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Biomedical subjects

T Horn

Publications and source records attributed to T Horn.

At least 145 records · Page 8Linked to original sources

Localization of transforming growth factor-alpha in human appendageal tumors.

Transforming growth factor-alpha (TGF alpha) is a potent mitogen for epithelial cells that has been localized to normal human appendageal epithelia. To further understand the role of TGF alpha in human appendages, we examined TGF alpha expression immunohistochemically in 17 types of human appendageal tumors differentiating toward hair follicles, eccrine, apocrine, and sebaceous glands. In order of decreasing degrees of differentiation, tumors could be divided into hyperplasias, adenomas, benign epitheliomas, and primordial epitheliomas. Using an antibody that recognizes primarily the 6-kd and 13-kd forms of TGF alpha, TGF alpha immunostaining in 16 of 17 tumor types analyzed was found to follow a similar pattern, with expression in hyperplasias greater than adenomas greater than benign epitheliomas greater than primordial epitheliomas. Within a given tumor, TGF alpha expression also correlated well with the known differentiation state of the tumor cell types. The results suggest that TGF alpha expression is directly correlated with the differentiation state of hair follicle, eccrine, apocrine, and sebaceous tumors in human skin, and raises the possibility that TGF alpha may play a role in the differentiation of appendageal epithelia.

Apocrine Glands↗

The pattern of fibrosis in the acinar zone 3 areas in early alcoholic liver disease.

The degree of fibrosis and the pattern of collagen distribution in the acinar zone 3, as well as the thickness of the terminal hepatic vein walls (THV) were analyzed in 48 consecutive liver needle biopsies from 48 alcoholics with preserved liver architecture. The fibrosis occurred to more or less the same degree in the whole circumference of each THV. A positive correlation was found between the degrees of perisinusoidal/pericellular fibrosis (PSF) and the occurrence of incomplete or complete septa. The thickness of THV walls (TTHV) varied from 1.0-12.5 microns with a median of 3.9 microns. No relationship was found between TTHV and PSF. The results were compared to similar data obtained in liver biopsies from 117 non-alcoholics with normal morphology or slight non-specific changes. No significant difference concerning TTHV and THV diameter was found between alcoholic and non-alcoholic patients. The results suggest that the initial liver fibrosis in alcoholics is slightly asymmetrical distributed in each acinar zone 3 area. With progression, the fibrosis tends to be more uniformly distributed and septa appear, eventually linking THV with portal tracts. Apparently, thickening of the THV walls does not occur in early alcoholic liver disease.

Adolescent↗

TGF-alpha is widely expressed in differentiated as well as hyperproliferative skin epithelium.

Transforming growth factor-alpha (TGF-alpha) is a potent mitogen for epithelial cells that is expressed at low levels in normal epidermis and overexpressed in psoriasis. Epidermal growth factor (EGF) has been shown to inhibit hair growth but stimulate the growth of sebaceous and sweat glands, suggesting a potential role for a member of the EGF/TGF-alpha family in the normal development and function of skin appendages as well as epidermis. The present work demonstrates TGF-alpha protein in eccrine ducts, and eccrine, sebaceous, and apocrine glands. The proliferative dermal hair bulb does not express TGF-alpha in contrast to the differentiated outer root sheath hair follicle epithelia. In addition, hyperproliferative skin diseases including bullous congenital ichthyosiform erythroderma, squamous cell carcinoma, and psoriasis show increased TGF-alpha expression. Thus, TGF-alpha may play a role in the morphogenesis and function of normal skin appendages and its overexpression is common in benign and malignant hyperproliferative skin diseases.

Blotting, Western↗

Enzyme immunoassay of oestrogen receptors in needle biopsies from human liver.

For quantitative assessments of sex hormone receptors in liver tissue, ligand binding assays are inconvenient, as they require large biopsies (0.5-1.0 g). The present study shows that it is possible to measure oestrogen receptors (ER) quantitatively in needle biopsy specimens as small as 10 mg by modifications of a commercial enzyme immunoassay employing monoclonal antibodies. Sucrose gradient centrifugation and the dextran charcoal method served as reference methods. A consecutive series of needle biopsies from patients suspected of liver disease were investigated. The biopsies (n = 37) had a median weight of 14 mg and cytosolic protein concentrations greater than 1 mg/ml (median 1.28 mg/ml). The median ER concentration was 20 fmol/mg cytosolic protein (range 5 to 57 fmol/mg). The intra-assay coefficient of variation was 8.9%, the inter-assay 13.2%, and the detection limit 2.7 fmol/ml cytosol. Women had significantly higher ER concentrations (median 22 fmol/mg) compared to male patients (median 16 fmol/mg) (P = 0.007). The enzyme immunoassay measures ER in liver specimens as small as 10 mg, compared to the large tissue specimens necessary for the conventional DCC assay, and the method is a convenient tool for further studies of ER in routine needle biopsies from the liver.

Biopsy, Needle↗

Eosinophilic renal cell tumours. A study on tumour heterogeneity with special emphasis on oncocytes.

Eosinophilic renal tumour cells are found in oncocytomas, granular cell carcinomas, clear cell carcinomas and in a recently defined entity known as "congeners of oncocytomas". Ultrastructural examination of paraffin embedded tumour tissue representing eosinophilic areas in 40 renal cell tumours was performed in order to characterize the different types of eosinophilic cells. The results showed all tumours diagnosed light microscopically as oncocytomas to be composed of cells containing abundant mitochondria. Similar cells were, however, also found in one case of a clear cell carcinoma and in one case diagnosed light microscopically as a "congener". Oncocytes may therefore be found as part of non-oncocytomas and there seems to be a gradual transition from oncocytes to other eosinophilic cells of renal cell carcinomas. Preoperative subclassification of renal cell tumours based on small biopsy specimens is thus of limited value.

Adenoma↗

Branched DNA amplification multimers for the sensitive, direct detection of human hepatitis viruses.

Branched oligonucleotides (bDNA) have been synthesized containing a unique primary segment and a set of identical secondary fragments covalently attached to the primary sequence through branch points. The primary sequence is designed to hybridize (directly or indirectly) to a target nucleic acid, such as hepatitis B virus (HBV) or hepatitis C virus (HCV) genomic DNA or RNA, respectively. The secondary fragments are used to direct the binding of multiple copies of a small oligonucleotide labelled with alkaline phosphatase. Assays for the presence of HBV and HCV based on the application of these branched amplification multimers have been devised. It is possible to detect as few as 1,000 hepatitis viral genomes directly.

Base Sequence↗

Persistence of systemic mastocytosis after allogeneic bone marrow transplantation in spite of complete remission of the associated myelodysplastic syndrome.

A myelodysplastic syndrome (MDS), type 5 (RAEB-t), and systemic mastocytosis affecting the spleen, the splenic lymph nodes, the bone marrow and the liver were diagnosed in a 38-year-old woman. The clinical course was complicated by splenic vein thromboses and iliac artery embolism. The thrombotic episodes might be secondary to mast cell mediator release. A complete remission of the MDS was obtained by allogeneic bone marrow transplantation, but the mastocytosis persisted. Thus, the possibility that the mast cell originates from a common myeloid precursor cell may be questioned.

Adult↗

Transforming growth factor alpha expression helps to distinguish keratoacanthomas from squamous cell carcinomas.

Keratoacanthomas may be difficult to distinguish histologically from squamous cell carcinomas. We studied 20 keratocanthomas and 22 squamous cell carcinomas immunohistochemically using an antibody directed against transforming growth factor alpha to determine if the pattern of transforming growth factor alpha expression would provide a useful method of differentiating these tumors. Ninety percent of the keratoacanthomas demonstrated a diffuse pattern within tumor lobules in which all but the most peripheral rim of cells were stained. A similar localization of transforming growth factor alpha was not identified in squamous cell carcinomas. In addition, 40% of the squamous cell carcinomas but none of the keratoacanthomas showed focal transforming growth factor alpha immunostaining. Our results suggest that transforming growth factor alpha expression may be a marker of epithelial differentiation and may help distinguish between these two tumors.

Carcinoma, Squamous Cell↗

Malignant giant cell tumour of the uterus.

Two rare cases of malignant giant cell tumours of the uterus in pure heterologous form are presented. Light microscopy showed numerous osteoclast-like cells in a background of spindle cells. Immunohistochemistry demonstrated Vimentin, Actin, alpha-1-antitrypsin and LCA in the latter, and Vimentin, alpha-1-antitrypsin and LCA in the giant cells while tartrate resistant acid phosphatase reactivity was demonstrated in both mononuclear cells and giant cells. Electron microscopy did not reveal smooth muscle or epithelial differentiation. The findings suggest a common origin of malignant giant cell tumours and malignant fibrous histiocytomas.

Aged↗

Ultrasonically guided fine-needle biopsies from adrenal tumors.

Ultrasonically guided fine-needle biopsies were performed from 28 adrenal lesions in 28 patients. In 15 patients adrenal enlargement was an incidental finding. In 17 of 18 (94%) patients with metastatic spread combined cytological and histological examination disclosed secondary malignancy, and in 4 of 5 patients with primary neoplastic disease the combined microscopic examination concluded primary neoplasia. However, it was not possible to classify these lesions as being of a malignant or a benign nature. A false positive diagnosis of a hepatocellular carcinoma of the clear cell type was made in one case. In all 5 patients with non-neoplastic adrenal lesions cytological and histological examinations concluded non-neoplastic disease. Electron microscopy was of special benefit in two cases of a non-Hodgkin's lymphoma and a pheochromocytoma. Using ultrasonically guided biopsies it is possible to differentiate between adrenal lesions due to metastatic spread and adrenal lesions due to primary neoplasia or non-neoplastic disease. Compared to other imaging techniques ultrasonically guided punctures of adrenal masses is a simple procedure giving important diagnostic information.

Adrenal Gland Neoplasms↗

Correlation between in vitro tetraploidy in skin fibroblasts and development of sporadic colorectal carcinomas.

In vitro tetraploidy (IVT) in skin fibroblasts cultures measured by flow cytometry was compared with histological type and degree of dysplasia in 22 patients with adenomas of the colon and rectum. Furthermore, IVT was compared with stage and differentiation in 36 patients with carcinoma of the colon and rectum. In vitro tetraploidy in skin fibroblasts was correlated to type as well as dysplasia in adenomas and differentiation in carcinomas but was not correlated to Dukes' stage in carcinomas. Skin fibroblast genetic instability, expressed as increased IVT (IVT+), has been reported to reflect a genetic predisposition to colorectal cancer in the hereditary nonpolyposis colorectal cancer syndrome. Because IVT+, which appears to be associated with the progression of adenomas to carcinomas, also is found in many of the non-syndrome colorectal cancers, we suggest that development of colorectal cancer is considerably influenced by the constitutive genetic instability of the autosomal dominant colorectal cancer syndromes.

Adenoma↗

Impact of exercise training on plasma adrenocorticotropin response to a well-learned vigilance task.

Plasma adrenocorticotropin hormone (ACTH), cortisol, heart rate, self-reported state anxiety and total reaction time responses in physically active (n = 8) and sedentary (n = 11) middle-aged men were compared during performance of a well-learned, psychologically challenging task. The groups were similar in age (active: 39.9 +/- 8.4 yr vs. sedentary: 44.4 +/- 7.2 yr) and trait anxiety (29.4 +/- 5.2 vs. 34.5 +/- 12.6), but they had different maximal oxygen consumption relative to lean body weight (68.6 +/- 7.1 vs. 44.7 +/- 4.6 ml.kg(-1).min(-1)). During performance of the psychological protocol, the total group had significant increases in heart rate and state anxiety, whereas both ACTH and cortisol remained near baseline levels. ACTH and cortisol were not different between the groups. The sedentary group exercise trained for 4 mo, which resulted in an 18% improvement in maximal aerobic capacity (vO2 max). Exercise intervention did not significantly alter the neuroendocrine response compared to pre-training values or compared to a corresponding control group. These findings suggest that enhanced cardiovascular fitness resulting from exercise training does not affect anterior pituitary-adrenocortical activity during performance of a practiced vigilance task.

Adrenocorticotropic Hormone↗

Release of vasopressin and oxytocin by paraventricular stimulation in rats.

The nucleus tractus solitarius/dorsal motor nucleus of the vagus nerve (NTS/DMV) area was perfused by the push-pull perfusion technique in anesthetized rats, and perfusates were assayed for arginine vasopressin (AVP) and oxytocin (OXT) immunoreactivity. As compared with controls, electrical stimulation of the ipsilateral paraventricular nucleus (PVN) resulted in increased amounts of both AVP (approximately 5-fold) and OXT (approximately 10-fold, P less than 0.05 each) in the perfusates. During the poststimulation perfusion period, peptide concentrations were found to return to control levels. Elevation of circulating AVP and OXT by an osmotic stimulus did not result in increases of AVP and OXT in NTS/DMV perfusates. These data suggest that AVP and OXT are released from NTS/DMV area fiber terminals during electrical stimulation of descending PVN neurons. Furthermore, they are consistent with the view that both peptides are involved as neurotransmitters in autonomic regulation.

Animals↗

Dependence of antigen expression on functional state of beta-cells.

Antigen expression corresponding to anti-islet cell surface monoclonal antibodies IC2 and A2B5 was studied. IC2 is a rat-rat hybridoma autoantibody produced from the BB rat; among islet cells, IC2 is beta-cell specific. A2B5 is an anti-ganglioside antibody described as labeling beta-cells. Islets of Langerhans from Lewis rats were isolated and cultured for 18 h in RPMI-1640 with five different glucose concentrations (2.2, 3.3, 5.5, 11.1, and 18.3 mM). In some experiments, islets were precultured for 2 or 3 days. After isolation of islet cells and antibody labeling, the percent of IC2+ beta-cells in the different groups increased from 33.3, 34.5, 40.9, and 57.2 to 58.6% (P less than 10(-6). For A2B5, the percent of labeled islet cells increased from 37.4, 41.8, 46.7, and 53.8 to 56.2% (P less than 10(-4). Thus, increasing glucose concentration leading to higher beta-cell activity implies an increase in antigen expression. Neither A2B5 nor IC2 reacts with insulin, as shown by absorption experiments and immune electron microscopy of binding sites. Electron microscopy of IC2-gold-labeled islet cells substantiated the beta-cell specificity of IC2. In conclusion, expression of the corresponding antigens to IC2 and A2B5 depends on the functional state of the beta-cells; because this has been shown to be an important factor in the development of insulin-dependent diabetes, our findings may be of potential pathogenetic interest.

Animals↗

Brown-bowel syndrome. Review of the literature and presentation of cases.

Four cases of brown-bowel syndrome (BBS) are presented. BBS is found in malabsorptive conditions secondary to diseases involving the liver, pancreas, and gastrointestinal tract. Morphologically, BBS is characterized by deposition of lipofuscin in the tunica muscularis, and electron microscopy shows degradation of smooth-muscle cell mitochondria. It is probable that BBS is a manifestation of vitamin E deficiency causing smooth-muscle cell 'mitochondrial myopathy'. Normal bowel function is retained, causing bowel hypotonia, and an aggravation of the underlying disease occurs. On suspicion of BBS, diagnosis is obtained in full-wall biopsy specimens of the intestine.

Aged↗

Interleukin 6: a functional and structural in vitro modulator of beta-cells from islets of Langerhans.

The direct in vitro effect of interleukin-6 (IL-6) on pancreatic beta-cells was studied using isolated Lewis rat islets (25/ml/well) precultured for 7 days and then incubated with or without human recombinant IL-6 (rIL-6) or purified human natural IL-6 (nIL-6). Both sources of IL-6 stimulated insulin secretion over a period of 6 days (P less than 0.01), whereas the levels of insulin within the islets were unaffected. At concentrations above 1.5 ng/ml, rIL-6 almost doubled the content of insulin in the supernatants. At an intermediate concentration, 0.5 ng/ml, rIL-6 preserved insulin secretion by islets cocultured with 2 ng/ml of human recombinant interleukin 1 beta (rIL-1 beta) which otherwise inhibited insulin secretion to 60% of islets cultured in medium alone. Electron microscopic studies showed that rIL-6, 1.5 ng/ml, caused beta-cell specific degenerative changes similar to those previously described after treatment with IL-1 beta; i.e. appearance of opaque intracytoplasmic bodies, autophage vacuoles and signs of mitochondrial degeneration. We conclude that human IL-6 stimulates insulin production and secretion in vitro and induces similar ultrastructural changes in beta-cells as does IL-1 beta. IL-6 may be an endogenous mediator of some of the effects on beta-cells ascribed to IL-1.

Animals↗

Immunohistochemical identification of neuron-specific enolase, synaptophysin, chromogranin and endocrine granule constituent in neuroendocrine tumours.

Immunohistochemical identification of neuroendocrine tumour markers in paraffin embedded material from 22 tumours (5 small cell carcinomas of the lung (SCCL), 12 carcinoids, 2 medullary thyroid carcinomas, 2 pheochromocytomas and one paraganglioma) with electron microscopically verified dense-core granules revealed neuron-specific enolase in all but one tumour, synaptophsin in 15/22 (2 SCCL and 6 carcinoids negative), chromogranin in 16/22 (all SCCL and one carcinoid negative), and endocrine granule constituent in 18/22 (4 SCCL negative). The Grimelius silver methods stained 13/22 (all cases of SCCL and 4 carcinoids negative).

Adrenal Gland Neoplasms↗