C3123A polymorphism of the angiotensin II type 2 receptor gene and salt sensitivity in healthy Japanese men.
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Biomedical subjects
Publications and source records attributed to L Zhang.
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Autoantibodies specific for the beta(1)-adrenoceptor (beta(1)-AR) have been implicated in the pathology of congestive heart failure (CHF). We hypothesized that the presence of autoantibodies against beta(1)-AR (anti-beta(1)-AR) is associated with left ventricular (LV) remodelling in response to metoprolol. Synthetic beta(1)-AR peptides served as the target antigen in an ELISA (enzyme-linked immunosorbent assay) were used to screen the sera of 106 CHF patients. Patients were separated into positive (+) anti-beta(1)-AR or negative (-) anti-beta(1)-AR groups according to their anti-beta(1)-AR reactivity. Echocardiography (ECG) was performed at baseline and after one year of metoprolol therapy in combination with standard treatment regime for CHF, that is, digoxin, diuretics and an ACEI (angiotensin-converting enzyme inhibitor). The dose of metoprolol was doubled on a biweekly basis up to 50 mg x 2 daily (b.i.d./day) or attainment of maximum tolerated dose. Ninety-six patients completed final data analysis. Fifty-four patients with (+) anti-beta(1)-AR had greater improvements than 42 patients with (-) anti-beta(1)-AR in LVEDD (left ventricular end-diastolic dimension) (P < 0.01, from 69 +/- 0.8 to 58.0 +/- 0.5 mm vs. 69.0 +/- 0.8-63.6 +/- 0.9 mm) and LVESD (left ventricular end-systolic dimension) (P < 0.01, from 57.1 +/- 1.4 to 43.9 +/- 0.8 mm vs. 56.2 +/- 0.9-48.6 +/- 1.0 mm), and LVEF (left ventricular ejection fraction) (P < 0.01, from 35.4 +/- 1.3 to 49.8 +/- 0.6% vs. 34.4 +/- 1.0-44.3 +/- 1.1%) by metoprolol therapy in combination with standard treatment regime for one year. Of the CHF patients with (+) anti-beta(1)-AR, 65.4% responded to target metoprolol dose as compared to 21.4% of CHF patients without anti-beta(1)-AR (P < 0.01). Response to target metoprolol dose occurred more rapidly in (+) anti-beta(1)-AR than (-) anti-beta(1)-AR of CHF patients (67.5 +/- 2.4 vs. 100.8 +/- 3.0 days, P < 0.01). These results demonstrated that CHF patients with (+) anti-beta(1)-AR had greater improvements in LV remodelling and heart function by metoprolol as compared to (-) anti-beta(1)-AR patients. Moreover, patients with (+) anti-beta(1)-AR have better tolerance to metoprolol therapy than patients without anti-beta(1)-AR.
House flies were collected from four dairies in Maine, New York, North Carolina, and Florida, where high levels of resistance to permethrin have been documented. Regions of two genes, CYP6D1 and Vssc1, having alleles that confer resistance to permethrin (and other pyrethroids) were analysed from individuals at each collection site. The combinations of resistance alleles for Vssc1 and CYP6D1 were highly variable between each state. The resistance allele CYP6D1v1 was found at a high frequency (0.63-0.91) at all sites. Individuals homozygous susceptible for CYP6D1 were very rare and detected only at the dairy in Maine. In addition to the typical Vssc1 mutation responsible for resistance, kdr (L1014F), we also identified individuals with a L1014H mutation. Although house flies homozygous for the L1014H mutation had a lower level of resistance to permethrin, compared to L1014F, the H1014 resistance allele was frequently detected. No individuals with the super-kdr allele (M918T + L1014F) were detected from the field collections. The intron 3 bp downstream of the kdr mutation was found to be extremely variable, providing an opportunity to reconstruct a phylogeny of Vssc1 alleles. Based on this analysis it appears the kdr-his mutation had multiple evolutionary origins, but that the kdr mutation may have had a single origin. The impacts of these findings on resistance management are discussed.
Malaria infection results in increased expression of immune responsive genes, including those encoding antimicrobial peptides such as Gambicin (Gam1) and Cecropin A (Cec1). Understanding how these genes are regulated will provide insights how the mosquito immune system is activated by Plasmodium. We previously have shown that Cec1 was primarily regulated by the Imd-Relish (REL2) pathway in the Anopheles gambiae Sua1B cell line. We show here that expression of Defensin A (Def1) and Gam1 was reduced after RNA interference against components of the Imd-REL2 pathway in An. gambiae cell lines. Interestingly, promoter reporters of these antimicrobial peptides were expressed at very low level in the cell line MSQ43 from Anopheles stephensi. Surprisingly, over-expression of either NF-kappaB transcription factor REL1 or REL2 alone is sufficient to induce the expression of Cec1, Gam1 and Def1. These results suggest that expression of these antimicrobial peptides (AMP) in vivo may be regulated by both the Toll and Imd pathways. We also show here for the first time that Tep4, a gene encoding a thioester containing protein, is regulated by REL2. Taken together, these results suggest that there are significant overlaps of genes regulated by the Toll-Rel1 and Imd-Rel2 pathways. Further, the different expression patterns in two different Anopheline cell lines provide a platform to identify other key positive and negative regulators of the antimicrobial peptide genes.
AIMS: Identification of a gene for self-protection from the antibiotic-producing plant pathogen Xanthomonas albilineans, and functional testing by heterologous expression. METHODS AND RESULTS: Albicidin antibiotics and phytotoxins are potent inhibitors of prokaryote DNA replication. A resistance gene (albF) isolated by shotgun cloning from the X. albilineans albicidin-biosynthesis region encodes a protein with typical features of DHA14 drug efflux pumps. Low-level expression of albF in Escherichia coli increased the MIC of albicidin 3000-fold, without affecting tsx-mediated albicidin uptake into the periplasm or resistance to other tested antibiotics. Bioinformatic analysis indicates more similarity to proteins involved in self-protection in polyketide-antibiotic-producing actinomycetes than to multi-drug resistance pumps in other gram-negative bacteria. A complex promoter region may co-regulate albF with genes for hydrolases likely to be involved in albicidin activation or self-protection. CONCLUSIONS: AlbF is the first apparent single-component antibiotic-specific efflux pump from a gram-negative antibiotic producer. It shows extraordinary efficiency as measured by resistance level conferred upon heterologous expression. SIGNIFICANCE AND IMPACT OF THE STUDY: Development of the clinical potential of albicidins as potent bactericidial antibiotics against diverse bacteria has been limited because of low yields in culture. Expression of albF with recently described albicidin-biosynthesis genes may enable large-scale production. Because albicidins are X. albilineans pathogenicity factors, interference with AlbF function is also an opportunity for control of the associated plant disease.
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With chicken bacterial artificial chromosome (BAC) DNA as probes, 11 non-assigned functional genes were localized to chicken chromosomes 1 or 2 by fluorescence in situ hybridization (FISH). The 11 genes and their chromosomal positions are as follows: ALVEB5, 1p26-24; ACO2, 1p16-14; HSP108, 1p14-13; CD4, 1q11; HSD3B; 1q11; SOD1, 1q14-21; LAMP1, 1q24-31; P2Y5, 1q35-36; EN2, 2p31-24; NPY, 2p14-13 and CA2, 2q31-32. Metaphase chromosome spreads used for hybridization were prepared from embryonic chicken fibroblast cultures. The gene position was identified according to the international standardized G-banded karyotype of chicken by measuring the relative fractional length from the telomere of the p-arm to the hybridization signal (FLpter). The 11 genes mapped newly will enrich the cytogenetic map and serve as additional anchor markers for integrating the cytogenetic map with the genetic map of chicken.
OBJECTIVE: To assess the effectiveness of transvaginal, ultrasound-guided, ovarian, interstitial laser coagulation treatment in anovulatory women with polycystic ovary syndrome (PCOS). DESIGN: A pilot study. SETTING: Assisted reproductive technology unit. SAMPLE: Twenty-three anovulatory women with clomifene-citrate-resistant PCOS. METHODS: Ultrasound-guided, transvaginal, ovarian, interstitial yttrium-aluminium-garnet laser treatment. MAIN OUTCOME MEASURES: Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, prolactin and estradiol levels, spontaneous ovulation rate and pregnancy rate were measured over 6 months of follow up. RESULTS: Regular ovulation occurred in 19 out of 22 (86.4%) women in the 6 months following ovarian treatment (one woman was lost to follow up). On the postoperative second, fourth and sixth month, the mean serum LH levels were 4.54 SD 1.21 iu/l, 4.90 SD 2.18 iu/l and 4.42 SD 1.03 iu/l, significantly (P < 0.001, P < 0.001, P < 0.001) lower than the preoperative level of 13.89 +/- 3.62 iu/l; the mean serum testosterone levels were 2.69 SD 1.83 nmol/l, 2.42 SD 1.11 nmol/l and 2.28 SD 1.96 nmol/l and significantly (P < 0.001, P < 0.001, P < 0.001) lower than the preoperative baseline value of 5.37 SD 3.09 nmol/l; the mean LH/FSH ratios of 0.93 SD 0.26, 0.88 SD 0.17 and 0.81 SD 0.14 were also significantly lower than the preoperative value of 2.78 SD 1.21 (P < 0.001). Pregnancy occurred in eight women and there was a cumulative pregnancy rate at 6 months of 36% (8/22) among the subjects. There were no significant operative complications. CONCLUSION: Ultrasound-guided, transvaginal, ovarian, interstitial laser treatment appears effective in improving hormonal profiles and inducing ovulation and successful pregnancy in women with clomifene-resistant PCOS.
BACKGROUND: Dietary factors and history of smoking remain elusive in the pathogenesis of Parkinson's disease (PD). OBJECTIVE: We investigated the association of environmental factors with PD in a rural population in China. METHODS: Subjects were participants of a past nutritional intervention trial. Information on their characteristics was collected during the baseline interview of the trial. Control subjects were randomly selected from the same cohort and frequency matched for sex, age and residential area. RESULTS AND CONCLUSION: Among 16,488 subjects surveyed, we diagnosed 464 subjects with PD. Then, four sex- and age-matched controls were paired with each definite PD case. A total of 85 cases and 340 controls were analyzed. Meat consumption and the body mass index (BMI) were inversely associated with PD. The PD risk declined with the increment of BMI. A history of gastric ulcer was associated with an increased risk of PD. As to smoking, there seemed an increased risk of PD among individuals who smoked regularly, non-significantly. However, a significantly increased risk of PD was found among those who smoked more than 30 pack-years.
OBJECTIVE: To determine the prevalence of dementia and Alzheimer's disease (AD) in rural China. METHODS: A cross-sectional study was conducted within a cohort of adults older than 50 years of age in Linxian County, China. A Chinese version of the Mini-Mental State Examination (CMMSE) was used to screen cases of possible dementia. Three different cutoff points on CMMSE were applied depending on the participant's level of education. The participants then were given psychiatric interviews, medical and neurological examinations, and psychometric tests to ascertain the clinical diagnoses of dementia and AD. RESULTS: Among the 16,095 participants, 5.26% were screened positive with 374 diagnosed as having dementia. Among them, AD accounted for 80.5%. The adjusted prevalence rates were 0.33%, 0.89%, 3.43%, and 8.19% in people in age groups 50-54, 55-64, 65-74, and 75 and above, respectively. The prevalence of AD correlated with the participant's level of education, and was 2.61%, 0.94%, and 0.56% in the illiterate group, in the primary school group, and in the middle school or higher group, respectively. Adjusted by education levels a higher prevalence in women was observed in the illiterate group. CONCLUSIONS: The prevalence of dementia in this population is similar to that reported from other areas in mainland China and Taiwan with aging being a significant risk factor. After controlling for age, being a female and having received less number of years of education were associated with an higher prevalence of AD.
AIM: To determine the optic disc size in the adult Chinese population in an urban and a rural region of Beijing. METHODS: The population based, cross sectional cohort study included 4439 subjects out of 5324 subjects invited to participate (response rate 83.4%). It was divided into a rural part (1973 (44.4%) subjects) and an urban part (2466 (55.6%) subjects). Mean age was 56.2 (SD 10.6) years (range 40-101 years). Colour optic disc photographs were morphometrically examined. Main outcome measure was optic disc area. RESULTS: Optic disc photographs were available for 4027 (90.7%) subjects. Mean optic disc area measured 2.65 (0.57) mm2 (range 1.03 mm2-7.75 mm2). Optic disc area was significantly (p<0.001) correlated with myopic refractive error, with a steep decrease in optic disc area from high myopia to the mid-range of refractive error, a slightly horizontal course in the refractive error range between -8 dioptres and +4 dioptres, and a further decrease in optic disc area towards higher hyperopia. Optic disc area was not related to age (p = 0.14) or sex (p = 0.93) (optic disc area, males: 2.65 (0.56) mm2 versus females: 2.65 (0.57) mm2). "Microdiscs" may be defined as smaller than 1.51 mm2, and "macrodiscs" as larger than 3.79 mm2. CONCLUSIONS: Compared with data of preceding studies, mean optic disc size is larger in Chinese people than in white people. In Chinese people highly hyperopic eyes have significantly smaller optic discs, and highly myopic eyes have significantly larger optic discs than emmetropic eyes.
Attrition in longitudinal studies of survivors of childhood cancer reduces these studies' statistical power, introduces bias and threatens internal and external validity. This study investigated the variables associated with dropout of survivors of acute lymphoblastic leukemia in a trial investigating the effect of vitamin D and calcium supplementation and nutritional counseling on bone mineral density (BMD). Twenty-five participants withdrew from the study. Common reasons given for withdrawing were intolerance of the study drug, family hardship and schedule conflicts. Few statistically and clinically significant differences identified participants who completed the study. Nurses need to be aware of the reasons that participants withdraw from clinical trials, as they are in a strategic position to encourage patients to participate in health promotion studies.
We recently identified two compounds of 5-benzylidene-2-phenylimino-1,3-thiazolidin-4-one (BPT) analog, 5-(4-methylbenzylidene)-2-phenylamino-1,3-thiazolidin-4-one (MMPT) and 5-(2,4-dihydroxybenzylidene)-2-phenylimino-1,3-thiazolidin-4-one (DBPT), that can effectively induce apoptosis in cancer cells but not in normal cells, independently of P-glycoprotein status. To further investigate the antitumor activity of BPT analogs, we obtained 18 commercially available analogs of BPT and synthesized 7 analogs in our lab, and analyzed their antitumor activity in various cancer cells, including paclitaxel- and vinorelbine-sensitive and -resistant human lung cancer cells. Two of the compounds were more potent than MMPT or DBPT in induction of apoptosis in certain cancer cell lines and remained tumor selective. Seven compounds did not induce any cytotoxic effects in any of the cell lines tested at the highest concentration tested (31 microM). The other compounds induced cytotoxic effects in some cancer cells but not in others or were less potent than MMPT and DBPT. Cell uptake studies showed that analogs that effectively induced cell killing in paclitaxel- and vinorelbine-resistant cells could be taken up easily by those cells despite their high levels of P-glycoprotein expression. These data further demonstrate that thiazolidinone analogs are not P-glycoprotein substrates and could be useful for treatment of P-glycoprotein overexpressing refractory cancers.
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BACKGROUND AND PURPOSE: Professional boxing may result in brain injury. We hypothesize that quantitative MR diffusion imaging may be useful in determining early white matter changes. METHODS: Forty-nine professional boxers (age 30 +/- 4.5 years) and 19 healthy control subjects (age 32 +/- 9.5 years) were imaged on a clinical 1.5T scanner. None of the subjects had neurologic disorder or deficit. The average diffusion constant (D(av)) and diffusion anisotropy (FA) were determined pixel by pixel. Regional diffusion measurements were done in the corpus callosum (CC) and internal capsule (IC). The whole brain diffusion constant (BD(av)) was also determined. Student t test was used to analyze the diffusion difference between boxers and the healthy control subjects. P < .05 was considered statistically significant. RESULTS: Of the 49 professional boxers, 42 had normal conventional MRIs. The remaining 7 boxers had abnormal MR imaging findings dominated by nonspecific white matter disease. There was a significant difference in diffusion and anisotropy measurements in all the boxers compared with the healthy control subjects. In the boxer group, BD(av) increased and FA decreased significantly in the CC and posterior limb of IC. The measured FA and D(av) inversely correlated in regions of CC and IC in boxers but not in healthy control subjects. BD(av) also robustly correlated with both FA and D(av) in the splenium of CC in boxers. CONCLUSION: Increased BD(av) and the decreased FA in the CC and IC may represent preclinical signs of subtle brain injury in professional boxers.
BACKGROUND: To explore the relationship between hepatitis B virus (HBV) infection and development of IgA nephropathy. METHODS: HBsAg and HBcAg protein in renal biopsy specimens of 32 cases was detected on frozen sections and HBV DNA was detected in paraffin section of renal biopsies and in serum of 42 HBsAg positive cases. RESULTS: The positive rate of HBAg in renal biopsies of IgA nephropathy was 59.1%, and 63.6% in non-IgA nephropathy, there was no significant difference between them. In 42 cases biopsies of renal tissues, only five were HBV-DNA positive (11.9%). The five cases were HBsAg, HBcAb and HBeAg positive, the pathological diagnosis of two cases were mesangial proliferative glomerulonephritis; one had minimal change of glomerulonephritis; and one had basement membrane change; and only one had IgA nephropathy. At the same time, in 42 HBsAg+ cases the serum specimens were detected; 12 cases were positive for HBsAg, HBcAg and HBeAg, in whom serum HBV-DNA was positive, but only 5 were positive for HBV-DNA in renal biopsy tissue, and HBV-DNA was negative in other 30 blood serum and tissue specimens. CONCLUSION: The difference in expression of HBsAg, HBcAb and HBeAg protein between IgA nephropathy and non-IgA nephropathy tissue from renal biopsy was not significant. There is no direct relationship between HBV infection and IgA nephropathy.
Central nervous system myelin is a specialized structure produced by oligodendrocytes that ensheaths axons, allowing rapid and efficient saltatory conduction of action potentials. Many disorders promote damage to and eventual loss of the myelin sheath, which often results in significant neurological morbidity. However, little is known about the fundamental mechanisms that initiate myelin damage, with the assumption being that its fate follows that of the parent oligodendrocyte. Here we show that NMDA (N-methyl-d-aspartate) glutamate receptors mediate Ca2+ accumulation in central myelin in response to chemical ischaemia in vitro. Using two-photon microscopy, we imaged fluorescence of the Ca2+ indicator X-rhod-1 loaded into oligodendrocytes and the cytoplasmic compartment of the myelin sheath in adult rat optic nerves. The AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptor antagonist NBQX completely blocked the ischaemic Ca2+ increase in oligodendroglial cell bodies, but only modestly reduced the Ca2+ increase in myelin. In contrast, the Ca2+ increase in myelin was abolished by broad-spectrum NMDA receptor antagonists (MK-801, 7-chlorokynurenic acid, d-AP5), but not by more selective blockers of NR2A and NR2B subunit-containing receptors (NVP-AAM077 and ifenprodil). In vitro ischaemia causes ultrastructural damage to both axon cylinders and myelin. NMDA receptor antagonism greatly reduced the damage to myelin. NR1, NR2 and NR3 subunits were detected in myelin by immunohistochemistry and immunoprecipitation, indicating that all necessary subunits are present for the formation of functional NMDA receptors. Our data show that the mature myelin sheath can respond independently to injurious stimuli. Given that axons are known to release glutamate, our finding that the Ca2+ increase was mediated in large part by activation of myelinic NMDA receptors suggests a new mechanism of axo-myelinic signalling. Such a mechanism may represent a potentially important therapeutic target in disorders in which demyelination is a prominent feature, such as multiple sclerosis, neurotrauma, infections (for example, HIV encephalomyelopathy) and aspects of ischaemic brain injury.
Ion acceleration inside low-density foams irradiated by ultraintense laser pulses has been studied experimentally and theoretically. It is found that the ion generation is closely correlated with the suppressed hot electron transport inside the foams. Particle-in-cell simulations suggest that localized electrostatic fields with multi peaks around the surfaces of lamellar layers inside the foams are induced. These fields inhibit hot electron transport and meanwhile accelerate ions inside the foams, forming a bulk acceleration in contrast to the surface acceleration at the front and rear sides of a thin solid target.