Pure red cell aplasia and seronegative myasthenia gravis in association with thymoma.

Pure red cell aplasia is an uncommon paraneoplastic syndrome of thymoma. Myasthenia gravis is the most common paraneoplastic syndrome associated with thymoma. We present a case of a 79-year-old Pacific Islander female who presented with profound fatigue, generalized weakness, significant unintentional weight loss, bilateral ptosis, and anemia. The bone marrow biopsy showed near absence of erythroid elements consistent with pure red cell aplasia. Ice-pack test was consistent with myasthenia gravis and computed tomography of the chest demonstrated a thymoma. The patient was started on immunosuppressive treatment with prednisone and cyclosporine. This case demonstrates a rare combination of paraneoplastic manifestations of thymoma: pure red cell aplasia and myasthenia gravis.

Eruptive xanthoma associated with severe hypertriglyceridemia and poorly controlled type 1 diabetes mellitus.

Eruptive xanthoma is characterized by yellowish skin papules encircled by an erythematous halo and associated with severe hypertriglyceridemia above 2,000 mg/dl. Hypertriglyceridemia can be caused by primary genetic mutations, secondary causes, such as uncontrolled diabetes, obesity, alcohol overuse, or combinations of both. Eruptive xanthoma can serve as an important clinical indicator of underlying systemic conditions (e.g. hypertriglyceridemia and uncontrolled diabetes mellitus). It is important for clinicians to recognize it to prevent further complications such as pancreatitis and cardiovascular disease.

Impact of Oncotype DX on treatment decisions in ER-positive, node-negative breast cancer with histologic correlation.

Oncotype DX, a gene-expression profiling assay, provides stratification of patients with estrogen-receptor positive, lymph-node-negative early breast cancer into risk groups based on recurrence score, which are associated with distant recurrence and response to chemotherapy. This study aims to determine whether Oncotype DX influences clinicians' treatment decisions, and whether assay results correlate with histologic assessment. Fifty patients with estrogen-receptor positive, node-negative early breast cancer analyzed by Oncotype DX and operated on by two breast surgeons were included. To assess effect on treatment decisions, clinical vignettes were created by retrospective chart review. Physicians were then presented with the clinical vignettes and instructed to make a treatment decisions (i.e., hormone therapy alone versus hormone therapy combined with chemotherapy) both before and after knowledge of the recurrence score. To assess correlation with histologic assessment, a prospective, blinded review of tumor slides was performed by two pathologists. Based on this review, tumors were placed into low, intermediate and high risk groups for comparison with Oncotype DX assay results. Treatment decisions were changed based on Oncotype DX results in 36 and 18% of cases by breast surgeons and medical oncologists, respectively. All tumors categorized as high risk by Oncotype DX were categorized as high risk based on histologic assessment, and 96% of cases categorized as low risk by recurrence score were categorized as low or intermediate risk by histologic assessment. Oncotype DX significantly influences management of estrogen-receptor positive, lymph-node-negative early breast cancer. Further studies are needed to assess association of histologic categorization to assay results.

Inhibitor of apoptosis (IAP)-like protein lacks a baculovirus IAP repeat (BIR) domain and attenuates cell death in plant and animal systems.

A novel Arabidopsis thaliana inhibitor of apoptosis was identified by sequence homology to other known inhibitor of apoptosis (IAP) proteins. Arabidopsis IAP-like protein (AtILP) contained a C-terminal RING finger domain but lacked a baculovirus IAP repeat (BIR) domain, which is essential for anti-apoptotic activity in other IAP family members. The expression of AtILP in HeLa cells conferred resistance against tumor necrosis factor (TNF)-α/ActD-induced apoptosis through the inactivation of caspase activity. In contrast to the C-terminal RING domain of AtILP, which did not inhibit the activity of caspase-3, the N-terminal region, despite displaying no homology to known BIR domains, potently inhibited the activity of caspase-3 in vitro and blocked TNF-α/ActD-induced apoptosis. The anti-apoptotic activity of the AtILP N-terminal domain observed in plants was reproduced in an animal system. Transgenic Arabidopsis lines overexpressing AtILP exhibited anti-apoptotic activity when challenged with the fungal toxin fumonisin B1, an agent that induces apoptosis-like cell death in plants. In AtIPL transgenic plants, suppression of cell death was accompanied by inhibition of caspase activation and DNA fragmentation. Overexpression of AtILP also attenuated effector protein-induced cell death and increased the growth of an avirulent bacterial pathogen. The current results demonstrated the existence of a novel plant IAP-like protein that prevents caspase activation in Arabidopsis and showed that a plant anti-apoptosis gene functions similarly in plant and animal systems.

Heat-shock and redox-dependent functional switching of an h-type Arabidopsis thioredoxin from a disulfide reductase to a molecular chaperone.

A large number of thioredoxins (Trxs), small redox proteins, have been identified from all living organisms. However, many of the physiological roles played by these proteins remain to be elucidated. We isolated a high M(r) (HMW) form of h-type Trx from the heat-treated cytosolic extracts of Arabidopsis (Arabidopsis thaliana) suspension cells and designated it as AtTrx-h3. Using bacterially expressed recombinant AtTrx-h3, we find that it forms various protein structures ranging from low and oligomeric protein species to HMW complexes. And the AtTrx-h3 performs dual functions, acting as a disulfide reductase and as a molecular chaperone, which are closely associated with its molecular structures. The disulfide reductase function is observed predominantly in the low M(r) forms, whereas the chaperone function predominates in the HMW complexes. The multimeric structures of AtTrx-h3 are regulated not only by heat shock but also by redox status. Two active cysteine residues in AtTrx-h3 are required for disulfide reductase activity, but not for chaperone function. AtTrx-h3 confers enhanced heat-shock tolerance in Arabidopsis, primarily through its chaperone function.

[Ultrastructural Changes Of The Hepatocytes And Biliary Epithelia Due To Clonorchis Sinensis In Guinea Pigs]

The present study was undertaken to observe the changes of hepatocyte and biliary epithelium in the liver of guinea pigs infected with C. sinensis. Ten guinea pigs infected with 500 metacercariae of C. sinensis each were reared for 11 weeks. After sacrifice, the liver tissues were processed both for conventional light microscopy and for electronmicroscopy. The following results were obtained by light and electronmicroscopic observation of these tissue preparations. 1. The dilatation of bile ducts with chronic inflammatory cell infiltration and fibrosis, and flattening of lining epithelium were observed by light microscopy. Bile duct showed a single low columnar or cuboidal epithelium and subepithelial small round cell infiltration. Papillary proliferation, adenomatous hyperplasia and increase of goblet cells in the subepithelial glands were also noted in some areas of bile ducts. Occasionally, small fibrous nodules in the portal tract replacing bile ducts, surrounded by a heavy infiltrate of small round cells and neutrophils were observed. 2. On light microscopic examination, no cellular damages were seen in the liver cells except mild fatty degeneration. 3. Electronmicroscopic examination of the biliary epithelium revealed increased mucin granules, cytoplasmic projection into lumen, decreased microvilli and obstruction of bile canaliculi. Indistinct and/or irregular appearances of intercellular lateral interdigitation were observed in most of biliary epithelium. 4. On the electronmicrographs of hepatocytes, dilation of endoplasmic reticulum(ER) and destruction of cristae in some mitochondriae were prominent features. Disappearance of cytoplasmic organells and dilatation of bile canaliculi were also monitored. 5. Endothelial cells in the sinusoids were remained intact.