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T Horn

Publications and source records attributed to T Horn.

At least 55 records · Page 3Linked to original sources

Comparative studies of the colonic in situ expression of intercellular adhesion molecules (ICAM-1, -2, and -3), beta2 integrins (LFA-1, Mac-1, and p150,95), and PECAM-1 in ulcerative colitis and Crohn's disease.

A dysregulated local immune defense with a constant influx of leukocytes provides a basis for continuous intestinal inflammation in ulcerative colitis (UC) and Crohn's disease (CD). Cell adhesion molecules are pivotal for the migration of leukocytes from the circulation toward the colonic epithelium. A study quantifying the cells expressing intercellular adhesion molecules (ICAMs), beta2 integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the colon was performed to illustrate the leukocyte migration pathway in inflammatory bowel disease. Serial colonic sections (10 UC, 10 CD, and 10 controls) were stained immunohistochemically for ICAM-1, ICAM-2, ICAM-3, CD11a, CD11b, CD18, and PECAM-1. Cell adhesion molecule expression was evaluated quantitatively with reference to topographic localization. In UC, polymorphonuclear leukocytes (PMNs) in contact with the crypt epithelium and in crypt abscesses expressed CD11b. CD tissue was characterized by CD11a-, CD11c-, and ICAM-1-expressing cells. ICAM-1 was detected on endothelial cells, leukocytes, and apical parts of epithelial membranes, whereas ICAM-2 was expressed on basal epithelial membranes. Most infiltrating leukocytes expressed ICAM-3, whereas perivascular mononuclear cells expressed PECAM-1. Interestingly, the epithelial basement membrane in UC stained for CD18. In conclusion, CD11b, CD18, and ICAM-2 seem to be important for PMN transepithelial migration in UC, whereas CD11a, CD11c, ICAM-1, and ICAM-3 seem central in leukocyte locomotion and aggregation in CD. Differentiated upregulation of cell adhesion molecules is suggested to be essential for the diversities between UC and CD.

CD18 Antigens↗

Ultrastructure of human blastocyst-endometrial interactions in vitro.

The interactions of seven human blastocysts with cultured endometrial cells were investigated by light microscopy and transmission electron microscopy. Trophoblastic-endometrial contact was observed at the lateral border of endometrial epithelial cells where trophoblast and endometrial epithelial cells shared apical junctional complexes and desmosomes. The first sign of penetration was invasion of a trophoblastic cytoplasmic protrusion between endometrial epithelial cells. In broad contact areas, lateral displacement of endometrial epithelial cells and formation of a peripheral pseudostratified epithelium were observed. When trophoblastic cells were interposed fully among endometrial epithelial cells, they formed a penetration cone and appeared to dislodge endometrial epithelial cells from the stromal compartment. A single penetration cone only was found in each specimen. Endometrial or trophoblastic degeneration was not observed. Formation of multinucleate (>/= three nuclei per cell) trophoblast cells was not observed, but many cells displayed areas with abrupt disappearance of well-defined plasma membranes, which is indicative of syncytium formation. In this study, adhesion and penetration occurred at the same time. The human blastocysts penetrated the endometrial surface epithelium by intrusive penetration. Epithelial penetration was achieved primarily by cellular syncytiotrophoblast-like cells and the first indications of syncytium formation were observed simultaneously with penetration of the epithelium.

Cell Adhesion↗

[Amyloidosis. A review].

Amyloidosis is a heterogenous group of diseases, all characterized by extracellular deposition of amyloid either systemically or localized. Of wellknown diseases are Alzheimer's dementia, AL-amyloidosis (e.g. in multiple myeloma) and AA-amyloidosis (e.g. in rheumatoid arthritis). Amyloid is composed of three components of which the fibrillary component is the basis of amyloid classification. Many types of amyloid have a systemic distribution and give rise to varying symptoms. The diagnosis is based on biopsy, preferably of abdominal subcutis. The prognosis is poor, however, recent investigations on the three-dimensional structure of the P-component provide hope for future therapy.

Amyloid↗

[Amyloidosis: rapid course of AL-amyloidosis in a patient without myelomatosis].

A case of severe AL-amyloidosis in a 72-year-old man is presented. Amyloid was especially deposited in the kidneys and the liver. The patient died one year after diagnosis with impaired kidney function and severe ascites. Despite the type of amyloid (AL-type), multiple myelomata or lymphoproliferative disease could not be demonstrated.

Aged↗

Inhibition of insulin-specific autoreactive T-cells by sulphatide which is variably expressed in beta cells.

AIMS/HYPOTHESIS: Sulphatide and insulin are present in the secretory granules and at the surface of beta cells in islets of Langerhans. Insulin autoantibodies and T-cell reactivity against insulin exist during the development of Type I (insulin-dependent) diabetes during which active beta cells may be more vulnerable than passive. Our aims were to examine the presence of sulphatide in active and passive beta cells and to clarify whether sulphatide influences the direct autoimmunity against insulin. METHODS: We incubated rat islets in 2.8, 11.0 or 20.0 mmol/l glucose for 24 h and did an electron microscopic evaluation after labelling with a specific anti-sulphatide monoclonal antibody. The reactivity of an insulin-specific T-cell clone isolated from a patient with Type I diabetes, was examined using insulin or insulin B-chain (B11-27) peptide incubated together with sulphatide. RESULTS: We detected lower amounts of sulphatide per insulin secretory granule in active compared with passive beta cells (p = 0.003). The presence of sulphatide in vitro at doses of 43-8.3 micromol/l resulted in greatly reduced proliferation (median 3.4 % of control value, p = 0. 0004) of the insulin-specific T-cell clone. No inhibition was found using the precursor of sulphatide, galactosylceramide, or GM1. Sulphatide did not reduce non-aspecific proliferation (induced by phorbol myristate acetate plus anti-CD3) or specific proliferation induced by insulin peptide. CONCLUSION/INTERPRETATION: These results imply that sulphatide possibly affect processing of the insulin molecule. Sulphatide which has been reported to interfere with phagosome-lysosome fusion, conceivably interacts with insulin. We hypothesize a (patho)physiological role of sulphatide, variably expressed in beta cells, by reducing the antigenicity of insulin. [Diabetologia (1999) 42: 1212-1218]

Animals↗

Immune modulation in autologous bone marrow transplantation: cyclosporine and gamma-interferon trial.

From March 1994 to November 1994, 16 patients with high risk hematological malignancies were entered in a phase I clinical trial, designed to confirm the toxicity of cyclosporine and gamma interferon given to induce autologous graft-versus-host disease (GVHD) after autologous bone marrow transplantation (ABMT). This trial was based on the results in a rodent model, in which cyclosporine given after ABMT induces an autoimmune syndrome (autologous GVHD) identical to allogeneic GVHD. Further, this autologous GVHD is associated with a graft-versus-tumor effect augmented by interferon that upregulates MHC class II expression on normal and tumor cells, the target of the cytolytic T cells in autologous GVHD. In this trial, cyclosporine 1 mg/kg/day was given from the day of bone marrow reinfusion until the completion of the interferon and gamma-interferon. Gamma-interferon at 0.025 mg/m2 every other day was started when the total white cell count was >200 cells/ml for 2 consecutive days and continued for a total of 10 doses after ABMT. The preparative regimens were busulfan and cyclophosphamide, or cyclophosphamide with total body irradiation. All patients received 4HC-purged marrow grafts. Median age was 45 years (range 19-68). The diagnoses included chemo-resistant non-Hodgkin's lymphoma (10), acute lymphoblastic leukemia (two), chemo-resistant Hodgkin's disease (two), acute myeloid leukemia (one), and multiple myeloma (one). Median absolute neutrophil count recovery was 25.5 days (range 19-46 days). Median platelet count recovery was 40.5 days (range 28-279 days). There were nine deaths, two were related to transplant toxicity (infection), while the other seven were due to relapse. Event-free survival with a median of 964 days (range 19-1441 days of follow-up was 44%. In conclusion, treatment with cyclosporine, and gamma-interferon after ABMT was well tolerated and did not impair engraftment. Further studies with a larger number of patients are required to document any beneficial anti-tumor effect of autologous GVHD induction after ABMT.

Adolescent↗

[Stimulation of Schwann cell growth and axon regeneration of peripheral nerves by the immunosuppressive drug FK 506].

BACKGROUND: Nerve allografts are highly antigenic and, thus, require the continuous use of immunosuppressive drugs. The immunosuppressant Cyclosporine A was used in most studies. More recently, the immunosuppressive effect of FK 506 on peripheral nerve allografts and xenografts has been studied, and the drug has been found to prevent rejection successfully. However, neurotoxic complications have been noted in the central and peripheral nervous system although an increased rate of axonal regeneration has also been shown. METHODS: Schwann cells were cultured from the sciatic nerve of the rat. The effect of 100 microM FK 506 administered daily on these cultures was assessed over a period of seven days and compared to an untreated control group of cultures. To visualize a direct effect of FK 506 on Schwann cells, the changes in intracellular calcium were recorded using fluorescence imaging of primary rat Schwann cell cultures loaded with Fluo-3. Regeneration of autologous nerve grafts was assessed in a rat model clinically and morphometrically after daily administration of 0.6 mg FK 506/kg body weight. RESULTS: FK 506 increases the number of Schwann cells in culture significantly compared to the control group, while the fibrocyte population is decreased. FK 506 caused a transient increase of intracellular calcium levels of cultured cells. A significantly higher axon count was observed in the FK 506-treated grafts after two weeks of regeneration compared with controls. Additionally, less myelin debris was evident in the FK 506 treated group after two weeks compared with the control group. Good regeneration was noted in all grafts after six weeks of regeneration. CONCLUSION: The increased axon counts and decreased myelin debris in the FK 506 grafts after two weeks indicate an accelerated Wallerian degeneration and increased axon sprouting into the graft initially. FK 506 promotes axonal regeneration through binding to FKBP-12, thus activating GAP-43 (growth associated protein) and the TGF beta 1-pathway (transforming growth factor). In addition, the increase of the intracellular calcium may induce Schwann cell proliferation via Calmodulin which in turn promotes axonal regeneration.

Animals↗

Presence of uterine pinopodes at the embryo-endometrial interface during human implantation in vitro.

In order to study changes occurring on the surfaces of human endometrial epithelial cells in the presence of an implanted blastocyst, we used scanning electron microscopy for investigation of five endometrial biopsies and three human implantation sites obtained in vitro. All specimens showed areas with endometrial pinopodes, separated by cells displaying microvilli or cilia at the apical surface. Pinopode formation was more pronounced in endometrial biopsies than in cell cultures. All blastocysts adhered to pinopode presenting cells. Endometrial surface changes were not seen around the blastocysts. The results of this study demonstrate that cultured endometrial epithelial cells are capable of pinopode formation. Furthermore, endometrial epithelial pinopodes, generally considered as a marker of endometrial receptivity, seem to be directly involved in the adhesion of the blastocyst to the endometrial surface.

Blastocyst↗

Assessment of patients with metastatic transitional cell carcinoma of the urinary tract.

PURPOSE: We propose an appropriate assessment of patients with disseminated transitional cell carcinoma of the urothelial tract, and investigate the pattern of metastases relative to pathological features and primary tumor treatment. MATERIALS AND METHODS: A total of 156 consecutive patients with recurrent locally advanced (nonresectable, radioresistant) and/or metastatic transitional cell carcinoma of the urothelial tract were evaluated with blood tests, chest x-ray, bone scintigraphy, bone marrow biopsy, and abdominal and brain computerized tomography. RESULTS: Distant metastases were evident in 86% of the patients, with lymph nodes and bones being the most frequent sites. Bone metastases were mostly in the pelvis or lower spine and were asymptomatic in 19% of patients. Bone marrow metastases were noted in 14% of these patients. However, most of them also had radiological bone metastases and bone marrow biopsy is not recommended for routine evaluation. Approximately 2% of patients had brain metastases without symptoms at recurrence. Elevated lactate dehydrogenase was predictive of disseminated disease. Patients receiving radical radiotherapy as primary treatment had an increased rate of recurrent locally advanced disease but the same frequency of distant metastases compared to those undergoing cystectomy. Primary tumor features did not relate to the pattern of metastases. CONCLUSIONS: We recommend chest x-ray, whole abdominal computerized tomography and routine blood tests, including lactate dehydrogenase, for patients with recurrent locally advanced or metastatic disease. Skeletal symptoms should be examined radiologically, while asymptomatic patients with recurrence in sites other than bone should be evaluated with bone scintigraphy.

Adult↗

Gastric mucosal interleukin-8 and IL-8 antibody concentrations related to prevailing Helicobacter pylori infections. A Danish-Albanian study.

OBJECTIVES: Helicobacter pylori (H. pylori) appears to initiate an inflammatory cascade. Thus, phagocytes are accumulated in the gastric mucosa, in inflammatory conditions. Further, a potent chemotactic mediator, interleukin 8 (IL-8) is synthesized at such sites. The recently described IL-8 autoantibodies may, however, counteract the pro-inflammatory actions of IL-8. The aim was to study the correlation between H. pylori infection and IL-8, together with IL-8 autoantibodies in two different populations from a developed and a developing country. METHODS: Two different endoscopically characterized populations (65 Danes and 89 Albanians) were examined. IL-8 and IL-8 autoantibodies were detected by ELISA techniques, and H. pylori was identified by histological examinations. RESULTS: Significantly more Albanian controls and dyspeptic patients (80 out of 89 persons) were H. pylori positive as compared to 24 of 65 Danes (p < 0.001). The median IL-8 level among Albanian controls 349 pg/mg protein was significantly higher than among Danes < 61 pg/mg protein (p < 0.001), and was at the same level as found in Danish peptic ulcer patients (p > 0.05). Further, H. pylori positive patients from both countries had significantly higher levels of IL-8 as compared to H. pylori negative patients (p < 0.001). However, significantly higher levels of IL-8 autoantibodies were found in the Albanian sub-population (median 138 O.D. units versus 52 O.D. units among Danes) (p < 0.001). CONCLUSIONS: In H. pylori related disorders, a high mucosal IL-8 production has been found. However, this investigation further demonstrates higher levels of IL-8 autoantibodies among dyspeptic patients from a developing country, which might possibly counteract the pro-inflammatory actions of IL-8 by binding the molecule. The physiological significance of an altered immune response as described here needs to be elucidated in future studies.

Adolescent↗

[Behavior of piglets during castration with and without local anesthesia].

According to the German welfare act of 1998 (Art.5(3)1.), surgical castration of up to 4 wk old pigs does not require anaesthesia. However, the application of a local anaesthesia is discussed in the context of pain related responses to this procedure. In these experiments, effects of different methods of application on the behaviour of piglets during castration are evaluated as a contribution to the welfare assessment of this procedure. A total of 36 piglets between 10 and 14 days of age were castrated with and without a local anaesthesia. Local anaesthesia with Lidocaine 2% was applied in two ways: a) via intratesticular (i.t.) injection and b) intratesticular injection combined with subcutaneous (s.c.) infiltration of the anaesthetic into the tissue around the spermatic cord. The assessment of pain was performed on the basis of vocalisations and resistance movements of the animals during the procedure. Local anaesthesia resulted in a reduction of the relative proportion of resistance movements from the entire period of fixation (castration with i.t. anaesthesia 12.73%, with i.t. and s.c. anaesthesia 14.50% or without a local anaesthesia 18.96%; P < 0.05). In particular, local anaesthesia resulted in a reduction of resistance movements during the cutting of the spermatic cord. The response of piglets to additional skin stimulation of the scrotum was not different between the three treatments.

Anesthesia, Local↗

Lipodrama.

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Anti-HIV Agents↗

Outpatient diabetes management of Medicare beneficiaries in four Mississippi fee-for-service primary care clinics.

BACKGROUND: As part of a quality improvement initiative aimed at increasing physician compliance with standards of care for diabetes patients, diabetes practice patterns among Medicare beneficiaries in four primary care clinics were examined in Mississippi. METHODS: Retrospective chart reviews of Medicare beneficiaries with a diagnosis of diabetes were conducted to examine physician compliance with recommended diabetes monitoring services. RESULTS: Fifty-three percent of all beneficiaries did not have a recorded A1c test while 54 percent did not have a recorded foot exam. The percentage without foot exams decreased with quarterly visits. Seventy-two percent and 68 percent of patients had testing for lipids and proteinuria, respectively, although variability in types of testing performed was seen. Seventy-six percent of beneficiaries did not have a referral for a dilated eye exam. CONCLUSIONS: The study has uncovered, within several primary care sites in Mississippi, variable documentation of compliance with many clinically relevant recommendations relating to the care of elderly patients with diabetes. These items can be targeted for improvement as part of a statewide quality improvement initiative for Medicare beneficiaries.

Aged↗

Measurements of behavior in the naked mole-rat after intraperitoneal implantation of a radio-telemetry system.

The naked mole-rat (Heterocephalus glaber) is a unique fossorial mammal that is eusocial, object blind, and virtually poikilothermic. This animal is an ideal model to examine questions pertaining to the thermoregulatory aspects of sleep/wake cycles and other circadian events. However, the monitoring of mammalian sleep usually involves implanting permanent electrodes into the skull which are linked to a counter-weighted cable apparatus. This is not a viable option for H. glaber because of the tunneled environments and sensitive social milieu. Instead, to monitor sleep, core temperature, and activity we have utilized intraperitoneal telemetry, a technique that transmits biopotential signals by radio waves. Here we describe the surgical procedure used to implant the device, the anesthesia technique developed, and the social reintroduction method devised for this novel animal model.

Anesthesiology↗

The influence of the level of lamina propria invasion and the prevalence of p53 nuclear accumulation on survival in stage T1 transitional cell bladder cancer.

PURPOSE: We assessed the influence of the level of lamina propria invasion and the prevalence of p53 nuclear immunoreactivity on the survival of patients with stage T1 transitional cell bladder cancer. MATERIALS AND METHODS: All patients presenting with stage T1 bladder cancer were prospectively and routinely grouped according to the level of lamina propria invasion. Invasion of the tumor stalk was defined as stage T1a, invasion of the lamina propria proper superficial to the level of muscularis mucosa as stage T1b and into or deeper than the muscularis mucosa as stage T1c. The p53 nuclear immunoreactivity was determined with antibody PAB 1801. RESULTS: The study comprised 143 patients including 31 (22%) with stage T1a disease, 60 (42%) with stage T1b and 52 (36%) with stage T1c. Mean patient age was 67 years (range 38 to 92) and mean followup was 4.7 years (range 2.4 to 9.7). Tumor grade related to the depth of lamina propria invasion (p < 0.05) and the prevalence of dysplasia in random mucosal biopsies was higher in stage T1b and T1c tumors than in stage T1a. Of all tumors 42% expressed p53 nuclear reactivity which correlated with tumor grade (p < 0.05). Also the prevalence of nuclear p53 was higher in stages T1b and T1c compared with T1a disease. Of the patients 115 were treated with transurethral resection alone and 28 underwent radical cystectomy. Overall survival was 60.1%. Age was the only independent predictor of survival in patients older than 75 years. For patients up to 75 years old survival related to age, level of lamina propria invasion and presence of p53 nuclear accumulation. For this subpopulation overall survival was 67%, and 79% for stage T1a, 70% for stage T1b and 57% for stage T1c (p < 0.05). Survival was higher in patients with p53 negative (73%) than in those with p53 positive (61%) tumors (p < 0.05). A multivariate analysis of the influence of lamina propria invasion and nuclear p53 status on survival histology was found to be the only independent predictor of survival. CONCLUSIONS: Immediate radical cystectomy should be considered for patients with stage T1c tumors and for some patients with stage T1b disease, particularly those with tumors expressing p53 nuclear reactivity and with dysplasia in the random mucosal biopsies.

Adult↗

Expression of E-selectin, sialyl Lewis X, and macrophage inflammatory protein-1alpha by colonic epithelial cells in ulcerative colitis.

The pathogenic significance of cell adhesion molecules (CAMs) in ulcerative colitis (UC) is largely unknown. Colonic expression of E-selectin, sialyl Lewis X (sLe(x)), and macrophage inflammatory protein-1x (MIP-1alpha) as well as serum concentrations of E-selectin and MIP-1alpha in UC were studied. Thirty patients with UC, 10 patients with irritable bowel syndrome, and 10 healthy subjects were included. Colonic biopsies were stained immunohistochemically, and blood concentrations were measured with an ELISA technique. Soluble E-selectin did not correlate with diagnosis or disease activity. MIP-1alpha was below the detection limit. Epithelial cells expressed all three molecules, both on surface membranes and intracellularly. sLe(x) staining was weaker (P = 0.0002) and MIP-1alpha staining stronger (P = 0.014) in UC patients than in controls. Leukocyte MIP-alpha staining correlated with diagnosis (P = 0.021), sLe(x) staining (P = 0.023), and colonoscopy (P = 0.018). It is shown that E-selectin, sLe(x), and MIP-1alpha are synthesized and expressed by epithelial cells, indicating that CAMs are not only involved in leukocyte extravasation and migration, but also in the interaction between leukocytes and colonic epithelium. This knowledge might contribute to the development of improved treatments in UC.

Adult↗