively. No correlation was seen between the ploidy distribution and the stage or histologic grade of the carcinomas. The S-phase fractions of both adenomas and carcinomas significantly increased from the diploid (8.1 +/- 0.8% and 7.8 +/- 0.9% respectively; mean +/- SEM) to the "near diploid" (14.9 +/- 1.2% and 12.6 +/- 1.5%) and aneuploid (20.4 +/- 1.3% and 11.4 +/- 1.6%) lesions. To better understand neoplastic progression at very early stages, flow cytometry was also performed on 195 colonic specimens of 44 rats treated by weekly subcutaneous injections of 21 mg/kg Dimethylhydrazine. There was a single "near diploid" carcinoma in this group, and all other induced neoplasms (39 carcinomas and 27 adenomas) revealed a diploid DNA pattern. The S-phase fractions were as follows: controls (38 untreated animals) 8.6 +/- 0.1%, normal mucosa (of Dimethylhydrazine exposed rats) 10.1 +/- 0.25% (p less than 0.0001), adenomas 13.9 +/- 0.6% (p less than 0.01), and carcinomas 14.7 +/- 0.6% (p less than 0.01). These findings support the conclusion that genomic alterations and proliferative abnormalities may already be present in premalignant human colonic lesions. However, despite strong morphological similarities, major biological differences exist between the Dimethylhydrazine-induced murine intestinal carcinogenesis and spontaneously occurring human colorectal neoplasms.

Adolescent↗
PubMed1991

What does routine upper gastrointestinal endoscopy contribute to the staging of non Hodgkin's lymphoma?

In view of the discrepancy between the incidence of gastrointestinal involvement by malignant lymphomas, as established in postmortem studies, and the rareness of the corresponding clinical diagnosis, we carried out routine upper gastrointestinal endoscopy in 82 consecutive patients with newly diagnosed non-Hodgkin's lymphoma. 11/40 patients (27.5%) with non-Hodgkin's lymphoma of low-grade malignancy, and 11/42 (26.2%) of those with highly malignant non-Hodgkin's lymphoma revealed involvement of the gastric and/or duodenal mucosa, as diagnosed by oesophagogastroduodenoscopy. Two patients in stage III, two in stage II, and two further patients with presumptive stage I had to be reclassified as stage IV. Due to gastrointestinal involvement, two patients changed from radiation to chemotherapy, and another two patients underwent gastric resections to avoid possible treatment related complications. In the light of these results and the fact that a major basis for the therapeutic strategy in non-Hodgkin's lymphomas represents tumor stage, routine oesophagogastroduodenscopy within the framework of the usual staging examinations should be discussed. In the individual case, this procedure may be of decisive importance for the therapeutic approach and the prevention of complications.

Adolescent↗
PubMed1990

Tissue carcinoembryonic antigen and DNA aneuploidy in precancerous and cancerous colorectal lesions.

Chronic inflammatory bowel disease (CIBD) and colorectal adenoma are considered as precancerous conditions and lesions of large bowel carcinoma, respectively. They, therefore, may be used to study the behavior of such different factors as tumor-associated antigens and nuclear DNA content abnormalities in colorectal carcinogenesis. Tissue concentrations of carcinoembryonic antigen (CEA) were significantly higher in those precancerous lesions (CIBD: 61 +/- 11.2 ng/mg, adenoma: 70 +/- 6 ng/mg; mean +/- standard error of the mean) than in normal colonic mucosa (36 +/- 4.7 ng/mg). Colorectal carcinoma had still higher tissue levels (437 +/- 108.2 ng/mg). No correlation between tissue CEA and tumor differentiation could be found, but there was a significant difference between aneuploid (747 +/- 354 ng/mg) and diploid (139 +/- 43 ng/mg) tumors. Using flow cytometry DNA aneuploidy was present in 31.6%, 10.5%, and 51.6% of CIBD, colorectal adenoma, and carcinoma, respectively. These data suggest that the occurrence of aneuploidy is not strongly dependent on a malignant transformation, but it may also be present in premalignant colorectal lesions without cellular dysplasia.

Adenoma↗
PubMed1990

Squamous cell carcinoma antigen in the diagnosis and treatment follow-up of oral and facial squamous cell carcinoma.

The squamous cell carcinoma (SCC) antigen was determined by radioimmunoassay in the serum of 40 untreated patients with SCC of the oromaxillofacial region. The mean (+/- SEM) serum concentration for these patients (3.8 +/- 0.8 ng/ml) was significantly higher than that of 52 disease-free patients coming to routine postoperative care (1.2 +/- 0.1 ng/ml) and of 74 healthy controls (1.1 +/- 0.07 ng/ml). Using a arbitrary limit of 2.2 ng/ml, pathologic serum levels of SCC were observed in 15 (38%) of 40 untreated patients, whereas only four (7.7%) of 52 tumor-free patients revealed an elevated serum SCC. Serial measurements of SCC were pretherapeutically available in 28 patients as well as during individual therapy and further follow-up. All but one of these patients had a normal serum SCC postoperatively. The authors' results demonstrate that the clinical value of SCC lies mainly in monitoring the course of the disease. Careful follow-up studies should be undertaken to determine whether serial determination of SCC is promising in early prediction of tumor reoccurrence.

Antigens, Neoplasm↗
PubMed1989

Neuron-specific enolase and thymidine kinase as an aid to the diagnosis and treatment monitoring of small cell lung cancer.

The serum levels of neuron specific enolase (s-NSE) and thymidine kinase (s-TK) were studied in detail in patients with small cell lung cancer (SCLC) to evaluate as to whether their combined use may aid to diagnosis and follow-up of this particular tumor. Only s-NSE could differentiate between SCLC and non-small cell lung cancer (NSCLC) or benign pulmonary diseases (BPD) to some extent, pathologic serum concentrations occurring in 81%, 17%, and 0%, respectively. The comparable figures for s-TK were 62%, 24%, and 28%, respectively. Serum NSE decreased and increased paralleling tumor regression and progression, respectively, except when brain metastases were present. Alterations of s-TK, in contrast, did not usually mirror the course of disease. During initial chemotherapy (CT) a transitory increase of serum levels was observed for both NSE and TK. Monitoring, based on daily blood samples, showed comparable peaks only for s-TK during the following CT cycles, whereas s-NSE was within the normal range even when tumor mass was still present. Those subsequent s-TK peaks under CT may be due to tumor cell lysis as a result of CT indicating the efficacy of treatment by this way. Rapidly proliferating tissues such as bone marrow or bowel mucosa, however, have also to be considered as possible sources of s-TK.

Aged↗
PubMed1989

Kinetic data of in-vivo labeled granulocytes in humans with a murine Tc-99m-labelled monoclonal antibody.

Twenty-five patients were examined in vivo with 99mTc labelled monoclonal antibodies; 15 with suspected infections with an antigranulocyte antibody (BW 250/183), 10 with suspected recurrence of a colorectal carcinoma with an anti CEA antibody (BW 431/26). Both antibodies were IgG1 isotypes. In the patients with suspected infections no change of the peripheral leukocyte count could be observed after the antibody injection (1 mg, n = 9; 0.5 mg, n = 1; 0.25 mg, n = 6). In 2 patients examined with the anti CEA antibody (2 mg), a significant decrease of the peripheral leukocyte count could be observed. The recovery rate of the 99mTc antibody labelled granulocytes was calculated to be about 10%. The increase of the antibody-antigen binding was calculated to be 0.2%/min. In vivo the organ distribution curves demonstrated an increase of 99mTc activity over spleen and bone marrow of 1.1%/min, which was interpreted as antigen-antibody reactivity. The organ distribution curves of the anti granulocyte antibody over spleen and bone marrow showed typical binding characteristics to the local granulocyte epitopes. The curves over other organs showed a simple perfusion pattern. The curves of the anti CEA antibody showed a perfusion pattern over all the examined organs. A sham dialysis model in one patient with renal insufficiency undergoing regular dialysis treatment demonstrated the viability of 99mTc antibody labelled granulocytes in vivo. The kinetic patterns of the 99mTc antibody in patients with Crohn's disease were interpreted as CEA binding of the antibody in the bowel wall.

Animals↗
PubMed1989

Role of glucocorticosteroids in the regulation of pancreatic amylase synthesis.

Both adrenalectomy and chemically induced diabetes mellitus cause a marked decrease of pancreatic amylase activity in rats, but it is unknown whether these effects are the result of a direct or indirect mechanism. The synthesis of various pancreatic enzymes has been studied in isolated pancreatic acini from sham-operated, castrated, and adrenalectomized animals as well as in animals that have been both adrenalectomized and castrated. Protein synthesis was measured by pulse labeling of acini with [35S]methionine followed by either trichloroacetic acid precipitation of total protein and counting or by SDS-PAGE and autoradiography, and additionally by in vitro translation of extracted pancreatic RNA using rabbit reticulocytes. Adrenalectomy resulted in a 70% reduction of amylase activity per milligram of acinar protein as a result of a decrease in amylase synthesis. This reduction in amylase synthesis is a consequence of a decrease in the amount of mRNA coding for amylase. After adrenalectomy, plasma concentrations of the following were reduced compared to controls: corticosterone to 0.45%, insulin to 11%, and glucose to approximately 66%. Addition of glucose to the drinking water caused an increase in insulin and plasma glucose, but this was not followed by an increase in amylase activity. We postulate that corticosterone directly regulates amylase synthesis in the rat pancreas.

Adrenalectomy↗
PubMed1989

Influence of treatment with pancreatic extracts on pancreatic enzyme secretion.

We have evaluated the effects of porcine pancreatic extracts on human pancreatic secretion. Ten male volunteers were intubated with a 4-lumen jejunal tube to collect gastric and duodenal secretions separately via the first and third tube, to infuse PEG 4000 distal the pylorus via the second tube and to apply porcine pancreatic extracts via the fourth tube distal the ligament of Treitz. Pancreatic extracts were given four times at 40 minute intervals; the first two as active enzymes and subsequently as heat denatured proportions. Secretin was continuously infused intravenously (0.5 E/kg bw/h) to achieve minimal pancreatic flow. Lipase, amylase, trypsin, chymotrypsin, volume, and bicarbonate were measured in duodenal contents in eight pooled 15 minute fractions. Three subjects who received HEPES-Ringer buffer instead of pancreatic enzymes served as controls. Plasma cholecystokinin (CCK) was measured using a sensitive bioassay. Both active and heat denatured pancreatic extracts caused a small but significant increase in amylase and chymotrypsin secretion. Basal plasma CCK values were 0.85 (0.05) pM. After intrajejunal instillation of either active or heat denatured pancreatic extracts plasma CCK rose to 3.25 (0.30) pM and to 3.28 (0.36) pM respectively. In a second group of five volunteers, plasma CCK concentrations were measured after a test meal. On day 1, volunteers received a liquid fat and protein rich meal and on day 2, the same test meal containing porcine pancreatic extracts. In both cases, a similar increase in plasma CCK was observed. We conclude that therapy with pancreatic extracts stimulate pancreatic enzyme secretion. This may be mediated through release of CCK.

Adult↗