NO LINKAGE OR ASSOCIATION OF TELOMERIC AND CENTROMERIC T-CELL RECEPTOR β-CHAIN MARKERS WITH SUSCEPTIBILITY TO TYPE 1 INSULIN-DEPENDENT DIABETES IN HLA-DR4 MULTIPLEX FAMILIES

The T-cell receptor β locus (TCRB) on chromosome 7q35 was studied as a candidate region for genetic susceptibility to type 1 insulin-dependent diabetes (IDDM). A highly polymorphic microsatellite marker mapping to the TCRBV6.7 gene and a TCRB C-region RFLP were used to genotype the members of a total of 21 multiplex IDDM families from two different geographical areas. There was no evidence to support linkage to either of these markers with IDDM, and conventional two-point analysis excluded linkage to the telomeric end of the TCRB complex, in the region of the highly informative TCRBV6.7 marker. There was significant linkage of IDDM to the class II HLA-D locus with significant lod scores >3.0 obtained for the HLA-DRB1 and HLA-DQB1 genes. Affected sib-pair (ASP) and transmission disequilibrium (TDT) association tests confirmed these findings.     

RecurrentStreptococcus pneumoniae endocarditis

A case of recurrent endocarditis due toStreptococcus pneumoniae, a rare cause of endocarditis, is reported. The first episode of infection resulted in valvular damage, necessitating replacement of the aortic and mitral valves, and the second episode was treated successfully with antibiotics alone. Recurrence occurred even though the organism was fully susceptible to the antibiotics used and the patient showed no evidence of immune deficiency.     

Pathological changes in broiler chickens fed ochratoxin A and inoculated with Escherichia coli.

A study was conducted to evaluate the effects of ochratoxin A (OA) on Escherichia coli-challenged broiler chickens. One hundred and eighty-four one-day-old broiler chicks were divided into two groups of 92 chicks each, with one group fed a control mash diet and the other fed a mash diet containing 2 parts/10(6) OA. On day 14, each group was further subdivided into two groups with one group inoculated with E. coli O78 (1 x 10(7) colony-forming units/0.5 ml) by the intraperitoneal route, whereas the other group was not inoculated with E. coli. Four birds from each group were sacrificed at 1, 2, 3, 5, 7, 10, 14 and 21 days post-inoculation to record pathological changes in the liver, kidneys, heart, lungs, bursa, spleen and thymus. E. coli infection induced perihepatitis and pericarditis in the liver and heart, respectively, in chickens infected with E. coli alone or in OA-fed birds from 1 day post-infection (DPI) onwards. At 1 DPI, a thin fibrin layer covered the liver and heart; however, at subsequent days, the layer became thicker. E. coli infection did not produce appreciable changes in the kidneys, bursa or thymus. However, there was congestion of the lungs along with mononuclear cell infiltration. Ochratoxin feeding induced changes from 10 DPI onwards in chicks fed OA alone and those infected with E. coli. The changes in kidneys included swollen proximal convoluted tubules, degeneration of tubular epithelium and interstitial nephritis. Degenerative changes and mononuclear cell infiltration were recorded in the liver. There was atrophy of the lymphoid organs along with depletion of lymphocytes. Gross and histopathological changes were more severe in chickens fed OA and inoculated with E. coli than the chickens fed OA alone or those infected with E. coli, indicating combined action of these two.     

Hepatic angiomyolipoma and hepatic stellate cells share a similar gene expression profile

BACKGROUND AND AIMS: Angiomyolipomas (AMLs) of the liver are rare neoplasms composed of large epithelioid cells with intermixed fat and blood vessels. Hepatic AMLs have no clear normal-cell counterpart in the liver. However, AMLs and stellate cells both are positive for neural crest-derived markers including HMB-45 antigen. METHODS: To further explore the similarities between hepatic AMLs and stellate cells, gene expression of a hepatic AML was studied by cDNA microarray. Real-time polymerase chain reaction was used to confirm gene expression. Hepatic stellate cells can be quiescent, activated, or have a myofibroblastic phenotype depending on their state of activation. Expression of known markers of activated stellate cells was compared between the AML, activated primary mouse stellate cells, and stellate cell lines with activated and myofibroblastic phenotypes. Next, 5 novel genes from the AML were selected because they were not previously known to be markers of stellate cells and mRNA expression measured in the activated mouse stellate cells and in myofibroblastic stellate cell lines. Finally, expression levels of 10 novel genes were determined in 5 cirrhotic and 5 noncirrhotic human livers. RESULTS: Overexpression of known markers of activated stellate cells including transforming growth factor beta (TGF- beta ), smooth muscle actin, and collagen was found in the hepatic AML. Three of 5 novel markers that were identified in the AML, RRAD (Ras-related associated with diabetes), CTSK (cathepsin K), and NIBAN were also found to be overexpressed in activated stellate cells compared with quiescent or myofibroblastic stellate cells. In addition, 9 of 10 novel genes overexpressed in AML were also overexpressed in cirrhotic human livers versus noncirrhotic livers. CONCLUSIONS: Hepatic AMLs share a similar gene expression profile and may differentiate toward activated stellate cells.     

Targeting myeloperoxidase to azurophilic granules in HL-60 cells

Myeloperoxidase (MPO) is a cationic protein and one of the major constituents of azurophilic granules in neutrophils. Here, we examined whether intracellular transport of MPO and serglycin, a chondroitin sulfate (CS)-bearing proteoglycan, is correlated. First, we examined binding of MPO to CS-Sepharose and measured an ionic interaction, which was disrupted by 200-400 mM NaCl. Next, HL-60 promyelocytes were activated with a phorbol ester, which induced an almost complete rerouting of serglycin from the granular to the secretory pathway, concomitant with a similar effect on MPO transport and secretion. We then used the membrane-permeable cross-linker dithiobis(succininmidylpropionate; DSP) after labeling HL-60 cells with [35S]methionine and [35S]cysteine for 19 h. Immunoprecipitation of MPO revealed its cross-linking to high molecular material having the appearance of a proteoglycan in sodium dodecyl sulfate-polyacrylamide gels. This assumption was confirmed by labeling HL-60 cells with [35S]sulfate for 10 min followed by DSP cross-linking and immunoprecipitation. From three granular enzymes immunoprecipitated, only the cationic MPO was cross-linked to [35S]sulfate-labeled serglycin in appreciable quantities, whereas cathepsin D or beta-N-acetylhexosaminidase was not. Thus, intracellular transport of MPO appears to be linked to that of serglycin. Extracts from high buoyant density organelles from human placenta containing MPO activity were subjected to CS-affinity chromatography. Proteins binding to CS were identified by mass spectrometry as MPO, lactoferrin, cathepsin G, and azurocidin/cationic antimicrobial protein of molecular weight 37 kDa, suggesting that serglycin may be a general transport vehicle for the cationic granular proteins of neutrophils.     

Pitfalls in the diagnosis of epithelioid sarcoma presenting in an unusual site: a case report

The cytologic appearance of epithelioid sarcoma in fine-needle aspiration biopsy cytology (FNABC) smears has not been extensively described. We report a case of epithelioid sarcoma in a 55-year-old male who presented with nodular swellings in the abdominal wall and scrotum. The scrotal swelling was subsequently demonstrated to arise from the vas deferens. We highlight the cytomorphologic, immunocytochemical, and histopathologic features of this rare lesion in an unusual site, with particular emphasis on the dilemma encountered in the cytodiagnosis of this lesion.