New insights into hyperglycemia-induced molecular changes in microvascular cells.

Hyperglycemia is the most prevalent characteristic of diabetes and plays a central role in mediating adverse effects on vascular cells during the progression of diabetic vascular complications. In diabetic microangiopathy, hyperglycemia induces biochemical and molecular changes in microvascular cells that ultimately progress to retinal, renal, and neural complications and extends to other complications, including advanced periodontal disease. In this review, we describe changes involving basement membrane thickening, tissue remodeling, gap junctions, inflammation, cytokines, and transcription factors, and their effects on the pathogenesis of diabetic microvascular complications. The majority of the changes described relate to retinal microangiopathy, since ultrastructural, structural, and biochemical alterations have been well-characterized in this tissue.

Motivation to quit using substances among individuals with schizophrenia: implications for a motivation-based treatment model.

Although the motivation to quit using substances is an important prognostic and treatment-matching factor in substance abuse treatment, there is limited information on motivation to quit among individuals with schizophrenia. This study used the five-stages-of-change model to evaluate the motivational levels of 497 individuals with schizophrenia or schizoaffective disorder in an outpatient mental health clinic. Rates of substance abuse, motivation levels to quit each specific substance, and correlates to motivational levels were evaluated. At least one substance use disorder was diagnosed in 224 of the subjects (45%); however, there was significant variability among the caseloads of the outpatient division teams. The patients in the triage/acute services and community outreach teams had substance abuse rates of about 70 percent. Most subjects had low motivation to quit substances, and the rates varied according to substance (range of 41% for opiates to 60% for cocaine). Treatment-matching strategies are suggested in the motivation-based treatment model.

Identification and characterization of FrzZ, a novel response regulator necessary for swarming and fruiting-body formation in Myxococcus xanthus.

The frz genes of Myxococcus xanthus constitute a signal-transduction pathway that processes chemotactic information in a manner analogous to that found in enteric bacteria. Ultimately, these genes regulate the frequency of individual cell reversal. We report here the identification of a novel component of this signal-transduction pathway, designated frzZ, which was discovered as an open reading frame located 5' to the frz operon but transcribed in the opposite orientation. The translational start site of frzZ is 170 base pairs from that of frzA.frzZ utilizes a promoter similar to the sigma 70 promoters of Escherichia coli, and encodes a 290-amino-acid soluble protein, FrzZ (M(r) 30,500). FrzZ contains two domains, both of which show strong homology to CheY and other members of the response-regulator family. Linking these domains is a 39-amino-acid region that is very rich in alanine and proline (38% Ala and 33% Pro). A frzZ null mutant showed abnormally low reversal rates when compared to the wild-type control and was unable to form fruiting bodies on starvation medium, but it did form 'frizzy' aggregates. In addition, the frzZ mutant was defective in swarming, particularly on soft agar (0.3% w/v). However, unlike most frz mutants, the frzZ mutant was able to respond to attractants and repellents in the spatial chemotaxis assay. The discovery of FrzZ demonstrates that the M. xanthus frz signal-transduction pathway utilizes multiple response-regulator (CheY-like) proteins.

The 'CheA' and 'CheY' domains of Myxococcus xanthus FrzE function independently in vitro as an autokinase and a phosphate acceptor, respectively.

FrzE is a chemotaxis protein in Myxococcus xanthus which has sequence homology to two different chemotaxis proteins of enteric bacteria, CheA (autokinase) and CheY (phosphate acceptor) [Proc. Natl. Acad. Sci. USA 87 (1990) 5898-5902]. It was also shown that a recombinant FrzE protein was autophosphorylated when incubated in the presence of ATP and Mn2+ [J. Bacteriol. 172 (1990) 6661-6668]. In this study, we further investigated the biochemical properties of FrzE. Two recombinant proteins were produced: one containing only the 'CheA' domain of FrzE and the second only the 'CheY' domain. The CheA domain polypeptide contained the autokinase activity which was absent from the CheY domain polypeptide. The phosphorylated CheA domain polypeptide as well as the intact FrzE protein were able to transfer phosphate groups to the CheY domain peptide. These results indicate that FrzE has structural as well as functional homologies to CheA and CheY in a single polypeptide.