Induction of apoptotic nuclei by interferon-gamma and by predesquamin in cultured keratinocytes

Predesquamin is a glycoprotein found in the transition layer and the lower stratum corneum of human epidermis. Interferon-gamma (IFN-gamma) induces the synthesis of predesquamin by keratinocytes in culture. We now show ultrastructurally that exogenous addition of either predesquamin or IFN-gamma to cultured keratinocytes induces apoptotic nuclei with condensed chromatin. Degradation of cellular DNA is also evident as a ladder pattern in an agarose gel. After incubation with both predesquamin and IFN-gamma (but not either alone), the mobility of plasmid DNA in a gel shows retardation specific for guanine residues. This binding to the DNA may impart to it a conformational change that facilitates access by endogenous cellular nucleases. In epidermal cells cultured with IFN-gamma supplementation, we also show by RT-PCR that there is an upregulation of the genes c-myc, p53, gadd45, dsRNA-activated protein kinase, and 2'-5'-oligo(A)-dependent RNase, which have all been implicated in apoptosis in other cell types. These results are pertinent to the mechanism of occurrence of apoptosis in the epidermis in vivo, where predesquamin and IFN-gamma are endogenous. Programmed cell death is an inherent step in the terminal differentiation and desquamation of the epidermis.     

Calbistrins, novel antifungal agents produced by Penicillium restrictum. I. Production, taxonomy of the producing organism and biological activity

Over a 14-year period, from 1971 to 1985, there were 15 patients referred to the Princess Margaret Hospital in Toronto for postoperative radiotherapy to the cervical lymph nodes following radical neck surgery for metastatic cancer. An intensive investigation failed to yield a primary site in any patient. All of the patients had extensive neck disease with significant indications for postoperative radiotherapy (massive neck nodes, invasion of extra nodal structures or fixation to unresectable adjacent structures). Of this highly selected group of patients with advanced neck disease: 4/15 (27%) died within one year of uncontrolled local disease, a further 2/15 (13%) died within four years of metastatic/recurrent disease, 6/15 (33%) died of intercurrent disease and 3/15 (20%) were alive with at least four years follow-up. Although all patients presented with advanced disease, survival and significant palliation was possible in this select group of patients.     

Functional development of the neonatal rat retinotectal pathway

Electrophysiological activity in the neonatal rat superior colliculus was recorded to measure neuronal and synaptic activity, and, therefore, functional development. Neonatal rat pups were studied from five days to two weeks of age. The earliest activity in the superior colliculus were spontaneous discharges at a frequency of one unit per animal on postnatal day 6 (P6). Spontaneously discharging units were more numerous at P8, and the number peaked on P10. The first clear response to optic nerve stimulation was seen on P10, with relatively long and variable latencies. By P14, electrically evoked responses had much shorter latencies. The results are in line with the first response to light flash in the superior colliculus at P12/13. The evidence suggests that functional development of the rat retinotectal pathway begins at the end of the first week after birth, and that much of the functional maturation occurs mainly during the second week after birth.     

Abortion patients in 1994-1995: characteristics and contraceptive use

Results of a 1994-1995 national survey of 9,985 abortion patients reveal that women who live with a partner outside marriage or have no religious identification are 3.5-4.0 times as likely as women in the general population to have an abortion. Nonwhites, women aged 18-24, Hispanics, separated and never-married women, and those who have an annual income of less than +15,000 or who are enrolled in Medicaid are 1.6-2.2 times as likely to do so; residents of metropolitan counties have a slightly elevated likelihood of abortion. When age is controlled, women who have had a live birth are more likely to have an abortion than are those who have never had children. Catholics are as likely as women in the general population to have an abortion, while Protestants are only 69% as likely and Evangelical or born-again Christians are only 39% as likely. Since 1987, the proportion of abortions obtained by Hispanic women and the abortion rate among Hispanics relative to that for other ethnic groups have increased. The proportion of abortion patients who had been using a contraceptive during the month they became pregnant rose from 51% in 1987 to 58%. Nonuse is most common among women with low education and income, blacks, Hispanics, unemployed women and those who want more children. The proportion of abortion patients whose pregnancy is attributable to condom failure has increased from 15% to 32%, while the proportions reporting the failure of other barrier methods and spermicides have decreased.     

Long-term outcome of adult-onset minimal-change nephropathy

BACKGROUND: Adult-onset minimal-change nephropathy has been associated with a slower response to corticosteroids and a less benign prognosis when compared to children. However, there are few long-term outcome data reported. METHODS: We have reviewed retrospectively 51 idiopathic adult-onset minimal-change nephropathy patients investigated and treated at a single centre. RESULTS: Male to female ratio was 1:1.4, mean age at diagnosis was 37 years, and average length of follow-up was 14.1 years. Significant comorbidity was identified in 33%. A raised serum creatinine was found in 55% but returned to normal almost invariably upon remission. At presentation, hypertension was found in 47% of patients, microscopic haematuria in 33%, hypercholesterolaemia and hypertriglyceridaemia in 96%, and hyperuricaemia in 42%. Remission (complete or partial) was achieved by 46, 70 and 92% within 4, 8 and 21 weeks respectively, in patients treated with steroids; steroid resistance was encountered in 8%. The time to remission was positively correlated with age (P = 0.002) and initial albumin level (P = 0.005), and negatively correlated to the number of subsequent relapses (P = 0.029); 33% of patients had a spontaneous remission at some time during the disease course. Patients with multiple relapses were treated with cyclophosphamide and 63% of them had remained in remission after 5 years. Hypertension was present in 25% of patients after an average interval of 11 years. At the time of the final follow-up, only three patients had a raised creatinine and all but three patients were in complete remission. CONCLUSIONS: Adult-onset minimal-change nephropathy shares the same good long-term outcome as the childhood counterpart, with sustained remission and preserved renal function.