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Biomedical subjects

T Horn

Publications and source records attributed to T Horn.

At least 91 records · Page 5Linked to original sources

Stabilization of triple-stranded oligonucleotide complexes: use of probes containing alternating phosphodiester and stereo-uniform cationic phosphoramidate linkages.

Pyrimidine oligonucleotides containing alternating anionic and stereo-uniform cationic N-(dimethylamino-propyl)phosphoramidate linkages [e.g. d(T+T-)7T, d(T+T-)2(T+C-)5T and (U'+U'-)7dT, where U' is 2'-O-methyluridine)] are shown to bind to complementary double-stranded DNA segments in 0.1 M NaCl at pH 7 to form triple-stranded complexes with the pyrimidine.purine.pyrimidine motif. For each of the sequences investigated, one stereoisomer bound with higher affinity, and the other stereoisomer with lower affinity, than the corresponding all-phosphodiester oligonucleotide. The stereoisomer of d(T+T-)7T that interacted weakly with a dT.dA target in 0.1 M NaCl formed a novel dA.dA.dT triple-stranded complex with poly(dA) or d(Al5C4A15) in 1 M NaCl; in contrast, the stereoisomer that bound strongly to the dT.dA target failed to form a dA.dA.dT triple-stranded complex.

DNA Probes↗

Presence of sulphatide (3'-sulphogalactosylceramide) in pericytes in the choroid layer of the eye: sharing of this glycolipid autoantigen with islets of Langerhans.

The aim of the study was to investigate the distribution in the eye of sulphatide, an acid glycolipid which has previously been demonstrated in islets of Langerhans, nervous tissue and in kidney glomeruli of diabetic patients, and against which antibodies have been found in patients with newly diagnosed insulin-dependent diabetes mellitus. A specific monoclonal antibody, Sulph I, was used for detection of sulphatide by thin-layer chromatography, and light and electron microscope immunohistochemistry. A distinct, patchy staining was found in the choroid layer and the ciliary processes. The antigen was confirmed to be sulphatide and its concentration in human eyes was 30 nmol sulphatide/g wet tissue. By electron microscopy, anti-sulphatide choroid labelling was demonstrated in pericytes and in smooth muscle cells surrounding vessels. No Sulph I-negative pericytes were seen. Double labelling with Sulph I and anti-smooth muscle actin revealed that only pericytes in the eye contained sulphatide and not those in heart, lung, liver, adrenal, spleen, lymph node, thymus, or pancreatic tissue. Thus, sharing of the autoantigen sulphatide has been demonstrated between islets of Langerhans and pericytes in the choroid layer of the eye.

Aged↗

Involvement of interleukin-4 and -10 in inflammatory bowel disease.

The pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD) may be associated with a decreased production of cytokines suppressing macrophage and T-cell functions: interleukins (IL) -4 and IL-10. Serum concentrations of IL-4 and IL-10 were measured using an ELISA technique, and intestinal IL-4 and IL-10 mRNA was detected by a reverse transcriptase polymerase chain reaction (RT-PCR) in 34 patients with inflammatory bowel disease (IBD) (20 with UC and 14 with CD) and compared to 12 control subjects. The superoxide production was measured spectrophotometrically in activated PMNs initially incubated in the presence of IL-4 or IL-10. No differences were found in numbers of cells that might be potential IL-4 or IL-10 producers (T cells, macrophages, B cells, and mast cells) in biopsy specimens using immuno- and histochemistry. IL-4 mRNA was detectable in specimens from 77.8% of the UC patients (P > 0.05) and 0% of the CD patients (P < 0.05), as compared to 81.8 in controls, and was significantly different (P < 0.0001) between UC and CD patients. The IL-10 amplification product was detectable in specimens from 30.0% UC patients (P < 0.003), but not in CD patients (78.6%, P > 0.05) as compared to controls (91.7%). The circulating protein levels of IL-4 were below the detection limit in all groups (detection limit 4 pg/ml), while the median IL-10 concentration was 12.5 pg/ml in UC, 18.1 pg/ml in CD, and 19.5 pg/ml among controls (detection limit 3 pg/ml), which did not differ in any of the three groups (P > 0.05). Finally, the superoxide production was inhibited and delayed by the addition of IL-10 (P < 0.01), whereas IL-4 only delayed this parameter. In conclusion, apart from the well-known suppressive effect on proinflammatory cytokine production, IL-4 delays and IL-10 inhibits superoxide generation. IL-4 mRNA expression is decreased in intestinal tissue from CD patients, while IL-10 mRNA expression is decreased in majority of UC patients, suggesting different immunopathogenesis of the two diseases.

Adult↗

A new technique for detrusor biopsy and its applicability in the ultrastructural study and diagnosis of voiding dysfunction.

OBJECTIVE: To determine the clinical applicability of ultrasound-guided detrusor biopsy from the anterior bladder wall and to assess whether it is as representative and as sufficient for determining detrusor ultrastructure as the traditional transurethral biopsy from the lateral bladder wall. MATERIALS AND METHODS: The detrusor structure in 22 biopsies. 11 obtained transabdominally and 11 transurethrally from 11 patients, was evaluated without knowledge of the biopsy method by light and electron microscopy, including morphometric analysis. In addition, several specimens from each of three bladders were evaluated, also 'blindly', for ultrastructural diagnosis of the detrusor in an independent current study of voiding dysfunction in geriatric patients. RESULTS: There were no differences in intercellular distances and cell: nucleus ratios between transabdominal and transurethral biopsies in eight of the 11 patients. Furthermore, ultrasound-guided transabdominal biopsies were as representative of the detrusor as were transurethral biopsies. CONCLUSION: The transabdominal approach is recommended as an easy, relatively inexpensive and efficient method of obtaining biopsies of the detrusor for study of its structure in voiding dysfunction. On the other hand, the observations and diagnoses made by 'blind' qualitative study of several specimens from the same bladder were identical. This, together with the similarity of detrusor structure in the transabdominal and transurethral biopsies, strongly supports the idea that such structure is relatively uniform throughout the entire bladder wall.

Aged↗

Glassy cell carcinoma of the colon with human chorionic gonadotropin-production. A case report with immunohistochemical and ultrastructural analysis.

An unusual tumor in the descending colon with human chorionic gonadotropin-beta (HCG-beta) production and histological features of a "glassy cell" carcinoma is presented. Glassy cell carcinoma has been described in the uterus and fallopian tubes as well as the cervix, but in these locations the tumor is not HCG-beta producing. Glassy cell carcinomas have been described in some cases as having glandular and squamous differentiation as well as marked cellular pleomorphism. The tumors are generally associated with a poor prognosis.

Adult↗

Systemic cytokine administration alters the histology of the eruption of lymphocyte recovery.

The eruption of lymphocyte recovery occurs after marrow ablative antineoplastic chemotherapy, with the earliest reappearance of lymphocytes in the peripheral circulation. The typical histopathologic findings are not specific, consisting of a perivascular lymphocytic infiltrate in the upper dermis with mild overlying epidermal changes. Since the initial report, 21 additional biopsy specimens from eruptions of lymphocyte recovery were obtained at our institution. Of these specimens, 18 displayed the expected findings while 3 specimens contained a relatively heavy lymphocytic infiltrate with nuclear pleomorphism and hyperchromasia. The majority of lymphocytes from the heavily inflamed tissues expressed CD3 and CD4; rare CD8+ cells were observed. The cells with large irregular nuclear contours displayed an "activated" phenotype, consisting of CD30, HLA-DR, and CD25, accounting for roughly 50% of the total infiltrate. The three patients from whom these specimens were obtained had received human recombinant cytokines in pharmacologic doses (2 granulocyte-macrophage colony stimulating factor, 1 interleukin-3). Three patients in this series also received human recombinant cytokines, but developed eruptions with the typical scant infiltrate of small lymphocytes. These findings extend the histologic spectrum of the eruption of lymphocyte recovery and suggest that the administration of human recombinant cytokines prior to marrow recovery may alter the appearance and phenotype of lymphocytes migrating into the skin.

Adult↗

Fluorescence-activated cell sorted rat islet cells and studies of the insulin secretory process.

Studies of individual cell types in the islets of Langerhans are complicated by the cells' functional coupling by gap junctions and paracrine interaction. Access to purified alpha and beta cells is therefore desirable. We present a simplified and optimized method for fluorescence-activated cell sorting of endocrine pancreatic rat islets. For dispersion of the islets, dispase was superior to trypsin, as the number of vital single cells was higher (1.1 +/- 0.1 x 10(3) vs 0.6 +/- 0.1 x 10(3)/islet, P < 0.05). The purity of the sorted cells was 96.7 +/- 1.2% for the non-beta cells and 97.8 +/- 0.6% for the beta cells (numbers in percentages of endocrine cells). In culture, isolated beta cells, non-beta cells and mixtures of beta and non-beta cells formed aggregates, but not at low temperature (4 degrees C) and not in medium with low serum content (2%). Finally, in pure beta cell aggregates, glucose stimulated changes in cytoplasmic free Ca2+ concentration although both glucose- and arginine-induced insulin secretion was much reduced. We conclude that alpha cells are necessary for insulin secretion but not for glucose sensing.

Animals↗

Prostatic specific antigen and benign prostatic hyperplasia.

The aim of this study on patients (n = 51) with urodynamically proven obstruction was to search for correlations between serological levels of prostatic specific antigen (PSA) and age of patients, volume of prostate and prostatic morphology as evaluated on transurethral resection specimens. No correlations could be found between PSA levels and morphological parameters such as degree of inflammation and relative degree of stromal or epithelial hyperplasia. Significant correlations were demonstrated between PSA levels and age of patients and prostatic volume.

Age Factors↗

Benign prostatic hyperplasia. Does a correlation exist between prostatic morphology and irritative symptoms?

Fifty-two consecutive patients with prostatism who underwent a prostatectomy were investigated with regard to irritative symptom score, age, prostate volume, urine culture results, degree of detrusor instability, inflammation in the prostate, and stromal, glandular or mixed prostatic histopathology. We did not find any statistical correlations between irritative symptom score and the mentioned parameters. This indicates that irritative symptoms should rather be attributed to extraprostatic factors such as e.g. bladder reaction.

Age Factors↗

Treatment of chronic graft-versus-host disease with ultraviolet irradiation and psoralen (PUVA).

Chronic graft-versus-host disease (GVHD) remains a difficult clinical problem to treat and manage. We have reviewed our treatment of 40 patients treated at a single institution with PUVA (ultraviolet irradiation and psoralen) over a 14 year period. Thirty-five patients were treated for refractory chronic GVHD and five patients were treated at presentation of high-risk chronic GVHD. Overall, 31 of 40 patients improved on PUVA treatment. Sixteen patients achieved a complete response to PUVA added to their GVHD regimen. Four of the 15 partial responders had complete resolution of cutaneous GVHD but persistence of other systemic manifestations. The remaining partial responders had at least a 50% improvement in GVHD. We have also used PUVA with a glass fiber extension to treat intra-oral GVHD. PUVA is well tolerated with a high rate of response in the skin and mild side effects except for three patients who had therapy discontinued after phototoxicity (burn).

Adolescent↗

Transduodenal excision of tumours of the ampulla of Vater.

OBJECTIVE: To evaluate the symptoms, diagnostic procedures, and treatment by transduodenal excision, of tumours in the ampulla of Vater. DESIGN: Open study of consecutive patients. SETTING: University hospital, Denmark. SUBJECTS: Six patients with tumours in the ampulla of Vater. INTERVENTIONS: Ultrasonography, duodenoscopy, and endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic biopsy if tumour was visible at the papilla. Transduodenal excision of the ampulla and anastomoses of the common duct and pancreatic duct to the duodenum. MAIN OUTCOME MEASURES: Postoperative complications and survival. RESULTS: None of the tumours could be seen on ultrasonography. All the tumours were diagnosed on duodenoscopy with ERCP. The histopathological diagnoses of the endoscopic biopsy specimens were adenoma (n = 3), suspicion of adenocarcinoma (n = 2), and adenocarcinoma (n = 1). Curative resection by transduodenal excision of the ampulla of Vater was possible in all cases. Pathological examination of the surgical specimens showed three adenomas and three adenocarcinomas. One patient had a recurrence after 2.5 years and had a further resection. Three patients died after one, three, and nine years, respectively; two had no recurrence and one was suspected of having one. The other three patients were alive 8-20 months after the operation. CONCLUSION: The procedure is recommended for small and probably benign tumours and, when technically possible, in malignant tumours in patients at high operative risk. Close postoperative follow-up with duodenoscopy and ERCP is recommended.

Adenoma↗

Ultrastructure of endometrial epithelial cells in a three-dimensional cell culture system for human implantation studies.

PURPOSE: A three-dimensional cell culture system imitating normal uterine endometrium has previously been established. To what degree do cultured epithelial cells retain their morphological characteristics as compared to in vivo material obtained simultaneously from the same tissue donor. RESULTS: We found a high degree of similarity between the in vivo and in vitro situations. The present culture system furthermore imitates the day-to-day morphology of the cycle. CONCLUSIONS: This indicates, that a correct timing of the biopsy tissue is important for future human implantation studies.

Biopsy↗

Urine profiles and kidney histology after ionic and nonionic radiologic and magnetic resonance contrast media in rats with cisplatin nephropathy.

RATIONALE AND OBJECTIVES: The nephrotoxic drug cisplatin has been used successfully in treating some cancers. Patients with suspected carcinoma frequently undergo examinations with contrast media. We examined whether ionic and nonionic radiologic and magnetic resonance contrast media would have any effect on cisplatin nephropathy in rats. METHODS: Urine and serum profiles were monitored for 24 days after intravenous (i.v.) injections of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide in high doses (4.59 mmol/kg body weight) in rats that received a weekly intraperitoneal (i.p.) injection of cisplatin (1 mg/kg) for 10 weeks. There were 10 rats in each group. Another 10 rats injected with both i.p. and i.v. saline served as control subjects. After euthanization, rats' kidneys were removed for examination by light microscopy and electron microscopy. RESULTS: Light and electron microscopy showed severe morphologic changes, including tubular dilatation, atrophy, and necrosis induced by cisplatin; however, the contrast media did not induce any additional morphologic changes. Gadopentetate dimeglumine, diatrizoate, and iohexol significantly increased (3-20 times) albuminuria compared with i.v. saline in cisplatin nephropathy, whereas gadodiamide did not. Albuminuria was highest after diatrizoate injection. All four contrast media caused an immediate and transient significant increase in the excretion of the brush border enzymes alkaline phosphatase and gamma-glutamyltransferase (125-500 times) and the cytoplasmatic enzymes alanine aminopeptidase and lactate dehydrogenase (16-100 times). Compared with saline, the ionic agents significantly increased the excretion of both glucose (two times) and sodium (three to five times), whereas the nonionic agents did not. CONCLUSION: High doses of radiologic and magnetic resonance contrast agents cause temporary dysfunction in rats with cisplatin nephropathy. Gadodiamide caused the least dysfunction and diatrizoate the most.

Animals↗

Microdialysis with high NaCl causes central release of amino acids and dopamine.

Recent studies have shown that the neuropeptides arginine-8-vasopressin (AVP) and oxytocin (OXT) are released within the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus in response to microdialysis of these nuclei with high-NaCl perfusion media. These results suggest an inherent osmosensitivity of SON and PVN neurons. To investigate whether the observed release of AVP/OXT is a unique phenomenon to these neuropeptides, several brain regions were examined for the release of amino acids or dopamine in response to high- or low-NaCl stimulation. Urethane-anesthetized male Sprague-Dawley rats were perfused with five-ion solution using U-shaped microdialysis probes. Samples were collected at 30-min intervals and analyzed for amino acids and dopamine by HPLC. In the dialysates of all perfusion areas, including the SON, PVN, hippocampus, and striatum, concentrations of Asp, Glu, Ser, Gln, Gly, taurine (Tau), and gamma-aminobutyric acid (GABA) were significantly increased during perfusion with high-NaCl medium. This release was found to be dose dependent when tested in the hippocampus and striatum with perfusion medium containing 0.5 or 1.0 M NaCl. However, only the release of Glu and Ser was found to be Ca2+ dependent. In contrast, the use of mannitol, a nonionic osmolyte, for perfusions in the striatum in concentrations of 0.5 and 1 M resulted in reduced levels of amino acids in the dialysates (Glu, Ser, Gln, and Tau). Low-NaCl perfusion medium (0.01 M) resulted in significantly increased Glu, Tau, Gly, and GABA levels in the striatum. In addition, dopamine levels in striatal dialysates were significantly increased during stimulation with 1 M NaCl. These results indicate that stimulation with high NaCl concentrations affects the release of several neurotransmitters and is not specific for AVP and OXT. The described phenomenon of the release of amino acids in response to this stimulation seems to be a response to the changed ionic concentration rather than to the osmolality. In light of these findings shown for amino acids and dopamine as well as those previously reported for AVP, OXT, and angiotensin, it would appear that sensitivity to tonicity changes brought about by microdialysis may be a feature of many transmitter systems.

Amino Acids↗

Detrusor in ageing and obstruction.

It is disputed whether fibrosis of the detrusor is a consequence of obstruction or ageing. In the present study, bladder wall morphology was analyzed semiquantitatively in biopsies from "normal" young persons, infravesically obstructed and non-obstructed elderly persons. Fibrosis occurring around and inside muscle fascicles was demonstrated to the same degree with obstruction as well as ageing. Our results give rise to the question whether "prostatism" is related to obstruction per se or to ageing or both.

Aged↗