Conformational behavior of the HAV-VP3(110-121) peptidic sequence and synthetic analogs in membrane environments studied by CD and computational methods

The present study was undertaken to examine the structural features that may be important to explain the immunogenicity of the (110-121) peptide sequence (FWRGDLVFDFQV) of VP3 capsid protein of hepatitis A virus. A conformational analysis of the preferred conformations by CD and molecular mechanics was carried out. Present results suggest that the interaction with liposomes as biomembrane model induces and stabilizes the amphipathic beta-structure of the peptide. To study the contribution of amino acid replacements at the RGD tripeptide as well as the influence of the peptide chain length on peptide conformation, solid-phase peptide synthesis of several peptide analogs was carried out and the peptide conformation was studied using CD spectroscopy. The results show that the RGD sequence is necessary to induce the beta-structure in the presence of liposomes.     

Postural motor programming in paraplegic patients during rehabilitation

One of the basic aims in the rehabilitation of thoracic spinal cord injured (SCI) patients concerns the regaining of sitting posture control. This implies the development of new postural strategies requiring the adjustment of motor programming processes. The aim of this study was to investigate the time course of postural reorganization during active, clinical rehabilitation of thoracic SCI patients with different SCI levels. Thus changes in motor programming in sitting balance control were investigated in two groups of complete low or high thoracic SCI patients. At several stages during the rehabilitation process an experiment was held in which sitting posture was perturbed systematically using submaximal reaching movements over four reaching distances. This bimanual reaching task was presented as a visual precue choice reaction time (RT) task in which reaching distance (i.e. grade of postural perturbation) was precued. Results indicated that in both high and low thoracic SCI patients RTs in movements involving postural perturbation became shorter during the course of the rehabilitation period. However, low thoracic SCI patients were generally slower in the programming of balance perturbing movements than high thoracic SCI patients, a phenomenon that did not change over time. Furthermore, initial differences in RTs as a function of grade of postural perturbation disappeared in both groups in the course of the rehabilitation phase. Precue benefit, equally large for both groups, did not change as a function of rehabilitation time. It is concluded that the observed phenomena signify the gradual development of new central postural control processes in both SCI groups during rehabilitation. Low thoracic SCI patients, having more residual sensorimotor functions, seem to adopt more complex strategies in maintaining and restoring sitting balance that take longer to specify and to programme. High thoracic SCI patients seem to rely on simpler strategies using more passive postural support.     

HEp-2 cell-adherent Escherichia coli in patients with human immunodeficiency virus-associated diarrhea

Diarrhea occurs commonly in African human immunodeficiency virus (HIV) infections. A case-control (HIV-positive vs. -negative) study of adults with diarrhea was done in Lusaka, Zambia, to determine the prevalence of intestinal infection by HEp-2 cell-adherent Escherichia coli. Adherent E. coli were more common in HIV-positive patients with acute diarrhea than among HIV-negative controls (60% vs. 33%) and were found significantly more often in HIV-positive patients with chronic diarrhea than among HIV-negative controls with chronic diarrhea (79% vs. 17%, P < .002). Adherent strains were found significantly more often among HIV-positive patients (69%) than in 22 asymptomatic subjects (36%, P < .02). The HEp-2 cell adherence of the E. coli strains did not show a common pattern. Adherent bacteria were also observed in colonic biopsies from 32% of Zambians with chronic diarrhea who underwent endoscopy. Adherent E. coli may be an important cause of HIV-associated diarrhea in Zambia.     

Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors

BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years.     

National annual dioxin emissions estimate for hazardous waste incinerators

Reducing emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans, commonly known as dioxins, is a high priority for environmental regulatory bodies throughout much of the world. In the United States, Section 112 (c)(6) of the Clean Air Act (CAA) requires the Environmental Protection Agency (EPA) to identify and control emissions from sources that are responsible for at least 90% of the overall emissions of seven targeted hazardous air pollutants, including dioxins. On April 19, 1996, the EPA proposed Maximum Achievable Control Technology (MACT) Standards for Hazardous Waste Combustors (HWCs). In that preamble, the EPA estimated annual dioxin emissions from the nation's hazardous waste incinerators (HWIs) to be 79 grams expressed as 2,3,7,8 tetrachloro dibenzo-p-dioxins (TCDD) international toxic equivalents (ITEQs). However, early EPA dioxin emission estimates from medical waste incinerators and cement kilns were significantly overestimated; so, the following independent national dioxin emissions estimate for HWIs was prepared. This estimate corrects the errors in the EPA's HWI emissions database, uses an updated inventory of HWIs in the United States, and applies statistical imputation techniques that take maximum advantage of the limited dioxin emissions data for HWIs.     

Conditional reasoning with inducements and advice

In an earlier study of conditional reasoning, Newstead et al. [Newstead, S.E., Ellis, C.E., Evans, J.St.B.T., Dennis, I., (1997). Conditional reasoning with realistic material. Thinking and Reasoning 3, 49-96] found that people drew more inferences from conditionals framed as inducements (threats and promises) than from conditionals phrased as advice (tips and warnings). The present study was designed to test the hypothesis that this difference arose from the fact that the speaker of an inducement is normally seen to have control over the consequent event whereas the giver of advice does not. In the experiment reported here, inducement and advice conditionals were constructed in brief contexts such that in either case the speaker could be seen to have high or low control. Participants drew many more conditional inferences of all kinds for high control than for low control conditionals in either context. A second finding of interest was that participants drew many more forward (antecedent to consequent) inferences than backward inferences with these kinds of realistic conditionals.     

A survey of mental health consumers' and family members' involvement in advocacy

As the service delivery system is redesigned, the involvement of consumers and family members in mental health policy-making is essential. Advocacy is a way for them to have an impact on policy or decision-making. To determine the extent of their participation in advocacy efforts, consumers and family members were surveyed by other consumers and family members about their involvement in advocacy and mental healthcare reform. Although more family than consumers reported receiving mental healthcare reform information, both groups had difficulty understanding this information. Consumers were more likely to have received information from a mental health professional while family were more likely to have received information from an advocacy group. Lack of economic resources and communication problems were the most often cited barriers to advocacy for consumers. Strategies are suggested for how to increase involvement of consumers and family in advocacy efforts. The limitations of conducting a state-wide study with consumers and family as data collectors is discussed.     

Inhibition of diabetic nephropathy by a GH antagonist: a molecular analysis

Streptozotocin-treated C57B1/SJL mice developed glomerular hypertrophy and light microscopic lesions mimicking human diabetic glomerulosclerosis. In contrast, there were no glomerular hypertrophy and lesions in diabetic mice transgenic (TG) for a mutated growth hormone (bGH-G119K) that competes with native endogenous GH and results in dwarfism. We examined the molecular events underlying these findings. The non-transgenic (non-TG) diabetic mouse glomeruli had an increase in mRNA coding for alpha 1IV collagen, laminin B1, TGF-beta 1, 72 kDa collagenase, and TIMP-3. In contrast, glomerular type IV collagen and laminin B1 mRNA levels were normal in diabetic TG dwarf mice. However, the 72 kDa gelatinase, TIMP-3, and TGF-beta 1 mRNAs were elevated in the diabetic dwarfs. Type IV collagen and laminin accumulated in the glomeruli of diabetic non-TG, but not of diabetic dwarf mice, by immunofluorescence microscopy, confirming the mRNA data. GH binding protein mRNA levels were comparable in glomeruli from dwarf and non-TG mice, both diabetic and non-diabetic. We did not detect GH receptor mRNA in glomeruli. These data suggest that diabetic glomerulosclerosis is associated with an increase in type IV collagen and laminin synthesis, and that these changes do not occur in mice transgenic for bGH119K, a functional antagonist of GH. The increase of 72 kDa gelatinase, TIMP-3 and TGF-beta 1 mRNAs, independent of GH, suggested that these changes induced by hyperglycemia were not sufficient for the induction of glomerulosclerosis.     

Vitamin E modifies neither fructosamine nor HbA1c levels in poorly controlled diabetes

OBJECTIVE: To examine the effects of vitamin E on total serum protein glycation (fructosamine), hemoglobin glycation (HbA1c), and serum levels of glucose, total cholesterol, triglycerides, LDL-C, HDL-C, apolipoprotein A1 and apolipoprotein B. MATERIAL AND METHODS: Sixty poorly controlled diabetic patients were randomly assigned to receive either 1200 mg/day of vitamin E or identical placebo capsules during a two month period following a double blind cross-over design with a four week wash-out period between regimens. RESULTS: Seven patients were excluded from the study because of reasons not related to the medication. In the remaining 53 patients, the levels of serum glucose, fructosamine, HbA1c, total cholesterol, HDL-C, LDL-C, Apo A1 and Apo B did not vary significantly with vitamin E as compared with placebo. CONCLUSIONS: No significant effects of vitamin E on any of the parameters evaluated were observed in poorly controlled diabetic patients.