Mixed connective tissue disease--various neuromuscular complications prior to the elevation of antibody to RNP]

A 47-year-old woman with mixed connective tissue disease (MCTD) was reported. She developed various neuromuscular complications including carpal tunnel syndrome, narrowing of visual field, dysesthesia on face and extremities and weakness before elevation of antibody to RNP. On the examination of biopsied specimens of muscle and peripheral nerve, myositis and demyelination were suspected, respectively. Electroencephalography showed diffuse slowing which was without clinical evidence of the central nervous system involvement and was normalized by the treatment with prednisolone. Present case seems to provide some insights into the neuromuscular complications in MCTD.     

A case of bladder transitional cell carcinoma with sigmoidovesical fistula due to diverticulitis

We present a case of bladder transitional cell carcinoma with sigmoidovesical fistula due to diverticulitis. The patient was a 65-year-old male who had been suffering from recurrent abdominal pain with high fever for the past 6 months. He noticed pneumaturia and cloudy urine several times. He visited a doctor complaining of macroscopic hematuria and high fever, and was treated under the diagnosis of acute prostatitis. In our University Hospital cystoscopy showed a papillary bladder tumor. Pathological study of the tumor revealed transitional cell carcinoma, grade II, noninvasive type. Multiple diverticulosis of sigmoid colon was identified with barium enema examination. We performed transurethral resection of the bladder tumor. Three weeks later, the sigmoidovesical fistula was treated by primary resection of the sigmoid colon and wedge resection of the bladder including fistula.     

Hypersensitivity of skin fibroblasts from patients with chronic actinic dermatitis to ultraviolet B (UVB), UVA and superoxide radical.

The sensitivity of fibroblasts derived from patients with chronic actinic dermatitis (CAD) ultraviolet B (UVB), UVA and superoxide radical was examined. Fibroblasts from the skin of 3 patients with CAD showed abnormal hypersensitivity after exposure to mid-UV (UVB) and near-UV (UVA) radiation in both the dividing and quiescent phases. In their dividing phases, the 3 cell strains (CAD1TO, CAD2TO and CAD3TO) exhibited 78, 55 and 82 J/m2 for the mean lethal dose (Do) values in UVB survival curves. In the quiescent phases their Do values were 262, 226 and 165 J/m2, respectively. Regarding UVA sensitivity, Do value in the dividing phases were 4.9, 3.9 and 3.8 x 10(4) J/m2, and in the quiescent phases, 2.0, 1.9 and 1.7 x 10(5) J/m2. Do values were lower than in the cell strains derived from healthy individuals (Do = 120 +/- 18 and 390 +/- 72 J/m2) for UVB sensitivity in the dividing and quiescent phases and (5.9 +/- 0.6) x 10(4) and (3.2 +/- 1.0) x 10(5) J/m2 for UVA sensitivity in the dividing and quiescent phases. DNA repair synthesis was similar between the cell lines. Furthermore, the 3 CAD cell lines showed a higher sensitivity to superoxide radical generated by hypoxanthine/xanthine oxidase treatment. These results suggest that patients with CAD may suffer from a defect in dealing with damage induced by oxygen radicals.     

In vitro effect of chlorpromazine on the mineralization of tooth germ in mice--comparison with that of retinoic acid and HEBP

Effects of chlorpromazine on the mineralization and alkaline phosphatase activity (ALP) in the tooth germ were examined and compared with those of retinoic acid and HEBP (1-hydroxyethylidene-1, 1-bisphosphonate). Mandibular first molars from 17-day-old mouse embryos were cultured with or without drugs. Calcium content and ALP in the tooth germ increased gradually from 0 to 7 days in culture, the increase of calcium being preceded by that of ALP. Retinoic acid suppressed increases of calcium and ALP in the tooth germ but not in the specimens precultured for 2 days, suggesting that retinoic acid inhibits the mineralization at an early developmental stage of the tooth. HEBP, a physiochemical inhibitor of mineralization, suppressed the increase of calcium, but significantly enhanced the increased of ALP in the tooth germ. Chlorpromazine, which has an antagonistic action towards calmodulin, also suppressed the increases of calcium and ALP in the tooth germ. Calmodulin antagonists W-7 and W-5 similarly suppressed the increases of calcium and ALP; W-5 had less effects on both calcium and ALP. These results indicate that calmodulin may be involved in the regulation of the mineralization in the tooth germ. These drugs are shown to possess different modes of inhibitory action on the mineralization.     

Induction of in vitro differentiation of mouse embryonal carcinoma (F9) cells by inhibitors of topoisomerases.

To investigate the possible involvement of topoisomerases in embryonal differentiation, we examined the effect of topoisomerase inhibitors on the in vitro differentiation of mouse embryonal carcinoma F9 cells. We found that camptothecin, teniposide (VM-26), or genistein, specific inhibitors of topoisomerases, induced morphological as well as biochemical changes (production of tissue plasminogen activator, synthesis of laminin, and disappearance of stage-specific embryonic antigen 1) specific to F9 cell differentiation. Since these changes were indistinguishable from those observed in F9 differentiation induced by retinoic acid (plus dibutyryl cyclic AMP), it was suggested that inhibition of cellular topoisomerase activities triggered F9 cell differentiation into parietal endoderm-like cells in the same manner as retinoic acid (plus dibutyryl cyclic AMP). Experiments using differentiation-resistant mutant F9 cell lines, however, indicated that the molecular cascade involved in topoisomerase inhibitor-induced differentiation involves different steps from those functioning in the retinoic acid-induced differentiation cascade.     

Enhanced replication of herpes simplex virus by hexamethylene bisacetamide.

Hexamethylene bisacetamide (HMBA) is a potent inducer of differentiation of tumor cells. The effect of HMBA on cell growth and replication of herpes simplex virus (HSV) was investigated in HEp-2 epidermal cells, IMR-32 neuronal cells, K562 myeloid cells, Daudi Burkitt lymphoma cells, and CCRF-CEM T-lymphoid cells. The growth of HEp-2 and IMR-32 cells was not affected by HMBA at concentrations from 0.5 through 2 mM. The growth of K562, Daudi, and CCRF-CEM cells was inhibited by HMBA at concentrations from 1 through 5 mM. When HSV-infected cells were incubated with 0.5 through 5 mM HMBA, a dose-dependent increase in virus yield was observed in HEp-2 and IMR-32 cells, but not in the other cell lines. These findings indicate that HMBA enhances the replication of HSV in epidermal and neuronal cells and that HMBA therapy may be responsible for the development of herpetic lesions.