Biomedical subjects

C Löser

Publications and source records attributed to C Löser.

68 records · Page 4Linked to original sources

PubMed1990

Polyamines in human gastrointestinal malignancies.

This study was designed to investigate the clinical relevance of polyamine determination in human tissue, serum, and urine as diagnostic markers in the diagnosis or postoperative control of patients with gastrointestinal cancer. Total, free, and acetylated polyamines were measured simultaneously in tissue, serum, and urine of patients with esophageal (n = 16), gastric (n = 40), pancreatic (n = 20) or colorectal (n = 50) carcinoma, in 40 patients with non-malignant gastrointestinal diseases, and 30 healthy volunteers. Though sensitivity of polyamines for gastrointestinal cancer proved to be high, non-malignant gastrointestinal diseases partly showed similar elevated polyamine concentrations in urine and serum which resulted in a low specificity of polyamines for gastrointestinal cancer. Therefore polyamines are not suitable as diagnostic markers in tumor screening. Furthermore, since polyamine concentrations in serum and urine normalized after curative operation while they were further increased and elevated in patients with proven relapse of the tumor or metastases, polyamines might be of clinical value in postoperative monitoring of therapeutical success or predicting relapse of the tumor.

Biogenic Polyamines↗

PubMed1990

[Serous cystadenoma and mucinous cystadenoma/cystadenocarcinoma of the pancreas. Clinical manifestation, diagnostic procedure and therapeutic concept].

Cystic neoplasms are rare but in the last ten years more frequently detected tumors of the pancreas. The clinical symptoms as abdominal pain, abdominal mass, diarrhoea or weight loss are rather unspecific. There are no typical laboratory findings. Localization, size and cystic character of these tumors are well documented by ultrasound or abdominal computed tomography while typical features in CT as well as US-guided fine needle biopsy may contribute to further differentiation of the tumors. Exocrine and endocrine pancreatic function are frequently weakened which might falsly lead to the diagnosis of chronic pancreatitis. Because of their malignant potential mucinous cystadenoma should be treated by complete surgical resection while serous cystadenoma are exclusively benign and might therefore be treated conservatively in uncomplicated cases or high-risk patients. The prognosis of pancreatic cystadenocarcinoma is obviously better compared to adenocarcinoma of the pancreas.

Cystadenocarcinoma↗

PubMed1989

Dose-dependent inhibition by cyclosporine A of the induction of pancreatic ornithine decarboxylase (ODC) in rats.

The effect of cyclosporine A (CsA) and alpha-difluoromethylornithine (DFMO) on the camostate-induced increase in pancreatic ornithine decarboxylase (ODC) activity and polyamine biosynthesis has been studied in vivo. Six hours after application of the synthetic trypsin inhibitor camostate (200 mg/kg b wt orally) pancreatic ODC activity increased about 140-fold and putrescine concentration about ninefold. CsA inhibited the elevation of both parameters in a dose-dependent manner. CsA pretreatment for 3 d with doses of 7.5, 10.0, and 12.5 mg/kg b wt orally once a day and consecutive CsA blood levels 24 h after the last CsA application of 751 +/- 62, 968 +/- 70, and 1,395 +/- 79 ng/mL, respectively, resulted in a complete inhibition of the camostate-stimulated increase in pancreatic ODC activity and putrescine concentration in vivo. DFMO (2% in drinking water and additionally 300 mg/kg b wt intraperitoneally at 8 AM, 12 noon, and 4 PM) inhibited the increase in both, ODC activity, and putrescine, significantly in an equipotent degree as 2.5 mg CsA/kg b wt, whereas higher doses of CsA proved to be more effective than DFMO in the chosen subtoxic dose. In all cases, no significant changes in pancreatic spermidine and spermine concentration, DNA and protein content, or pancreatic and body weight were observed. It is concluded that CsA in doses used for immunosuppression in clinical practice is a very potent and more effective inhibitor of ODC activity and polyamine synthesis in vivo than DFMO. This ODC inhibitory effect of CsA is a further detail to elucidate the up to now incompletely understood mechanisms of action of this immunosuppressive agent.

Animals↗

PubMed1989

CCK-antagonist L-364,718: influence on rat pancreatic growth induced by caerulein and bombesin-like peptides.

The present study investigates the inhibitory effect of the novel potent benzodiazepine-related CCK-antagonist L-364,718 on pancreatic growth in the rat induced by chronic administration of caerulein and bombesin-like peptides. Caerulein, injected s.c. twice daily at a dose of 1 microgram/kg body weight, and bombesin (10 micrograms/kg) induced a similar increase (1.5-3-fold) in pancreatic wet weight, total protein, amylase, trypsin, putrescine and spermidine content after 14 days of treatment. Growth induced by caerulein showed a significant increase in total DNA content suggesting cellular hyperplasia, whereas bombesin-like peptides led to cellular hypertrophy. In comparison to bombesin the decapeptide neuromedin C (10 micrograms/kg) was found to be 30-50% less potent. In the same dose range, neuromedin B and the tachykinins neurokinin A and B, all structurally related to bombesin, had no significant trophic effect on the rat pancreas. Administration of the CCK-antagonist L-364,718 twice daily at a dose of 0.1 mg/kg or at 1.0 mg/kg, either s.c. or orally, led dose-dependently to a near-complete inhibition of the caerulein-induced trophic effect. In contrast, L-364,718 administered at identical dosages, did not affect pancreatic hypertrophy induced by bombesin and neuromedin C. It is concluded that both peptides mediate their effect on the rat pancreas directly and not via release of endogenous cholecystokinin. Tachykinins are not involved in the regulation of pancreatic growth. Caerulein- and bombesin-like peptides have comparable effects on the stimulation of protein and polyamine synthesis.

Amino Acid Sequence↗

PubMed1989

Ornithine decarboxylase and polyamines in cholecystokinin-induced pancreatic growth in rats: effects of alpha-difluoromethylornithine and the CCK receptor antagonist L-364,718.

Acute and long-term changes of ornithine decarboxylase and polyamines during pancreatic adaptation in response to cholecystokinin administration (1 microgram kg-1 body wt every 8 h) were studied in rats. alpha-difluoromethylornithine, an irreversible and specific inhibitor of ornithine decarboxylase, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. In the cholecystokinin-treated animals ornithine decarboxylase activity was increased after 2 h, reached a maximum after 8 h (444.6 pmol 14CO2 h-1 mg-1 DNA, about 65-fold greater than controls, P less than 0.001) followed by a significant increase of putrescine after 6 h and spermidine after 24 h while spermine remained unchanged. The trophic parameters increased in the following time sequence: thymidine kinase (12 h), DNA polymerase (24 h), pancreatic weight (2 days), protein (2 days) and DNA (5 days). alpha-difluoromethylornithine significantly delayed the increase in ornithine decarboxylase, putrescine and spermidine as well as all trophic parameters. Increases in ornithine decarboxylase, polyamines and all trophic parameters were completely inhibited by simultaneous application of the CCK receptor antagonist L-364,718. These data indicate an important role for ornithine decarboxylase and polyamines in cholecystokinin-induced pancreatic growth in rats.

Amylases↗

PubMed1989

Role of ornithine decarboxylase and polyamines in camostate (Foy-305)-induced pancreatic growth in rats.

This study was designed to investigate changes of ornithine decarboxylase and polyamines during pancreatic adaptation in response to feeding of the synthetic protease inhibitor camostate. alpha-Difluoromethylornithine, an irreversible and specific inhibitor of ornithine decarboxylase, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. Cholecystokinin (CCK) plasma levels in camostate-fed rats increased from basal values of 3-4 pmol/l to a maximal level of 27.4 pmol/l after 2h; they then decreased up to 12 h but remained elevated above controls throughout the 30-day experiments. In the camostate group pancreatic ornithine decarboxylase activity was elevated after 2 h, reaching a maximum after 6 h (1,858.5 pmol 14CO2/h/mg DNA, about 200-fold above controls) followed by a significant increase in putrescine after 4 h and spermidine after 24 h while spermine remained unchanged. The trophic parameters increased in the following time sequence: thymidine kinase (12 h), DNA polymerase (12 h), protein (24 h), pancreatic weight (24 h) and DNA (5 days). alpha-Difluoromethylornithine significantly delayed and reduced the camostate-induced increase in ornithine decarboxylase activity and polyamine concentrations as well as the trophic parameters. Application of the CCK receptor antagonist L-364,718 resulted in complete inhibition of the increases in ornithine decarboxylase, polyamines and all trophic parameters. These data indicate an important role for ornithine decarboxylase and polyamines in camostate-induced pancreatic growth and hormonal mediated pancreatic adaptation in rats.

Animals↗

PubMed1989

Polyamines in human gastric and esophageal cancer.

Total, free, and acetylated polyamine concentrations were investigated in gastric or esophageal tissue, serum, and urine of 40 patients with gastric and 16 patients with esophageal cancer, 40 patients with non-malignant gastrointestinal diseases, and 30 healthy volunteers by means of automated reversed-phase liquid chromatography. In both types of carcinoma polyamine levels were highly elevated in tissue, serum, and urine as compared with healthy controls, which supports the concept that polyamines play an important role in proliferating tissues. However, non-malignant gastrointestinal diseases partly showed similar elevations. A significant linear correlation of polyamines in both carcinomas was found for erythrocyte sedimentation rate but not for tumor stage, tumor size, localization, carcinoembryonic antigen, CA 19-9, and CA 125. It is concluded that owing to its low specificity, polyamine determination in serum and urine has no clinical relevance in the screening for gastric or esophageal carcinoma.

Adenocarcinoma↗

PubMed1988

Reversed-phase liquid chromatographic separation and simultaneous fluorimetric detection of polyamines and their monoacetyl derivatives in human and animal urine, serum and tissue samples: an improved, rapid and sensitive method for routine application.

A highly sensitive and precise method for the determination of the polyamines putrescine, cadaverine, spermidine and spermine and all their monoacetyl derivatives in a single analysis in human and animal urine, serum and tissue samples is described. For polyamine separation, an ion-pairing reversed-phase high-performance liquid chromatographic (HPLC) method is used, followed by post-column derivatization with o-phthalaldehyde and consecutive fluorescence detection. Urine and serum samples are purified with a Bond Elut silica cartridge. The detection limit for polyamines is 0.5-1.0 pmol and excellent linearity is achieved in the range from 3 pmol up to more than 10 nmol. The influence of some modifications of different analytical steps such as the temperature of the HPLC column and the derivatization reaction coil and the o-phthalaldehyde flow-rate is described. Quality control data and measurements of the reproducibility of the method are presented. In order to establish a rapid analytical method for easy routine use, all steps for preparation and quantitative analysis are minimized. This method was applied to the determination of total polyamines in human urine and serum hydrolysate and of free and acetylated polyamines in human urine and pancreatic tissue of the rat. Values for normal polyamine concentrations in the urine and serum of fifteen male and fifteen female healthy volunteers and in the pancreas of ten normal rats are presented.

Acetylation↗

PubMed1988

Ornithine decarboxylase and polyamine biosynthesis in pancreatic adaptation.

This study was designed to investigate the role of ornithine decarboxylase (ODC) and polyamines in pancreatic adaptation. Cholecystokinin (CCK) is well-known to be a potent trophic stimulus on the pancreas. On the other hand, the oral application of the synthetic trypsin inhibitor camostate results in an extensive release of endogenous CCK in rats. alpha-difluoromethylornithine (DFMO), an irreversible and specific inhibitor of ODC, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. Camostate feeding (200 mg/kg b.wt. orally twice a day) resulted in a rapid elevation of ODC activity already after 2 hours, reaching a maximum after 6 hours (about 200fold above controls) followed by a significant increase in putrescine after 4 hours and spermidine after 24 hours while spermine remained unchanged. The trophic parameters increased as expected in following time-course: thymidine kinase (12 hours), DNA polymerase (12 hours), protein (24 hours), pancreatic weight (24 hours) and DNA (5 days). DFMO (2% in drinking water + 3 x 300 mg/kg b.wt. i.p. during daytime) was not able to prevent but significantly delayed and reduced the camostate-induced increase in ODC and polyamines as well as the trophic parameters. These data indicate an essential role for ODC and polyamines in camostate-induced pancreatic growth and hormonal mediated pancreatic adaptation.

Animals↗

PubMed1988

Pancreatic polyamine concentrations and cholecystokinin plasma levels in rats after feeding raw or heat-inactivated soybean flour.

We investigated the trophic effect on the pancreas of male Wistar rats fed up to 20 days with either raw soybean flour (RSF) containing an active trypsin inhibitor or heat-inactivated soybean flour (HSF). The concentrations of the polyamines putrescine, spermidine, and spermine in the pancreas as well as cholecystokinin (CCK) concentrations in arterial and portal vein plasma were measured. Plasma CCK concentrations were measured by a sensitive radioimmunoassay specific for the sulfated region of CCK, whereas polyamine concentrations are determined by reversed phase high-performance liquid chromatography. The levels of CCK in both arterial and portal vein plasma were significantly higher in RSF- compared with HSF-fed rats, the concentration in the portal vein being twice as high compared with the aorta. A significant increase in pancreatic weight and protein content was positively correlated to an increase in putrescine and spermidine in the pancreas of RSF-fed rats compared with HSF-fed controls, whereas the spermine content did not differ between the two groups. The pancreatic DNA content in RSF-fed rats was significantly above control values of day 20 only. These data support the hypothesis that the trophic effect of soybean trypsin inhibitor on the pancreas is mediated by CCK and that polyamines might play an important role in CCK-induced pancreatic growth.

Animals↗

PubMed1987

Adaptive responses to pharmacological inhibition of small intestinal alpha-glucosidases in the rat.

Intestinal adaptation (small intestinal weight and length, weight of the caecum and of the residual colon) to feeding different doses (0-5-50-500 mg/kg bw) of the absorbable, competitive alpha-glucosidase inhibitors BAY m 1099 and BAY o 1248 for three, seven, or 28 days was studied in rats. With the highest dose of either inhibitor, a significant and time dependent growth of the caecum was observed. Under these conditions, caecal tissue polyamine concentrations (spermidine and spermine) were slightly higher after three, unaffected after seven and slightly decreased after 28 days. Comparing the trophic effect both of BAY m 1099 and BAY o 1248 with that of the almost unabsorbed glucosidase inhibitor acarbose in fed rats showed that caecal weight was higher in response to the absorbed compounds than in response to acarbose, while total caecal carbohydrate content was unaffected by the absorbed and about nine fold increased by the unabsorbed inhibitors. These findings suggest that acarbose may partially inhibit bacterial carbohydrate degradation in the caecum.

1-Deoxynojirimycin↗

PubMed1982

Evolutionary conservation of a common pattern of activity of nucleolus organizers during spermatogenesis in vertebrates.

The patterns of activity of the nucleolus organizer regions (NORs) in the spermatogeneses of ten species of all non-mammalian classes of vertebrates and one species of the cephalochordates were investigated with the silver (Ag)-staining technique. The Ag-stainability of the NORs is a measure of the transcriptional activity of the ribosomal RNA genes. In all species, there is a very similar pattern of NOR-activity in the various stages of spermatogenesis. The qualitative analysis of the Ag-stainability of the NORs was in very good agreement with the results obtained for mammals: Ag-stained NORs are detectable during the entire meiotic prophase up to the pachytene stage, completely absent in the meiotic metaphases I and II, and again demonstrable in early spermatid nuclei. The results confirm the occurrence of postmeiotic reactivation of the RNA genes. The preferential inhibition of rRNA synthesis by low doses of actinomycin D induced a rapid decline of the Ag-stainability of the postmeiotically reactivated NORs. The significance of the evolutionary conservation of the postmeiotic NOR-reactivation is discussed.

Animals↗

PubMedDate not supplied

Rheolytic thrombectomy of an acutely thrombosed transjugular intrahepatic portosystemic stent shunt.

As an alternative to chemical thrombolysis, an acutely occluded transjugular intrahepatic portosystemic stent shunt in a 72-year-old woman was successfully recanalized using a 5 Fr rheolytic catheter system. No adjunctive thrombectomy treatment was necessary. The underlying stenotic leason was treated with percutaneous transluminal angioplasty and a Palmaz stent. Immediately after the intervention optimal shunt flow was achieved. Ascites vanished within a few days and no further bleeding complications appeared.

Aged↗

PubMedDate not supplied

Sperm acrosome antigen-1, a molecule intimately involved in the regulation of the acrosome reaction: analysis of expression on spermatozoa from infertile couples.

Sperm acrosome antigen-1 (SAA-1) is a molecule on the acrosomal cap of sperm from the human and a number of mammalian and lower species. SAA-1 was initially characterized by a monoclonal antibody (mab) AG7 directed against SAA-1. Previous studies indicate that SAA-1 may play an important role in the regulation of the acrosome reaction in the human and other species. Unselected couples seeking infertility treatment were subjected to an analysis of the amount of SAA-1 present on washed husband sperm. Using indirect immunofluorescence as well as radioimmunobinding assay, the expression of SAA-1 on patient spermatozoa was found to be significantly decreased compared to a group of healthy sperm donors. The decrease in SAA-1 did not correlate well with sperm morphology. Couples entered into the study were followed for an average of 12 months, while they received infertility treatment. Most couples conceived after a variable number of treatment cycles. It is concluded that a decrease of SAA-1 expression may contribute to subfertility, which can be overcome by the aid of assisted reproduction.

Acrosome↗