INTRODUCTION:High dietary intake of long chain, polyunsaturated fatty acids is associated with lower Alzheimer's disease (AD) risk. METHODS:Washington Heights-Hamilton Heights-Inwood Columbia Aging Project is a multiethnic, prospective observational study of aging and dementia among elderly (≥ 65 years). Dietary intake was measured using a food frequency questionnaire. Dietary short-, medium-, and long-chain fatty acid intakes were categorized by number of carbons and double bonds. Consensus AD diagnoses were made. Associations between AD risk and dietary fatty acid and cholesterol intakes were estimated using multivariable Cox proportional hazards regression models. RESULTS:Of 2612 multiethnic women (67%) and men (baseline age 76.3 [6.4] years), 380 developed AD over an average 4.5 years follow-up. Lower risk of AD was associated with increasing intakes of docosahexaenoic acid (DHA; hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.57 to 0.95, P = 0.018) and eicosapentaenoic acid (EPA; HR = 0.74, 95% CI: 0.57 to 0.95, P = 0.021), and longer AD-free survival (P < 0.05). DISCUSSION:Higher intake of DHA and EPA are protective for AD.

Background The efficacy of psychoeducation for bipolar disorder has been demonstrated in clinical trials, but it is not known if the results translate into effectiveness in routine clinical practice. The aim was to determine the effectiveness of psychoeducation for bipolar disorder in a routine clinical setting. Method We identified 2819 patients with at least three registrations in the Swedish Quality Assurance Register for Bipolar Disorder. Among those, 402 had not been exposed to psychoeducation at the first visit, but received psychoeducation during any of the following registrations. Using within-individual analyses, the risk of recurrence after having received psychoeducation was compared with the risk prior to psychoeducation. Results In adjusted within-individuals comparisons, periods after psychoeducation was associated with decreased risks of any recurrence [odds ratio (OR) 0.57, 95% CI 0.42-0.78], (hypo-)manic or mixed episodes (OR 0.54, 95% CI 0.39-0.76), depressive episodes (OR 0.63, 95% CI 0.47-0.86), and inpatient care (OR 0.54, 95% CI 0.33-0.86) relative to periods prior to psychoeducation. There was no association with rates of involuntary sectioning or suicide attempts. Conclusions The results suggest that psychoeducation for bipolar disorder reduces the risk of mood episodes and inpatient care also when implemented in routine clinical practice.

Background: High midlife and late-life adiposity may increase risk for dementia. Late-life decrease in body mass index (BMI) or body weight within several years of a dementia diagnosis has also been reported. Differences in study designs and analyses may provide different pictures of this relationship.Methods: Thirty-two years of longitudinal body weight, BMI, waist circumference, and waist-to-hip ratio (WHR) data, from the Prospective Population Study of Women in Sweden, were related to dementia. A representative sample of 1,462 nondemented women was followed from 1968 at ages 38-60 years, and subsequently in 1974, 1980, 1992, and 2000, using neuropsychiatric, anthropometric, clinical, and other measurements. Cox proportional hazards regression models estimated incident dementia risk by baseline factors. Logistic regression models including measures at each examination were related to dementia among surviving participants 32 years later.Results: While Cox models showed no association between baseline anthropometric factors and dementia risk, logistic models showed that a midlife WHR greater than 0.80 increased risk for dementia approximately twofold ( odds ratio 2.22, 95% confidence interval 1.00-4.94, p = 0.049) among surviving participants. Evidence for reverse causality was observed for body weight, BMI, and waist circumference in years preceding dementia diagnosis.Conclusions: Among survivors to age 70, high midlife waist-to-hip ratio may increase odds of dementia. Traditional Cox models do not evidence this relationship. Changing anthropometric parameters in years preceding dementia onset indicate the dynamic nature of this seemingly simple relationship. There are midlife and late-life implications for dementia prevention, and analytical considerations related to identifying risk factors for dementia. Neurology (R) 2009; 73: 1559-1566

Nowadays, the isolation of a gene from one organism, and its subsequent cloning and expression in another organism, under the control of regulatory elements from yet a third source, is commonplace. The spectrum of applications for such a process has included the production of therapeutic proteins, the alteration of intracellular physiological processes, and the analysis of the effects of certain genes during development. A mere three decades ago, this procedure, colloquially referred to as genetic engineering, was not just unknown, it was entirely unimagined in any meaningfully specific way.

An analysis of progression of sialadenitis in patients with primary and secondary SS has been performed. For this purpose patients were prospectively followed and evaluated with respect to stimulated whole salivary secretion and morphology of labial salivary gland biopsies. Twenty-one patients with primary SS and 18 with secondary SS were followed for a mean of 39 +/- 20 months (range 11-112 months). During this observation period the lymphocytic infiltration in minor salivary glands, measured as focus score, increased in 14/21 (67%) patients with primary SS and in 14/18 (78%) patients with secondary SS. Altogether there was a statistically significant increase in focus score in both primary and secondary SS, but no reduction in salivary production. Consequently, no correlation between changes in focus score and stimulated salivary secretion was found in either primary or secondary SS.

The methionine salvage pathway converts the methylthioribose moiety of 5'-(methylthio)-adenosine to methionine via a series of biochemical steps. One enzyme active in this pathway, a bifunctional enolase-phosphatase called E-1 that promotes oxidative cleavage of the synthetic substrate 2,3-diketo-1-phosphohexane to 2-keto-pentanoate, has been purified from Klebsiella pneumoniae and is characterized in the preceding paper (Myers, R., Wray, J., Fish, S., and Abeles, R. H. (1993) J. Biol. Chem. 268, 24785-24791). We synthesized degenerate oligonucleotides corresponding to portions of the amino terminus of E-1. These oligonucleotides were used as polymerase chain reaction primers on whole genomic DNA from Klebsiella oxytoca. This resulted in an 82-base pair DNA fragment that was used as a hybridization probe to obtain a clone of the E-1 gene from a K. oxytoca gene library. The DNA sequence of the E-1 coding region was determined, and the amino acid sequence of E-1 was deduced. E-1 appears to represent a novel class of enzymes since no homology to known enzymes was found. Cloning the gene from K. oxytoca on a multicopy plasmid leads to overproduction of E-1 enzyme that has properties indistinguishable from those of the enzyme from K. pneumoniae.

Estrogen is known to influence immune responses in healthy subjects in a dichotomous fashion. Thus, in number of previous studies we and others have demonstrated that B cell activities are augmented after exposure to estrogen whereas T cell reactivity is suppressed. Furthermore, it has been shown that this hormone has significant impact on the course of certain human and experimental autoimmune diseases. In this study we report that treatment with physiological doses of estradiol exerts dichotomous effects on different manifestations of the lupus disease in MRL/1 mice. On one hand immune complex-mediated glomerulonephritis was significantly accelerated. This outcome was due to polyclonal B cell activation with increased production of antibodies to double-stranded DNA and formation of circulating immune complexes. In contrast, T cell-mediated lesions such as focal sialadenitis, renal vaculitis, and periarticular inflammation were all significantly ameliorated in MRL/1 mice exposed to estrogen. Thus, we were able to demonstrate that, within one subject and even within one organ, administration of estrogen leads to differential outcome of SLE morbidity. We propose that the differential effect of estrogen on the manifestations of the autoimmune disease of MRL/1 mice is due to its dichotomous effects on B and T cell-mediated immune responses.

Annals of the New York Academy of SciencesVolume 589, Issue 1 p. 16-24 Genetic Engineering of Metabolic Pathways Applied to the Production of Phenylalanine KEITH BACKMAN, KEITH BACKMAN Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorMARY JANE O'CONNOR, MARY JANE O'CONNOR Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorAIKO MARUYA, AIKO MARUYA Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorEDWIN RUDD, EDWIN RUDD Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorDIANE McKAY, DIANE McKAY Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorR. BALAKRISHNAN, R. BALAKRISHNAN Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorM. RADJAI, M. RADJAI Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorV. DIPASQUANTONIO, V. DIPASQUANTONIO Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorDIANE SHODA, DIANE SHODA Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorRANDOLPH HATCH, RANDOLPH HATCH Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorK. VENKATASUBRAMANIAN, K. VENKATASUBRAMANIAN H. J. Heinz Company Pittsburgh, Pennsylvania 15230 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this author KEITH BACKMAN, KEITH BACKMAN Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorMARY JANE O'CONNOR, MARY JANE O'CONNOR Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorAIKO MARUYA, AIKO MARUYA Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorEDWIN RUDD, EDWIN RUDD Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorDIANE McKAY, DIANE McKAY Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorR. BALAKRISHNAN, R. BALAKRISHNAN Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorM. RADJAI, M. RADJAI Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorV. DIPASQUANTONIO, V. DIPASQUANTONIO Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorDIANE SHODA, DIANE SHODA Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorRANDOLPH HATCH, RANDOLPH HATCH Bio Technica International Cambridge, Massachusetts 02140 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this authorK. VENKATASUBRAMANIAN, K. VENKATASUBRAMANIAN H. J. Heinz Company Pittsburgh, Pennsylvania 15230 Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854Search for more papers by this author First published: May 1990 https://doi.org/10.1111/j.1749-6632.1990.tb24231.xCitations: 51AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Metzler, D. E. 1977. Biochemistry, p. 849. Academic Press. New York . 2 Zurawski, G., K. Brown & C. Yanofsky. 1978. Proc. Natl. Acad. Sci. U.S.A. 75: 4271. 3 Hudson, G. S. & B. E. Davidson. 1984. J. Mol. Biol. 180: 1023. 4 Duncan, K., A. Lewendon & J. R. Coggins. 1984. FEBS Lett. 170: 59. 5 Millar, G. & J. R. Coggins. 1986. FEBS Lett. 200: 11. 6 Defeyter, R. C., B. E. Davidson & J. Pittard. 1986. J. Bacteriol. 165: 233. 7 Cornish, E. C., V. P. Argyropoulos, J. Pittard & B. E. Davidson. 1986. J. Biol. Chem. 261: 403. 8 Gowrishankar, J. & J. Pittard. 1982. J. Bacteriol. 152: 1. 9 Backman, K. & R. Balakrishnan. 1988. United States patent no. 4,753,883. 10 Balakrishnan, R. & K. Backman. 1988. Gene 67: 97. 11 Backman, K. & R. Balakrishnan. 1988. United States patent no. 4,743,546. Citing Literature Volume589, Issue1Biochemical EngineeringMay 1990Pages 16-24 ReferencesRelatedInformation

We have used recombinant DNA techniques to construct a derivative of phage λ, called an excision vector, which retains only those functions necessary for conditional maintenance of lysogeny and integration/excision. The tyrA+ gene was cloned on this excision vector, integrated into the Escherichia coli chromosome, and stably maintained and expressed under permissive conditions. Upon shift to non-permissive conditions, the excision vector and its passenger gene were very efficiently excised from the chromosome and lost, leaving a culture of Tyr− bacteria. This illustrates a new class of conditional mutations in which the genotype changes in response to external stimuli.

The autoimmune MRL/Mp-lpr/lpr (MRL/l) mouse spontaneously develops sialadenitis with a morphological and phenotypical pattern similar to that seen in human Sjögren's syndrome (SS). This makes the MRL/1 mouse a suitable model for therapeutical studies of autoimmune sialadenitis. We have, by histological and immunohistochemical techniques, analyzed the therapeutical effect of treatment with LS2616, a recently synthesized oxokinolinamide derivative, on sialadenitis in submandibular glands of MRL/1 mice. The results were compared with effects obtained after treatment with cyclophosphamide (CY) and physiologic saline. Administration of both LS2616 and CY to MRL/1 mice has previously been found to result in prolongation of survival and amelioration of organ pathology. However, only CY treatment reduced sialadenitis, while LS2616 increased the semiquantitatively assessed focal inflammation of salivary glands in 6 months old mice. No differences in T-cell phenotypes of infocal the frequency of B-cells in the sialadenitis was decreased in the CY treated group. In contrast, CY but not LS2616 treatment normalized expression of T-helper and cytotoxic T-cell phenotypes as well as reduced the B-cell portion in lymph nodes. It is concluded that CY treatment can suppress sialadenitis although both LS2616 and CY are effective in prolongation lifespan of MRL/1 mice. This may implicate different immunopathogenic mechanisms for development of sialadenitis versus other organ lesions in the autoimmune disease of MRL/1 mice.

The nature and distribution of mononuclear cells in non-ulcerated oral lesions of discoid (DLE) and systemic lupus erythematosus (SLE), were investigated and compared to other chronic inflammatory oral diseases (lichen planus (LP), contact lesion (CL), unspecified inflammation (UI), geographic tongue (GT), and leukoplakia (LK). For this purpose an immunoperoxidase technique based on staining with monoclonal antibodies was employed. In most LE specimens examined infiltrating cells consisted predominantly of a mixture of T cells (Leu 3a+ and Leu 2a+) that were distributed in the lamina propria, the submucosa, and occasionally also in the epithelium. In general, only few B cells were detected while macrophages were more frequent. In all LE specimens examined beta 2-microglobulin expression was observed on a large proportion of cells including infiltrating mononuclear cells as well as resident keratinocytes. In addition, most infiltrating cells displayed MHC Class II antigens according to a pattern HLA-DR greater than DQ greater than DP. Interestingly, expression of Class II antigens was also observed on epithelial keratinocytes but was restricted to HLA-DR and -DP gene products (DR much greater than DP). HLA-DQ expression was never observed on keratinocytes. In most LE specimens studied a small proportion (less than 5%) of inflammatory cells had detectable interleukin-2 receptors (IL-2R) and/or transferrin receptors (transf-R). However, expression of transf-R was also observed on basal epithelial cells, being more pronounced in DLE than in SLE lesions. The above staining patterns observed in LE lesions, when compared to other chronic inflammatory oral lesions, did not disclose any striking differences that could support the specific diagnosis of LE. However, the findings of Class I and II MHC gene products on oral keratinocytes suggest an important accessory role for these cells in directing the migration of activated lymphoid cells in the epithelium in chronic inflammatory lesions of the oral mucosa.

The spontaneously developing sialadenitis in female autoimmune NZB X NZW F1 (NZB/W) mice has been studied with the help of immunohistochemistry and monoclonal antibodies to cell surface antigens. Semiquantitative assessment of stained cells within the infiltrates disclosed a progressive focal inflammation most pronounced in submandibular and parotid glands. The majority of cells expressed Ly-1 (all T cells) and L3T4 (T helper) phenotype, whereas only few Lyt-2 (cytotoxic/suppressor) expressing T cells were seen. A large proportion of the infiltrating cells stained for Ia antigens, which was also found on salivary gland ductal epithelium in the proximity of lymphoid infiltrates. The phenotypic pattern in sialadenitis of NZB/W mice thus closely resembles the pattern previously described for human Sjögren's syndrome (SS). Accordingly, immunomorphological analysis of the NZB/W sialadenitis may be useful in further studies of pathogenesis and therapy of both experimental and human SS.