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J Mössner

Publications and source records attributed to J Mössner.

At least 145 records · Page 8Linked to original sources

[Tertiary gummatous syphilis of the liver--an unexpected disease today. Report of two cases].

Today the luetic hepatitis and gummata of liver are very rare manifestations of a tertiary syphilis because of the antibiotic therapy. Therefore a luetic involvement of liver is a most unexpected and at first mostly misinterpreted finding. In the both represented cases foci in the liver were present, which were suspicious for a metastasizing malignoma and set off the search for an unknown primary tumor. In liver biopsies no malignant process was seen, but necroses with a granulomatous reaction at the border were found which were classifiable definitively only after serological investigations as gummata of liver. Especially by the presence of an additionally reactive hepatitis in the remaining liver parenchyma, possibly with some sarcoid-like granulomas, a tertiary gummatous syphilis should be taken into consideration. The regression of gummata in sonography and computertomography as well as the return to normal of the laboratory findings are important parameters in the follow-up to confirm the diagnosis under antibiotic therapy. The described cases stress the importance that even today the tertiary lues should be taken into consideration by liver foci of unknown origin and should be excluded serologically.

Biopsy↗

[Tertiary syphilis with liver gummata].

Sonography revealed multiple echo-poor lesions in the liver of a 51-year-old man with nonspecific symptoms (fatigue, drop in performance, pressure sensation in the upper abdomen), increased blood sedimentation rate (68/110 mm) and evidence of cholestasis (gamma-GT 126 U/l, alkaline phosphatase 444 U/l, leucine-aminopeptidase 64 U/l). Under the diagnosis of liver metastases the primary tumour was looked for. These investigations and a fine-needle biopsy having proved unsuccessful, laparoscopy was performed. The biopsies so obtained showed whitish yellow, tight elastic structures indicating gummas of the liver in tertiary syphilis. Treponema-specific IgM antibodies in serum characterized active syphilis requiring treatment. Administration of antibiotics (penicillin 1 mega U daily i.m.; because of allergy replaced after four days by erythromycin 2 g daily for six weeks) resulted in complete normalization of all biochemical findings and, some time later, regression of the gummas. The patient has now been symptom-free for three years. This case illustrates the need even to-day of including syphilis in the differential diagnosis of unclear space-occupying lesions of the liver.

Biopsy↗

Influence of exogenous application of pancreatic extracts on endogenous pancreatic enzyme secretion.

The existence of negative feedback inhibition of human pancreatic enzyme secretion by proteases is controversially discussed. We have recently demonstrated that jejunal application of porcine pancreatic extracts, in a dose commonly used to treat digestive insufficiency, stimulated rather than inhibited, human pancreatic enzyme secretion. We have now studied the influence of duodenal application of high concentrations of either pure trypsin or porcine pancreatic extracts with trypsin-equivalent activity, on human pancreatic enzyme secretion. Twenty-three male volunteers were intubated with a gastric tube and a two-lumen jejunal tube to collect secretions separately via the first and third tubes and to perfuse either pure trypsin or porcine pancreatic extracts distal to the pylorus via the second tube. PEG-4.000 was continuously perfused via the second tube to correct for losses of volume. Volunteers received PEG alone during the first hour, phenylalanine during the second, PEG alone again during the third, and either phenylalanine together with trypsin or porcine pancreatic extracts during the fourth h. Activities of lipase, amylase, and chymotrypsin were measured in 15-min fractions. In addition, human lipase secretion was measured with an enzyme immunoassay, which does not crossreact with porcine lipase. Plasma cholecystokinin (CCK) was measured using a sensitive bioassay, which utilizes amylase release by isolated rat pancreatic acini. Perfusion of the duodenum with phenylalanine caused a statistically significant stimulation of enzyme secretion. This stimulation could be inhibited by high concentrations of pure trypsin. In contrast, application of porcine pancreatic extracts, which contained the equivalent activity of trypsin, caused further increases of lipase secretion when compared to phenylalanine alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

Determination of various molecular forms of cholecystokinin from canine mucosa by radioimmunoassay and bioassay.

Bioassays using amylase release from isolated pancreatic acini measure only cholecystokinin (CCK) forms with an intact carboxyl terminus ending with phenylalanine amide, but it cannot be excluded that peptides not structurally related to CCK are also responsible for CCK-like bioactivity. CCK exists in several molecular forms in intestinal mucosa which are released into the circulating blood. We studied the molecular forms of CCK in canine intestinal extracts after separation by high performance liquid chromatography by bioassay and compared them with those detected by radioimmunoassay. For the radioimmunoassay, an antibody was used which needs the carboxyl terminal phenylalanine amide for recognition. Three immunoreactive peaks were reproducibly seen in HPLC eluates which eluted in the regions of synthetic CCK-8, purified porcine CCK-33-39 (which co-elute using this gradient) and purified canine CCK-58. All these peaks were bioactive for amylase release from isolated pancreatic acini. No further bioactive peaks were detected in the HPLC eluates. When an antibody was used which recognizes the midregion of CCK-58, an additional peak was detected which eluted between CCK-33-39 and CCK-58. This form presumably represents an amino terminal fragment of CCK lacking the carboxyl terminus. It can be concluded that bioassays of CCK measure only CCK bioactivity in intestinal mucosal extracts, whereas radioimmunoassays may detect biologically inactive forms depending on the antibody recognition site.

Amylases↗

Effect of CCK on food intake in man: physiological or pharmacological effect?

The present study was designed to determine in humans the dose of CCK which suppresses food intake. 18 male subjects received in randomized order either i.v. saline or Thr28 Nle31 CCK 25-33 (CCK-9) at 100 or 500 pmol/kgh, respectively. In addition, 7 subjects received CCK together with the opiate receptor antagonist naloxone to examine if activation of endogenous opioids might interfere with the potential satiating effect of CCK. Food intake during saline was 32 +/- 2 sandwiches (mean +/- SEM), during CCK-9 100 pmol/kgh 28 +/- 2 (n.s.) and only 12 +/- 3 during CCK-9 500 pmol/kgh (p less than 0.01). The respective water intake was 730 +/- 70 ml, 590 +/- 60 ml (n.s.) and 320 +/- 50 ml (p less than 0.01). Naloxone further reduced food and water intake during high but not low dose CCK or saline. During saline postprandial insulin levels rose by 49 +/- 6 microU/ml within 45 min which was attenuated during low dose (23 +/- 6 microU/ml; p less than 0.01) and high dose CCK-9 (1 +/- 1 microU/ml; p less than 0.001). Plasma glucagon did not change in control or CCK experiments. The postprandial rise of pancreatic polypeptide was attenuated during high dose CCK. Naloxone had no effect on the hormonal response except for a prolonged reduction of insulin and glucose levels following high dose CCK + naloxone. Plasma CCK levels rose by 5.4 pmol/l in controls but by 55 and 255 pmol/l during the low and high dose CCK infusion, respectively. These data demonstrate that suppression of food intake in man by i.v. CCK is a pharmacological rather than a physiological effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

[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↗

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↗

[Therapy of chronic pancreatitis].

Therapy of chronic pancreatitis is dependent on the stage of the disease and its possible complications. A conservative therapy has to focus 1) on pain relief which implicates an understanding of the multiple causes of pain, 2) on therapy of the exocrine insufficiency by application of the appropriate pancreatic enzymes, dietary regimes, and substitution of fat soluble vitamins, and finally 3) therapy of endocrine insufficiency with insulin. The most important therapy is abstinence from alcohol. One special topic of this review is a discussion about the problem of "negative feedback regulation" of the exocrine pancreas with its question whether one can inhibit pancreatic secretion by application of pancreatic enzymes and, thus, reach a pain relieving effect. Various surgical procedures and possibilities of interventional endoscopy are briefly discussed.

Analgesia↗

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↗

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↗

[Gastrointestinal hormones--function and clinical significance. 2: Somatostatin, PYY, neurotensin and other regulatory peptides].

Part 1 of this review described the three classical gut hormones gastrin, cholecystokinin and secretin, with particular emphasis on newly discovered biological effects. Part 2 deals largely with a further aspect of gastrointestinal endocrinology, namely the discovery of numerous new regulatory peptides. The possible physiological effects and pathophysiological significance of which are discussed.

Gastrointestinal Hormones↗

[Gastrointestinal hormones--function and clinical significance. 1: The classical enterohormones gastrin, cholecystokinin and secretin].

Gastrointestinal endocrinology is undergoing a variety of different changes. Thus, many of the known hormones are seen no longer to fit the definition of endocrinology--rather, their regulation mechanism may be of a paracrine, neurocrine, neuroendocrine or autocrine nature, or the peptide may be a neurotransmitter. A better term than hormone would thus be regulatory peptide. A knowledge of the physiological mode of regulation of a peptide impacts not only on our understanding of pathophysiological processes, but also on the therapeutic use of peptides. In this Part, the classical gut hormones gastrin, secretin and cholecystokinin are described with the above aspects in mind. The well-known hormones have also been shown to have previously unsuspected biological actions, whose biological significance is, as yet, unknown. For example, cholecystokinin is now being considered as a regulator of glucose homeostasis, satiety and pancreatic growth.

Cholecystokinin↗

Pancreatic enzyme synthesis and secretion are independently regulated by insulin and glucocorticosteroids.

Both insulin and glucocorticosteroid (GS) deficiency causes a reduction of amylase synthesis and changes in the dose-response curve of cholecystokinin (CCK) stimulated enzyme secretion in rats. Since we found a reduction of plasma insulin in adrenalectomized rats, we now tested the hypothesis that the regulation of amylase synthesis by insulin may be mediated by GS. Three groups of male rats were investigated: controls, streptozotocin induced diabetics, and diabetics treated with GS. Animals were sacrificed 10-14 days after injection of streptozotocin and isolated pancreatic acini prepared by collagenase digestion. Protein synthesis was measured on the translational level by incubation of acini with 35S-methionine followed by lysis of cells and separation of proteins by SDS-PAGE. In addition, protein synthesis was measured on the transcriptional level by isolation of mRNA from pancreatic acini and translation of proteins using the rabbit reticulocyte lysate system. The loss of insulin in diabetic rats was associated with a 70-90% decrease in amylase synthesis and increases of synthesis of various proteases. This was due to a specific decrease in mRNA coding for amylase and increase in mRNA coding for proteases. Furthermore, the known rightward shift of the dose response curves of CCK stimulated amylase secretion was seen in diabetic animals. Treatment of diabetic rats with GS did deteriorate the catabolic status seen in diabetes with increases in mortality as compared to diabetes alone. However, neither the overall pattern of enzyme synthesis seen in diabetic rats nor the alterations in CCK stimulated enzyme secretion were changed by treatment with GS. We conclude that the regulation of amylase synthesis and enzyme secretion by insulin is not mediated via GS.

Amylases↗

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↗