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Biomedical subjects

M Gregor

Publications and source records attributed to M Gregor.

At least 91 records · Page 5Linked to original sources
PubMed1997

Activin A: a novel player and inflammatory marker in inflammatory bowel disease?

Recently, we demonstrated a strong induction of activin expression after cutaneous injury. We speculated, therefore, that activin may be overexpressed during inflammatory processes in other tissues characterized by mesenchymal/epithelial structure. Herein, we show a strikingly increased expression of the activin beta A-subunit in surgical specimens from the gut of patients suffering from ulcerative colitis and Crohn's disease, whereas no activin beta A mRNA could be detected in the normal human digestive tract. The levels of activin beta A expression showed an outstanding correlation with the degree of inflammation as assessed by histologic analysis of adjacent tissue and expression analysis of the proinflammatory cytokine interleukin-1 beta. In situ hybridization studies revealed the highest levels of activin mRNA in the mucosa and submucosa of highly inflamed areas, particularly where the intestinal epithelium was damaged, but not in control tissue. In contrast, activin beta B mRNA levels in most specimens from inflamed areas were only slightly higher compared to control tissue. The strong overexpression of activin beta A in inflammatory bowel disease suggests a novel and important role of this growth and differentiation factor during inflammatory processes of the gut.

Activins↗
PubMed1996

Identification of GBV-C hepatitis G RNA in chronic hepatitis C patients.

Sera from patients with chronic hepatitis C were examined for the presence of GBV-C/HGV RNA by RT-PCR. The amplified products, derived from the 5' non-coding, NS3, and NS5a regions, were detected in 19 (19%) of the 100 HCV RNA-positive samples. Analysis of GBV-C/HGV prevalence rates revealed that dual infections are related to shared parenteral risk factors. Intravenous drug abuse and multiple transfusions were the factors clearly associated with a simultaneous HCV and GBV-C/HGV infection. Apart from this, patients with dual infections had a statistically significant lower mean age compared to those patients infected solely by HCV. Determination of HCV genotypes involved in GBV-C/HGV coinfection by RFLP analysis showed no correlation between the presence of GBV-C/HGV and a distinct HCV genotype. The study demonstrates that, based on the assessment of risk criteria, GBV-C/HGV is transmitted efficiently parenterally and is frequently linked to hepatitis C coinfection, regardless of HCV genotype.

Adolescent↗
PubMed1996

Guanylin strongly stimulates rat duodenal HCO3- secretion: proposed mechanism and comparison with other secretagogues.

BACKGROUND & AIMS: Guanylin and heat-stable enterotoxin (STa) stimulate intestinal Cl- secretion via activation of the cystic fibrosis transmembrane regulator (CFTR)-encoded Cl- channel. It was speculated that CFTR activation also regulates electrogenic duodenal HCO3- secretion. Therefore, the effect of guanylin/STa and other secretagogues on rat duodenal HCO3- secretion was studied. METHODS: The HCO3- secretory rate of in vitro rat proximal duodenum was determined by pH stat titration and paracellular permeability by 3H-mannitol fluxes, bidirectional 36Cl- fluxes were measured, and the short-circuit current (Isc) was recorded. RESULTS: Luminal guanylin and STa concentration dependently stimulated the HCO3- secretory rate and Isc. Guanylin-stimulated HCO3- secretion was independent of luminal Cl-, inhibited by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate, and additive to the HCO3- secretory rate stimulated by glucagon and carbachol but not by the tested adenosine 3',5'-cyclic monophosphate (cAMP)-dependent agonists. The ratio of the HCO3- secretory rate/Isc stimulated by the tested guanosine 3',5'-cyclic monophosphate (cGMP)-dependent agonists was markedly higher than the cAMP-dependent agonists. Prostaglandin E2 and 8-bromo-cAMP but not STa/guanylin also transiently increased paracellular permeability. CONCLUSIONS: Guanylin and STa stimulate electrogenic HCO3- secretion in rat duodenum, most likely via CFTR Cl- channel activation, but the different relationship for HCO3- to Isc in cGMP-than in cAMP-stimulated anion secretion suggests a different cellular source and/or signaling pathways.

Animals↗
PubMed1996

Keratinocyte growth factor is highly overexpressed in inflammatory bowel disease.

Recently we demonstrated an important function of keratinocyte growth factor (KGF) in wound re-epithelialization. As KGF is mitogenic for various epithelial cells, we speculated about a role of KGF in epithelial repair processes of other organs as seen in a variety of inflammatory diseases. Here we demonstrate a strikingly increased expression of KGF in surgical specimens from patients suffering from Crohn's disease and ulcerative colitis. The levels of KGF expression strongly correlated with the degree of inflammation as assessed by histological analysis of adjacent tissue and expression analysis of the pro-inflammatory cytokine interleukin-1 beta. The highest levels of KGF mRNA and protein were found in mesenchymal cells of the lamina propria, particularly in highly inflamed areas. As the KGF receptor is expressed in intestinal epithelial cells, KGF seems to act in a paracrine manner to stimulate proliferation of these cells. These data suggest a crucial role of KGF in epithelial repair after injury caused by inflammatory processes.

Blotting, Western↗
PubMed1995

Glucagon-like peptide-1 modulates Ca2+ current but not K+ATP current in intact mouse pancreatic B-cells.

The influence of GLP-1 on electrical activity and ion currents of mouse pancreatic B-cells was studied with intracellular microelectrodes and the whole-cell configuration of the patch-clamp technique. In the presence of 15 mmol/l glucose 5, 50 and 100 nmol/l GLP-1 slightly increased electrical activity. This effect may be caused by the slowing of Ca2+ channel inactivation observed with GLP-1. Thus, changes in Ca2+ channel kinetics are suggested to contribute to the insulinotropic action of the hormone. The most prominent effect of GLP-1 on the membrane potential was the conversion of irregular electrical activity into regular oscillations of the membrane potential. At the threshold concentration for insulin secretion (7 mmol/l glucose) GLP-1 did not alter the membrane potential. Accordingly, in patch-clamp experiments GLP-1 had no effect on the whole-cell K+ATP current.

Adenosine Triphosphate↗
PubMed1994

Effects of osmotic changes in extracellular solution on electrical activity of mouse pancreatic B-cells.

The influence of changes in the osmolarity of the extracellular solution on electrical activity of mouse pancreatic B-cells was studied with intracellular microelectrodes. In the presence of 15 mmol/l glucose the membrane potential of B-cells oscillates. A reduction of the osmolarity by 40 mosmol/l caused a small temporary hyperpolarization in six out of eight cells. After 2 to 3 min electrical activity was increased in all cells. However, this effect was also transient. 5 to 8 min after onset of exposure to hypotonic solution the cells repolarized again and electrical activity decreased. Increasing the osmolarity of the extracellular solution by 40 mosmol/l led to a sustained and reversible depolarization of the membrane potential. However, the electrical activity was transiently suppressed. The changes in electrical activity observed in hypotonic solution might explain the previously described transient rise in insulin secretion provoked by osmotic cell swelling.

Animals↗
PubMed1994

[Therapeutic bilateral renal artery embolization in the nephrotic syndrome].

Amyloidosis with renal involvement was diagnosed in a 52-year-old man with Crohn's disease for 15 years. A severe nephrotic syndrome developed (proteinuria 40 g daily) with oedema and arterial hypotension (80/60 mm Hg). As adequate substitution treatment was not possible an attempt at medical renal ablation was made with a combination of captopril (25 mg daily), frusemide (80 mg daily) and indomethacin (200 mg daily). The proteinuria decreased to 18 g daily, but serum creatinine concentration rose to 5.8 mg/dl so that chronic haemodialysis had to be undertaken. Yet the patient's clinical state hardly improved and, because of his poor general condition, bilateral nephrectomy was contraindicated. In consequence bilateral catheter embolization of the renal arteries was performed. The urinary protein loss fell at once to 0.5 g daily. Serum protein rose from 3.1 g/dl under substitution to 5.7 g/dl without. During the following six months, while on chronic haemodialysis, the nephrotic syndrome did not recur. However, cardiac involvement in the amyloidosis was demonstrated so that the prognosis is poor. Permanent bilateral embolization of the renal arteries is a feasible method of managing a treatment-resistant nephrotic syndrome in selected patients.

Amyloidosis↗
PubMed1994

Neutrophil autoantibodies: a genetic marker in primary sclerosing cholangitis and ulcerative colitis.

BACKGROUND/AIMS: Perinuclear antineutrophil cytoplasmic antibodies (pANCA) were found at high frequency in patients with primary sclerosing cholangitis and ulcerative colitis. In this study, to accumulate further evidence for the importance of genetic factors in pathogenesis of inflammatory bowel disease, sera of patients with inflammatory bowel disease and primary sclerosing cholangitis and their unaffected family members were tested for pANCA. METHODS: Three hundred twenty-seven sera from 11 families of patients with primary sclerosing cholangitis, 43 families of patients with ulcerative colitis, 11 families of patients with Crohn's disease, and 11 healthy families were tested for pANCA in immunofluorescence on cytospin slides with isolated neutrophils. RESULTS: pANCA were found in 82% of the patients with primary sclerosing cholangitis and in 25% of their relatives. In ulcerative colitis, 70% of the patients and 30% of their relatives had pANCA. pANCA were found only in low titers in 27% of patients with Crohn's disease and in 6% of their relatives. pANCA were not detected in members of healthy families. Only 16% of the patients with ulcerative colitis and their families and none of the patients with primary sclerosing cholangitis and their families were completely negative for pANCA. CONCLUSIONS: These data show that pANCA may be a genetic marker in families of patients with ulcerative colitis and primary sclerosing cholangitis.

Adolescent↗
PubMed1994

Therapeutic principles in the management of metastasising carcinoid tumors: drugs for symptomatic treatment.

Malignant carcinoid syndrome is characterized most commonly by flushing and diarrhea of varying severity when tumors metastasize to the liver. Besides supportive measures for mild symptoms, the pharmacological management includes drugs to inhibit synthesis, release or peripheral actions of the circulating tumor products either alone or in combination. Among those agents octreotide, a synthetic long-acting analogue of somatostatin, is the drug of choice because it has proved useful for ameliorating symptoms in most patients with this syndrome. Although there is a multitude of potential and actual side effects, this antihormonal drug is very well tolerated and is a significant advance in therapy.

Carcinoid Tumor↗
PubMed1993

Inter-organ communication between intestine and liver in vivo and in vitro.

The maintenance of body homeostasis requires a finely tuned system of interorgan communication. The intimate metabolic interrelation between intestine and liver is characterized by the unique anatomic position of both tissues using the portal vein as a private channel with the pancreas in optimal position to modulate hepatic metabolism. Gut-derived peptides (such as glucagon-like peptide-1) appear to be involved in the process of liver regeneration by regulating the release of pancreatic hormones (e.g. insulin). Extensive bowel resection or functional exclusion of small intestine may lead to severe liver dysfunction and even cirrhosis, which may be due to the lack of some intestine-derived and as yet unknown factor(s). Here a close cooperation between small intestinal mucosa and hepatocytes is demonstrated leading to the concept of a metabolic gut-liver unit. This metabolic interaction forms a wide spectrum ranging from the secretion of peptide hormones to changes in (portal-venous) substrate availability or hepatocyte cell volume. Further investigation and identification of the mechanisms of such regulatory processes may be facilitated by combined perfusion of isolated rat intestine and liver. Using this in vitro approach we could demonstrate the presence of metabolic interorgan communication between isolated perfused tissues independent of plasma borne hormones or extrinsic neural control.

Animals↗
PubMed1993

Lithotripsy of an impacted calcified stone in the cystic duct accompanied by cholecystitis in severe Crohn's disease.

A 35 year old women patient with Crohn's disease and previous multiple abdominal operations presented with a calcified stone of 12 mm diameter in the cystic duct giving rise to cholecystitis. The surgeons declined to operate because of extensive intra-abdominal adhesions caused by multiple intestinal resections and chronic enterocutaneous fistulas. It was possible to fragment the stone in three lithotripsy sessions. The fragments were excreted spontaneously through the ductus choledochus and the cholecystitis was cured by antibiotic treatment. The patient remained symptom free after 12 months.

Adult↗
PubMed1992

[Combination therapy of gallbladder stones using extracorporeal shock waves and bile acids: results in relation to stone diameter and stone number].

420 patients were referred to our center for gallstone lithotripsy. 97 patients (23%) with radiolucent gallbladder stones (total diameter less than or equal to 3 cm) and intact gallbladder function were found suitable for extracorporal shock-wave lithotripsy. Disintegration of gallbladder stones was achieved in 92 of the 97 patients (95%). Chenodeoxycholic acid and ursodeoxycholic acid were used as adjuvant litholytic therapy. The therapeutic results were evaluated cumulatively in 90 patients after a follow-up of 10 months. 80% of patients with solitary stones (less than or equal to 20 mm in diameter (n = 46) had a stone-free gallbladder, whereas patients with solitary stones greater than 2 cm, less than or equal to 3 cm in diameter (n = 20) and multiple stones (n = 22) became stone-free in only 28% (p less than 0.01). During the observation period 21 patients (23%) experienced biliary colics, 2 (2%) mild pancreatitis, 2 (2%) showed fragment impaction in the common bile duct, and 17 (19%) displayed transient microscopic hematuria. Our results confirm previous studies showing that solitary stones sized up to 2 cm in diameter represent the best suited subgroup for extracorporeal shock-wave lithotripsy.

Aged↗
PubMed1991

[Glomerular hyperfiltration following unilateral nephrectomy in healthy subjects].

23 living related kidney transplant donors were prospectively studied to determine the degree of hyperfiltration which occurs after uninephrectomy and to monitor potential consequences of this procedure such as hypertension, microalbuminuria or renal functional impairment. Standard inulin and PAH clearance studies were performed immediately before (n = 23), one week after (n = 22) and one year after nephrectomy (n = 12). Hyperfiltration was defined as the ratio of (post-nephrectomy inulin clearance)/(0.5 x pre-nephrectomy inulin clearance), hyperperfusion was defined in an analogous way for PAH clearance. One week after uninephrectomy, hyperfiltration averaged 134 +/- 6% (SEM) and hyperperfusion was 138 +/- 6%. The degree of hyperfiltration did not correlate with donor age. One year after nephrectomy, hyperfiltration was nearly unchanged (130 +/- 7%) whereas hyperperfusion had significantly decreased to 119 +/- 8% (p less than 0.05). Blood pressure did not increase after nephrectomy and no new cases of hypertension were observed during follow-up. In contrast, there were two new cases of microalbuminuria at one week and one year after nephrectomy. Further follow-up of these kidney donors is warranted.

Adult↗