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Biomedical subjects

T von Schrenck

Publications and source records attributed to T von Schrenck.

At least 19 recordsLinked to original sources
PubMed2003

Oral lichen planus in patients with chronic liver diseases.

BACKGROUND: The possible increased risk of oral lichen planus (OLP) in patients with chronic liver diseases is a controversial issue. PATIENTS AND METHODS: We investigated a total of 156 outpatients with known liver diseases for occurrence of OLP. Hepatitis C virus (HCV) infection was proven for 117 patients (75%) and hepatitis B virus (HBV) infection for 16 patients (10.3%). Four patients were coinfected with HCV and HBV. An alcohol-derived hepatic cirrhosis was found in 23 patients (14.7%). Three patients had a biliary cirrhosis and one had a primary sclerosing cholangitis. Patients suspected of having OLP were transferred to the Department of Oral and Maxillofacial Surgery where excisional biopsies were taken. RESULTS: Eight patients had a white alteration of the oral mucosa. OLP was suspected in five of them and was confirmed histologically in four. The alteration of the fifth patient disappeared during continued interferon therapy. CONCLUSION: Our results show that there is no increased prevalence of OLP manifestation in patients suffering from HCV infection.

Adult↗
PubMed2000

CCKB/gastrin receptors mediate changes in sodium and potassium absorption in the isolated perfused rat kidney.

BACKGROUND: To evaluate the function of cholecystokinin B (CCKB)/gastrin receptors in the rat kidney, we identified the receptors by Northern blot and localized the receptors by immunohistochemistry. The functional effects of gastrin were studied under standardized in vitro conditions using the isolated perfused kidney. METHODS: Rat kidneys were mounted in an organ bath by attaching the renal artery to a perfusion system. A catheter was inserted into the renal vein and the ureter to collect samples that were analyzed for the concentrations of electrolytes. After a preperfusion period, gastrin-17-I was given via the renal artery (10-8 to 10-6 mol/L). Subsequently, hemodynamic parameters (for example, perfusate flow) and changes in sodium and potassium absorption were determined. All data were subjected to a nonparametric analysis of variance and, in case of significant results, to subsequent paired comparisons by the a posteriori Wilcoxon test. RESULTS: Northern blot analysis detected CCKB receptor transcripts in total RNA isolated from kidneys. Immunohistochemistry localized CCKB receptors on tubules and collecting duct cells. Compared with controls, gastrin (10-6 mol/L) caused a decrease in the fractional sodium reabsorption (basal 80%, 10 minutes after application of gastrin 71%, after 20 minutes 62%, P < 0.05). This effect was inhibited by the CCKB receptor antagonist L-365,260. Gastrin decreased urinary potassium excretion at 10-8 and 10-6 mol/L [maximal decrease at 10-6 mol/L from baseline values (100%) to 49% after 10 minutes and to 69% after 20 minutes, P < 0.05, N = 6]. This effect was also abolished by the CCKB receptor antagonist L-365,260. Gastrin (10-6 mol/L) reduced perfusate flow by 31% (P < 0.05). CONCLUSIONS: CCKB receptors are expressed in the rat kidney on tubules and collecting ducts. These receptors mediate changes in renal potassium and sodium absorption. In addition, gastrin causes a decrease in perfusate flow, indicating that CCKB receptors might also modulate vascular resistance in the kidney.

Animals↗
PubMed2000

[Diagnosis of gastroesophageal reflux and Barrett esophagus].

Gastroesophageal reflux is a very common disorder. Typical symptoms are heartburn, regurgitation and chest pain. Recently, it has been demonstrated that gastroesophageal reflux may generate or worse extraesophageal symptoms such as asthma, chronic bronchitis, posterior laryngitis, and chronic cough. The diagnosis of gastroesophageal reflux is suggested by typical symptoms which improve under a therapy with proton pump inhibitors. pH-monitoring over 24 hours is able to establish directly the diagnosis by measuring acid reflux into the esophagus. Manometry detects the two most common causes of gastroesophageal reflux: insufficiency of the lower esophageal sphincter or esophageal motility abnormalities. Gastroesophageal reflux can lead to reflux esophagitis, which is diagnosed endoscopically. An endoscopy should routinely be performed in case of dysphagia, anemia, or loss of weight. A long-term sequela of gastroesophageal reflux is the development of Barrett's-esophagus, a condition which has to be verified by endoscopy and biopsy. This premalignant lesion is defined by a metaplastic change from the normal squamous mucosa to a specialized intestinal epithelium characterized by goblet cells. Because dysplasia in these metaplastic areas can lead to esophageal adenocarcinoma, regular endoscopic surveillance with biopsies is recommended. Gastroesophageal reflux can significantly impair the quality of life and can cause complications that include the neoplastic progression from Barrett's esophagus to carcinoma. Therefore, appropriate diagnostic procedures and adequate therapy are required. This article summarizes the diagnostic approach to patients with gastroesophageal reflux, reflux esophagitis and Barrett's-esophagus. The impact of endoscopy, pH-monitoring, esophageal manometry, radiology and scintigraphy are reviewed.

Adenocarcinoma↗
PubMed2000

[Endoscopic argon plasma coagulation of Barrett mucosa].

BACKGROUND: Up to 10% of patients with Barrett's esophagus develop adenocarcinoma of the distal esophagus. Endoscopic surveillance is recommended. We studied the potential of Argon plasma coagulation (APC) for eradication of Barrett's esophagus. METHODS: Indication for APC was the histologic evidence of columnar epithelium with a length of > or = 2 cm, located proximal of the cardia and with the presence of goblet cells. Endoscopic therapy was performed using an Argonbeamer (Beamer 2, Erbe Company, Tübingen, Germany) under i.v. sedation and repeated in intervals of 2-3 weeks with the aim of complete eradication of Barrett's epithelium. One month after macroscopic Barrett eradication, superficial and deep biopsies were obtained every 2 cm in 4 quadrant technique to confirm the endoscopic aspect of complete eradication. RESULTS: We report our results (follow-up median: 12 mths., 3-25) in the first 12 patients (8m/4f, median age 57 yrs., 42-69) in which treatment was completed. In one case there was evidence of moderate dysplasia. A mean of 5 (4-11) sessions were required for complete Barrett eradication in 11 patients (median size of Barrett-segment: 4 cm, range 2-11), in one patient partial regression of 50% was observed treatment was discontinued after 17 sessions while only. Deep biopsies showed subepithelial columnar epithelium islands in one case, recurrence of Barrett occurred in 2 cases after 3 and 6 months. Under APC-treatment, 11/12 patients complained about retrosternal pain and odynophagia. No other complications were observed. CONCLUSION: Our preliminary results indicate that APC is safe and effective to eradicate Barrett's epithelium. Follow-up in a larger number of patients is necessary to assess longterm results (Barrett recurrence, decrease in the incidence of the adenocarcinoma), before APC may generally be recommended.

Adenocarcinoma↗
PubMed1999

[Receptors for cholecystokinin and gastrin].

Cholecystokinin (CCK) and gastrin belong to one family of gastrointestinal peptides that regulate a variety of functions in the gastrointestinal tract and in the central nervous system. On the basis of pharmacological, physiological and molecular studies, receptors for these peptides can be divided into at least two different types: CCKA- and CCKB-receptors. CCKA- and CCKB-receptors are both G-protein coupled receptors and are highly conserved between species. Molecular techniques have revealed a distinct species- and tissue-specific variation in receptor expression and pharmacology. In addition, previously unknown targets for CCK and gastrin such as the kidney were identified. This review discusses the physiological functions of the hormones CCK and gastrin and their receptors. The molecular structure of these receptors and the results of recent structure-function analysis are reviewed.

Amino Acid Sequence↗
PubMed1998

Evidence for CCK(B) receptors in the guinea-pig kidney: localization and characterization by [125I]gastrin binding studies and by RT-PCR.

Two types of receptors for gastrin and cholecystokinin (CCK) have been identified in the gastrointestinal tract and in the central nervous system: CCK(A) and CCK(B) receptors. Here we report evidence for the expression of CCK(B) receptors in the guinea-pig kidney. Specific binding sites for [125I]gastrin were detected in sections of the guinea-pig kidney: Binding was saturable, pH-, temperature- and time-dependent, and specific for gastrin-related peptides. The potencies for inhibition of binding of [125I]gastrin were CCK-8 > gastrin 17-I > CCK(B) receptor antagonist L-365,260 > des(SO3)CCK-8 > CCK(A) receptor antagonist L-364,718. Autoradiography demonstrated specific [125I]gastrin binding to medullary collecting ducts and to a much lesser extent to glomeruli, but not over other structures. CCK(B) receptor cDNA fragments were amplified by RT-PCR from total kidney, isolated tubuli and from tissues known to express CCK(B) receptors such as stomach and brain. The kidney might therefore be a previously unidentified site of action for gastrin and cholecystokinin-related peptides.

Aldosterone↗
PubMed1998

Gastrin/cholecystokinin type B receptors in the kidney: molecular, pharmacological, functional characterization, and localization.

BACKGROUND: Gastrin/cholecystokinin type B receptors (CCKBRs) can be found on parietal cells and smooth muscle cells and are the predominant brain CCK receptors. Recent cloning studies indicate that this is receptor type might also be expressed in the kidney. MATERIALS AND METHODS: We used Northern blot analysis in guinea pig. kidney and reverse transcriptase polymerase chain reaction (RT-PCR) in several murine kidney cells lines to evaluate this organ for the expression of the CCKBRs. The receptor was pharmacologically characterized by displacement experiments using [125I]-BH-CCKs and various agonists and antagonists. Polyclonal antibodies vs. the CCKBRs were raised in chicken, and immunohistochemistry on tissue sections was used to localize the receptor within the organ. The effect of gastrin on renal cell growth was measured using proximal tubulus (MCT) cells, which were cultured with gastrin (10-9 M) for 24-72 h. Cell counts and [3H]-thymidine incorporation experiments were performed. RESULTS: CCKBR transcripts can be detected in kidney RNA (tubules > glomeruli > interstitium). RT-PCR revealed CCKBR transcripts in proximal tubules (MCT cells) and in mesangium (MMC). The medullary thick ascending limb of Henle's loop and several control tissues such as liver and muscle were negative. Displacement experiments using [125I]-BH-CCK and various agonists and antagonists identified binding sites with typical CCKBR pharmacology. CCKBRs were localized in the proximal tubulus, distal collecting ducts and mesangium cells. Treatment of rested MCT cells with gastrin 17-1 induced cell proliferation and [3H]-thymidine incorporation by at least 40% compared with normal growth (P < 0.05). CONCLUSION: These results show for the first time that CCKBRs are present in selected areas of the kidney, and strongly confirm our previous observation that this organ expresses binding sites for [125I]-gastrin. Furthermore, gastrin might act as a growth factor in the kidney.

Animals↗
PubMed1997

Characterization of CCK receptors in stomach smooth muscle: evidence for two subtypes.

Cholecystokinin (CCK) and related peptides such as gastrin are important regulators of gastric smooth muscle contraction. Several studies have shown that these effects of CCK and gastrin are mediated by CCK(B) receptors. However, recent studies suggest the expression of an additional CCK receptor subtype distinct from CCK(B) receptors in this tissue. This study was designed to distinguish between CCK(A) and CCK(B) receptors on guinea-pig stomach smooth muscle cells and to evaluate these cells for additional receptor subtypes. We cloned these receptors by hybridization screening of a guinea-pig smooth muscle cDNA library using 32P random primed labeled cDNA probes from the recently cloned rat CCK(A) and CCK(B) receptor coding regions. In addition to clones representing the CCK(B) subtype, clones of CCK(A) receptor subtype, but no additional CCK receptor subtypes, could be identified. All isolated clones displayed highly homologous nucleotide sequences in comparison to previously characterized CCK(A) and CCK(B) receptors from different species. The results of cDNA hybridization at different levels of stringency and Southern blot analysis using guinea-pig genomic DNA suggest that it is unlikely that additional CCK receptors despite CCK(A) and CCK(B) receptors exist in stomach smooth muscle.

Animals↗
PubMed1994

Signal transduction pathway of the muscarinic receptors mediating gallbladder contraction.

In gallbladder smooth muscle, carbachol interacts with M3 receptors to mediate contraction. To examine components of the intracellular second messenger system that is coupled to these receptors we have tested whether carbachol stimulates the formation of inositol phosphates (IP) to cause contraction. Guinea pig gallbladder muscle strips were prelabeled with [3H]inositol and were incubated with 0.1 mmol/l carbachol, a concentration causing maximal contraction. [3H]inositol monophosphates, [3H]inositol bisphosphates and [3H]inositol trisphosphates and contraction were measured at various times (0-90 s). To examine whether a pertussis toxin-sensitive guanine nucleotide binding protein is coupled to the muscarinic receptors, guinea pigs were pretreated with pertussis toxin (180 micrograms/kg i.v./24 h). The effectiveness of pertussis toxin treatment was determined by measuring [32P]ADP-ribosylation of a approximately 40/41 kDa protein from gallbladder homogenates. Carbachol caused a significant time-dependent increase in the formation of [3H]inositol monophosphates, [3H]inositol bisphosphates and [3H]inositol trisphosphates. The time course of [3H]inositol trisphosphate turnover caused by carbachol was biphasic, and was detectable at 15 s and maximal at 60 s; at 75 s and 90 s formation of [3H]inositol trisphosphates decreased, whereas the time course of carbachol-induced contraction of the gallbladder smooth muscle strips reached a plateau after 90 s. The effects of carbachol on [3H]inositol trisphosphates and on contraction were abolished by atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗
PubMed1993

Characterization of muscarinic receptors on guinea pig gallbladder smooth muscle.

BACKGROUND: Cholinergic agonists are of major importance for the regulation of gallbladder motility. However, the gallbladder muscarinic receptors have not been localized or characterized directly using radioligands, and it has not been clearly established which subtype of muscarinic receptor mediates contraction. The aim of the present study was to characterize the gallbladder muscarinic receptors. METHODS: Binding studies to guinea pig gallbladder sections were performed using 1-[N-methyl-3H] scopolamine methyl chloride. Carbachol-induced contraction was measured using muscle strips. RESULTS: Binding of 1-[N-methyl-3H] scopolamine methyl chloride was reversible, dependent on time, temperature, and pH. Autoradiography showed binding only over the smooth muscle. Binding and carbachol-induced contractions were inhibited by muscarinic receptor antagonists with the following potencies: atropine > N-methyl-scopolamine > silahexocyclium-methylsulfate > AF-DX 384 [(+-)-5,11-dihydro-11-([(2-(2-[(dipropylamino)-methyl]-1- piperidinyl)ethyl)amino]carbonyl)-6H-pyrido (2,3b) (1,4)-benzodiazepine-6-one] > hexahydro-siladifenidol hydrochloride > AF-DX 116 [(+-)-11-([2-[(diethylamino)methyl]-1- piperidinyl]-acetyl)-5,11-dihydro-6H-pyrido (2,3b)(1,4)benzodiazepine-6-one] > pirenzepine. Carbachol inhibited binding to gallbladder sections over the same range of concentrations that caused contractions. The concentration-contraction curves for carbachol were not altered by tetrodotoxin. CONCLUSIONS: Gallbladder smooth muscle cells possess muscarinic receptors of the M3 type. These receptors mediate carbachol-induced contraction.

Animals↗
PubMed1990

Potent bombesin receptor antagonists distinguish receptor subtypes.

To determine whether newly described bombesin (BN) receptor antagonists distinguish subtypes of BN receptors, we investigated their abilities to interact with BN receptors on esophageal muscle or pancreatic acinar tissue. For inhibition of binding of 125I-[Tyr4]BN to rat pancreatic tissue, the relative potencies were [D-Phe6]BN-(6-13)ethyl ester (5 nM) greater than Ac-gastrin-releasing peptide (GRP)-(20-26)ethyl ester (17 nM) greater than [D-Phe6,Cpa,14, psi 13-14]BN-(6-14) (40 nM) greater than [Leu14, psi 13-14]BN (0.43 microM) greater than [Tyr4,D-Phe12]BN = [D-Pro4, D-Trp7,9,10]substance P (SP)-4-11 (13 microM) greater than [Leu14, psi 9,10]BN (32 microM) greater than [D-Arg1,D-Trp7,9,Leu11]SP (70 microM). Each antagonist also inhibited binding of 125I-[Tyr4]BN or 125I-Bolton-Hunter-neuromedin B to rat esophageal tissue, and the potency of each antagonist for each tracer was similar. In comparison to rat pancreas, [D-Phe6]BN-(6-13)ethyl ester, Ac-GRP-(20-26)ethyl ester, [D-Phe6,Cpa14, psi 13-14]BN-(6-14), [Leu14, psi 13-14]BN, and [Leu14, psi 9,10]BN had a 10,000-, 2,940-, 1,425-, 122-, and 4-fold, respectively, weaker affinity for BN receptors. In contrast [Tyr4,D-Phe12]BN, [D-Pro4,D-Trp7,9,10]SP-4-11, and [D-Arg1,D-Trp7,9,Leu11]SP had a 4-, 4-, and 9-fold, respectively, higher affinity compared with pancreatic tissue. Comparison of the activity of each peptide at inhibiting the ability of equipotent concentrations of BN or neuromedin B to stimulate contraction of rat esophageal muscle demonstrated that each peptide had the same relative potencies as for inhibiting binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Characterization of cholecystokinin receptors on the sphincter of Oddi.

To characterize directly the ability of cholecystokinin (CCK) to interact with receptors on the sphincter of Oddi (SO), we measured binding of 125I-labeled Bolton-Hunter-labeled COOH-terminal octapeptide of cholecystokinin (125I-BH-CCK-8) to tissue sections from the guinea pig SO. Autoradiography localized binding of 125I-BH-CCK-8 over the SO smooth muscle layer. Binding was saturable, specific, dependent on time, pH, and temperature, and was reversible. Binding of 125I-BH-CCK-8 was inhibited by various CCK receptor agonists with the following potencies: CCK-8 much greater than des(SO3)CCK-8 much greater than gastrin-17-I and by various CCK receptor antagonists with the following potencies: L-364,718 greater than proglumide analogue 10 much greater than carbobenzoxy-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-NH2 greater than N2,O2' dibutyryl guanosine 3',5'-cyclic monophosphate. The potencies of agonists in stimulating and of antagonists in inhibiting CCK-8-stimulated SO contractions correlated closely with their abilities to inhibit binding of 125I-BH-CCK-8. Analysis of binding of 125I-BH-CCK-8 to SO tissue sections revealed two classes of CCK binding sites: a high-affinity site [dissociation constant (Kd) 0.2 nM] and a low-affinity site (Kd 70 nM). Atropine or tetrodotoxin (TTX) caused a similar rightward shift of the CCK-8 dose-response curve for stimulation of SO contraction. Comparison of receptor occupation to CCK-8-induced contraction suggested that CCK-8 occupation of the high-affinity binding site correlated with contraction in the absence of atropine and the low-affinity CCK binding with contraction in the presence of atropine or TTX.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Prospective study of chemotherapy in patients with metastatic gastrinoma.

Ten consecutive patients with metastatic gastrinoma that increased in size over time were studied prospectively during treatment with monthly cycles of streptozotocin (3 g/m2), 5-fluorouracil (1.2 g/m2), and adriamycin (40 mg/m2) to determine the response rate and time-courses of changes during chemotherapy and to assess various methods of evaluating the effect of chemotherapy. Forty percent of patients demonstrated an initial objective response (greater than or equal to 25% decrease in tumor size with no new lesions) and 60% failed chemotherapy (greater than or equal to 25% increase in tumor size or appearance of new lesions). The mean dose of streptozotocin was 27 g/m2 with objective responses occurring at 3.7 +/- 0.7 mo and failures at 4.5 +/- 0.7 mo. Responses lasted 9.7 +/- 2.8 cycles and no complete responses occurred. Survival was not significantly different in responders versus nonresponders (26 +/- 11 vs. 15 +/- 4.8 mo, p greater than 0.1). Changes in serum gastrin concentration, basal acid output, or sensitivity to a given dose of histamine H2-receptor antagonist did not reflect changes in tumor size. Computed tomography and angiography were the best methods to assess changes in tumor size during chemotherapy, whereas liver-spleen scan and ultrasound were relatively insensitive. All patients developed side effects with chemotherapy: 100% had vomiting, 80% alopecia, 40% transient proteinuria, and 20% leukopenia. The present results indicate that chemotherapy with streptozotocin, 5-fluorouracil, and adriamycin is much less effective in patients with extensive metastatic gastrinoma than previously reported. Computed tomography scanning is the method of choice to assess changes in tumor size. Changes in serum gastrin concentration, acid secretion, or tumor size assessed by liver-spleen scan or ultrasound are not sensitive indicators of the tumor response during chemotherapy.

Adult↗
PubMed1988

Cholecystokinin receptors on gallbladder muscle and pancreatic acinar cells: a comparative study.

To compare receptors for cholecystokinin (CCK) in pancreas and gallbladder, we measured binding of 125I-Bolton-Hunter-labeled CCK-8 (125I-BH-CCK-8) to tissue sections from guinea pig gallbladder and pancreas under identical conditions. In both tissues, binding had similar time-, temperature-, and pH dependence, was reversible, saturable and inhibited only by CCK related peptides or CCK receptor antagonists. Autoradiography localized 125I-BH-CCK-8 binding to the smooth muscle layer in the gallbladder. Binding of 125I-BH-CCK-8 to gallbladder sections was inhibited by various agonists with the following potencies (IC50):CCK-8 (0.4 nM) greater than des(SO3)CCK-8 (0.07 microM) greater than gastrin-17-I (1.7 +/- 0.3 microM) and by various receptor antagonists with the following potencies: L364,718 (1.5 nM) greater than CR 1409 (0.19 microM) greater than asperlicin = CBZ-CCK-(27-32)-NH2 (1 microM) greater than Bt2cGMP (120 microM). Similar potencies were found for the agonists and antagonists for pancreas sections. Inhibition of binding of 125I-BH-CCK-8 by 11 different analogues of proglumide gave similar potencies for both pancreas and gallbladder. The potencies of agonists in stimulating and antagonists in inhibiting CCK-stimulated contraction or amylase release correlated closely with their abilities to inhibit 125I-BH-CCK-8 binding to gallbladder or pancreas sections or acini, respectively. The present results demonstrate and characterize a method that can be used to compare the CCK receptors in guinea pig gallbladder and pancreas under identical conditions. Moreover, this study demonstrates that gallbladder and pancreatic CCK receptors have similar affinities for the various agonists and antagonists tested and, therefore, provides no evidence that they represent different subtypes of CCK receptors that can be distinguished pharmacologically.

Animals↗
PubMed1985

Characterization of insulin resistance in type I diabetes.

Insulin sensitivity was assessed using the euglycaemic clamp technique in eight type I diabetic patients (after overnight blood glucose normalization with an artificial pancreas) and in six healthy subjects. Basal insulin concentrations were higher in diabetic patients (25 +/- 4 microU/ml) than in control subjects (17 +/- 1 microU/ml; P less than 0.05). Insulin infusion of 0.5, 1.0, 2.0 and 5.0 mU/kg per min during subsequent 2-h periods resulted in similar mean steady-state insulin concentrations in both groups. The mean dextrose requirements during the last 40 min of each period were nevertheless decreased in diabetic patients (1.6 +/- 0.5, 3.5 +/- 0.8, 6.5 +/- 0.7, 10.2 +/- 0.7 mg/kg per min) as compared with control subjects (4.7 +/- 0.3, 8.2 +/- 0.9, 10.2 +/- 0.9, 12.4 +/- 0.9 mg/kg per min). At low insulin concentrations dextrose requirements were diminished in all diabetic subjects. At the highest insulin levels, individual dose-response curves from only four patients were within the normal range. Under basal conditions, the monocyte receptor number was significantly reduced in diabetic patients (17,500 +/- 2,800 sites/cell) as compared with control subjects (26,700 +/- 2,500 sites/cell; P less than 0.05), whereas there were no differences regarding empty site affinities. Receptor data did not differ in patients with normal and decreased maximal dextrose requirements. Insulin resistance is apparently a common feature of type I diabetes at serum insulin concentrations of approximately 100 microU/ml. Normalization of the insulin effect by higher insulin concentrations is not possible in all patients. Insulin antibodies at concentrations observed in this study (less than 0.16 mU/ml) do not contribute significantly to insulin resistance; receptor and postreceptor defects are possibly more important.

Adolescent↗