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Biomedical subjects

J Ng

Publications and source records attributed to J Ng.

At least 73 records · Page 4Linked to original sources

HLA-A*28 allele frequencies in the five major U.S. ethnic groups.

The frequency of each A*28 allele was determined by PCR-SSOP typing in 5 major U.S. ethnic populations: Caucasians, African Americans, Asians/Pacific Islanders, Hispanics, and Native Americans. The percent of serologically defined A28-positive individuals in the 5 populations ranged from 2.7-17.9%. Fifty-nine individuals who were previously serologically typed as A28, A68 or A69 were randomly chosen for allele-level typing from each ethnic group from a database of 82,979 consecutively typed unrelated individuals. The most common A*28 allele for Caucasians, Asians/Pacific Islanders, Hispanics, and Native Americans was A*68012, while A*6802 was found in the majority of African Americans. Only four and three A*28 alleles were seen in Caucasians and African Americans, respectively, while five to six A*28 alleles were seen in the other population groups. The A*6804 and A*6806 alleles were not observed in any of the five ethnic groups.

Alleles↗

Relative HLA-DRB1*13 allele frequencies and DRB3 associations of unrelated individuals from five US populations.

The frequencies of 30 HLA-DRB1*13 alleles and 15 DRB3 alleles were determined for the 5 major U.S. ethnic populations: Caucasians, African Americans, Asian/Pacific Islanders, Hispanics, and Native Americans. A random sampling (163) of DRB1*13-positive individuals from each self-described ethnic group was selected out of a pool of 82,979 unrelated individuals, providing at least an 80% probability of detecting a rare allele that occurred at 1%. These 815 samples were subjected to allele-level SSOP typing and/or DNA sequencing which identified 11 different DRB1*13 alleles. DRB1*1301 and DRB1*1302 were the most common alleles seen in the five major ethnic groups while DRB1*1304 was not detected among Caucasians and DRB1*1305 was not detected among African Americans. DRB1*13 allele diversity was surprisingly more limited among African Americans compared to both Caucasians and Asian/Pacific Islanders. To determine the extent of DRB1*13-DRB3 associations, 504 of these samples expressing only one DRB3-associated DRB1 allele were subjected to PCR-SSOP typing and 14 DRB1*13-DRB3 haplotypes were detected. The distribution revealed that African Americans were significantly different from Caucasians, Asian/Pacific Islanders, and Hispanics. Allele frequency studies such as this further support previous findings that the distribution of HLA types can differ significantly among different ethnic populations.

Alleles↗

The effects of rehydration on phonation in excised canine larynges.

Experiments using excised canine larynges were conducted to study the restoration of vocal efficiency in dehydrated larynges. Excised larynges were dehydrated with warm, dry air to the point that airflow through the approximated vocal folds would not entrain the folds to produce phonation. The dehydrated vocal folds were then bathed in a saline solution. The rehydrated larynges were then remounted on the bench apparatus that enabled phonation with a constant humidified airflow, and measurements were made of phonation threshold pressure, glottal airflow, and amplitude. Hydration resulted in significantly increased efficiency and decrease in phonation threshold pressure. The findings confirm clinical impressions that hydration is critical in the physiology of normal phonation.

Animals↗

The relative frequencies of HLA-A*10 alleles in five major United States ethnic populations.

The frequency of each A*10 allele was determined in 5 major United States ethnic populations randomly selected from a pool containing 82,979 unrelated individuals. The phenotype frequency of A10 was 10.5% in Caucasians, 14.0% in African-Americans, 21.1% in Asians/Pacific Islanders, 10.6% in Hispanics, and 9.8% in Native Americans. Fifty-nine individuals who had at least one A10 antigen were randomly chosen from each ethnic group for polymerase chain reaction using sequence-specific oligonucleotide probes (PCR-SSOP) typing. Thirteen of sixteen known A10 alleles were identified in this pool. The most common alleles observed were: A*2601 in Caucasians (55%), Hispanics (58%), and Native Americans (45%); A*3402 in African-Americans (34%); and A*3401 in Asians/Pacific Islanders (61%). The African-American and Asian/Pacific Islander populations differ from all other populations in the distribution of A*10 alleles, particularly, A*2601, A*3401, and A*3402.

Black or African American↗

Sleep paralysis in the elderly.

Isolated sleep paralysis (SP) is a common sleep phenomenon that is highly colored by indigenous beliefs. In Hong Kong Chinese, the 'ghost oppression phenomenon' (GO) has been shown to be descriptively identical to SP. The prevailing concept is that the majority of cases with SP have their onset during adolescence, but the lack of any systematic study on an older population means that late-onset cases can not be excluded. In a study investigating the prevalence of mental disorders in Chinese elderly aged above 70 y in Hong Kong, we employed the revised GO questionnaire to study the prevalence of SP in this group of elderly as well. One hundred and fifty-eight subjects were finally analyzed for the study. Almost 18% (95% C.I. 11.77%, 23.68%) of the subjects reported experiences of GO. Their description of the features of GO showed striking similarity to those of SP. There was a clear bimodal distribution of onset of GO with peaks during adolescence and after age 60 y. At least one-third of the cases were late onset. In concordance with the rapid eye movement (REM)/wakefulness dissociation hypothesis of SP, those elderly with GO+ experiences also had more frequent nocturnal sleep disturbances. A family history was reported in 10% of subjects.

Age of Onset↗

Are performance-based measures sufficiently reliable for use in multicenter trials? Musculoskeletal Impairment (MSI) Study Group.

BACKGROUND: The literature contains few reports of the test-retest reliability of performance-based measures. The purpose of this study was to determine the test-retest reliability of a battery of seven timed, performance-based measures used to assess the functional limitations of frail, older adults. METHODS: One hundred and five frail, elderly subjects were twice administered a battery of timed tests approximately 2 weeks apart: 8-foot walk, get-up-and-go test, stair climb, single and repetitive standing from a chair, and single and repetitive 10-pound lifts with the upper limbs. Agreement between the mean times recorded for accomplishing each task at the two administrations was assessed. RESULTS: Intraclass correlation coefficients ranged from .25 for the single chair stand to .79 for the 8-foot walk. Only the time taken for the single 10-pound lift was significantly greater at the first administration as compared with the second. CONCLUSIONS: Timed performance-based measures have a wide range of test-retest reliability. Performance-based protocols that reflect familiar tasks with discrete starting and ending points may achieve higher reliability than tasks that are unfamiliar to subjects or may have ambiguous elements in them.

Activities of Daily Living↗

Identification of Lactobacillus isolates from the gastrointestinal tract, silage, and yoghurt by 16S-23S rRNA gene intergenic spacer region sequence comparisons.

Lactobacillus isolates were identified by PCR amplification and sequencing of the region between the 16S and 23S rRNA genes (spacer region). The sequences obtained from the isolates were compared to those of reference strains held in GenBank. A similarity of 97.5% or greater was considered to provide identification. To check the reliability of the method, the V2-V3 region of the 16S rRNA gene was amplified and sequenced in the case of isolates whose spacer region sequences were less than 99% similar to that of a reference strain. Confirmation of identity was obtained in all instances. Spacer region sequencing provided rapid and accurate identification of Lactobacillus isolates obtained from gastrointestinal, yoghurt, and silage samples. It had an advantage over 16S V2-V3 sequence comparisons because it distinguished between isolates of Lactobacillus casei and Lactobacillus rhamnosus.

Bacterial Typing Techniques↗

Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group.

Growth hormone (GH) stimulates osteoblasts in vitro and increases bone turnover and stimulates osteoblast activity when given to elderly subjects. Probably a major effect of GH on bone is mediated through stimulation of either circulating or locally produced insulin-like growth factor I (IGF-I). We determined the effect of chronic administration of the GH secretagogue, MK-677, on serum IGF-I and markers of bone turnover in 187 elderly adults (65 years or older) enrolled in three randomized, double-blind, placebo-controlled clinical studies lasting 2-9 weeks. Urine was collected for determination of N-telopeptide cross-links (NTXs), a marker of bone resorption, and blood was collected for determination of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), as bone formation markers, and serum IGF-I levels pre- and post-treatment. Dose response data were initially obtained in healthy elderly subjects who received oral doses of 10 mg or 25 mg of MK-677 or placebo for 2 weeks (n = 10-12/group). Treatment with 10 mg and 25 mg of MK-677 for 2 weeks increased mean urine NTXs 10% and 17%, respectively (p < 0.05 vs. placebo). Additionally, 50 healthy elderly subjects received either placebo (n = 20) for 4 weeks or 25 mg of MK-677 (n = 30) daily for 2 weeks followed by 50 mg daily for 2 weeks. MK-677 increased mean serum osteocalcin by 8% (p < 0.05 vs. placebo). In both studies, MK-677 increased serum IGF-I levels significantly (55-94%). Subsequently, the biological effects of MK-677 were studied in 105 elderly subjects who met objective criteria for functional impairment. Subjects were randomized to receive oral doses of placebo for 9 weeks or either 5, 10, or 25 mg of MK-677 daily for an initial 2 weeks followed by 25 mg of MK-677 daily for the next 7 weeks(n = 63 on MK-677 and n = 28 on placebo completed 9 weeks of therapy). Treatment with MK-677 (all MK-677 groups combined) for 9 weeks increased mean serum osteocalcin by 29.4% and BSAP by 10.4% (p < 0.001 vs. placebo) and mean urinary NTX excretion by 22.6% (p < 0.05 vs. placebo). The change from baseline serum osteocalcin correlated with the change from baseline serum IGF-I in the MK-677 group (r = 0.37; p < 0.01). In conclusion, once daily dosing with MK-677, an orally active GH secretagogue, stimulates bone turnover in elderly subjects based on elevations in biochemical markers of bone resorption and formation.

Aged↗

Changing the institutional practice of prolonged mechanical ventilation after coronary artery bypass graft surgery to early extubation.

Since 1997 some of our cardiac anaesthetists have, whenever possible, extubated the patients early after cardiac surgery to improve their level of comfort, to allow an early return of the cardiopulmonary physiological function, and to help reduce health care costs. After a few months of implementing this practice, an audit was carried out to evaluate the success of early extubation after coronary artery bypass graft (CABG) surgery. Over a 6-month period starting from May 1997, the perioperative data of 110 consecutive patients with good or moderate left ventricular function scheduled for elective CABG were prospectively collected and analysed. The anaesthetic regime was according to the preference of the anaesthetists. Initially consent was obtained from the surgeons when the extubation criteria were fulfilled, but subsequently as the practice became more accepted by the surgeons, extubation was initiated by the anaesthetists. Within 4 hours of admission into the intensive care unit (ICU), 50 (45.5%) of the 110 patients satisfied the early extubation criteria and were extubated. The extubation criteria are described in the article. For the remaining patients, the median duration of mechanical ventilation was 14.3 hours. The profiles of the two groups of patients and the possible reasons for not extubating early are discussed. Forty-five per cent of the patients with moderate to good ventricular function were extubated safely within 4 hours of admission into the ICU after CABG surgery. With gradual acceptance of the practice and a change in mindset amongst all the care givers, more patients can benefit from this practice. This article highlights the challenges associated with changing institutional practices with respect to the postoperative care of cardiac patients.

Analysis of Variance↗

Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine.

CD8+ cytotoxic T lymphocytes (CTLs) are critical for protection against intracellular pathogens but often have been difficult to induce by subunit vaccines in animals. DNA vaccines elicit protective CD8+ T cell responses. Malaria-naïve volunteers who were vaccinated with plasmid DNA encoding a malaria protein developed antigen-specific, genetically restricted, CD8+ T cell-dependent CTLs. Responses were directed against all 10 peptides tested and were restricted by six human lymphocyte antigen (HLA) class I alleles. This first demonstration in healthy naïve humans of the induction of CD8+ CTLs by DNA vaccines, including CTLs that were restricted by multiple HLA alleles in the same individual, provides a foundation for further human testing of this potentially revolutionary vaccine technology.

Adult↗

Subacute Pb exposure during development and unbaited tunnel maze performance in mice.

Although research has linked chronic, low-level Pb exposure to behavioral and cognitive changes in humans and animals, far less is known about the effects of transient, subchronic Pb exposure during early postnatal development. The need to understand such effects is underscored by the possibility that subchronic Pb exposure may not produce chronically elevated blood-Pb levels, but may produce long-term behavioral changes. To test this hypothesis, we investigated the effect of low-level Pb exposure on unbaited tunnel maze performance in Binghamton Heterogeneous Stock mice. Mice were either nontreated or given subchronic sodium acetate, 5, 10, or 25 mg/kg Pb acetate intragastrically on postnatal (PN) days 6, 9, 12, 15, and 18. No further Pb exposures were given after postnatal day 18. Blood-Pb measurements were taken from selected mice on PN 18, 19, 23, 28, and 38. On PN 38-42, all mice were individually tested in an unbaited tunnel maze under nondeprived conditions. Locomotor activity, exploration, and experience-dependent changes in cul-de-sac entries were recorded. Although Pb did not affect bodyweight and blood-Pb levels were below 10 microg/dl at the time of behavioral testing, a history of low-level preweaning Pb exposure caused a dose-dependent increase in cul-de-sac entries. This behavioral change was dissociable from changes in bodyweight, degree of exploration or an a priori bias to enter cul-de-sacs. The current results support the hypothesis that brief, subchronic Pb exposure during development produces behavioral changes that last well beyond the exposure period, even when blood Pb declines to within "acceptable" levels (l0 microg/dl).

Analysis of Variance↗

Novel HLA-A and HLA-B alleles.

Nine novel HLA-A and HLA-B alleles are described: A*2609, A*6803, A*6806, B*1539, B*1540, B*2712, B*4103, B*5109, and B*5603. Most appear to have arisen by gene conversion events. B*5603 appears to have arisen by a reciprocal recombination event joining exon 2 of a B*55/ *56 allele with exon 3 of a B*15 allele. Serologically, the antigen encoded by this allele types with broad B22- and Bw6-specific alloantisera. Also unique, the antigen encoded by B*2712 does not react with B27-specific alloantisera but does react with Bw6-specific alloantisera.

Alleles↗

The Drosophila esc and E(z) proteins are direct partners in polycomb group-mediated repression.

The extra sex combs (esc) and Enhancer of zeste [E(z)] proteins are members of the Drosophila Polycomb group (Pc-G) of transcriptional repressors. Here we present evidence for direct physical interaction between the esc and E(z) proteins using yeast two-hybrid and in vitro binding assays. In addition, coimmunoprecipitation from embryo extracts demonstrates association of esc and E(z) in vivo. We have delimited the esc-binding domain of E(z) to an N-terminal 33-amino-acid region. Furthermore, we demonstrate that site-directed mutations in the esc protein previously shown to impair esc function in vivo disrupt esc-E(z) interactions in vitro. We also show an in vitro interaction between the heed and EZH1 proteins, which are human homologs of esc and E(z), respectively. These results suggest that the esc-E(z) molecular partnership has been conserved in evolution. Previous studies suggested that esc is primarily involved in the early stages of Pc-G-mediated silencing during embryogenesis. However, E(z) is continuously required in order to maintain chromosome binding by other Pc-G proteins. In light of these earlier observations and the molecular data presented here, we discuss how esc-E(z) protein complexes may contribute to transcriptional silencing by the Pc-G.

Amino Acid Sequence↗

Prevalence of dementia in Chinese elderly in Hong Kong.

This study examines the prevalence of dementia in elderly Chinese aged 70 years and older in Hong Kong using a two-phase design. In phase 1, 1,034 elderly were interviewed with the Cantonese version of the Mini-Mental State Examination. Those who scored below the cutoff points and a subsample of those with scores in the normal range were interviewed in phase 2 to identify those with dementia. The overall weighted prevalence of dementia in our subjects was 6.1 +/- 0.7%, which is at the lower end of the range of rates reported in whites. Alzheimer's disease (AD) accounted for 64.6% and vascular dementia, 29.3%. Our results, together with previous studies in Chinese populations, suggest that the rates of AD in Chinese are low compared with those in whites. Substantial differences are possible in the epidemiology of dementia across cultures related to interactions of genetic and environmental factors.

Age Distribution↗

Aminopeptidase activities in Peptostreptococcus spp. are statistically correlated to gelatin hydrolysis.

One hundred Peptostreptococcus isolates from five species were assessed for their ability to hydrolyze gelatin. Most Peptostreptococcus magnus (95.8%) and Peptostreptococcus micros isolates (79.0%) hydrolyzed gelatin in contrast to Peptostreptococcus asaccharolyticus (8.0%), Peptostreptococcus anaerobius (10.0%), and Peptostreptococcus prevotii isolates (16.7%). Gelatin hydrolysis in Peptostreptococcus magnus and Peptostreptococcus micros isolates correlated (r = 0.80; P = 0.0019) with more aminopeptidases produced than Peptostreptococcus asaccharolyticus, Peptostreptococcus anaerobius, or Peptostreptococcus prevotii. The five species were further classified into three groups using the extended Tukey test (P < 0.0001) based on the mean percentage of aminopeptidases produced by each species with Peptostreptococcus magnus and Peptostreptococcus micros belonging to group I, Peptostreptococcus asaccharolyticus and Peptostreptococcus prevotii belonging to group II, and Peptostreptococcus anaerobius forming group III. An analysis of possible proteolytic activity of four selected Peptostreptococcus magnus isolates indicated that only 5 of 11 substrates were hydrolyzed as compared to a control isolate of Porphyromonas gingivalis W83, which had a strong proteolytic profile. Therefore, gelatin hydrolysis by Peptostreptococcus spp., in particular Peptostreptococcus magnus and Peptostreptococcus micros, is probably due to a variety of aminopeptidases rather than proteinases.

Aminopeptidases↗

STAT3 is a serine kinase target in T lymphocytes. Interleukin 2 and T cell antigen receptor signals converge upon serine 727.

Interleukin 2 (IL-2) induces tyrosine phosphorylation of STATs 3 and 5 (signal transducer and activator of transcription). We now show that IL-2 regulation of STAT3 proteins in T cells is a complex response involving activation of two forms of STAT3: 90-kDa STAT3alpha and an 83-kDa carboxyl-terminal truncated STAT3beta. The phosphorylation of STAT proteins on serine residues is also required for competent STAT transcription. A critical serine phosphorylation site in STAT3alpha is at position 727. In this study we have produced an antisera specific for STAT3alpha proteins phosphorylated on serine 727 and used this to monitor the phosphorylation of this residue during T lymphocyte activation. Our results show that phosphorylation of STAT3alpha on serine 727 is not constitutive in quiescent T cells but can be induced by the cytokine IL-2. Interestingly, triggering of the T cell antigen receptor complex or activation of protein kinase C with phorbol esters also induces phosphorylation of serine 727 but without simultaneously inducing STAT3 tyrosine phosphorylation or DNA binding. Hence, the present results show that STAT3 serine phosphorylation can be regulated independently of the tyrosine phosphorylation of this molecule. IL-2 and T cell antigen receptor complex induction of STAT3alpha serine 727 phosphorylation is dependent on the activity of the MEK/ERK pathway. Previous studies have identified H-7-sensitive kinase pathways that regulate STAT3 DNA binding. We show that H-7-sensitive pathways regulate STAT3 DNA binding in T cells. Nevertheless, we show that H-7-sensitive kinases do not regulate STAT3 tyrosine phosphorylation or phosphorylation of serine 727. These results thus show that STAT3 proteins are targets for multiple kinase pathways in T cells and can integrate signals from both cytokine receptors and antigen receptors.

Amino Acid Sequence↗

Some statistical methods for multiple endpoints in clinical trials.

This paper summarizes, defines, and discusses multiple endpoints comparison procedures, concepts, and methodologies for applications to clinical trials. We address the more widely used methods of alpha-level, p-value, and critical value adjustments. We examine global assessment measures such as O'Brien's test and Simes' procedure and contrast them with the alpha-adjustment procedures of Bonferroni and Holm. We propose a global assessment procedure based on categorization of the individual endpoints to form an overall composite endpoint. Additionally, we discuss a new weighting scheme for Holm's sequentially rejective alpha-adjustment procedure. Investigation of the correlation between endpoints is examined in relation to adjustment of the alpha-level. In the context of a clinical trial, the above multiplicity procedures are applied and compared. Finally, some comments concerning ease of use and relevance are summarized for the above methods.

Asthma↗