Laryngocoele

Three cases of laryngocoele operated in ENT Department University of Medical Sciences in Poznań by an external approach are presented. Role of larynx tomography in diagnosis procedure and surgical technique is emphasised. Origin, classification, diagnosis and treatment methods are discussed.     

Epimorphin expression in intestinal myofibroblasts induces epithelial morphogenesis

The formation of the crypt-villus axis during gut ontogeny requires continued reciprocal interactions between the endoderm and mesenchyme. Epimorphin/syntaxin 2 (epimorphin) is a mesenchymal protein expressed in the fetal gastrointestinal tract during villus morphogenesis. To elucidate its role in gut ontogeny, the epimorphin cDNA was transfected, in sense and antisense orientations, into a rat intestinal myofibroblast cell line, MIC 216. To determine the effects of epimorphin on the epithelium, myofibroblasts were cocultured with the Caco2 cell line. Caco2 cells spread in a simple monolayer over antisense-transfected cells lacking epimorphin. In contrast, sense-transfected myofibroblasts induced Caco2 cells to form compact, round clusters with small lumens. These morphologic differences were preserved in Transwell cocultures in which cell-cell contact was prevented, suggesting that epimorphin's effects were mediated by secreted factor(s). To determine the effects of epimorphin on crypt-villus axis formation in an in vivo model, rat gut endoderm was combined with epimorphin-transfected myofibroblasts and implanted into the chick intracoelomic cavity. The grafts in which epimorphin was overexpressed revealed multiple well-formed villi with crypt-like units, whereas those in which epimorphin expression was inhibited developed into round cystic structures without crypts or villi. Of several potential secreted morphogens, only the expression of bone morphogenetic protein 4 (Bmp4) was increased in the epimorphin-transfected cells. Incubation with noggin partially blocked the transfected myofibroblasts' effects on Caco2 colony morphology. These results indicate that mesenchymal epimorphin has profound effects on crypt-villus morphogenesis, mediated in part by secreted factor(s) including the Bmp's.     

Mapping myasthenia gravis-associated T cell epitopes on human acetylcholine receptors in HLA transgenic mice

Susceptibility to myasthenia gravis (MG) is positively linked to expression of HLA-DQ8 and DR3 molecules and negatively linked to expression of the DQ6 molecule. To elucidate the molecular basis of this association, we have induced experimental autoimmune MG (EAMG) in mice transgenic for HLA-DQ8, DQ6, and DR3, and in DQ8xDQ6 and DQ8xDR3 F(1) transgenic mice, by immunization with human acetylcholine receptor (H-AChR) in CFA. Mice expressing transgenes for one or both of the HLA class II molecules positively associated with MG (DQ8 and DR3) developed EAMG. T cells from DQ8 transgenic mice responded well to three cytoplasmic peptide sequences of H-AChR (alpha320-337, alpha304-322, and alpha419-437), of which the response to alpha320-337 was the most intense. DR3 transgenic mice also responded to this sequence very strongly. H-AChR- and alpha320-337 peptide-specific lymphocyte responses were restricted by HLA class II molecules. Disease resistance in DQ6 transgenic mice was associated with reduced synthesis of anti-AChR IgG, IgG(2b), and IgG(2c) Ab's and reduced IL-2 and IFN-gamma secretion by H-AChR- and peptide alpha320-337-specific lymphocytes. Finally, we show that DQ8 imparts susceptibility to EAMG and responsiveness to an epitope within the sequence alpha320-337 as a dominant trait.     

Potential therapeutic role of cationic peptides in three experimental models of septic shock

The therapeutic efficacies of buforin II, indolicidin, and KFFKFFKFF were investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 10 microg of Escherichia coli O111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 x 10(10) CFU of Escherichia coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and single puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1 mg of buforin II per kg of body weight, 1 mg of indolicidin per kg, 1 mg of KFFKFFKFF per kg, and 20 mg of imipenem per kg. The main outcome measures were bacterial growth in abdominal exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and lethality. Treatment with all peptides resulted in significant reductions in plasma endotoxin and TNF-alpha concentrations compared with those resulting from the imipenem and saline treatments. On the other hand, imipenem treatment significantly reduced the levels of bacterial growth compared with the reductions achieved with the peptide and saline treatments. All compounds reduced the rates of death compared to that for the controls. Although the peptides demonstrated lower levels of antimicrobial activity than imipenem, they exhibited the dual properties of antimicrobial and antiendotoxin agents.     

Persistent abnormalities in lymphoid tissues of human immunodeficiency virus-infected patients successfully treated with highly active antiretroviral therapy

Effective highly active antiretroviral therapy (HAART) for human immunodeficiency virus type 1 is associated with virus suppression and immune reconstitution. However, in some patients, this reconstitution is partial or incomplete because CD4(+) cell counts do not increase significantly. This may be due to damage in the microenvironment of lymphoid tissues (LTs), where CD4(+) T cells reside. To test this hypothesis, LT samples were obtained from 23 patients enrolled in a prospective trial that compared 3 different HAART regimens. Analysis of LT architecture and CD4(+) T cells populations revealed abnormalities in 100% of the LT samples, especially in the follicles, with 43% showing absence, 14% showing regression, and 43% showing hyperplasia. CD4(+) T cell populations were abnormal in 16 (89%) of 18 tissue samples, with 7 (39%) of 18 decreased by >50% of normal levels. These data are consistent with the hypothesis that persistent abnormalities in the microenvironment can influence immune reconstitution and document persistent LT abnormalities with HAART not detected by measures of peripheral CD4(+) T cell count.     

Influence of acute and chronic 1,2,3,4-tetrahydroisoquinoline administration on the expression of proenkephalin mRNA in the rat striatum

Animal studies have shown that a depletion of dopamine or blockade of dopamine D2 receptors in the striatum produces an increase in striatal proenkephalin (PENK) mRNA expression and an increase in GABAergic transmission in the globus pallidus. Therefore, it has been suggested that an enhanced striatal PENK mRNA expression may reflect to some extent an increase in the activity of the GABAergic striatopallidal pathway whose overactivity has been suggested to take place in the course of Parkinson's disease. Therefore, the aim of the study was to investigate the role of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endogenous substance suspected of producing parkinsonism in humans, in the regulation of the activity of GABAergic striatopallidal pathway in rats. TIQ administered acutely at the dose of 100 mg/kg ip increased the PENK mRNA expression in the dorsal part of the striatum at two levels I and II (rostral and central striatum, respectively). No changes were noticed in the ventral part of the striatum. Moreover, TIQ given chronically to rats for 3 weeks did not modify the level of PENK mRNA in any examined part of the striatum. The present results show that the effect of TIQ on the PENK mRNA expression is different from that described for proparkinsonian model neurotoxins (MPTP, 6-OHDA) as well as for typical neuroleptics, such as haloperidol.     

Changes in lens and retina and parameters of lipid metabolism and glycosylated hemoglobin levels in young patients with diabetes

PURPOSE: The aim of the work was, to find out the relations between the lipid profile and glycosylated hemoglobin in blood and eye changes in the diabetic young people. MATERIAL AND METHODS: There were 39 patients (19 women and 20 men), aged 14-27 years (mean 19.5), treated for diabetes during the period 6-23 years (mean 9.6). The ophthalmological examinations have included anterior segment and lens, as well as the fundus of the eye. There also have been made the blood serum examinations of cholesterol (CHC), LDL-CHC, HDL-CHC, trigliceride (TG), apolipoproteins B (ApoB) and glycosylated hemoglobin (HbA1c). RESULTS: Basing on these examinations it has been stated that: 1. the lens changes were observed in the patients of increased LDL-CHC level and ApoB, who suffered from diabetes shorter than 10 years, while in the patients suffering longer, lens changes correlate with the high level of HbA1c; 2. the eye fundus changes correlated substantially in the patients with the high levels of HbA1c, TG, HDL-CH (negatively), LDL-CH and ApoB, suffering less than 10 years; in the patients suffering longer, correlation was also with the increased level of HbA1c, CHC and LDL-CHC. 3. The increased levels of lipids were noted in the patients with the high level of HbA1c. CONCLUSIONS: The stated data have indicated, that the eye changes are caused by disturbances of lipid parameters, but besides of the glycaemia disorders. The diabetic duration does not matter for the lipid profile and HbA1c level, but it is important for the occurrence of eye fundus changes. The HbA1c essentially influences on the occurrence of eye fundus changes, but in the longer suffering patients, also on the lens changes. The high HbA1c level shifts the lipid profile towards atherogenic factors. It is purposeful, to decrease its level below 7%, which is accepted as good diabetes control.