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Biomedical subjects

I Rantala

Publications and source records attributed to I Rantala.

At least 37 records · Page 2Linked to original sources

Expression of HSP-65 in jejunal epithelial cells in patients clinically suspected of coeliac disease.

BACKGROUND: Coeliac disease (CD) can be classified both clinically and biologically an autoimmune disease. A close relationship obtains between heat shock proteins (HSPs) and numerous autoimmune diseases. HSPs are overexpressed when protecting the host against environmental insult. We sought here to establish whether dietary gluten is such a stress stimulus in patients clinically suspected of CD, and whether the expression of HSP-65 associates with densities of intraepithelial gammadelta+ T cells and/or with expression of mucosal HLA-DR. METHODS: Seventy-eight children with clinical suspicion of CD underwent a jejunal biopsy. Monoclonal antibodies were used to stain jejunal epithelial HSP-65, intraepithelial lymphocytes and mucosal HLA-DR. Serum IgA-class endomysial autoantibodies (EMA) were measured by an indirect immunofluorescence method. CD susceptibility HLA DQA1*0501 and DQB1*0201 alleles (HLA DQ2) were determined. RESULTS: Enhanced expression of epithelial cell mitochondrial HSP-65 was found in 80% (16/20) of coeliacs and in 24% (14/58) of children excluded for the disease, but in only 7% (2/28) of control subjects (p < 0.001, p = 0.049, respectively). Children with enhanced expression of HSP-65 had significantly higher gammadelta+ T cell densities than those with normal HSP-65 expression. A clear association between HSP-65 and serum IgA-class EMA were also ascertained in patients with normal jejunal mucosal morphology. HLA DQ2 positivity did not correlate with the HSP-65 expression. CONCLUSIONS: Gluten might be an environmental insult not only in CD patients but also in some patients excluded for the disease on biopsy. Enhanced expression of epithelial cell stress proteins might be an indicator of such an insult.

Adolescent↗

Cytoplasmic accumulation of alpha-catenin is associated with aggressive features in laryngeal squamous-cell carcinoma.

Aberrations in the function of alpha-catenin (alpha-cat), the anchoring protein of E-cadherin, are believed to cause dysfunction of the cadherin-catenin complex, leading to disturbed cell-cell adhesion. It has been suggested that expression of alpha-cat in human tumours might be a better indicator of aggressive phenotype than expression of E-cadherin. The value of alpha-cat as a prognostic marker in laryngeal squamous cell carcinoma (LSCC) is unclear. To determine the potential prognostic significance of alpha-cat, paraffin-embedded samples from 159 patients with invasive carcinoma left in the section and with long-term follow-up were evaluated immuno-histochemically for alpha-cat expression, and the results were related to histopathological grade, tumour stage and survival. Two patterns of staining were observed: pure membranous staining (57%) and membranous staining with cytoplasmic involvement (43%). Cytoplasmic involvement of alpha-cat was associated with dedifferentiation, advanced tumour stage and nodal status. In addition, supra-glottic tumours showed more often cytoplasmic involvement of alpha-cat than glottic tumours. Patients with cytoplasmic involvement appeared to have a trend towards poor overall survival, though without statistical significance. These results suggest that cytoplasmic involvement of alpha-cat is associated with aggressive behaviour and metastatic phenotype of LSCC.

Adult↗

Demonstration of Chlamydia trachomatis in Papanicolaou-stained gynecological smears.

A fluorescent antibody staining method was developed to detect Chlamydia trachomatis elementary bodies in Papanicolaou-stained cervical smears. Twenty-five known chlamydia-positive and 12 chlamydia-negative smears were correctly identified using this method. Smears from individuals with culture-positive chlamydia infections showed a high density of elementary bodies. Among 64 routine cervical smears, 27% (6/22) of smears that showed inflammatory changes were positive by fluorescent antibody staining for chlamydia, compared to 2.4% (1/42) of smears that were negative for inflammatory changes. This method should facilitate detection of chlamydia infections in populations undergoing cytological screening.

Cervix Uteri↗

Histone mRNA in-situ hybridization in astrocytomas: a comparison with PCNA, MIB-1 and mitoses in paraffin-embedded material.

AIMS: Non-isotopic histone mRNA in-situ hybridization (HmRNA NISH) allows detection of cells in the S phase of the cell cycle in paraffin-embedded tissue. The aim of this study was to evaluate the technique in measuring the proliferative activity of astrocytic neoplasms, and to compare the results with other proliferation estimates and patient survival. METHODS AND RESULTS: The proliferative activity of 71 routinely fixed and paraffin-embedded astrocytomas was studied by light microscopic HmRNA NISH, proliferating cell nuclear antigen (PCNA), Ki67MIB-1 and mitoses. A significant correlation was found between the labelling indices of histone mRNA (the percentage of histone-positive tumour cells: HmRNA-LI), immunohistochemical proliferation marker labelling indices (PCNA-LI: r = 0.64 and Ki67MIB-1-LI: r = 0.44) and mitotic indices (r = 0.45). The results were reproducible as judged by intra- and interobserver agreement (HmRNA/10 HPF (high power fields): r = 0.91 and r = 0.75, respectively, and HmRNA-LI: r = 0.61 and r = 0.62, respectively). The fraction of the cells in the most active cell cycle phases, as suggested by the HmRNA/Ki67 and mitotic index/Ki67 ratios, increased significantly with malignancy grade. In the univariate analysis the association of HmRNA-LI with survival was highly significant (P < 0.0001). Multivariate survival analysis showed that HmRNA-LI was an independent prognostic marker. CONCLUSIONS: Non-isotopic histone mRNA in-situ hybridization assay offers an alternative and reproducible method for measuring proliferative activity (S phase) in tumours under morphological control.

Antigens, Nuclear↗

A reversible neuronal antibody (anti-Tr) associated paraneoplastic cerebellar degeneration in Hodgkin's disease.

Paraneoplastic cerebellar degeneration (PCD) has been associated with a variety of neoplasms, most commonly with gynecologic tumors, breast cancer, small cell lung cancer, and Hodgkin's disease (HD). In some patients PCD is associated with circulating antineuronal antibodies like anti-Hu, anti-Yo or anti-Ri. Previously, only 5 patients with a new antineuronal antibody called anti-Tr, proposed to be specific for HD, have been reported. We describe 1 further patient with HD and reversible PCD with a decline in anti-Tr antibody titers in cerebrospinal fluid and serum corresponding to the improvement of clinical symptoms. At the present time the immunoreactive pattern observed in rat cerebellum is the only way to identify anti-Tr antibodies and differentiate them from other antibodies that immunoreact with the Purkinje cells.

Adult↗

Increased cell proliferation activity and decreased cell death are associated with the emergence of hormone-refractory recurrent prostate cancer.

The tumour growth kinetics (cell proliferation and apoptosis) of ten hormone-refractory locally recurrent prostate cancers were compared with their matched untreated primary tumour specimens. All recurrent tumours had a higher cell proliferation activity, as defined by Ki-67 immunohistochemistry, than corresponding primary tumours from the same patients. The mean cell proliferation activity in recurrences (13.5 +/- 3.8 per cent) was over two times higher (P < 0.0001) than that in primary tumours (5.5 +/- 2.4 per cent), suggesting that cell clones which progress during androgen withdrawal are actively stimulated to proliferate. The mean percentage of apoptotic cells, as estimated by the in situ end-labelling technique, was 5.4 +/- 4.7 per cent in untreated primary tumours, whereas it was 2.3 +/- 1.5 per cent in locally recurrent tumours (P = 0.05). In all but two cases, the apoptotic index was lower in recurrent than in corresponding primary tumours, suggesting that recurrent prostate carcinomas are able to avoid apoptosis in the androgen-deprived environment. In conclusion, the clinical progression of prostate cancer during androgen withdrawal is associated with increased cell proliferation and decreased apoptosis.

Antineoplastic Agents, Hormonal↗

IFN-gamma enhances macromolecular transport across Peyer's patches in suckling rats: implications for natural immune responses to dietary antigens early in life.

BACKGROUND: The capacity to generate (interferon-gamma) IFN-gamma, a potent immunoregulatory and inflammatory cytokine, is low in neonates and deficient in patients with food allergy. METHODS: We investigated the effect of IFN-gamma on antigen transport in the gut. In experiment I rat pups were randomized into two groups at the age of 14 days i.e., before gut maturation: Group IFN was given intraperitoneally recombinant rat IFN-gamma on days 14, 16, 18, 20. In experiment II, rats were randomized into two groups at the age of 26 days, i.e., after gut maturation: Group IFN received the IFN-gamma treatment on days 26, 28, 30, 32. Controls in both experiments received sterile saline. The absorption of horseradish peroxidase (HRP) across jejunal segments with and without Peyer's patches was studied in Ussing chambers on days 21 and 33 for experiments I and II, respectively. RESULTS: In experiment I, the absorption of intact HRP across both types of segments was significantly increased in Group IFN compared to controls. The mean (95% confidence interval) rate of degraded HRP absorption across patch-containing segments in Group IFN was significantly greater than in controls, 4420 (3162-6179) ng.h-1.cm-2 in comparison to 1550 (633-3790) ng.h-1.cm-2; F = 8.96, p = 0.009. CONCLUSION: IFN-gamma increases macromolecular transport before gut maturation particularly across Peyer's patches. This Peyer's patch-targeted effect can be important eliciting mucosal immune responses against dietary antigens early in life and aiding their immune exclusion.

Animals↗

Wound healing and soft tissue effects of CO2, contact Nd: YAG and combined CO2-Nd: YAG laser beams on rabbit trachea.

Rabbit trachea was used as an experimental model to study tissue effects and healing of full-thickness tracheal lesions produced by CO2, contact Nd: YAG and combined, coaxial CO2-Nd: YAG (Combo) laser beams. Two power settings (10 W and 16 W) were used with CO2 and contact Nd: YAG lasers. Three different CO2/Nd:YAG power ratios (1:1, 1:2 and 1:4) and power settings (12 W 15 W and 16 W) were used with the Combolaser. Histological specimens for light and transmission electron microscopy were prepared immediately and 1, 3, 5, 7, 14 and 21 days postoperatively. The wound with the most precise and fastest healing was produced by contact Nd: YAG laser. CO2 laser produced a moderate amount of charring and the largest amount of coagulated tissue with a slightly prolonged healing period. In the acute phase, tissue defects produced by the Combolaser with power ratios 1:1 and 1:2 resembled the CO2 laser lesions but with slightly less charring. The power ratio 1:4 diminished the cutting properties of the beam considerably. During the healing period the Combolaser produced the most intensive inflammation and granulation tissue formation resulting in delayed regeneration of the lesion. In transmission electron micrographs the most severe damage to chondrocytes was seen after using the Combolaser. These findings indicate that the Combolaser produces deeper tissue damage than CO2 or contact Nd:YAG laser. However, the Combolaser appears to be suitable for tracheobronchial operations, owing to its good simultaneous cutting and haemostatic properties.

Animals↗

Immediate histological changes in soft palate after uvulopalatopharyngoplasty with CO2, contact Nd:YAG or combined CO2 and Nd:YAG laser beams.

CO2, contact Nd:YAG and Combolaser (combined, simultaneous and coaxial CO2 + Nd:YAG laser beam) were used for uvulopalatopharyngoplasty (UPPP). It has been proposed that the combined beam geometry diminishes thermal damage to surrounding tissues when compared with single laser radiation. To study the extent of thermal tissue damage produced by the lasers, tissue samples for light (LM) and transmission electron microscopy (TEM) were taken from the surface of the resected area and 2 and 4 mm below the resection plane. The depth of tissue damage and coagulation was measured. The results showed no consistent differences in the inflammatory reactions or the amount and depth of tissue coagulation observed in samples taken immediately after the operation. The CO2 laser typically produced a carbonized and coagulated wound edge. Combolaser and contact Nd:YAG lasers generated slightly less charring but otherwise resembled each other with coagulated and vacuolized resecate margins. These results indicate that the beam geometry in Combolaser does not diminish thermal damage to surrounding tissues.

Humans↗

Fibroblasts and transforming growth factor beta induce organization and differentiation of T84 human epithelial cells.

BACKGROUND & AIMS: The gut epithelium in the crypt-villus axis represents a continuous developmental system in which the role of fibroblast-epithelial interactions is obvious. The aim of this study was to establish an in vitro method whereby fibroblast-guided differentiation of crypt-like gut epithelial cells can be studied. METHODS: Intestinal epithelial cells (T84 and HT-29) were cultured within type I collagen gel together were fibroblasts without cell-to-cell contact. T84 cells were also grown in the presence of transforming growth factor beta and hepatocyte growth factor. The gels were studied using light and electron microscopy and histochemical and immunohistochemical methods. RESULTS: The epithelial cells formed unorganized cell clusters within the gels, but when given fibroblast support, 76% of the T84 cell colonies (not HT-29) organized into luminal formations, and basement membranes including laminin were well deposited. The cells in the columnar single cell-layer luminal formations (49% of all colonies) were differentiated, showing microvilli, up-regulated alkaline phosphatase brush border activity, and mucin profiles typical for small intestine. This fibroblast-induced organization and differentiation was induced by transforming growth factor beta. CONCLUSIONS: Crypt-like T84 epithelial cells are able to differentiate when grown three-dimensionally together with fibroblasts or transforming growth factor beta. This method may be used for mesenchymal-epithelial cell cross-talk studies.

Cell Communication↗

Persistent cutaneous pseudolymphoma after intradermal gold injection.

After intradermal testing with goldsodiumthiomalate (GSTM), 5 out of 8 patients developed skin papules at the test sites, which persisted up to 20 months. The lesions were surgically excised. Histology revealed pseudolymphoma of B and T cell type containing follicular structures and occasional small granulomas. The amount of histiocytic cells among B and T lymphocytes was pronounced, including acid cysteine proteinase inhibitor (ACPI) positive follicular dendritic cells, CD68 positive macrophages, factor XIIIa positive dermal dendrocytes and S-100 positive cells. By electron microscopy, the macrophages contained endosomes loaded with crystalloid material which contained gold in X-ray microanalysis. Atomic absorption spectrophotometry also confirmed the presence of gold in one specimen. Thus GSTM seemed to accumulate in tissue macrophages leading to constant immunologic activation with lymphoid proliferation and histiocytic response.

Adolescent↗

Enterochromaffin cell density in the gastric mucosa of patients with chronic renal failure.

Thirty patients with chronic renal failure (CRF) and 30 age- and sex-matched controls were assessed for gastrointestinal diseases by gastroscopy, serum gastrin determination, and routine clinical and laboratory evaluation. Biopsy specimens from their gastric oxyntic mucosa were immunohistochemically stained with monoclonal antibodies against serotonin (5-hydroxytryptamine) and chromogranin A, the latter staining all gastric endocrine cells, the former disclosing serotonin-containing enterochromaffin (EC) cells only. The average EC cell density (cells/mm2) in the CRF patients was significantly lower than in the controls: 2.6 vs 12.9 (p = 0.0005). The EC cell counts also correlated negatively with serum gastrin values (p = 0.0031). The densities of the chromogranin-positive cells did not differ between CRF patients (74 cells/mm2) and controls (76 cells/mm2) (p = 0.7559). We conclude that, in addition to the previously known findings of hypoacidity, persistent hypergastrinaemia, and G and parietal cell hyperplasia, CRF also reduces the number of oxyntic EC cells. The negative correlation between EC cell density and serum gastrin levels reflects the complex interplay between different endocrinological activities in the gastrointestinal tract.

Adult↗

Effect of cetirizine on the inflammatory cells in mosquito bites.

BACKGROUND: Mosquito bites frequently cause wealing and delayed papules which appear within a few hours after the bites and may persist for several days. Cetirizine is an effective drug against mosquito bites by decreasing wealing and also the size and pruritus of the delayed bite papules. OBJECTIVES: To characterize inflammatory cells in the delayed mosquito-bite lesions, and to study the effect of cetirizine on the inflammatory cell response. METHODS: Twenty-six mosquito-bite sensitive subjects received cetirizine 20 mg (14 subjects) or placebo (12 subjects) in a double-blind fashion. Aedes aegypti-bites were given on a forearm and serial punch biopsies were taken at 2-, 6- and 24h after the bite exposure. Eosinophils, neutrophils, mast cells, mononuclear cells and T- helper (CD4+) and suppressor (CD8+) lymphocytes were counted from dermal infiltrates. RESULTS: Eosinophils and neutrophils were found already in 2-h bite lesions. Moreover, the number of mononuclear and CD4+ cells increased significantly (P < 0.01) from 2- to 24-h bite lesions. Unexpectedly, the overall numbers of eosinophils (P < 0.05), mononuclear cells (P < 0.01) and CD4+ cells (P < 0.01) were significantly higher in the cetirizine-treated subjects compared with the placebo-treated subjects. CONCLUSIONS: The results suggest that the inflammatory cell response in the delayed mosquito-bite lesions is similar to that occurring in allergic late-phase responses, i.e. an early influx of eosinophils, neutrophils and subsequent accumalation of CD4+ lymphocytes. The reason for the high numbers of eosinophils and CD4+ cells in the cetirizine-treated subjects is not known.

Adult↗

Human papillomavirus type 16 capsids expose multiple type-restricted and type-common antigenic epitopes.

The study of viral infectivity and detection of viral capsid antigens of the major cervical cancer-associated human papillomavirus (HPV) type, HPV-16, requires knowledge of which epitopes are exposed in clinical specimens of infected tissue or on intact capsids. To define the antigenic epitopes of HPV-16, antisera to 66 overlapping synthetic peptides corresponding to the HPV-16 capsid proteins L1 and L2 and to seven peptide analogues were tested in immunoperoxidase stainings of consecutive sections from formalin-fixed, paraffin-embedded HPV infected tissue. Antisera against eleven different peptides from L1 and against seven different peptides from L2 recognized the HPV capsid antigen. Most epitopes were only found on the capsid antigen of certain genital HPV types, but four antigenic epitopes in L1 were detectable also in cutaneous wart specimens. All antigenic epitopes in L2 were restricted to genital HPV types and four L2 epitopes were only detectable in HPV-16 or HPV-33 positive specimens. The surface exposure of the antigenic epitopes was investigated by comparing the reactivity of the antipeptide antisera with intact or disrupted virions or capsids of HPV-11, HPV-16 and bovine papillomavirus (BPV). Twenty antipeptide sera from L1 and seven antipeptide sera from L2 were reactive with intact HPV-16 capsids at titres up to 1:146,000. Sixteen of these antisera were also reactive with disrupted HPV-16 capsids. Cross-reactivity with disrupted HPV-11 and BPV was detected for eleven and six antisera, respectively, whereas intact HPV-11 or BPV virions showed only weak cross-reactivity. In conclusion, the HPV-16 L1 and L2 capsid proteins contained multiple antigenic epitopes, most of which were shared with one or several additional HPV types.

Amino Acid Sequence↗

The effect of topical oestradiol on skin collagen of postmenopausal women.

OBJECTIVE: To examine the effect of topical oestradiol on skin collagen and elastin. SUBJECTS: Twelve postmenopausal women, aged 52 to 76 years. INTERVENTIONS: Topical oestradiol treatment on the skin of lower abdomen and the vehicle only on the contralateral site; once a day for three months. MAIN OUTCOME MEASURES: The content of skin hydroxyproline; the levels of the carboxyterminal propeptide of human type I procollagen (PICP) and of the aminoterminal propeptide of human type III procollagen (PIIINP). The number and the quality of collagen and elastic microfibrils. RESULTS: The amount of hydroxyproline in the skin significantly (P = 0.012) increased from 11.8 to 16.3 micrograms (38%) during oestradiol treatment. After treatment, the PICP level in the blister fluid was significantly (P = 0.024) higher on the treated site than on the control site. Also the level of PIIINP increased, but the change was not statistically significant. Electron microscopy showed morphologic improvement of elastic and collagen fibres, while the number of oxytalan and elaunin fibres was unchanged in light microscopy. CONCLUSIONS: Topical oestradiol treatment increases the amount of skin collagen. The increase in the level of PICP and PIIINP in skin blister fluid indicates that oestradiol treatment stimulates collagen synthesis. Furthermore, our results show that topical ostradiol treatment has a greater influence on the amount than on the quality of skin collagen. On the contrary, in elastic tissue the oestradiol treatment will only result in morphologic improvement.

Administration, Topical↗

Sources of variation in the assessment of cell proliferation using proliferating cell nuclear antigen immunohistochemistry.

The reproducibility in quantitation of proliferation activity, determined using the monoclonal antibody 19A2 to proliferating cell nuclear antigen (PCNA), was tested in visual and computer-assisted analyses of brain tumor material. The PCNA labeling index was scored using count (PCNA-LI, visual and computer analyses) and area (PCNA-LIa, computer analysis) estimates of immunopositivity. The quality of immunostaining was the most important reason for variation in the assessment results. Other significant variation sources in the assessment were experience in selecting microscopic fields and distinguishing immunopositive nuclei from immunonegative ones. Computer-assisted analysis improved the reproducibility of quantitation between different observers (visual rPCNA-LI = 0.624 versus computer assisted rPCNA-LI = 0.904). Also, the use of PCNA-LIa improved the intraobserver and interobserver reproducibility in different stainings (observer 1:rPCNA-LI = 0.857 versus rPCNA-LIa = 0.874; observers 1 and 2: rPCNA-LI = 0.904 versus rPCNA-LIa = 0.927; observers 3 and 4: rPCNA-LI = 0.848 versus rPCNA-LIa = 0.906). PCNA-LIa by computerized image analysis improves accuracy in the evaluation of the granularly expressed PCNA level. Furthermore, the effect of tumor heterogeneity on the assessment results can be diminished with the computerized method because large tissue areas can be analyzed faster.

Astrocytoma↗