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T Horn

Publications and source records attributed to T Horn.

At least 19 recordsLinked 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

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

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

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

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

Lack of fever suppression or central AVP release in 1K1C hypertensive rats.

Previous studies from our laboratory showed a transient suppression of the febrile response to intracerebroventricular (i.c.v.) PGE1 in the one-kidney, one-clip (1K1C) model of hypertension. This may have been due to an enhanced vasopressinergic transmission since arginine vasopressin (AVP), acting within the central nervous system (CNS), is thought to mediate endogenous antipyresis. These initial experiments utilized a protocol for the induction of 1K1C hypertension which produced an initial rapid rise in blood pressure, evident by day 4 following surgery, with a corresponding inhibition of the febrile response. The present experiments utilized a more slowly developing 1K1C hypertension (evident by day 12 following surgery) to firstly attempt to determine if inhibition of the febrile response is due to the actual change in blood pressure or to neural signals arising from the clipped kidney, and secondly to determine if the concentration of AVP in push-pull perfusates of the ventral septal area (VSA) of pyrogen-treated sham-operated and 1K1C rats were altered. In urethane-anaesthetized rats, i.c.v. PGE2 evoked brisk monophasic fevers in both 1K1C and sham-operated animals, with no significant difference between fever heights. Consistent with this, we found no increase in immunoreactive AVP from perfusates of the VSA of 1K1C rats. These results suggest that there is no inhibition of the febrile response to PGE2 when a slower developing hypertension is induced, nor is there an elevated release of AVP into the VSA under our conditions. We conclude that a rapid increase in blood pressure, and not high blood pressure per se, is required to produce an inhibition of the febrile response.

Alprostadil

Electromyographic activity of selected trunk and hip muscles during a squat lift. Effect of varying the lumbar posture.

Electromyographic (EMG) activity of selected hip and trunk muscles was recorded during a squat lift, and the effects of two different lumbar spine postures were examined. Seven muscles were analyzed: rectus abdominis (RA), abdominal obliques (AO), erector spinae (ES), latissimus dorsi (LD), gluteus maximus (GM), biceps femoris (BF), and semitendinosus (ST). The muscles were chosen for their attachments to the thoracolumbar fascia and their potential to act on the trunk, pelvis, and hips. Seventeen healthy male subjects participated in the study. Each subject did three squat lifts with a 157-N crate, with the spine in both a lordotic and kyphotic posture. The lift was divided into four equal periods. EMG activity of each muscle was quantified for each period and normalized to the peak amplitude of a maximal voluntary isometric contraction (MVIC). A two-way analysis of variance (ANOVA) for repeated measures was used to analyze the effects of posture on the amplitude and timing of EMG activity during the lift. Two patterns of EMG activity were seen: a trunk muscle pattern (RA, AO, ES, and LD) and a hip extensor pattern (GM, BF, ST). In the trunk muscle pattern (TP), EMG activity was greatest in the first quarter and decreased as the lift progressed. In the hip extensor pattern (HP), EMG activity was least in the first quarter, increased in the second and third quarters, and decreased in the final phase of the lift. Differences (P < .05) were seen among subjects and in the timing of the muscle activity in all muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Sulphatide in islets of Langerhans and in organs affected in diabetic late complications: a study in human and animal tissue.

Sulphatide has been found in rat islets of Langerhans and anti-sulphatide antibodies have been demonstrated in patients with insulin-dependent diabetes mellitus. Using a specific monoclonal antibody, Sulph I, directed against sulphatide, we investigated the in situ distribution of this glycolipid immunohistochemically; furthermore, the sulphatide concentration was determined in several organs and cells by thin-layer chromatography. The islets of Langerhans in all species examined, mouse, rat, pig, and monkey were intensively stained but exocrine tissue remained unlabelled. The sulphatide concentration in human islets was 150 +/- 46 pmol/100 islets. The only glycolipid-antigen detected was sulphatide. Regarding other tissues, sulphatide was found to be located in distal tubules in the kidney, peripheral nerves, distinct scattered spot-like structures in the choreoid layer of the eye, the ovum, and peripheral granulocytes. Sulph I injection in mice showed homing to kidney tubules, Lung, heart, liver, adrenal, spleen, lymph node and thymus were not stained by Sulph I. Thus, the distribution of sulphatide shows an association with organs known to be affected in diabetes, either initially or in late complications.

Adult

Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients.

BACKGROUND: Psoriasis vulgaris may benefit from treatment with fumaric acid and/or its derivatives; however, because different preparations have been used, results have been contradictory and difficult to interpret. OBJECTIVE: The purpose of this clinical trial was to evaluate the therapeutic value of fumaric acid derivatives. METHODS: A randomized double-blind study was carried out in patients with psoriasis, comparing a well-characterized formulation of fumaric acid derivatives with placebo. RESULTS: The results indicated statistically significant superiority of the fumaric acid derivatives over placebo. Adverse events (flush, gastrointestinal disturbances) were initially relatively frequent, but decreased thereafter. CONCLUSION: Fumaric acid derivatives were found to be effective and safe in the treatment of psoriasis.

Abdominal Pain

Histiocytic sarcomas and monoblastic leukemias. A clinical, histologic, and immunophenotypical study.

Eight histiocytic sarcomas, identified by examination of more than 2000 malignant lymphomas, are described. For comparison, tumor infiltrates from five monoblastic leukemias were also analyzed. The histiocytic sarcomas were all high-grade malignancies consisting of markedly pleomorphic large cells with many mitotic figures. At presentation, six of the patients had systemic symptoms (fever, fatigue, loss of weight), skin infiltrates, and lymphadenopathy. Despite aggressive chemotherapy, clinical remissions were short, and six patients died of disease .5-48 months (mean, 6.5 months) after diagnosis. The remaining two patients are alive and in partial or complete remission 7 and 12 months after diagnosis. Immunotypic examination showed that all the histiocytic sarcomas were positive for macrophage-related antigens and negative for antigens on B cells, T cells, myeloid cells, epithelial cells, and melanocytes. T-cell receptor and immunoglobulin genes were studied in three cases and were present in a germline configuration. One of the histiocytic sarcomas resembled Langerhans' cells in phenotype and morphology; it was classified as a Langerhans' cell sarcoma. The remaining histiocytic sarcomas did not express accessory cell-associated antigens, but more closely resembled "ordinary" tissue macrophages; they were positive for lysozyme and/or CD68, followed in frequency by CD11c, CD4, CD11b, CDw32, peanut agglutinin receptor, and CD13. Similar features were seen in the monoblastic leukemias. These conditions could only be distinguished from histiocytic sarcoma by clinical and morphologic, rather than immunophenotypic, criteria. Expression of oncoprotein p53 was studied in nine cases and was positive in six of six histiocytic sarcomas and one of three monoblastic leukemias. Rare malignancies show features consistent with the derivation from macrophages. Two entities may be distinguished: those that resemble antigen-presenting accessory cells and those that more closely resemble ordinary tissue macrophages. Recognition of these tumors is important clinically and requires assessment of clinical, morphologic, and immunophenotypic features, supplemented by analysis of T-cell receptor and immunoglobulin genes. Whether (or how) p53 gene mutations are implicated in their pathogenesis will be an important topic for future investigation.

Adolescent

Osmotic stimulation of the supraoptic nucleus: central and peripheral vasopressin release and blood pressure.

Experiments were performed to determine the effect of direct osmotic stimulation of the supraoptic nucleus (SON) on central and peripheral vasopressin (AVP) release and arterial pressure. A microdialysis method was used to deliver hyperosmotic NaCl, mannitol or urea bilaterally into the SON and to sample SON extracellular fluid and blood. Simultaneous brain and blood microdialysis showed that hyperosmotic NaCl increased central and peripheral AVP release and increased mean arterial pressure (MAP). The pressor response was not blocked by intravenous injection of a V1-receptor antagonist, D(CH2)5Tyr(Me)AVP, suggesting that circulating AVP was not involved in that response. Hyperosmotic mannitol or urea caused an increase in central peptide release, but failed to affect MAP or peripheral AVP release. The results suggest that central AVP release within the SON may be due to osmoreceptor stimulation while the peripheral effects on AVP release and MAP are specific for sodium. The results also demonstrate the utility of brain and blood microdialysis for the delivery of stimuli into specific brain regions with simultaneous monitoring of central and peripheral peptide release.

Animals

Nitric oxide actions in paraventricular nucleus: cardiovascular and neurochemical implications.

We have examined potential functions of nitric oxide (NO) within the paraventricular nucleus (PVN) in urethan-anesthetized male Sprague-Dawley rats. Initial experiments demonstrated microinjection of 50 pmol of the NO donor, sodium nitroprusside (SNP), directly into the PVN resulted in significant decreases in mean blood pressure (BP) (-3,312 +/- 1,189 mmHg/s over 300-s response time; P < 0.05). To determine whether such effects were attributable to SNP-induced NO release, NO was administered into PVN directly by bilateral microdialysis of NO-containing artificial cerebrospinal fluid (NO-aCSF), a process that results in delivery of approximately 50 pmol NO.PVN-1 x min-1. Such microdialysis resulted in significant decreases in BP (-5,121 +/- 817 mmHg/s over 1,200-s response time; P < 0.005), while aCSF microdialysis was without effect (1,298 +/- 1,071 mmHg/s over 1,200-s response time; P > 0.1). Amino acid concentrations were measured in dialysates collected during perfusion of the same PVN sites with either aCSF or NO-aCSF by high-performance liquid chromatography (HPLC) analysis. NO-aCSF induced significant increases in aspartate (aCSF 31 +/- 7 pmol/30 min; NO-aCSF 134 +/- 33 pmol/30 min; P < 0.05), glutamate (aCSF 36 +/- 5 pmol/30 min; NO-aCSF 417 +/- 108 pmol/30 min; P < 0.02), gamma-aminobutyric acid (aCSF 4.1 +/- 0.7 pmol/30 min; NO-aCSF 104 +/- 29 pmol/30 min; P < 0.02), and taurine (aCSF 34 +/- 3 pmol/30 min; NO-aCSF 117 +/- 24 pmol/30 min; P < 0.01) concentrations, while alanine, glutamine, and serine concentrations were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Reduced febrile responses to pyrogens after lesions of the hypothalamic paraventricular nucleus.

The hypothalamic paraventricular nucleus (PVN) is recognized as a major site of autonomic control, but the role of this nucleus in thermoregulation is unclear. Therefore the role of the PVN in the febrile response and in the maintenance of normal body temperature was investigated. Conscious, unrestrained rats with chronic lesions of the PVN received intracerebroventricular injections of several doses of prostaglandin (PG) E2 or intraperitoneal applications of Escherichia coli lipopolysaccharide. The body temperatures of both lesioned and sham-operated animals, monitored via radio telemetry, were compared. Intracerebroventricular PGE2 at doses of 10, 25, and 50 ng caused dose-dependent fevers in both PVN-lesioned and sham-operated animals, which at lower doses were smaller in the lesioned animals than in the sham-operated animals. Intraperitoneal lipopolysaccharide application, 50 micrograms/kg body wt, evoked a significantly lower febrile response in PVN-lesioned animals than in controls. The body temperature of PVN-lesioned animals and controls showed no difference during 300 min of exposure to heat (32 degrees C) or cold (7 degrees C). These results suggest that the PVN contributes to the complex regulation of temperature during the febrile response but not during the maintenance of normal body temperature.

Animals

Isolation and culture of human endometrial cells in a three-dimensional culture system.

A cell culture system was established in which endometrial stromal cells were embedded in a collagen matrix and separated from the endometrial epithelium by basement membrane material (Matrigel). The epithelium, seeded on top of the collagen matrix, grew in a monolayer. The cultures were evaluated by light microscopy and transmission and scanning electron microscopy. Light and transmission electron microscopy indicated a polarized columnar epithelium in monolayer with basally positioned nuclei. Scanning electron microscopy revealed a confluent epithelium with an abundance of microvilli and cilia, as well as pinopodes on the apical surface. Immunohistochemical staining for cytokeratin confirmed the epithelial origin of the surface cells, and staining for human collagen IV demonstrated its presence underneath the epithelial cells. This culture system represents a three-dimensional system that imitates the normal endometrium.

Biocompatible Materials