Identification of the blood-borne somatotroph-differentiating factor during chicken embryonic development

Somatotrophs become a significant population by day 16 of chicken embryonic development. We have previously demonstrated that an earlier induction of GH cell differentiation is possible with the addition of day 16 embryonic serum to cultures of day 12 pituitary cells, an age when somatotrophs are rare. The present study was designed to identify the blood-borne signal(s) responsible for the serum activity, using reverse hemolytic plaque assays to identify individual GH-secreting cells. The activity was found to be a heat-stable, ether-soluble compound(s) that is bound or inhibited by a trypsin-sensitive protein. The extent of GH cell differentiation was greater (P < 0.05; n = 3) in response to the ether phases of heated day 16 (14.1 +/- 0.4% of all cells) and day 12 sera (9.3 +/- 0.4%) than with untreated serum from days 16 and 12 (6.1 +/- 0.4% and 0.82 +/- 0.4%, respectively). Furthermore, ether-extracted day 16 serum was more effective than ether-extracted day 12 serum, which was also different from basal (0.85 +/- 0.4%; P < 0.05). Based on this biochemical profile, the abilities of various steroids to stimulate differentiation were tested. Three steroids were found to stimulate somatotroph differentiation in vitro: 17beta-estradiol, corticosterone, and progesterone. However, the estradiol receptor antagonist, tamoxifen, while abolishing the effect of estradiol, had no effect on the induction of differentiation by day 16 serum. In contrast, RU486, a specific glucocorticoid receptor antagonist in chickens, blocked the stimulatory effects of corticosterone, progesterone, and day 16 serum on somatotroph differentiation. We next tested whether the active compound in day 16 embryonic serum was corticosterone, the predominant glucocorticoid in chickens. Incubation of day 16 serum with corticosterone antiserum, but not control antiserum, suppressed day 16 serum-induced GH cell differentiation. Therefore, we conclude that corticosterone is the blood-borne signal capable of stimulating somatotroph differentiation in vitro. The present findings together with previous reports indicate that somatotroph differentiation during embryonic development may result from an increase in circulating glucocorticoid concentrations.     

An empirical study of information technology enabled business process redesign and corporate competitive strategy

Business process redesign (BPR) has been widely touted as a means for leveraging the power of information technology to change business processes radically, resulting in substantial improvements in organizational effectiveness and efficiency. This study represents an early attempt at examining the strategic nature of the phenomenon. Because BPR is radical change and has the ability to alter both the competitive and operational nature of the corporation, it is critical that BPR be coordinated with corporate strategy. Through a survey of information system executives, the relationships between corporate competitive strategy and three types of BPR – intrafunctional, interfunctional and interorganizational – were examined. It was found that organizations following a cost strategy tended to do more BPR projects on interfunctional processes. Furthermore, the positive effect of a cost strategy on interfunctional BPR was found to be strengthened by the degree of integration of IS and business planning. It was also found that while interorganizational BPR was not related to a specific strategy, it was strongly related directly with IS–business planning integration.     

Screening demand-side management programs with a value-based test

A value-based test is presented for economic screening of electric utility demand-side management (DSM) programs. The widely used least cost test is valid if the programs do not alter the amount or value of energy services provided to customers. But, in general, DSM programs have such effects and, as a result, the value consumers receive is changed. A more general economic efficiency test, the most value test, provides a practical method for considering the effects of DSM on customer value. The version presented allows for multiple load periods and can account for rate impacts on several customer classes. Four typical DSM programs are evaluated as illustrations     

Enhancing effect of natural killer cell stimulatory factor (NKSF/interleukin-12) on cell-mediated cytotoxicity against tumor-derived and virus-infected cells

Natural killer cell stimulatory factor (NKSF) or interleukin-12 (IL-12) is a heterodimeric cytokine with pleiomorphic effects on T and NK cells, including induction of lymphokine production, mitogenesis, and enhancement of spontaneous cytotoxic activity. Similarly to IL-2, NKSF/IL-12 enhances NK cell-mediated cytotoxicity within a few hours and independently from induced proliferation. This effect is independent from other induced cytokines, because it is not prevented by antibodies neutralizing interferon (IFN)-alpha, IFN-beta, IFN-gamma, IL-2 or tumor necrosis factor (TNF)-alpha and, unlike the induction of IFN-gamma production by peripheral blood lymphocytes, it does not require HLA class II-positive accessory cells. Enhanced cytotoxicity is accompanied by morphologic changes in NK cells, including a significant increase in the number of cytoplasmic granules. In addition to the previously described ability to enhance the cytotoxic activity of NK cells against tumor-derived target cells, NKSF/IL-12 is also a potent stimulator of cytotoxicity against virus-infected cells, either fibroblasts acutely infected with herpes viruses or T cell lines chronically infected with human immunodeficiency virus-1. NK cell-mediated antibody-dependent cytotoxicity or anti-CD16 antibody-redirected lysis is not significantly enhanced by NKSF/IL-12. However, the ability of resting peripheral blood T cells to mediate anti-CD3 antibody-redirected lysis is enhanced by 18-h incubation with NKSF/IL-12, indicating that this lymphokine can modulate the cytotoxic capability of both NK and T cells.     

Evidence for disturbed S-adenosylmethionine : S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions?

BACKGROUND: Elevated homocysteine concentrations have been associated with premature arteriosclerosis and with impairment of key methylation reactions through accumulation of the homocysteine metabolite S-adenosylhomocysteine. In end-stage renal failure high homocysteine concentrations are commonly found but thus far the concentrations of related adenosylated metabolites in plasma have not been assessed. METHODS: In this prospective study we determined plasma homocysteine and related metabolites in 25 patients on regular haemodialysis, and in 40 healthy volunteers. Blood samples from patients were drawn immediately before and in 10 patients additionally after the dialysis session. RESULTS: Folic acid and vitamin B12 in plasma were similar in patients (mean +/- SEM 25+/-2 nmol/l and 400+/-41 pmol/l respectively) and controls (24+/-3 and 324+/-23 respectively). In patients plasma homocysteine, S-adenosylmethionine and S-adenosylhomocysteine were markedly elevated (36.6+/-3.6 micromol/l, 381+/-32nmol/l and 1074+/-55 nmol/l respectively) compared to the control values (6.8+/-0.4 micromol/l, 60+/-3 nmol/l and 24.4+/-1.1 nmol/l respectively) whereas the molar ratio of plasma S-adenosylmethionine and S-adenosylhomocysteine was significantly decreased (0.36+/-0.02 and 2.7+/-0.2 in patients and controls respectively). Haemodialysis failed to normalize the abnormal levels of these metabolites. CONCLUSION: Since the ratio of S-adenosylmethionine : S-adenosylhomocysteine is closely linked to the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients.     

Fluconazole versus itraconazole for candida esophagitis in acquired immunodeficiency syndrome. Candida Esophagitis

BACKGROUNDS & AIMS: Contrasting opinions exist about the pharmacological treatment of esophageal candidiasis in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to assess the long-term efficacy of fluconazole and itraconazole treatment. METHODS: This study evaluated 2213 human immunodeficiency virus-positive patients at first episode of esophageal candidiasis diagnosed by endoscopy; 1105 received fluconazole and 1108 received itraconazole. The endoscopic and clinical response to treatment was assessed periodically until the end of the follow-up period (1 year). RESULTS: At week 2, endoscopic cure occurred in 81.2% of patients treated with fluconazole and in 65.6% of patients treated with itraconazole (P < 0.001). Clinical cure was observed in 81.5% of patients treated with fluconazole and in 75.2% of patients treated with itraconazole (P < 0.001). At the end of the follow-up period, endoscopic and clinical cure were observed in 96% of patients treated with fluconazole and in 95.6% of patients treated with itraconazole (P = 0.788), with similar differences by intention-to-treat analysis (93.6% vs. 93.3%; P = 0.853). Treatment failure was observed in 22.3% of fluconazole-treated patients and in 26.6% of itraconazole-treated patients (P = 0.022). CONCLUSIONS: Fluconazole and itraconazole are provided with good long-term therapeutic efficacy in the treatment of Candida esophagitis in patients with AIDS. Fluconazole is associated with a higher rate of cure than itraconazole in short-term treatment.