Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation.

BACKGROUND: The cytokine interleukin-4 (IL-4) is secreted mainly by activated T lymphocytes and characterizes the T-helper 2 (Th2) sub-type. In transplantation Th2 cells are believed to induce graft tolerance. Previous studies revealed that patients with a relatively high frequency of IL-4 producing helper T lymphocytes (HTL) before heart transplantation (HTX) had no or less rejection episodes compared with patients with a low frequency of IL-4 producing HTL. Three single nucleotide polymorphisms (SNPs) have been identified in the promoter region of the IL-4 gene, which influence promoter strength. We investigated whether there was a correlation between SNP genotypes in the IL-4 promoter and heart failure, and rejection after HTX. METHODS: Seventy HTX patients, 61 donors, and 36 controls were genotyped for the 3 SNPs by sequencing. RESULTS: Of the SNPs at -285 and -81, only the C and A alleles, respectively, were found in this study. Both alleles were found for the -590 SNP. No relation between patient genotype of the SNP at -590 and heart failure and rejection was found. However, incidence of rejection was significantly lower in patients that received a donor heart with the T-positive genotype compared with patients that received a heart from a T-negative donor. Patients who had the T-negative genotype and received a heart from a T-positive donor, suffered significantly less from rejection than T-negative patients that received a T-negative donor heart. This was not significant in the T-positive patient group. CONCLUSIONS: This indicates that IL-4 production within the donor heart and by cells from the donor is important for reducing incidence of episodes of rejection.     

Probable gas embolism during operative hysteroscopy caused by products of combustion

PURPOSE: Gas embolism is a rare but well documented entity during operative hysteroscopy, with an incidence of 10-50%. Catastrophic outcomes occur at a rate of three in 17,000 procedures. The purpose of this report is to present a non-fatal case of gas embolism probably caused by the gaseous products of combustion. CLINICAL FEATURES: A 50-yr-old woman with a history of menorrhagia was scheduled for hysteroscopy and endometrial ablation and polypectomy. Fifteen minutes into the procedure, with the patient in lithotomy position, 20 degree head down tilt, and breathing spontaneously, a sudden oxygen desaturation occurred from 97% to 87%. The patient's end-tidal carbon dioxide dropped from 46 mmHg to 27 mmHg. The patient's breathing pattern remained normal, respiratory rate remained 11-12 breaths x min(-1) but amplitude of the reservoir bag movement was increased. Cardiovascular variables remained stable. She responded rapidly to 100% oxygen and made an uneventful recovery. Having ruled out other possible causes, we concluded gas embolism was responsible for the fall in oxygen saturation and end-tidal CO(2). CONCLUSION: With all the precautions in place to minimize the likelihood of fluid overload and ambient air embolism occurring, we surmised that products of combustion were the cause of the gas embolism. During endometrial ablation, gaseous products of combustion, mainly carbon dioxide, accumulate. The gases may then contribute to the rise in uterine pressure that occurs as irrigation fluid enters the uterus and this rise in pressure in turn encourages passage of gas into the open venous sinuses.     

Mutational analysis of HOXD13 and HOXA13 genes in the triphalangeal thumb-brachyectrodactyly syndrome.

The triphalangeal thumb-brachyectrodactyly syndrome is a very rare autosomal dominant disorder of unknown etiology characterized by an unusual pattern of limb malformations: triphalangeal thumbs and brachyectrodactyly in the hands, and ectrodactyly in the feet. In a previous report, we described the clinical and radiographical features of three related subjects with the disease and suggest that due to the unusual combination of limb defects and to its phenotypic similarity with the limb malformative pattern induced by disrupting the Hoxd13 gene in mouse, the triphalangeal thumb-brachyectrodactyly syndrome might be caused by mutations in a HOX gene. After sequencing the entire coding region of HOXD13 and the highly conserved homeodomain encoding region of HOXA13, we do not detect any deleterious mutation in any of the patients excluding that alterations at these sequences are responsible for the disease. Mutations in regulatory regions of these genes or in other genes involved in limb development might be responsible for the disease.     

Pr?senile Demenz bei polyzystischer lipomembran?ser Osteodysplasie

Wir berichten über den ersten Fall von polyzystischer lipomembran?ser Osteodysplasie oder “brain, bone and fat disease” in Deutschland. Die nach dem Erstbeschreibern auch als Morbus J?rvi-Hakola-Nasu bezeichnete Erkrankung ist bisher vor allem in Japan und in Finnland beschrieben worden. Einzelne F?lle wurden aus Schweden, Norwegen, Italien, Südafrika, Belgien und den USA berichtet. Im deutschsprachigen Raum ist bisher ein Fall aus ? ver?ffentlicht worden.     

Interaction of the leucine-rich repeats of polycystin-1 with extracellular matrix proteins: possible role in cell proliferation.

Polycystin-1, the product of the PKD1 gene, is a membrane-bound multidomain protein with a unique structure and a molecular weight of approximately 460 kD. The purpose of this study is to investigate the binding of the cystein-flanked leucine-rich repeats (LRR) of polycystin-1 to extracellular matrix (ECM) components. These interactions may play a role in normal renal development as well as the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). In vitro assays were used to assess the binding of a fusion protein containing the LRR of polycystin-1 and that of affinity purified polycystin-1 to a number of ECM components. The results showed that the LRR modulate the binding of polycystin-1 to collagen I, fibronectin, laminin, and cyst fluid-derived laminin fragments. The addition of the LRR fusion protein to cells in culture resulted in a significant dose-dependent reduction in the rate of proliferation. Cyst fluid-derived laminin fragments had a stimulatory effect on cell proliferation, which was reversed by the LRR fusion protein. These results suggest that the LRR of polycystin-1 act as mediators of the polycystin-1 interaction with the ECM. The observed suppression effect of the LRR on cell proliferation suggests a functional role of the LRR-mediated polycystin-1 involvement in cell-matrix and cell-cell interactions. These interactions may result in the enhanced cell proliferation that is a characteristic feature of ADPKD.     

Erythroleukemia with high fetal hemoglobin after therapy for ovarian carcinoma

The authors report the association of erythroleukemia (FAB M6) and fetal hemoglobin (HbF) level of at least 65% after therapy for ovarian carcinoma. The patient's erythrocytes had many signs of reversion to fetal-like erythropoiesis including: elevated HbF with a fetal G gamma/A gamma (gly/ala) of 3/1, low hemoglobin A2 (HbA2), macrocytosis, and increased i antigen. These data and data from other case reports suggest that elevation of HbF to greater than 25% with reversion to fetal-like erythropoiesis is useful in differentiating erythroleukemia from other preleukemic disorders.     

Statistical analysis of gait patterns of persons with cerebral palsy

Patients at Boston's Children's Hospital diagnosed as having cerebral palsy were filmed walking. These films were digitized and translated into measurements associated with leg motion. In this paper we use the gait measurements of 128 such patients to illustrate that the kth nearest neighbour clustering procedure results in a gait typology for patients with cerebral palsy. The procedure identifies four subpopulations from the sample data; the membership of a patient within this typology is mostly determined by the patient's motor control. The developed typology differs from the present diagnostic system which classifies a cerebral palsy patient as either quadriplegic, diaplegic or hemiplegic.