Complex karyotypic abnormality in ovarian fibroma associated with Gorlin syndrome

Nevoid basal cell carcinoma (NBCC) syndrome is an autosomal dominant disorder characterized by distinctive congenital malformations and a variety of benign and malignant neoplasms, including ovarian fibromas. We describe pathologic and cytogenetic findings in a large unilateral ovarian fibroma from a 12-year-old female with NBCC syndrome. The pathologic findings were characteristic for ovarian fibroma, but were unusual for the ovarian fibromas associated with NBCC syndrome because of the absence of calcification, the lack of bilaterality, and the presence of focal hypercellularity. The karyotype of tumor tissue showed complex numerical and structural abnormalities. Although there is frequent loss of heterozygosity of 9q22.3 and mutations in the PTCHgene in Gorlin syndrome, the ovarian fibroma in this case did not have cytogenetically detectable abnormalities of chromosome 9.     

On the various manifestations of spontaneous autoimmune diabetes in rodent models

Autoimmune (type 1) diabetes mellitus in mouse, rat, and humans shares several features, including T lymphocyte infiltration into pancreatic islets and a dependence on permissive class II major histocompatibility complex (MHC) alleles. We report here on an experimental model involving mice that express influenza hemagglutinin (HA) under the control of the insulin promoter and, at the same time, a transgenic class II MHC-restricted T cell receptor (TcR) specific for an HA peptide. These mice spontaneously develop islet infiltrates resembling those found in NOD mice and most animals become diabetic within 8 weeks of age. Because of the availability of a clonotypic TcR antibody, we can be confident that the Ins-HA transgene does not induce any measurable alterations in the vast majority of T cells with the transgenic TcR in primary and secondary lymphoid organs. Continuous export of large numbers of HA-specific lymphocytes from the thymus was not required for the manifestation of the disease since mice thymectomized at 3 days after birth still developed the disease albeit with smaller infiltrates.     

Direct isolation of Candida spp. from blood cultures on the chromogenic medium CHROMagar Candida

CHROMagar Candida is a selective and differential chromogenic medium that has been shown to be useful for identification of Candida albicans, Candida krusei, Candida tropicalis, and perhaps Candida glabrata. Colony morphology and color have been well defined when CHROMagar Candida has been used to isolate yeast directly from clinical specimens, including stool, urine, respiratory, vaginal, oropharyngeal, and esophageal sources. Direct isolation of yeast on CHROMagar Candida from blood cultures has not been evaluated. We evaluated whether the color and colony characteristics produced by Candida spp. on CHROMagar Candida were altered when yeasts were isolated directly from blood cultures. Fifty clinical isolates of Candida were inoculated into aerobic and anaerobic blood culture bottles and incubated at 35 degrees C in an automated blood culture system. When growth was detected, an aliquot was removed and plated onto CHROMagar Candida. As a control, CHROMagar Candida plates were inoculated with the same isolate of yeast grown on Sabouraud dextrose agar simultaneously. No significant difference was detected in color or colony morphology between the blood and control isolates in any of the tested organisms. All C. albicans (n = 12), C. tropicalis (n = 12), C. glabrata (n = 9), and C. krusei (n = 5) isolates exhibited the expected species-specific colony characteristics and color, whether isolated directly from blood or from control cultures. CHROMagar Candida can be reliably used for direct isolation of yeast from blood cultures. Direct isolation could allow mycology laboratories to more rapidly identify Candida spp., enable clinicians to more quickly make antifungal agent selections, and potentially decrease patient morbidity and mortality.     

CD1d-restricted NKT cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses

CD1d-restricted NKT cells are a novel T cell lineage with unusual features. They co-express some NK cell receptors and recognize glycolipid antigens through an invariant T cell receptor (TCR) in the context of CD1d molecules. Upon activation through the TCR, NKT cells produce large amounts of IFN-gamma and IL-4. It has been proposed that rapid cytokine output by activated NKT cells may induce bystander activation of other lymphoid lineages. The impact of CD1d-restricted NKT cell activation in the induction of B cell-mediated immune responses to infection is still unclear. We show here that CD1-restricted NKT cells contribute to malarial splenomegaly associated with expansion of the splenic B cell pool and enhance parasite-specific antibody formation in response to Plasmodium berghei infection. The increased B cell-mediated response correlates with the ability of NKT cells to promote Th2 immune responses. Additionally, antibody responses against the glycosylphosphatidylinositol (GPI)-anchored protein merozoite surface protein 1 (MSP-1) were found to be significantly lower in CD1(-/-) mice compared to wild-type animals. P. berghei-infected MHC class II (MHCII)(-/-) mice also generated antibodies against MSP-1, suggesting that antibody production against GPI-anchored antigens in response to malaria infection can arise from both MHCII-dependent and independent pathways.     

Novel TAP1 polymorphisms in indigenous Zimbabweans: their potential implications on TAP function and in human diseases

Because of the essential role of transporter associated with antigen processing (TAP1 or TAP2) molecule in antigen processing, the implication of its polymorphism as a factor involved in human diseases and the possible genetic variation at this locus among ethnically diverse populations, we underwent a study to analyze the full extent of TAP1 polymorphism in an indigenous Zimbabwean population (Shona ethnic group). Using single-stranded conformation polymorphism and DNA direct sequencing procedures, we detected the presence of 11 nucleotide sequence variations in the entire coding region of TAP1. Of these variants, eight are nonconservative substitutions with respect to amino acid composition and are located in a critical part of the protein that could modulate its function. Five new polymorphic sites were identified in exon 1 (codons 7 Pro --> Ser, 17 Gly --> Arg, 141 Val --> Val), exon 6 (codon 419 Gly --> Cys), and exon 7 (codon 487 Arg --> Arg). Significant differences were seen in the distribution of TAP1*0201 and TAP1*0401 alleles, and codon 333 (Ile --> Val) polymorphism among African and non-African populations. Thus, TAP1 polymorphism has evolved differently among populations presumably because of the evolutionary pressures generated by prevalent pathogens in these geographically distinct regions.     

Allele sharing for schizophrenia and schizo‐affective disorder within a region of Homo sapiens specific XY homology

A case (based upon an association with cerebral asymmetry) has been presented for a gene for psychosis within the Xq21.3/Yp region of homology that is specific to Homo sapiens. We tested this hypothesis using the pentanucleotide marker DXYS 156 that is located within this region. In 84 families affected by schizophrenia or schizo‐affective disorder no tendency toward increased allele sharing amongst siblings was observed (χ² = 0.002). We conclude either that this region does not include a gene predisposing to psychosis or that if it does, the relevant variation is epigenetic rather than sequence‐based. With respect to the latter possibility we draw attention to the recent evolutionary history of the Xq21.3/Yp region. Genes within the region are in transition to protection from X inactivation and therefore may be epigenetically labile. © 2002 Wiley‐Liss, Inc.