3-Hydroxy-3-methylglutaryl-CoA reductase gene of Gibberella fujikuroi: isolation and characterization

PURPOSE: Cardiovascular disease is a major cause of morbidity and death in non-insulin-dependent diabetes mellitus (NIDDM). While hyperglycemia is clearly related to diabetic microvascular complications, it contribution to large-vessel atherosclerosis is controversial. PATIENTS AND METHODS: We performed an analysis of the association between glycemic control and prevalent cardiovascular disease in 1,539 participants in the NIDDM Patient Outcomes Research Team study who were under usual care in a health maintenance organization. Prevalent cardiovascular disease and its risk factors were identified by self-administered questionnaire. Cardiovascular disease was defined by the presence of coronary heart disease, peripheral vascular disease, and/or cerebrovascular disease. Glycohemoglobin and lipid levels were obtained from a computerized laboratory database. RESULTS: The mean age of participants was 63 years (range 31 to 91); 51% were women. The mean duration of NIDDM was 9 years (range < 1 to 50), 35% took insulin, and 48% took sulfonylureas. Mean glycohemoglobin was 10.6%. Sixty percent had hypertension, 16% currently smoked cigarettes, and the mean total high-density lipoprotein (HDL) cholesterol ratio was 5.7. Fifty-one percent had cardiovascular disease. Cardiovascular disease prevalence remained constant across increasing quartiles of glycohemoglobin for both men and women. In contrast, prevalent cardiovascular disease was associated with established cardiovascular disease risk factors including age (67 versus 59 years, P < 0.0001), hypertension (66% versus 54%, P < 0.0001), current cigarette smoking (17% versus 13%, P < 0.005), and total/HDL cholesterol ratio (5.9 versus 5.6, P < 0.005). Cardiovascular disease was also associated with duration of NIDDM (11 versus 8 years, P < 0.0001). In multiple logistic regression analysis controlling for established cardiovascular disease risk factors and diabetes duration and therapy, glycohemoglobin remained unassociated with cardiovascular disease. CONCLUSIONS: Glycemic control is not associated with prevalent cardiovascular disease in this large population of individuals with NIDDM. Conventional cardiovascular disease risk factors are independently associated with cardiovascular disease and be a more promising focus for clinical intervention to reduce atherosclerotic complications in NIDDM.     

Cooperative thermal transitions of bovine and human apo-alpha-lactalbumins: evidence for a new intermediate state

The thermal denaturation of bovine and human apo-alpha-lactalbumins at neutral pH has been studied by intrinsic protein fluorescence, circular dichroism (CD), and differential scanning microcalorimetry (DSC) methods. Apo-alpha-lactalbumin possesses a thermal transition with a midpoint about 25-30 degrees C under these conditions (pH 8.1, 10 mM borate, 1 mM EGTA), which is reflected in changes in both fluorescence emission maximum and quantum yield. However, the CD showed a decrease in ellipticity at 270 nm with a midpoint at about 10-15 degrees C, while DSC shows the transition within the region of 15-20 degrees C. The non-coincidence of transition monitored by different methods suggests the existence of an intermediate state in the course of the thermal denaturation process. This intermediate state is not the classical molten globule state which occurs at higher temperature (i.e. denatured state at these conditions) [D.A. Dolgikh, R.I. Gilmanshin, E.V. Brazhnikov, V.E. Bychkova, G.V. Semisotnov, S.Y. Venyaminov and O.B. Ptitsyn, FEBS Letters, 136 (1981) 311-315] and has physical properties intermediate between the native and molten globule states.     

MRI demonstration of impairment of the blood-CSF barrier by glucose administration to the thiamin-deficient rat brain

Contrast-enhanced T1-weighted spin-echo magnetic resonance imaging (MRI) has demonstrated that Gd-diethylenetriaminepentaacetate (Gd-DTPA), which normally does not cross the blood-brain or blood-CSF barriers, does so approximately 40 min after administration of glucose to a vitamin B1 deficient rat. The period of the onset of this blood-CSF or blood-brain barrier dysfunction coincides with our previous observations of accumulation of glutamate or glutamate derivatives following an equivalent glucose load under identical conditions of thiamin deficiency, consistent with a relationship between these two observations. The dysfunction was reversed when a thiamin deficient animal was made thiamin replete.     

Characterization of the immune response after local delivery of recombinant adenovirus in murine pancreas and successful strategies for readministration

The pancreas is an ideal organ for adenoviral gene therapy because of the high level of gene transfer that can be achieved and because of the many diseases that can potentially be treated using this technology. In this report, we characterize the immune response to direct pancreatic injection of adenovirus and we overcome some of the limitations it imposes by using immunosuppression. Direct injection of recombinant adenovirus into the pancreas leads to the production of neutralizing antibodies and to sensitized splenocytes which engage in increased cytotoxic, lymphoproliferative, and cytokine release activity when reexposed to adenovirus. Transgene expression is transient and the vector cannot be readministered. Deletion of CD4+ T helper cells improves expression over time (40% of pancreatic cells express transgene at day 28 vs. 5% in controls), and allows the vector to be readministered in the pancreas, albeit, inefficiently, when compared to naive animals. Similarly, blockade of CD40 ligand, which preserves the CD4+ T helper cell population, also improves expression over time (30% of pancreatic cells express transgene at day 28), and allows the vector to be readministered. With both approaches, neutralizing antibodies are decreased and the remaining splenocytes do not engage in activated immune responses. Thus, local delivery of the adenoviral vector induces a systemic response that prevents pancreatic readministration, even with direct injection. Blockade of CD40 ligand and T helper cell depletion are transient regimens that induce systemic immunosuppression. Until the development of newer strategies that selectively suppress adenoviral immune responses, these are viable alternatives for enhancement of pancreatic adenoviral delivery.     

Effects of changing skill mix

Although many facilities believe turning over some patient care to unlicensed caregivers will cut costs, results show otherwise. The greater the rate of change--patient acuity--the greater the need for an all-RN staff. Skill mix, length of stay and salary costs among five teaching hospitals measure the cost effects.     

Simple texture-based liberation modelling of ores

Mineralogical analysis is often used to assess the liberation properties of particles. A direct method of estimating liberation is to actually break particles and then directly obtain liberation information from applying mineralogical analysis to each size-class of the product.Another technique is to artificially apply random breakage to the feed particle sections to estimate the resultant distribution of product particle sections. This technique provides a useful alternative estimation method.Because this technique is applied to particle sections, the actual liberation properties for particles can only be estimated by applying stereological correction. A recent stereological technique has been developed that allows the discrepancy between the linear intercept composition distribution and the particle section composition distribution to be used as guide for estimating the particle composition distribution.The paper will show results validating this new technique using numerical simulation.