Search PubMed⌕ Search

Biomedical subjects

T Horn

Publications and source records attributed to T Horn.

At least 37 records · Page 2Linked to original sources
PubMed2001

The action of cysteinyl-leukotrienes on intracellular calcium mobilization in human detrusor myocytes.

OBJECTIVE: To investigate the presence of leukotriene D4 receptors in fura-2-loaded human detrusor smooth muscle cells (DSMCs) by examining the ability of leukotriene D4 to raise intracellular-free Ca2+ concentration ([Ca2+]i), to determine the origin of the leukotriene D4-mediated rise in [Ca2+]i and to investigate whether the specific leukotriene D4 receptor antagonist montelukast inhibits the Ca2+ response induced by leukotriene D4. MATERIALS AND METHODS: Detrusor muscle biopsies were obtained from patients with benign noninvasive bladder diseases undergoing cystoscopy. DSMCs were isolated using an explant technique and maintained in culture. Only primary cultures or cells passaged up to three times were used for experiments. DSMCs were characterized with immunohistochemical staining and their identity confirmed by transmission electron microscopy. [Ca2+]i was measured in single DSMCs using the Ca2+ probe fura-2 and fluorescence-ratio microscopy. RESULTS: Immunohistochemical staining showed that 80-99% of the cells were positive for smooth muscle alpha-actin. The ultrastructural features of the cultured cells were those of smooth muscle cells and showed no differentiation in a fibroblastic or myofibroblastic direction. Leukotriene D4 increased the level of [Ca2+]i in a dose-dependent manner. Calcium was mobilized almost exclusively from intracellular Ca2+ stores. There was a dose-dependent inhibition of the increase in [Ca2+]i by montelukast. CONCLUSION: The present study is the first to show the presence of specific leukotriene D4 receptors in human detrusor myocytes. This may have implications for a potential pathophysiological role of leukotriene D4 in patients with interstitial cystitis and other functional or inflammatory bladder disorders.

Calcium↗
PubMed2001

Renal function and structure in albuminuric type 2 diabetic patients without retinopathy.

BACKGROUND: In type 2 diabetic patients without retinopathy the cause of albuminuria is heterogeneous and our knowledge of the relationship between kidney structure and function in these patients is limited. Therefore, a long-term study evaluating the structural-functional relationship in albuminuric type 2 diabetic patients without retinopathy was performed. METHODS: Mesangial volume of total glomerular volume (Vv (mes/glom)), fractional area of focal interstitial fibrosis and tubular atrophy of cortical area (FF) and percentage of sclerosed glomeruli (S/G) were measured on kidney biopsies from 49 type 2 diabetic patients without retinopathy. Glomerular filtration rate (GFR) was determined at least 3 times (median 8 (range 3-20)) in each patient. Patients were followed for 7.0 (1.1-17) years. Albuminuria and blood pressure were measured every 3-6 months. RESULTS: Biopsies revealed diabetic glomerulopathy (DG-group) in 69% of the patients (27 male/7 female) and normal glomerular structure (n=9) or glomerulonephritis (n=6) were found in 31% (13 male/2 female) (NDG-group). In the DG-group GFR decreased from 97+/-5 to 66+/-5 ml/min/1.73 m(2) (mean+/-SE) (P<0.001), with a rate of decline in GFR of 5.3+/-0.8 ml/min/year and in the NDG-group from 93+/-7 to 74+/-11 ml/min/1.73 m(2) (P<0.01), with a rate of decline in GFR of 3.2+/-0.9 ml/min/year, P=0.09 between groups. Mean arterial blood pressure decreased from 109+/-2 to 100+/-2 mm Hg (P<0.001) (DG-group) and remained unchanged in the NDG-group. An association between Vv (mes/glom) and rate of decline in GFR was revealed mainly in the NDG-group (DG-group; r=0.31, P=0.07 and NDG-group; r=0.74, P<0.01). Furthermore, the rate of decline in GFR seemed to be associated with FF in the NDG group (r=0.48, P=0.07). Percentage of S/G was not associated with the rate of decline in GFR. Vv (mes/glom) was associated with mean albuminuria during follow-up in the DG group; r=0.38, P<0.03 (NDG group; r=0.51, P=0.09). Albuminuria was an independent predictor of the rate of decline in GFR in both groups (DG-group; r=0.40, P<0.05 and NDG-group; r=0.61, P<0.01). CONCLUSIONS: Our study revealed a tendency to a faster rate of decline in GFR in the DG-group compared to the much smaller NDG-group, characterized by marked heterogeneity of the underlying kidney lesions and rate of GFR loss. A large mesangial volume fraction was associated with increased albuminuria and loss in GFR. Albuminuria acted as a progression promoter in both groups.

Albuminuria↗
PubMed2001

Improved glucose tolerance and acinar dysmorphogenesis by targeted expression of transcription factor PDX-1 to the exocrine pancreas.

The homeodomain protein PDX-1 is critical for pancreas development and is a key regulator of insulin gene expression. PDX-1 nullizygosity and haploinsufficiency in mice and humans results in pancreatic agenesis and diabetes, respectively. At embryonic day (e) 10.5, PDX-1 is expressed in all pluripotential gut-derived epithelial cells destined to differentiate into the exocrine and endocrine pancreas. At e15, PDX-1 expression is downregulated in exocrine cells, but remains high in endocrine cells. The aim of this study was to determine whether targeted overexpression of PDX-1 to the exocrine compartment of the developing pancreas at e15 would allow for respecification of the exocrine cells. Transgenic (TG) mice were generated in which PDX-1 was expressed in the exocrine pancreas using the exocrine-specific elastase-1 promoter. These mice exhibited a marked dysmorphogenesis of the exocrine pancreas, manifested by increased rates of replication and apoptosis in acinar cells and a progressive fatty infiltration of the exocrine pancreas with age. Interestingly, the TG mice exhibited improved glucose tolerance, but absolute beta-cell mass was not increased. These findings indicate that downregulation of PDX-1 is required for the proper maintenance of the exocrine cell phenotype and that upregulation of PDX-1 in acinar cells affects beta-cell function. The mechanisms underlying these observations remain to be elucidated.

Adipose Tissue↗
PubMed2001

Osteoclast-like giant cells in leiomyomatous tumors of the uterus. A case report and review of the literature.

Osteoclast-like giant cells (OLGC) in leiomyomatous tumors of the uterus are rarely seen, and their significance is unknown. We present a case of a large leiomyomatous tumor in which OLGC were found in only few sections showing leiomyosarcoma whereas the majority of sections revealed a leiomyoma. Though radically operated, the patient died a few months later with recurrent tumor in the pelvis and metastases to the lungs.

Cell Transformation, Neoplastic↗
PubMed2001

[Quick intraoperative parathormone monitoring].

Successful parathyroidectomy for primary hyperparathyroidism has traditionally consisted of bilateral neck exploration with identification of all parathyroid glands and excision of grossly abnormal glands. Recently it has been reported that preoperative localization combined with intraoperative monitoring of parathyroid hormone enables performing directed unilateral cervical explorations while maintaining similar cure rates. This new surgical approach, feasible under local anesthesia as an outpatient procedure, decreases operative time, improves cosmetic results and may reduce morbidity. We report preliminary results of our experience in implementing this method.

Adult↗
PubMed2001

Increased urinary leukotriene E4 and eosinophil protein X excretion in patients with interstitial cystitis.

PURPOSE: The role of cysteinyl containing leukotriene C4, D4 and E4, and eosinophil protein X in interstitial cystitis is unknown. Leukotriene E4, the end product of cysteinyl containing leukotrienes, and eosinophil protein X are markers of the activation of mast cells and eosinophils, respectively. Cysteinyl containing leukotrienes are potent and specific chemoattractants for eosinophils. We compared the urinary excretion of leukotriene E4 and eosinophil protein X in patients with interstitial cystitis and in healthy controls. MATERIALS AND METHODS: Morning spot urine samples from nine patients with interstitial cystitis who fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria were collected on the day of cystoscopy with biopsies. Aliquots of urine specimens were immediately centrifuged and the supernatants were stored at -80C until use. Urine samples from 9 healthy women served as controls. Urinary leukotriene E4 and eosinophil protein X were measured by enzyme immunoassay and radioimmunoassay, respectively. All determinations were performed in duplicate and normalized to urine creatinine. RESULTS: Leukotriene E4 and eosinophil protein X were significantly increased in the morning urine of patients with interstitial cystitis compared with controls. The mean urinary excretion of leukotriene E4 plus or minus standard deviation was 148.8 +/- 62.5 and 62.2 +/- 17.5 ng./mmol. creatinine in patients and controls (p = 0.003), while the mean urinary excretion of eosinophil protein X was 109.7 +/- 70.4 and 43.7 +/- 22.0 microg./mmol. creatinine, respectively (p = 0.01). All urine cultures were negative. The mean mast cell count in detrusor biopsies in the interstitial cystitis group was 41 cells per mm.2 (range 5 to 84). Eosinophilic granulocytes were occasionally observed in the submucosa but not in the detrusor. CONCLUSIONS: Our study shows that patients with interstitial cystitis and detrusor mastocytosis have increased urinary leukotriene E4 and eosinophil protein X. It is possible that cysteinyl containing leukotrienes and eosinophil protein X are involved in the pathogenesis of interstitial cystitis. Urinary leukotriene E4 and eosinophil protein X may be useful markers for assessing the grade of activation of mast cells and eosinophils in patients with interstitial cystitis and/or for confirming the diagnosis. However, it remains to be investigated whether the increase in urinary leukotriene E4 and eosinophil protein X correlates with interstitial cystitis symptoms.

Adult↗
PubMed2000

Cytokine-induced impairment of short-chain fatty acid oxidation and viability in human colonic epithelial cells.

Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage was independent on NO formation and involved the IFN-gamma signalling pathway as well as induction of apoptosis. If cytokines have similar effects in vivo, these may lead to energy deficiency and thus contribute to CEC damage and disturbance of the epithelial integrity.

Apoptosis↗
PubMed2000

Colonic expression and synthesis of interleukin 13 and interleukin 15 in inflammatory bowel disease.

UNLABELLED: A dysregulated local immune reaction with unbalanced cytokine expression seems essential in inflammatory bowel disease (IBD), i.e. ulcerative colitis (UC) and Crohn's disease (CD). Since the roles of interleukin (IL-)13 and IL-15 remain unclear, this study aimed at studying intestinal expression of IL-13 and IL-15 in IBD. METHODS: In colonic biopsies from 24 UC, 18 CD, and 12 controls IL-13 and IL-15 were measured using ELISA, and their gene expressions were assessed by RT-PCR. Leukocytes were visualised histochemically. RESULTS: Concentrations of IL-13 were decreased in UC (median 56 pg/mg tissue; interquartile range 30-99 pg/mg) compared to CD (82 pg/mg tissue; 41-122;P=0.004) and controls (83 pg/mg tissue; 18-134;P>0.05), and lower in active UC (53 pg/mg tissue; 33-96) than in inactive UC (80 pg/mg tissue; 65-99;P=0.02). IL-15 concentrations were higher in CD patients (34 pg/mg tissue; 24-53) as compared to controls (20 pg/mg tissue; 15-21;P=0.001) whilst being 22 pg/mg tissue (15-32) in UC. IL-13 mRNA and IL-15 mRNA were detected in 20% and 15%, respectively. Infiltration of leukocytes correlated inversely with IL-13 levels (P=0.02). CONCLUSION: Active UC is associated with decreased colonic IL-13 suggesting that IL-13 levels are diminished as a part of UC exacerbations, or that exacerbations follow active downregulation of IL-13.

Adult↗
PubMed2000

Loss of heterozygosity at 1p, 8p, 10p, 13q, and 17p in advanced urothelial cancer and lack of relation to chemotherapy response and outcome.

Studies of urothelial tumors have identified structural abnormalities in a number of chromosomes. This study aimed to identify specific genetic changes of patients with advanced urothelial cancers, and relate these changes to increased chemotherapy sensitivity or good prognosis. We screened 56 muscle-invasive bladder cancer tumors for loss of heterozygosity (LOH) at chromosome 1p, 8p, 10p, 13q, and 17p with PCR using 6 microsatellite markers. All patients had recurrent locally advanced or metastatic disease. DNA was extracted after microdissection of the primary tumor and normal tissue from paraffin-embedded specimens. The PCR products were electrophoresed in an ABI Prism 377 DNA sequencer and the alleles from tumor DNA and normal tissue DNA were analyzed using the GeneScan program. The LOH findings were correlated with response to chemotherapy and survival. Allelic loss of specific markers was present in 26-50% of the informative tumors. The most frequent LOH was observed at 17p, supporting the notion that this region may contain genes of importance to urothelial cancer progression. The overall rate of response to chemotherapy was 48%, and ranged from 40% to 56% according to specific LOH changes. The median survival of all patients from start of chemotherapy was 5.8 months and ranged from 5.3 to 7.9 months for patients with specific LOH changes. Response and survival of patients with no lost markers was the same size, compared to patients with one, two, or more lost markers. Specific genetic changes were detected in a significant number of tumors from patients with advanced urothelial cancer. These changes were not predictive of response to chemotherapy or of the duration of survival.

Adult↗
PubMed2000

Causes of albuminuria in patients with type 2 diabetes without diabetic retinopathy.

BACKGROUND: The causes of albuminuria in patients with type 2 diabetes are heterogeneous and are scantily investigated, particularly if the patient has a lack of diabetic retinopathy. Therefore, we evaluated the structural background of albuminuria in a large consecutive group of Caucasian patients with type 2 diabetes without retinopathy. METHODS: Three hundred forty-seven consecutive patients with type 2 diabetes with persistent albuminuria (>300 mg/24 h) were recorded. Fundus photo (80%) and ophthalmoscopy were performed. Ninety-three (27%) had no retinopathy, and a kidney biopsy was performed in 52 (56%) of these patients. An insufficient tissue sample was obtained in one patient. The biopsies were evaluated by three masked nephropathologists. RESULTS: The biopsies revealed diabetic glomerulopathy in 69% of the patients (28 males and 7 females), while the remaining 31% (95% CI, 18 to 44) had either nondiabetic glomerulopathies such as glomerulonephritis (N = 7, 6 males and 1 female, 13%) or normal glomerular structure (N = 9, 7 males and 2 females, 18%). No significant differences in sex, age (56 +/- 8 vs. 53 +/- 10 years, mean SD), body mass index (30 +/- 4 vs. 31 +/- 8 kg/m2), known duration of diabetes (6 +/- 6 vs. 4 +/- 3 years), GFR (95 +/- 29 vs. 89 +/- 31 mL/min/1.73 m2), albuminuria (1304 +/- 169 to 4731 vs. 1050 +/- 181 to 5176 mg/24 hours), blood pressure (150/87 +/- 16/9 vs. 145/89 +/- 16/9 mm Hg), prevalence of hypertension (89 vs. 100%), hemoglobin A1c (8.2 +/- 1.6% vs. 9.0 +/- 2.5%), and serum total cholesterol (7.1 +/- 2.4 vs. 6.3 +/- 1.6 mmol/L) were found between patients with and without diabetic glomerulopathy. CONCLUSIONS: Albuminuric patients with type 2 diabetes without diabetic retinopathy have a prevalence of biopsies with normal glomerular structure or nondiabetic kidney diseases of approximately 30%. A separation between diabetic and nondiabetic glomerular lesions was not possible based on demographic, clinical, or laboratory data. Consequently, such patients may require further evaluation, including a kidney biopsy.

Adult↗
PubMed2000

Autologous graft-versus-host disease induction in advanced breast cancer: role of peripheral blood progenitor cells.

The purpose of the present study was to investigate the impact of the use of peripheral blood progenitor cells (PBPCs) on the induction of autologous graft-versus-host disease (GVHD) in patients with advanced breast cancer. 14 women with stage IIIB and 36 women with stage IV breast cancer received cyclosporine (CsA) 2.5 mg kg-1 i.v. daily, d 0-28, and interferon-gamma (IFNg) 0.025 mg/m2 s.c. qod, d7-28, following PBPC-T +/- bone marrow transplantation (BMT). Preceding high-dose chemotherapy consisted of cyclophosphamide 6 g/m2 and thiotepa 800 mg/m2. Histologically proven > or = grade II cutaneous GVHD was induced in18/50 (36%) of patients and was independent of the source of haematopoietic support. In vitro studies showed that post-transplant, 76% of patients had developed auto-cytotoxicity against their own pre-transplant PHA-lymphoblasts. A significant correlation between the occurrence of GVHD > or = grade II and cytolysis was observed in the NK cell-line K562 and the T47D breast cancer cell-line. With a median follow-up of 2(1/2) years, the overall survival (OS) is 58%, the disease-free survival (DFS) 26%, both independent of the development of GVHD and similar to what has been observed in other studies on high-dose chemotherapy in advanced breast cancer. It therefore remains unclear whether the induction of autologous GVHD with the occurrence of auto-cytotoxic lymphocytes can result in an anti-tumour effect in this group of patients.

Adult↗
PubMed2000

The glycosphingolipid sulfatide in the islets of Langerhans in rat pancreas is processed through recycling: possible involvement in insulin trafficking.

In previous studies we have shown that sulfatide (galactosylceramide-3-O-sulfate), in various species, is present in the insulin-producing cells in pancreatic islets of Langerhans. In this study the synthesis of sulfatide in the islets has been investigated by pulse chase labeling at varying glucose levels and in the presence or absence of the glycosphingolipid synthesis inhibitory agents, Brefeldin A, fumonisin B1 and chloroquine and the distribution of sulfatide by immune-electronmicroscopy. The data showed that (1) sulfatide was produced in islets of Langerhans, (2) the main pathway for synthesis was through recycling involving partial degradation in the lysosome, and that (3) high glucose levels, although not primarily reflected in an increased synthesis of sulfatide, lead to an increased expression of mRNA for the UDP-galactose:ceramide galactosyltransferase, producing the immediate precursor of sulfatide. Furthermore, mass spectrometry analyses revealed a high proportion of short chain fatty acids, C16:0 (50%) and no hydroxylated forms and thus special physicochemical properties, indicating important differences between pancreatic and brain/neural sulfatide. Immune electron microscopy revealed an intracellular expression of sulfatide in the secretory granules, the Golgi network and the lysosomes of the islets. These results indicate that sulfatide follows the same intracellular route as insulin and suggest a functional association between these molecules. We have raised the hypothesis that sulfatide possibly plays a role in the trafficking of insulin in the islets of Langerhans in rat pancreas.

Animals↗