Successful chemotherapy of carcinomatosis of the bone marrow with disseminated intravascular coagulation from a rectal carcinoma found by eosinophilia

A 71-year-old man with eosinophilia was given a diagnosis of poorly differentiated adenocarcinoma of the rectum. Further examination showed that it had invaded the bone marrow. He had disseminated intravascular coagulation (DIC) from disseminated carcinomatosis of the bone marrow after colostomy. Chemotherapy (mFOLFOX6) was successful and his eosinophil count, DIC score and tumor markers normalized. We were able to continue chemotherapy after 5 months from the outbreak of disseminated carcinomatosis of the bone marrow. It is said that disseminated carcinomatosis of the bone marrow has a poor prognosis, but we were able to obtain a good response in this case by chemotherapy.     

A case of extrapleural empyema

A 49-year-old man with diabetes mellitus and alcoholic liver cirrhosis presented with dyspnoea and fever. A chest computed tomography scan revealed three areas of loculated pleural effusion. Initially, the patient was thought to have an intrapleural empyema and was treated with intravenous antibiotics and closed drainage. However, as he did not improve, he was then treated with open drainage. During open drainage, the patient was diagnosed to have an extrapleural empyema and improved following open drainage treatment.     

Endobronchial ultrasonography in the assessment of centrally located early-stage lung cancer before photodynamic therapy

To evaluate the utility of endobronchial ultrasonography (EBUS) in selecting appropriate candidates with centrally located early-stage lung cancer for photodynamic therapy (PDT) with curative intent, we performed EBUS before PDT in 18 biopsy-proven squamous cell carcinomas (including three carcinoma in situ) that had been considered to be appropriate candidates for PDT by conventional bronchoscopy and high-resolution computed tomography (HR-CT). Nine lesions were diagnosed as intracartilaginous by EBUS and subsequently PDT was performed. Long-term complete remission has been achieved in these patients with a median follow-up term after PDT of 32 months. The remaining nine lesions were diagnosed as extracartilaginous by EBUS and were considered candidates for other therapies such as surgical resection, chemotherapy, and radiotherapy, although two were invisible by HR-CT, three were superficial, and five were < or = 1 cm in diameter on observation by bronchoscopy. The depth of tumor invasion estimated by EBUS was proven to be accurate by histopathologic findings in six specimens after surgical resection. We conclude that EBUS is a useful technique that might be considered in addition to conventional bronchoscopy and HR-CT to improve the efficacy of PDT in patients with centrally located early-stage lung cancer.     

Automated enzymatic mitochondrial antibody assay for the diagnosis of primary biliary cirrhosis: applications of a routine diagnostic tool for the detection of antimitochondrial antibodies

BACKGROUND AND AIMS: An automated enzymatic mitochondrial antibody assay (EMA) kit for the diagnosis of primary biliary cirrhosis (PBC) has become commercially available recently. The aim of this study was to assess the clinical utility of the enzyme inhibition assay using this EMA kit for the diagnosis of PBC. METHODS: We tested the immunoreactivity of sera from 54 histologically confirmed Japanese PBC patients to the 2-oxo-acid dehydrogenase complex (2-OADC) enzymes by enzyme inhibition assay using commercially available TRACE (EMA) assay kit, and compared the results with those of indirect immunofluorescence, commercial enzyme-linked immunosorbent assay (ELISA) using MESACUP Mitochondria M2 kit, and immunoblotting on bovine heart mitochondria. RESULTS: Of the 54 sera, 43 (80%) were positive for antimitochondrial antibodies (AMA) by immunofluorescence, 39 (72%) for enzymatic inhibitory antibody to pyruvate dehydrogenase complex (PDC) by EMA, 33 (61%) for immunoglobulin G (IgG) class anti-PDC antibody by ELISA, and 53 (98%) for IgG, IgM, or IgA class antibodies against at least one of the 2-OADC enzymes by immunoblotting. Of these, 43 (80%) were positive for IgG, IgM, or IgA class antibodies against the E2 subunit of PDC (PDC-E2) by immunoblotting. Thirty-six of the 54 sera (67%) showed identical results in all of the four assays, and 40 (74%) were all negative or positive by EMA, ELISA, and immunoblotting in PDC-relevant reactivity. There was a significant correlation between the number of detected immunoglobulin classes of anti-PDC-E2 by immunoblotting and anti-PDC by EMA (P < 0.0001), and a significant inverse correlation between IgG class anti-PDC by ELISA and units of PDC activity by EMA (r = -0.87, P < 0.0001). CONCLUSIONS: Although EMA had lower sensitivity compared with immunofluorescence and immunoblotting, this assay should be included among the routine diagnostic tools for the detection of AMA specific to PBC in clinical laboratories because of its high specificity, objective read-out, and rapid turnaround time.     

Proteasome Inhibitor MG132 Inhibits Angiogenesis in Pancreatic Cancer by Blocking NF-κB Activity

Since angiogenesis enables solid tumors, including pancreatic cancer (PaCa), to grow and metastasize, the development of anti-angiogenic agents is currently one of the urgent issues. Proteasome inhibitors are well known for inhibiting nuclear factor-kappa B (NF-κB) activity in various cancer cells, but little is known about their biologic mechanisms against angiogenesis in PaCa. We divided human PaCa cell lines into high-angiogenic (BxPC-3 and SW 1990) and low-angiogenic (MIA PaCa-2 and Capan-2) groups. The high-angiogenic PaCa cell lines constitutively expressed high NF-κB activity and produced high levels of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8). The conditioned media from BxPC-3 significantly enhanced both proliferation of and tube formation by human umbilical vein endothelial cells (HUVECs) and these enhancements were significantly inhibited by the proteasome inhibitor MG132 treatment. Collectively, MG132 blocked PaCa-derived VEGF and IL-8 production through inhibition of NF-κB activity. Thus, proteasome inhibitors may prove beneficial as anti-angiogenic therapy for PaCa. Our studies show that MG132, a proteasome inhibitor, significantly blocked pancreatic-cancer-associated angiogenesis through inhibition of NF-κB and NF-κB-dependent proangiogenic gene products VEGF and IL-8.     

T cell acute lymphoblastic leukemia arising from familial platelet disorder

Familial platelet disorder (FPD) is a rare autosomal dominant disorder which causes moderate thrombocytopenia with or without impaired platelet function. Patients have a propensity to develop acute myeloid leukemia (AML), and various types of second hits have been postulated in the evolution to AML. However, only a few cases of acute lymphoblastic leukemia (ALL) have been reported thus far. Here, we report a family of FPD with a germ-line hemi-allelic mutation R174X in the RUNX1 gene. The proband of the family developed AML and her son had ALL of the T cell lineage. The balanced translocation t(1;7)(p34.1;q22) was detected in the lymphoblasts from the patient with ALL. This translocation was not seen in any other affected members of the family or in the bone marrow sample of this patient in complete remission. Taken together, t(1;7)(p34.1;q22) is thought to be one of the somatic second hits that predisposes FPD to acute leukemia with T cell phenotype.     

Syndrome of inappropriate secretion of antidiuretic hormone induced by tacrolimus in a patient with systemic lupus erythematosus

We describe the first reported case of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) induced by low-dose tacrolimus in a patient with autoimmune disease. A 41-year-old man with systemic lupus erythematosus (SLE) developed hyponatremia induced by SIADH after administration of tacrolimus (0.06 mg/kg per day). In this case, the hyponatremia promptly resolved upon withdrawal of tacrolimus. This case strongly suggests that SIADH is a potentially important complication of tacrolimus administration, irrespective of dosage, and should be borne in mind whenever the drug is used.     

Pineal expression-promoting element (PIPE), a cis-acting element,directs pineal-specific gene expression in zebrafish

The pineal gland, sharing morphological and biochemical similarities with the retina, plays a unique and central role in the photoneuroendocrine system. The unique development of the pineal gland is directed by a specific combination of the expressed genes, but little is known about the regulatory mechanism underlying the pineal-specific gene expression. We isolated a 1.1-kbp fragment upstream of the zebrafish exo-rhodopsin (exorh) gene, which is expressed specifically in the pineal gland. Transgenic analysis using an enhanced green fluorescent protein reporter gene demonstrated that the proximal 147-bp region of the exorh promoter is sufficient to direct pineal-specific expression. This region contains three copies of a putative cone rod homeobox (Crx)Otx-binding site, which is known to be required for expression of both retina- and pineal-specific genes. Deletion and mutational analyses of the exorh promoter revealed that a previously uncharacterized sequence TGACCCCAATCT termed pineal expression-promoting element (PIPE) is required for pineal-specific promoter activity in addition to the CrxOtx-binding sites. By using the zebrafish rhodopsin (rh) promoter that drives retina-specific expression, we created a reporter construct having ectopic PIPE in the rh promoter at a position equivalent to that in the exorh promoter by introducing five nucleotide changes. Such a slight modification in the rh promoter induced ectopic enhanced green fluorescent protein expression in the pineal gland without affecting its retinal expression. These results identify PIPE as a critical cis-element contributing to the pineal-specific gene expression, in combination with the CrxOtx-binding site(s).