Enhanced Incorporation of 1-β-D-Arabinofuranosylcytosine by Pretreatment with Etoposide

We examined the effects of timing of administration of etoposide on cytosine arab-inoside (ara-C) incorporation into DNA in L1210 ascites tumor. At 1 hr after injection of ara-C, 3-hr and 6-hr pretreatments with 15 mg/kg of etoposide increased ara-C incorporation to more than 200% as compared to that of ara-C given alone. Simultaneous administration of etoposide, however, decreased ara-C incorporation to 33% of that of ara-C alone. These results might explain the previously reported sequence dependency of the antitumor effect of etoposide and ara-C.     

Mother-to-child transmission of human T-lymphotropic virus type I (HTLV-I): An extended follow-up study on children between 18 and 22-24 years old in Okinawa,Japan

The significant difference observed between the seroprevalence of HTLV-I in adults and in children is as yet unexplained. To evaluate a hypothetical explanation of the existence of seroconversion cases of ?seronegative carriers”? for this phenomenon, 21 of 55 children who had been born to seropositive mothers and who remained seronegative until the age of 18 years were further followed up at the ages of 22 and/or 24 years. None of the 21 seronegative children born to seropositive mothers seroconverted, either at 22 years or at 24 years. In addition, the polymerase-chain-reaction (PCR) technique could not prove the existence of the HTLV-I provirus genome in peripheral mononuclear cells (PBMC) of 10 of these children. Our results fail to prove the possibility of viral latency of HTLV-I in mother-to-child transmission. Therefore, the hypothetical seroconversion of ?seronegative carriers”? after adulthood can not be an explanation.     

Enhanced Antitumor Efficacy of a Combination of CPT-11, a New Derivative of Camptothecin, and Cisplatin against Human Lung Tumor Xenografts

The objective of this study was to evaluate the antitumor efficacy of combined use of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carhonyloxycamptothecin (CPT-11) and cisplatin (CDDP). The antitumor activities of CPT-11, CDDP and their combination against 3 human lung tumor xenografts were estimated using congenitally athymic BALB/c ( nu/nu ) mice. The doses were 47 mg/kg for CPT-11 and 6 mg/kg for CDDP on days 1, 5 and 9. In combination therapy, half of the single dosage of each agent was used. The doses were administered intraperitoneally. The antitumor activity and toxicity were evaluated in terms of the tumor volume and body weight change of mice, respectively. The combination therapy resulted in a statistically significant tumor regression compared to the use of only CPT-11 or CDDP in two tumor xenografts out of three. The toxicity of the combination therapy was no higher than that of CPT-11 or CDDP alone. These results suggest that the antitumor activity of the combination of CPT-11 and CDDP is superior to that of CPT-11 or CDDP alone.     

DNA Damage and Cell Killing by Camptothecin and Its Derivative in Human Leukemia HL-60 Cells

Camptothecin (CPT) has heen recognized as a topoisomerase I (Topo I) inhibitor. However, the mechanism of cytotoxicity of this agent remains unknown. In the present study, we analyzed the kinetics of Topo I-mediated DNA single-strand breaks and internucleosomal DNA cleavage produced by CPT and its derivative, 7-ethyl-10-hydroxycamptothecin (SN-38), in HL-60 cells. DNA single- strand breaks were detected using alkaline sucrose gradient centrifugation when HL-60 cells were incubated with 10 μM CPT or 10 μM SN-38 for 30 min. These DNA single-strand breaks were rapidly repaired after drug removal, while the cytotoxic action of these drugs was sustained. Treatment of HL-60 cells with CPT or SN-38 for 3 h produced extensive degradation of DNA. Agarose gel electrophoresis showed a ladder of DNA fragments consisted of multimers of approximately 200 base pairs, characteristic of apoptosis. Interestingly, this type of DNA fragmentation was also induced within 4 h after repair of DNA single-strand breaks, and subsequently loss of cell viability was observed. When zinc ion, a potent inhibitor of endonuclease, was added to drug-free medium after treatment with CPT or SN-38, internucleosomal DNA cleavage was abolished. Furthermore, addition of zinc ion reduced the loss of cell viability. These data suggest that Topo I-mediated DNA single-strand breaks may be necessary but are not sufficient for cell death, and the endonuclease involved in induction of internucleosomal DNA cleavage may play an important role in HL-60 cell death induced by Topo I inhibitor.     

HLA associations in otosclerosis in Japanese patients

Otosclerosis is a disease of the otic capsule that is caused by abnormal resorption and redeposition of bony tissue. Sixty-two unrelated Japanese patients exhibiting clinical otosclerosis were typed for HLA-A, -B,-C antigens. Twenty-one of the patients were also typed for DR antigens. The frequency of HLA-Aw33 was significantly higher in otosclerosis patients than in the control group (24.2% vs 9.5%). This finding suggests that the presence of HLA-Aw33 antigens may be related to an increased susceptibility to otosclerosis or to its clinical outcome.     

A Pelvic Retroperitoneal Schwannoma Arising in the Right Paracolpium

Nerve sheath tumors of the retroperitoneum are infrequently reported. In this paper, a rare case of a benign pelvic retroperitoneal schwannoma arising in the right paracolpium is presented. Preoperatively, magnetic resonance imaging revealed a solid tumor beside the vaginal canal with a clear margin. The tumor could be completely resected by the transvaginal approach and was diagnosed to be a benign schwannoma of the Antoni A type with palisade arrangement. The patient had no symptoms of motor or sensory disturbances after surgery.     

Influence of upright activity on plasma renin activity and aldosterone concentration in children

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 156 healthy infants and children under basal conditions of normal diet and recumbency. PRA and PAC were also evaluated during and after stimulation of the renin-angiotension-aldosterone system by postural change. Basal values of PRA significantly declined with increasing age. Postural change by standing up resulted in an increase of PRA and PAC in all age groups. The increment of PRA but not of PAC was greater in older than in younger children. Neither the basal nor the stimulated levels of PRA and PAC were influenced by sex, body weight, body surface area, serum sodium, serum potassium, creatinine, and 24-h urine secretion of sodium and potassium. Both PRA and PAC returned to the basal levels within 60 min after resuming recumbent posture.