Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH.

To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.     

Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA: Implication for L‐DOPA‐induced dyskinesia in Parkinson's disease

The medial globus pallidus plays a crucial role in generation of L‐DOPA‐induced dyskinesia in patients with Parkinson's disease. The 6‐hydroxydopamine‐lesioned rat exhibiting behavioral sensitization to L‐DOPA is one useful animal model for examining L‐DOPA‐induced dyskinesia. To determine neuropathological abnormality responsible for behavioral sensitization, the medial globus pallidus and the substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA were examined. Intermittent L‐DOPA treatment induced hypertrophy of the lesioned‐side of medial globus pallidus and substantia nigra reticulata of 6‐hydroxydopamine‐lesioned rats with behavioral sensitization to L‐DOPA. Additionally, coadministration of a 5‐HT_1A receptor agonist, 8‐hydroxy‐2(di‐n‐propylamino)tetralin with L‐DOPA, alleviated the hypertrophy with improvement of the behavioral sensitization. These results suggest that hypertrophy of the medial globus pallidus and substantia nigra reticulata is associated with induction of behavioral sensitization to L‐DOPA in 6‐hydroxydopamine‐lesioned rats. Therefore, neuropathological changes corresponding to hypertrophy might underlie L‐DOPA‐induced dyskinesia in patients with Parkinson's disease.     

CT findings in panacinar emphysema]

We analyzed the CT images (in vivo) of 5 lobes (right middle lobe, 1; left lower lobe, 1; right lower lobe, 3) with panacinar emphysema (PAE) obtained at autopsy or thoracotomy for solitary lung tumor. The lobes were inflation-fixed by the method of Heitzman and sliced axially for a CT-pathologic correlative study. One lobe with mild PAE had normal appearance on CT; however, the other four lobes with PAE demonstrated low-attenuation areas (LAAs) of various shapes and sizes on CT. LAAs were locally distributed on CT slices in one lobe, dominant in the inner zones in two lobes, and diffuse in one lobe. Relatively normal to diminished vasculature was observed within the LAAs of four lobes. These CT findings differed significantly from those of centriacinar emphysema (CAE) as reported in other studies. We conclude that CT is useful in the clinical diagnosis of PAE and its differentiation from CAE.     

A new method for the quantification of beta-glucan in plasma and its application in the diagnosis of postoperative infection

In order to correctly diagnose and treat severe postoperative infections, it may be critical to detect and differentiate between endotoxin derived from Gram-negative bacteria and/or beta-glucan derived from fungi. In addition to the chromogenic assay, the turbidimetric kinetic assay has been performed for the quantification of endotoxin in plasma using Limulus amebocyte lysate as previously reported. However, it is also known that beta-glucan triggers the coagulation of Limulus amebocyte lysate. In the present study, the differentiation of beta-glucan from endotoxin and its clinical application were studied. Endotoxin was able to be inactivated in plasma using one-tenth dilution by 10 per cent ethanol or distilled water, followed by heating at 100 degrees C for 120 min, without affecting the activity of coexisting beta-glucan. The treated sample was then subjected to the turbidimetric kinetic assay using Toxinometer ET-201. Using this method, as little as 30 pg/ml of beta-glucan in the plasma may be assayed separately, with the amount of circulating beta-glucan in the plasma of normal subjects being less than 50 pg/ml. On the other hand, in patients with a fungal infection, the amount of beta-glucan in their plasma was elevated significantly. Clinically, beta-glucanemia may often occur in severe postoperative infection even if fungi are not detected.     

Expression of Lewis Y (Ley) Antigen in Human Anagen Hair Follicles

Lewis Y (Le^y) antigen, a difucosylated tetrasaccharide found on type 2 blood group oligosaccharides of glycolipids and glycoproteins, is thought to be a phenotypic marker predictive of cell differentiation. The distribution of this antigen in human anagen hair follicles was examined by immunohistochemical staining using a monoclonal antibody (AH-6) to Le^y. In the bulbar and suprabulbar portion of anagen hair follicles, Le^y antigen was detected in the three layers of the inner root sheath. Subsequently, the positive staining became translocated to the innermost layer of the outer root sheath in the middle part of the hair follicles. In the upper portion of the hair follicles, Le^y antigen was found in the outer cells of the outer root sheath. These findings suggested that the expression of Le^y antigen in the anagen hair follicles was correlated with the processes of keratinization or terminal differentiation.     

Anorexia nervosa with neutropenia--response of neutrophils to G-CSF]

A 50-year-old woman with anorexia nervosa was admitted for evaluation of neutropenia (WBC 1,600/microliters). Her bone marrow was gelatinous, and myeloid cells had decreased. Homogeneous substance deposited in the marrow, stained by alcian blue (pH 2.5), indicative of acid mucopolysaccharides. CFU-G and CFU-GM were decreased in number and myeloid pool in the bone marrow also decreased. Anti-neutrophilic antibody was negative. Neutropenia may be related to myeloid hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells in the bone marrow under long-term mal-nutritional state. Neutrophils markedly increased by administration of rhG-CSF 5.0 micrograms/kg/day for 14 days without the first peak. Serum G-CSF level did not increase (less than 60 pg/ml). It is effective to administer G-CSF to anorexia nervosa with neutropenia.     

Vasodilator effects of C-type natriuretic peptide on cerebral arterioles in rats

The vasodilator effects of C-type natriuretic peptide (CNP) were investigated in isolated rat cerebral arterioles. CNP caused dose-dependent vasodilation, maximally by 10.0±2.2% at 10⁻⁶ M. The median effective concentration (EC₅₀) was 5.2×10⁻¹⁰ M. In contrast, atrial natriuretic peptide and B-type natriuretic peptide, other members of the natriuretic peptide family, produced little or no vasodilation. Pretreatment with methylene blue (10⁻⁴ M) abolished CNP-induced vasodilation, whereas pretreatment with N^G-monomethyl-

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-arginine or indomethacin did not inhibit vasodilation. Thus, CNP is suggested to cause significant vasodilation in cerebral arterioles via a cyclic guanosine monophosphate-dependent mechanism. © 1997 Elsevier Science B.V. All rights reserved.     

Cyclosporine overcomes cold preservation/reperfusion injury of liver graft: Chemokine release and liver ultrastructure

There is a growing body of evidence that the cytokine, tumor necrosis factor-α (TNF-ga), plays an important role in the development of hepatic ischemia/reperfusion injury. We found that the immunosuppressants, cyclosporine-A (CsA), azathioprine, and FK506, have protective effects on such injury. The purpose of the present study was to elucidate mechanisms involved in these beneficial effects of the immunosuppressant, CsA, on liver injury following cold preservation and transplantation, with special reference to the suppression of TNF-α release. Rat livers were stored in Euro-Collins solution (EC) at 4°C for 6h and orthotopically transplanted. The animals allotted to two groups: group A (untreated controls) and group B (CsA pretreatment of recipients). CsA (10 mg/kg, p.o.) was given for 3 consecutive days preoperatively. CsA pretreatment of the recipients significantly improved the 2-week survival rate (0/6 for group A, 3/6 for group B;P<0.05) and this was associated with a significant decrease in serum TNF-α levels 2h posttransplantation (group A, 69.8±15.7 pg/ml; group B, 22.8±6.8; mean±SEM;n=12 each;P<0.05) and amelioration of sinusoidal endothelial injury, assessed by electron microscopy. Plasma endotoxin levels following reperfusion of the grafts were not altered by the CsA therapy. Morphologically, CsA pretreatment of the recipients did not alter activation of Kupffer cells. CsA pretreatment of the recipient aids in preventing cold preservation/reperfusion injury of the liver graft, possibly by modulating effects of TNF-α.     

A case-control study on factors relating to discontinuation of domiciliary care for the bedridden elderly in a metropolitan area]

A case-control study was conducted to examine factors relating to discontinuation of domiciliary care for the bedridden elderly in Shinagawa-ku, Tokyo. Cases were bedridden residents aged 65 years and over who had abandoned home care and applied for admission to live in a special nursing home for the aged between April and September in 1990 after being recipients of welfare allowances for disabled elderly. Controls were bedridden residents who continued to be given home care and matched to cases by sex, age and beginning month of the receiving of allowances. Among 50 cases and 94 controls interviewed, we obtained responses from 31 cases (62%) and 60 controls (64%). The main results were as follows: 1. During the home-care period, ADL (activities of daily living) of cases, especially walking ability, deteriorated more severely than in controls. Night delirium also appeared more frequently in cases. 2. The primary caregivers of cases were older than those of controls. Remarkable differences between cases and controls were observed in the family structure, the number of family members and the number of sub-caregivers. Cases tended to live alone or live with a spouse only, and with smaller number of family members and caregivers. 3. Case lived more frequently in houses with small numbers of rooms and without rooms of their own. 4. As regards utilization of domiciliary care services, cases used dispatch of home helpers more frequently and used day services less frequently.