bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of diabetes mellitus and its treatment on ventricular arrhythmias complicating acute myocardial infarction
Authors: Rana J. S. , Mukamal K. J. , Nesto R. W. , Morgan J. P. , Muller J. E. , Mittleman M. A. 
Published: April 2005

AbstractAims  To evaluate the effect of diabetes mellitus and its treatment on the risk of arrhythmias among early survivors of acute myocardial infarction.Research design and method  The Onset Study was conducted in 64 US medical centres. Between August 1989 and September 1996, 3882 patients were interviewed after having an acute myocardial infarction. We used logistic regression models to examine the association of diabetes and its treatment with the risk of ventricular arrhythmia after adjustment for age, gender, hypertension, thrombolytic therapy, smoking, obesity, cardiac medicines and congestive heart failure.Results  During the index hospitalization, patients with diabetes (n = 814) were less likely to develop ventricular arrhythmias than patients without diabetes (6.8 vs. 13.3%, P < 0.001). The risk of ventricular arrhythmia in patients treated with first generation sulphonylureas or diet alone was similar to patients without diabetes (OR = 0.91; 95% CI, 0.39–2.15, and 0.76; 95% CI, 0.46–1.26, respectively). However, compared with patients without diabetes, the adjusted odds ratio (OR) for ventricular arrhythmias was lower among patients treated with insulin or patients treated with second generation sulphonylureas (OR = 0.54, 95% CI 0.32–0.92; OR = 0.45, 95% CI 0.27–0.75, respectively).Conclusions  Compared with patients without diabetes, the risk of ventricular arrhythmias complicating acute myocardial infarction is lower in patients with diabetes treated with second generation sulphonylureas or insulin, but not in those treated with first generation sulphonylureas or diet alone. This suggests that differences in the mechanism of action of different sulphonylureas may result in clinically relevant differences in arrhythmic risk.
A case of novel de novo paired box gene 6 (PAX6) mutation with early‐onset diabetes mellitus and aniridia
Authors: Nishi M. , Sasahara M. , Shono T. , Saika S. , Yamamoto Y. , Ohkawa K. , Furuta H. , Nakao T. , Sasaki H. , Nanjo K. 
Published: April 2005

AbstractBackground  Paired box gene 6 (PAX6) is a transcription factor involved in eye development. Mutations of PAX6 cause congenital eye anomalies, such as aniridia. PAX6 is also involved in the development of the endocrine pancreas, and reported to be a genetic factor common to aniridia and glucose intolerance, although the latter is usually mild. Here, we describe a case of PAX6 mutation with early‐onset diabetes mellitus.Case report  A 27‐year‐old woman was referred to our clinic. She was diagnosed having diabetes at the age of 15 with negative glutamic acid decarboxylase (GAD) antibody. Insulin treatment was started at age 24. Because she had aniridia, PAX6 gene mutation was investigated and a heterozygous 2‐bp deletion (c.402del2) was identified. Her parents did not have aniridia and PAX6 mutations. Heterozygous PAX6 mutation may cause glucose intolerance. However, cases of early‐onset diabetes mellitus have not been reported. Her parents did not have diabetes, but their insulinogenic indices were low (0.25 and 0.3, respectively). We thought her early‐onset diabetes was partly as a result of PAX6 mutation and partly because of an unknown insulin secretory defect inherited from her parents. We could not find any mutations in HNF‐1α, ‐1β, ‐4α, IPF‐1, ISL‐1, BEAT2/NeuroD1, PAX4, and amylin genes.Conclusions  We report a case of PAX6 gene mutation with early‐onset diabetes mellitus and aniridia. Low insulin secretory capacity in her parents suggested that her insulin secretory defect is as a result of not only PAX6 mutation but other genetic factors inherited from her parents.
Changing patterns of primary care for diabetes in Trinidad and Tobago over 10 years
Authors: Mahabir D. , Gulliford M. C. 
Published: April 2005

AbstractObjective  To evaluate standards of preventive medical care for Type 2 diabetes in the context of high prevalence and limited resources.Methods  Surveys of records for diabetic subjects attending 23 government primary care health centres in Trinidad and Tobago in 2003 and 1998 and nine health centres in 1993. Records were compared by study year for blood glucose and blood pressure, surveillance for complications, appropriate management advice and drug prescriptions. Relevant interventions included new clinical guidelines, training workshops for clinical staff and reports to the Ministry of Health. During this time, investment in primary care increased in the context of health sector reform policies and a favourable macroeconomic environment.Results  Comparing 1993 with 2003, the proportion with a blood glucose test in the past 12 months increased from 33% to 91%, urea or creatinine ever recorded increased from 14% to 61%, diet advice recorded in the first 12 months of follow‐up from 35% to 67%, exercise advice from 3% to 61%. The proportion prescribed metformin increased from 25% to 65%, while chlorpropamide decreased from 48% to 0%. The proportion of all subjects treated with antihypertensive drugs increased from 49% to 70%, and the proportion of treated patients prescribed angiotensin‐converting enzyme inhibitors increased from 8% to 72%. Most recent ever records of blood glucose, blood pressure and body weight showed no decrease.Conclusions  Repeated surveillance of processes of care provided information to stimulate and plan change. Process changes were associated with intervention at several levels and increased availability of resources.
Prevalence of obesity in Korea
Authors: Kim D. M. , Ahn C. W. , Nam S. Y. 
Published: April 2005

SummaryDuring the past decade, obesity has substantially increased in Korea, and this is leading to dramatic increases in complications such as type 2 diabetes. In this review, we discuss the past and the current situation of obesity in Korea based on the national health and nutrition surveys of 1995, 1998, and 2001. Because Korea is geographically isolated with relatively few migrants and has a low level of genetic heterogeneity, this report demonstrates the impact of environmental factors on the development of obesity beyond epidemiological information about one of the Asian countries. The third national health and nutrition survey reported in 2001 announced that the overall prevalence of obesity [body mass index (BMI) ≥ 25.0 kg m−2] in Korean adults is 30.6% (32.4% in men and 29.4% in women). The prevalence of obesity in adults and children has increased rapidly from 1990s through the beginning of the new millennium and is steadily increasing in parallel with our rapid socio‐economic progress. In particular, special attention should be paid to two groups in hormonal transition: first, middle‐aged men and women who experience a great increase in body weight, BMI and waist circumference because of andropause or menopause, and second, adolescents in middle to high school who are preparing for qualification or entrance examinations and are prone to overnutrition or nutritional imbalance and physical inactivity.
Stearoyl‐CoA desaturase as a new drug target for obesity treatment
Authors: Dobrzyn A. , Ntambi J. M. 
Published: April 2005

SummaryStearoyl‐CoA desaturase (SCD), the rate‐limiting enzyme in monounsaturated fatty acid synthesis, has recently been shown to be the critical control point regulating hepatic lipogenesis and lipid oxidation. As several manifestations of the metabolic syndrome and type 2 diabetes mellitus are associated with alterations in intracellular lipid partitioning, we propose that SCD1 may be a potential therapeutic target in the treatment of obesity and the metabolic syndrome. In support of this notion, we have shown that SCD1‐deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet‐induced obesity and liver steatosis. Furthermore, SCD1 was found to be specifically repressed during leptin‐mediated weight loss, and leptin‐deficient ob/ob mice lacking SCD1 showed marked correction of the hypometabolic phenotype and hepatic steatosis. Much evidence indicates that the direct anti‐steatotic effect of SCD1 deficiency stems from increased fatty acid oxidation and decreased lipid synthesis. All of these findings reveal that pharmacological manipulation of SCD activity might be of benefit in the treatment of obesity, diabetes, liver steatosis and other diseases of the metabolic syndrome.
The DotL Protein, a Member of the TraG-Coupling Protein Family, Is Essential for Viability ofLegionella pneumophilaStrain Lp02
Authors: Buscher Benjamin A. , Conover Gloria M. , Miller Jennifer L. , Vogel Sinae A. , Meyers Stacey N. , Isberg Ralph R. , Vogel Joseph P. 
Published: April 2005

ABSTRACTLegionella pneumophilais able to survive inside phagocytic cells by an internalization route that bypasses fusion of the nascent phagosome with the endocytic pathway to allow formation of a replicative phagosome. Thedot/icmgenes, a major virulence system ofL. pneumophila, encode a type IVB secretion system that is required for intracellular growth. One Dot protein, DotL, has sequence similarity to type IV secretion system coupling proteins (T4CPs). In other systems, coupling proteins are not required for viability of the organism. Here we report the first example of a strain,L. pneumophilaLp02, in which a putative T4CP is essential for viability of the organism on bacteriological media. This result is particularly surprising since the majority of thedot/icmgenes in Lp02 are dispensable for growth outside of a host cell, a condition that does not require a functional Dot/Icm secretion complex. We were able to isolate suppressors of theΔdotLlethality and found that many contained mutations in other components of the Dot/Icm secretion system. A systematic analysis ofdot/icmdeletion mutants revealed that the majority of them (20 of 26) suppressed the lethality phenotype, indicating a partially assembled secretion system may be the source ofΔdotLtoxicity in the wild-type strain. These results are consistent with a model in which the DotL protein plays a role in regulating the activity of theL. pneumophilatype IV secretion apparatus.
Staphylococcus epidermidis
Polysaccharide Intercellular Adhesin Production Significantly Increases during Tricarboxylic Acid Cycle Stress
Authors: Vuong Cuong , Kidder Joshua B. , Jacobson Erik R. , Otto Michael , Proctor Richard A. , Somerville Greg A. 
Published: April 2005

ABSTRACT

Staphylococcal polysaccharide intercellular adhesin (PIA) is important for the development of a mature biofilm. PIA production is increased during growth in a nutrient-replete or iron-limited medium and under conditions of low oxygen availability. Additionally, stress-inducing stimuli such as heat, ethanol, and high concentrations of salt increase the production of PIA. These same environmental conditions are known to repress tricarboxylic acid (TCA) cycle activity, leading us to hypothesize that altering TCA cycle activity would affect PIA production. Culturing
Staphylococcus epidermidis
with a low concentration of the TCA cycle inhibitor fluorocitrate dramatically increased PIA production without impairing glucose catabolism, the growth rate, or the growth yields. These data lead us to speculate that one mechanism by which staphylococci perceive external environmental change is through alterations in TCA cycle activity leading to changes in the intracellular levels of biosynthetic intermediates, ATP, or the redox status of the cell. These changes in the metabolic status of the bacteria result in the attenuation or augmentation of PIA production.
Requirements for
Vibrio cholerae
HapR Binding and Transcriptional Repression at the
hapR
Promoter Are Distinct from Those at the
aphA
Promoter
Authors: Lin Wei , Kovacikova Gabriela , Skorupski Karen 
Published: April 2005

ABSTRACT

Virulence gene expression in certain strains of
Vibrio cholerae
is regulated in response to cell density by a quorum-sensing cascade that influences the levels of the LuxR homolog HapR through small regulatory RNAs that control the stability of its message. At high cell density, HapR represses the expression of the gene encoding the virulence gene activator AphA by binding to a site between −85 and −58 in the
aphA
promoter. We show here that a second binding site for HapR lies within the
hapR
promoter from which it functions to repress its own transcription. This site, as determined by gel mobility shift assay and DNaseI footprinting, is located between +8 and +36 from the transcriptional start and is not strongly conserved with the site at the
aphA
promoter. At low cell density, when the expression of a transcriptional
hapR-lacZ
fusion was low, no autorepression was observed. However, at high cell density, when the expression of the
hapR-lacZ
fusion was approximately 15-fold higher, the presence of HapR reduced its expression. Introduction of a single base pair change within the binding site at +18 prevented HapR binding in gel mobility shift assays. In the absence of HapR, this mutation did not significantly influence the expression of the
hapR
promoter, but in its presence, the expression of the promoter was increased at high cell density. These results indicate that HapR autorepresses from a single binding site in the
hapR
promoter and suggest a model for the temporal regulation of its expression as its intracellular levels increase.
Functional Characterization of a Novel ArgA from
Mycobacterium tuberculosis
Authors: Errey James C. , Blanchard John S. 
Published: April 2005

ABSTRACT

The
Mycobacterium tuberculosis
gene
Rv2747
encodes a novel 19-kDa ArgA that catalyzes the initial step in
l
-arginine biosynthesis, namely the conversion of
l
-glutamate to α-
N
-acetyl-
l
-glutamate. Initial velocity studies reveal that Rv2747 proceeds through a sequential kinetic mechanism, with

K
m

values of 280 mM for
l
-glutamine and 150 μM for acetyl-coenzyme A and with a
k
cat
value of 200 min
−1
. Initial velocity studies with
l
-glutamate showed that even at concentrations of 600 mM, saturation was not observed. Therefore, only a
k
cat
/

K
m

value of 125 M
−1
min
−1
can be calculated. Inhibition studies reveal that the enzyme is strongly regulated by
l
-arginine, the end product of the pathway (50% inhibitory concentration, 26 μM). The enzyme was completely inhibited by 500 μM arginine, with a Hill coefficient of 0.60, indicating negatively cooperative binding of
l
-arginine.
Polyphosphate Kinase Protects
Salmonella enterica
from Weak Organic Acid Stress
Authors: Price-Carter Marian , Fazzio Thomas G. , Vallbona Ester Ibañez , Roth John R. 
Published: April 2005

ABSTRACT

Mutants of
Salmonella enterica
lacking polyphosphate kinase (
ppk
) grow poorly in the presence of the weak organic acids acetate, propionate, and benzoate. This sensitivity is corrected by methionine and seems to result from destabilization of MetA (homoserine transsuccinylase), the first enzyme in methionine biosynthesis. The MetA protein is known to be sensitive to thermal inactivation, and
ppk
mutants are more sensitive to heat-induced methionine auxotrophy. Peroxide increases the sensitivity of
ppk
mutants to both heat and acid and may oxidatively damage (carbonylate) destabilized MetA. While acid appears to impair methionine biosynthesis, it leads to derepression of MetA and may inhibit growth by causing toxic accumulation of denatured protein. This is supported by the observation that the overexpression of MetA in
ppk
mutants causes acid sensitivity that is not corrected by methionine. We propose that polyphosphate acts as a chemical chaperone that helps refold MetA and/or may stimulate proteolysis of toxic denatured protein. The instability of MetA protein may provide a metabolic fuse that blocks growth under conditions that denature proteins; the sensitivity of this fuse is modulated by polyphosphate.
The Soluble NAD+-Reducing [NiFe]-Hydrogenase fromRalstonia eutrophaH16 Consists of Six Subunits and Can Be Specifically Activated by NADPH
Authors: Burgdorf Tanja , van der Linden Eddy , Bernhard Michael , Yin Qing Yuan , Back Jaap W. , Hartog Aloysius F. , Muijsers Anton O. , de Koster Chris G. , Albracht Simon P. J. , Friedrich Bärbel 
Published: April 2005

ABSTRACTThe soluble [NiFe]-hydrogenase (SH) of the facultative lithoautotrophic proteobacteriumRalstonia eutrophaH16 has up to now been described as a heterotetrameric enzyme. The purified protein consists of two functionally distinct heterodimeric moieties. The HoxHY dimer represents the hydrogenase module, and the HoxFU dimer constitutes an NADH-dehydrogenase. In the bimodular form, the SH mediates reduction of NAD+at the expense of H2. We have purified a new high-molecular-weight form of the SH which contains an additional subunit. This extra subunit was identified as the product ofhoxI, a member of the SH gene cluster (hoxFUYHWI). Edman degradation, in combination with protein sequencing of the SH high-molecular-weight complex, established a subunit stoichiometry of HoxFUYHI2. Cross-linking experiments indicated that the two HoxI subunits are the closest neighbors. The stability of the hexameric SH depended on the pH and the ionic strength of the buffer. The tetrameric form of the SH can be instantaneously activated with small amounts of NADH but not with NADPH. The hexameric form, however, was also activated by adding small amounts of NADPH. This suggests that HoxI provides a binding domain for NADPH. A specific reaction site for NADPH adds to the list of similarities between the SH and mitochondrial NADH:ubiquinone oxidoreductase (Complex I).
Characterization of Enhancer Binding by the
Vibrio cholerae
Flagellar Regulatory Protein FlrC
Authors: Correa Nidia E. , Klose Karl E. 
Published: April 2005

ABSTRACT

The human pathogen
Vibrio cholerae
is a highly motile organism by virtue of a polar flagellum, and motility has been inferred to be an important aspect of virulence. It has previously been demonstrated that the σ
54
-dependent activator FlrC is necessary for both flagellar synthesis and for enhanced intestinal colonization. In order to characterize FlrC binding, we analyzed two FlrC-dependent promoters, the highly transcribed
flaA
promoter and the weakly transcribed
flgK
promoter, utilizing transcriptional
lacZ
fusions, mobility shift assays, and DNase I footprinting. Promoter fusion studies showed that the smallest fragment with wild-type transcriptional activity for
flaAp
was from positions −54 to +137 with respect to the start site, and from −63 to +144 for
flgKp
. Gel mobility shift assays indicated that FlrC binds to a fragment containing the region from positions +24 to +95 in the
flaAp
, and DNase I footprinting identified a protected region between positions +24 and +85. Mobility shift and DNase I footprinting indicated weak binding of FlrC to a region downstream of the
flgKp
transcription start site. These results demonstrate a relatively novel σ
54
-dependent promoter architecture, with the activator FlrC binding downstream of the σ
54
-dependent transcription start sites. When the FlrC binding site(s) in the
flaA
promoter was moved a large distance (285 bp) upstream of the transcription start site of either
flaAp
or
flgKp
, high levels of FlrC-dependent transcription resulted, indicating that this binding region functions as an enhancer element. In contrast, the relatively weak FlrC binding site(s) in the
flgK
promoter failed to function as an enhancer element at either promoter, suggesting that FlrC binding strength contributes to enhancer activity. Our results suggest that the differences in FlrC binding to various flagellar promoters results in the differences in transcription levels that mirror the relative requirement for the flagellar components within the flagellum.
Expression of the
melC
Operon in Several
Streptomyces
Strains Is Positively Regulated by AdpA, an AraC Family Transcriptional Regulator Involved in Morphological Development in
Streptomyces coelicolor
Authors: Zhu Dongqing , He Xinyi , Zhou Xiufen , Deng Zixin 
Published: April 2005

ABSTRACT

Dark brown haloes of melanin around colonies are an easily visualized phenotype displayed by many
Streptomyces
strains harboring plasmid pIJ702 carrying the
melC
operon of
Streptomyces antibioticus
IMRU3270. Spontaneous melanin-negative mutants of pIJ702 occur with a frequency of ca. 1%, and often mutation occurs in the
melC
operon, which removes the BglII site as part of an inverted repeat. Other melanin-negative mutations seem to occur spontaneously in
Streptomyces lividans
, resulting in white colonies from which intact, melanin-producing pIJ702 can be isolated by introduction into a new host.
S. lividans
ZX66 was found to be such a mutant and to have a secondary mutation influencing expression of the
melC
operon on the chromosome. A 3.3-kb DNA fragment was isolated from its progenitor strain, JT46, and a gene able to restore
melC
operon expression was found to encode a member of an AraC family of transcriptional regulators, which was equivalent to AdpA
c
in
Streptomyces coelicolor
and therefore was designated AdpA
l
. Lack of
melC
operon expression was correlated with a single A-to-C transversion, which altered a single key amino acid residue from Thr to Pro. The transcription of the
melC
operon was found to be greatly reduced in the
adpA
mutant background. The counterpart gene (
adpA
a
) in the
S. antibioticus
strain in which the
melC
operon carried on pIJ702 originated was also isolated and was found to have an identical regulatory role. Thus, we concluded that the
melC
operon is under general direct positive control by AdpA family proteins, perhaps at the transcriptional level and certainly at the translational level via
bldA
, in
Streptomyces
.
Exopolysaccharide Sugars Contribute to Biofilm Formation bySalmonella entericaSerovar Typhimurium on HEp-2 Cells and Chicken Intestinal Epithelium
Authors: Ledeboer Nathan A. , Jones Bradley D. 
Published: April 2005

ABSTRACTRecently, we demonstrated thatSalmonella entericaserovar Typhimurium can form biofilm on HEp-2 cells in a type 1 fimbria-dependent manner. Previous work onSalmonellaexopolysaccharide (EPS) in biofilm indicated that the EPS composition can vary based upon the substratum on which the bacterial biofilm forms. We have investigated the role of genes important in the production of colanic acid and cellulose, common components of EPS. A mutation in the colanic acid biosynthetic gene,wcaM, was introduced intoS. entericaserovar Typhimurium strain BJ2710 and was found to disrupt biofilm formation on HEp-2 cells and chicken intestinal tissue, although biofilm formation on a plastic surface was unaffected. Complementation of thewcaMmutant with the functional gene restored the biofilm phenotype observed in the parent strain. A mutation in the putative cellulose biosynthetic gene,yhjN, was found to disrupt biofilm formation on HEp-2 cells and chicken intestinal epithelium, as well as on a plastic surface. Our data indicate thatSalmonellaattachment to, and growth on, eukaryotic cells represent complex interactions that are facilitated by species of EPS.