Limited capacity of the nuclear matrix to bind telomere repeat binding factor TRF1 may restrict the proliferation of mortal human fibroblasts

The maintenance of telomere integrity is essential for prolonged cell proliferation, and failure in this mechanism is a most consistent manifestation of cellular senescence. In this study, we investigated the role of telomere repeat binding factor (TRF1) in the proliferation of human fibroblasts. TRF1 expression is upregulated in a large variety of immortal human cells and supports de novo telomere formation in a dose-dependent manner. These observations suggest that the suppression of TRF1 might limit telomere maintenance and thus the life span of mortal cells. However, primary fibroblasts ectopically overexpressing TRF1 were unable to avoid senescence. On the other hand, exogenously expressed TRF1 in primary fibroblasts neither supported de novo telomere formation nor bound to the nuclear matrix as tightly as observed in immortal cells that show upregulated TRF1 expression. We present evidence suggesting that mortal human cells lack specific ligand(s) that anchor TRF1 to the nuclear matrix and that this contributes to their limited lifespan.     

Childhood blastic NK cell leukemia successfully treated with L-asparagenase and allogeneic bone marrow transplantation

Blastic NK cell lymphoma/leukemia is a rare and highly malignant neoplasia in both adults and children. It is characterized by lymphoblastoid morphology without cytoplasmic granules and immature NK cell immunophenotypes (CD56+, CD57-, CD16-). It has predilection for extranodal organ involvement, and the prognosis of affected patients is extremely poor under the current chemotherapy. We present a 14-year-old girl who was diagnosed as having blastic NK cell leukemia with mediastinal, pleural, and pericardial involvement. Immunophenotyping of her leukemic cells showed positive for CD2, CD5, CD7, CD34, CD56, HLA-DR, and cytoplasmic CD3. T cell receptor (TCR) and Immunoglobulin heavy chain genes were not rearranged. She received chemotherapy for acute lymphoblastic leukemia incorporating L-asparaginase (L-asp) which successfully induced complete remission. Bone marrow transplantation (BMT) from her HLA-identical sibling was conducted after two courses of consolidation therapy. Expression of aspargine synthetase (AS) protein in the leukemic cells at diagnosis was examined by an immunocytochemical method. She remains in hematological remission for over 36 months after BMT. The expression of AS protein was negative, suggesting that the leukemic cells were sensitive to L-asp. Induction and consolidation therapy incorporating L-asp followed by allo-BMT might be a promising treatment for child hood blastic NK cell leukemia, but more samples of the rare leukemia need to be studied before any definitive conclusions can be drawn.     

Renal actinomycosis mimicking renal tumor: case report

A 68-year-old man was admitted after fever and general fatigue with severe inflammatory signs and anemia. T1- and T2-weighted magnetic resonance imaging showed low- to isointensity and low-intensity tumor in the right kidney, respectively, suggesting renal actinomycosis. However, the right kidney was explored transabdominally because the possibility of renal malignant lymphoma could not be excluded. After nephrectomy, characteristic colonies of Actinomyces were seen microscopically, and the histologic diagnosis was renal actinomycosis. The patient was treated with antibiotics and made good progress after operation. This case highlights the importance of magnetic resonance imaging for the diagnosis of renal actinomycosis.     

Nonoprerative management of obstructive jaundice caused by a benign hepatic cyst

A 64-year-old man with a 9.0 cm benign hepatic cyst near the hepatic hilum presented with obstructive jaundice caused by the compression of the hepatic ducts. The cyst was aspirated percutaneously, and minocycline hydrochloride was instilled as a sclerosant through a catheter inserted into the cyst. The cyst gradually became smaller, relieving the obstructive jaundice. There were no complications or side-effects. The instillation of minocycline hydrochloride is a useful alternative to ethanol instillation for treating benign hepatic cysts, even when the cyst is causing obstructive jaundice.     

Relationship between health status and psychological distress among the inhabitants in a methylmercury-polluted area in Japan

This study examined the relationship between health parameters and psychological distress among inhabitants of methylmercury-polluted areas in Japan. The subjects were 133 inhabitants over the age of 40 yr living in two methylmercury-polluted villages. Information on demographic factors, health status, and mental health was obtained using questionnaires, including the General Health Questionnaire (GHQ). The proportional odds model was used to estimate the adjusted odds ratios of factors associated with a higher GHQ score after adjustment for age, gender, and district. Very poor self-rated health status, a high number (5+) of subjective symptoms, having monthly outpatient visits and medical house calls, and receiving compensation for methylmercury poisoning were significantly associated with psychological distress. Poor physical condition may lead to the development of psychological distress.     

Enhanced S-cone syndrome in a Japanese family with a nonsense NR2E3 mutation (Q350X)

PURPOSE: To describe the clinical characteristics of a Japanese male patient with enhanced S-cone syndrome (ESCS) and investigate the existence of mutations in the NR2E3 gene, which encodes a photoreceptor cell-specific nuclear receptor. METHODS: Fundus examinations, fluorescein angiography, colour vision tests, spectral sensitivity, and full-field and spectral electroretinography were performed. Mutation screening of the NR2E3 gene was performed with polymerase chain reaction (PCR) amplification and direct sequencing. RESULTS: We identified a novel homozygous mutation (c.1048C > T), that converts glutamine (CAA) to a termination codon (TAA) at amino acid position 350. The subject's unaffected parents were heterozygous for the mutation, consistent with autosomal recessive transmission. The electroretinographic findings revealed that the patient had neither rod nor 30-Hz flicker responses but did have cone responses with large a-wave and low b-wave amplitudes, similar to the rod-plus-cone responses, and also substantial short wavelength-sensitive (S) cone and extremely diminished long/middle wavelength-sensitive (L/M) cone responses. In the right eye, spectral sensitivity in the fovea revealed both functional S-cone and remarkably reduced L- and M-cone sensitivities, which was compatible with the decreased visual acuity (VA) and red/green colour vision defects noted in this eye. In contrast, the patient had good VA and normal red/green colour vision in the left eye. CONCLUSION: The nonsense mutation results in a truncated NR2E3 protein lacking 61 amino acids within the ligand-binding domain (LBD) that consists of 190 amino acids of the C-terminus end. Therefore, null function of the LBD is likely to cause ESCS in the patient. The clinical findings for this patient suggest that his left eye, with its functional L/M- and S-cones, was at an earlier stage of the syndrome than his right eye.