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Biomedical subjects

N Chow

Publications and source records attributed to N Chow.

At least 19 recordsLinked to original sources

Epidemiology of conjugative plasmid-mediated AmpC beta-lactamases in the United States.

A sample of 752 resistant Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli strains from 70 sites in 25 U.S. states and the District of Columbia was examined for transmissibility of resistance to ceftazidime and the nature of the plasmid-mediated beta-lactamase involved. Fifty-nine percent of the K. pneumoniae, 24% of the K. oxytoca, and 44% of the E. coli isolates transferred resistance to ceftazidime. Plasmids encoding AmpC-type beta-lactamase were found in 8.5% of the K. pneumoniae samples, 6.9% of the K. oxytoca samples, and 4% of the E. coli samples, at 20 of the 70 sites and in 10 of the 25 states. ACT-1 beta-lactamase was found at eight sites, four of which were near New York City, where the ACT-1 enzyme was first discovered; ACT-1 beta-lactamase was also found in Massachusetts, Pennsylvania, and Virginia. FOX-5 beta-lactamase was also found at eight sites, mainly in southeastern states but also in New York. Two E. coli strains produced CMY-2, and one K. pneumoniae strain produced DHA-1 beta-lactamase. Pulsed-field gel electrophoresis and plasmid analysis suggested that AmpC-mediated resistance spread both by strain and plasmid dissemination. All AmpC beta-lactamase-containing isolates were resistant to cefoxitin, but so were 11% of strains containing transmissible SHV- and TEM-type extended-spectrum beta-lactamases. A beta-lactamase inhibitor test was helpful in distinguishing the two types of resistance but was not definitive since 24% of clinical isolates producing AmpC beta-lactamase had a positive response to clavulanic acid. Coexistence of AmpC and extended-spectrum beta-lactamases was the main reason for these discrepancies. Plasmid-mediated AmpC-type enzymes are thus responsible for an appreciable fraction of resistance in clinical isolates of Klebsiella spp. and E. coli, are disseminated around the United States, and are not so easily distinguished from other enzymes that mediate resistance to oxyimino-beta-lactams.

Bacterial Proteins↗

Overexpression of HER-2/neu enhances the sensitivity of human bladder cancer cells to urinary isoflavones.

Soybean foods have been suggested to be practical chemopreventives for human urinary tract cancers. Recently, we demonstrated that the co-operative action of isoflavones results in an increased dose-dependent growth inhibition and apoptosis than any single isoflavone compound. This study aimed to examine the potential of HER-2/neu as a biological target for soy isoflavones. The sensitivity of the bladder cancer cell lines (n=7) to the isoflavones was inversely related to the amount of HER-2/neu expressed. By using HER-2/neu transfection experiments, all three stable transfectants showed a significant growth inhibition by the isoflavone mixture at concentrations attainable in normal adult urine. An increased inhibition of tyrosine phosphorylation of proteins immunoprecipitated by HER-2/Neu was observed in the neu-transfectants compared with controls. The results of this study suggest that HER-2/neu may be a practical biochemical target for urinary isoflavones in vivo.

Antineoplastic Agents, Phytogenic↗

Proteinuria in obstructive sleep apnea.

BACKGROUND: Previous studies have reported an association between obstructive sleep apnea (OSA) and proteinuria, but are limited in their ability to assess proteinuria accurately, to adjust for confounders such as obesity, or to exclude confidently underlying renal disease in patients with OSA and nephrotic-range proteinuria. METHODS: The spot urine protein/creatinine ratio was measured in a prospective consecutive series of 148 patients referred for polysomnography who were not diabetic and had not been treated previously for OSA. The urine protein/creatinine ratio was compared across four levels of OSA severity, based on the frequency of apneas and hypopneas per hour: <5 (absent), 5 to 14.9 (mild), 15 to 29.9 (moderate), and > or =30 (severe). RESULTS: The median level of urine protein/creatinine ratio in all categories of OSA was <0.2 (range 0.03 to 0.69; median 0.06 in patients with normal apnea hypopnea index, 0.06, 0.07, 0.07 in patients with mild, moderate, and severe OSA, respectively). Eight subjects had a urine protein/creatinine ratio greater than 0.2. Univariate analysis showed a significant association between urine protein/creatinine ratio and older age (P < 0.0001), hypertension (P < 0.0001), coronary artery disease (P = 0.003), and arousal index (P = 0.003). Body mass index (P = 0.16), estimated creatinine clearance (P = 0.17), and apnea hypopnea index (P = 0.13) were not associated with the urine protein/creatinine ratio. In multiple regression analysis, only age and hypertension were independent positive predictors of the urine protein/creatinine ratio (P < 0.0001, R2 = 0.17). CONCLUSION: Clinically significant proteinuria is uncommon in sleep apnea. Nephrotic range proteinuria should not be ascribed to sleep apnea and deserves a thorough renal evaluation.

Adult↗

Expression profiles of multiple genes in single neurons of Alzheimer's disease.

Many changes have been described in the brains of Alzheimer's disease (AD) patients, including loss of neurons and formation of senile plaques and neurofibrillary tangles. The molecular mechanisms underlying these pathologies are unclear. Northern blot, dot-blot, and reverse transcription-coupled PCR analyses have demonstrated altered expression levels of multiple messages in AD brain. Because not all cells are equally affected by the disease, these methods obviously cannot study the changes in relation to disease states of individual cells. We address this problem by using antisense RNA profiling of single cells. We present expression profiles of single neurons at early and late stages of AD and describe statistical tools for data analysis. With multivariate canonical analysis, we were able to distinguish the disease state on the basis of altered expression of multiple messages. To validate this approach, we compared results obtained by this approach with results obtained by in situ hybridization analysis. When the neurofilament medium subunit was used as a marker, our results from an antisense RNA profiling revealed no change in neurofilament medium subunit expression between early- and late-stage AD, consistent with findings obtained with in situ hybridization. However, our results obtained by either analysis at the single-cell level differed from the reported decrease in AD neocortex obtained by Northern blot analysis [Kittur, S., Hoh, J., Endo, H., Tourtellotte, W., Weeks, B. S., Markesbery, W. & Adler, W. (1994) J. Geriatr. Psychiatry Neurol. 7, 153-158]. Thus, the strategy of using the single-cell antisense RNA approach to identify altered gene expression in postmortem AD brain, followed by detailed in situ hybridization studies for genes of interest, is valuable in the study of the molecular mechanisms underlying AD neuropathology.

Aged↗

The influence of total, dialysis, and residual renal urea clearances on serum albumin in peritoneal dialysis.

Though serum albumin (SA) and Kt/V predict mortality in peritoneal dialysis (PD), the relationship between them remains unclear. We report a cross-sectional study of factors associated with SA in PD, and a prospective study of the effect of increasing dialysis dose on SA in hypoalbuminemic patients with Kt/V < 2.1. Multiple linear regression was performed in 56 subjects with dependent variable SA at 4 months after starting PD (SA2), and independent variables: age, sex, diabetes, 4h-D/Pcr, predialysis SA (SA1), nPCR, PD-duration, modality, Kt/V, Ccr, and daily volume excreted normalized to body water (Vt/V). Forward stepwise selection (alpha = 0.05) produced a model (r2 = 0.492, P < 0.001) containing predictors of SA2: SA1 and nPCR (positive), and Vt/V (negative). With Vt/V excluded, Kt/V became significant (negative). Broken into components, dialysate Kt/V was significant, but residual Kt/V was not significant. In 14 hypoalbuminemic patients with Kt/V < 2.1, PD prescription was changed, targeting a Kt/V > 2.1. After 3.3 months, Kt/V rose from 1.7 +/- 0.25 to 2.21 +/- 0.36 (P = 0.0001), and nPCR rose slightly, 0.71 +/- 0.13 to 0.78 +/- 0.19 (P = NS), with no significant change in SA, 30.5 +/- 3.0 g/L to 31.4 +/- 3.8 g/L (P = 0.268). Dialysate and urine volumes are negative predictors of SA. Volume-dependent dialysate-protein loss could account for poor correlation between Kt/V and SA, and lack of improvement in SA with increased Kt/V.

Adolescent↗

Isolation of single immunohistochemically identified whole neuronal cell bodies from post-mortem human brain for simultaneous analysis of multiple gene expression.

In Alzheimer's disease (AD), one cell in the brain may clearly be affected, while an adjacent cell appears healthy or unaffected. Previous technology has allowed us to examine one message at a time, at the level of a single cell (in situ hybridization, ISH), or multiple messages in a heterogeneous population of cells (Northern analysis). We have developed a methodology to build up a profile of multiple mRNA expression in single, whole, post-mortem cells that have been immunohistochemically (IHC) characterized. Fresh post-mortem tissue is spread into a layer one cell thick and fixed. Neurons are identified using an antibody to neurofilament and isolated using a micropipette. The mRNA is reverse transcribed and PCR carried out to confirm that material is present. A radioactively labeled antisense aRNA probe, which is representative of the messages contained in the cell is then amplified. This aRNA is used as a probe for a reverse Northern blot, allowing us to profile many genes from one cell at the same time. This technology has the potential to be applied to a wide variety of diseases encompassing many different cell types.

Autopsy↗

APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein.

beta-Amyloid protein precursors (APPs, 695-770 amino acids) are the source of the 39-43 amino acid beta-amyloid (A beta) peptides that comprise diffuse and fibrillar deposits in the cerebral cortex and vasculature of Alzheimer's disease brains. A beta is thought to play a role in the pathogenesis of Alzheimer's disease, and, hence, considerable effort has been invested in defining the means by which A beta is generated from the APPs. Knowledge of the normal function of the APPs is sure to provide insights into the genesis and pathological persistence of A beta in Alzheimer's disease. APP is a cell surface protein with a large extracellular amino-terminal domain, a single transmembrane segment, and a short cytoplasmic tail. Its location and structural features characteristic of a receptor for signal transduction led us to search for potential effector proteins capable of binding and interacting with its cytoplasmic domain. Here, we report the cloning of a cDNA encoding one such protein. This ubiquitously expressed 59-kDa APP-binding protein, called APP-BP1, is 61% similar to a protein encoded by the Arabidopsis AXR1 gene, required for normal response to the hormone auxin, and is a relative of the ubiquitin activating enzyme E1.

Adult↗

The changing responsibilities of the state and family toward elders in Hong Kong.

With a predominantly Chinese population and a cultural tradition of respecting the old, Hong Kong has long relied on the family to support its elderly members. Economic success has, however, not spared Hong Kong from encountering the same problems as other industrial societies, such as the loosening of its traditional values. This article examines the changing responsibilities of the state and the family in Hong Kong in supporting the old, and in particular, the effectiveness of the "care in community" policy, which the Hong Kong Government has adopted since the mid-1970s. The examination concludes that the responsibility must now be shared between the state and the family.

Aged↗

The role of fitness on VO2 and VCO2 kinetics in response to proportional step increases in work rate.

The purpose of this study was to determine the effect of fitness and work level on the O2 uptake and CO2 output kinetics when the increase in work rate step is adjusted to the subject's maximum work capacity. Nine normal male subjects performed progressive incremental cycle ergometer exercise tests in 3-min steps to their maximum tolerance. The work rate step size was selected so that the symptom-limited maximum work rate would be reached in four steps at 12 min in all subjects. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were calculated breath by breath. For the group, the time (mean, SEM) to reach 75% of the 3-min response (T0.75) for VO2 increased significantly (P less than 0.01) at progressively higher work rate steps, being 53.3 (5.5) s, 63.5 (4.6) s, 79.5 (5.0) s, and 94.5 (5.8) s, respectively. In contrast, T0.75 for VCO2 did not change significantly [74.9 (7.4) s, 75.6 (5.0) s, 85.1 (5.3) s, and 89.4 (6.3) s, respectively]. VCO2 kinetics were slower than VO2 kinetics at the low fractions of the subjects' work capacities but were the same or faster at the high fractions because of the slowing of VO2 kinetics. The first step showed the fastest rise in VO2. While VO2 kinetics slowed at each step, they were faster at each fraction of the work capacity in the fitter subjects. The step pattern in VO2 disappeared at high work rates for the less fit subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Does filial piety exist under Chinese communism?

China has been known for centuries for its traditions of respecting the old. While this tradition has been weakened in the modern era, it still remains as the most important value underlying the practice of supporting the old in present-day China. This article looks into the meaning of filial piety, or xiao, and examines how it has been observed both in the old and modern times. It argues that though the Chinese communists have found filial piety ideologically repulsive, they have nevertheless tolerated it and even used it as the basis for a welfare network to support the elderly in the villages. However, in order to be truthful to their socialist ideology, they have also provided for urban workers the most sophisticated state-financed retirement benefits. Two different kinds of systems to support the elderly hence exist in China. The tensions resulting from this dichotomous situation are examined.

Aged↗

Effect of exercise testing protocol on parameters of aerobic function.

Four different patterns of increasing work rate (ramp and 1-min, 2-min, and 3-min steps) to maximum tolerance were studied in eight normal male subjects during cycle ergometer exercise testing to determine the effect of the work rate protocol on the parameters of aerobic function. The overall rate of work rate increase was kept constant. Measurements included VO2max, anaerobic threshold (AT), and the O2 uptake increase with respect to work rate increase (delta VO2/delta WR). VO2, VCO2, VE, respiratory exchange ratio (R), PETCO2, and PETO2 were calculated breath-by-breath. No significant difference was found in VO2max, AT, AT/VO2max, and delta VO2/delta WR among the four work rate protocols. Other measurements such as total work, maximal work rate, VCO2, VE, R, HR, O2 pulse, and the VO2 at which VE increases disproportionately to VCO2 (ventilatory compensation point) were also similar among the four protocols. Both the ramp and 1-min step work rate tests had no step pattern in either VO2 or VCO2, and the step pattern for the 2-min and 3-min step tests was attenuated or disappeared at work rates above AT. We conclude that the parameters of aerobic function, and other physiological responses at maximum work rate, were independent of the pattern of work rate increase, provided that the overall rate of work rate increase was the same.

Adult↗

Virus-specified protease in poliovirus-infected HeLa cells.

Previous studies have shown that primary cleavages in nascent picornavirus precursors are accomplished by cellular proteases. This study has characterized the enzyme in infected cells that produces the capsid polypeptides by secondary cleavages of viral precursors. The kinetics of the production of protease activity correlate with the time course of virus protein synthesis, and the new enzyme has characteristic pH and temperature optima. Guanidine and cycloheximide, which are inhibitors of virus RNA and protein synthesis, prevent production of the protease. As determined by introduction of amino acid analogs into the protease or inhibition by a leucyl chloromethyl ketone, the enzyme is synthesized at a time of infection when host cell proteins are not produced, and the enzyme copurified with a 40,000-dalton virus polypeptide present in the cytoplasm of infected cells. Wild-type levels of protease activity are produced by viral mutants that are defective in coat protein synthesis. The conclusion is that a non-structural poliovirus gene product participates in protein cleavages that produce the viral coat proteins.

HeLa Cells↗

Specificity of antitumor immune reactions mediated by xenogeneic immune RNA.

Evidence that xenogeneic immune RNA (I-RNA) mediated specific cytotoxic immune responses against human tumor-associated antigens was obtained from in vitro studies in two autologous melanoma systems. In these systems, malignant melanoma target cells, matching normal fibroblast target cells, lymphocyte effector cells, and melanoma and normal skin tissue used to immunize RNA donor animals were derived from the same autochthonous hosts. When incubated with autologous lymphocytes, I-RNA extracted from the lymphoid organs of donor animals immunized with melanoma tissue mediated immune reactions against autologous melanoma target cells in vitro. I-RNA from animals immunized with normal skin tissue from autochthonous hosts did not increase the cytotoxicity of autologous lymphocytes for autologous melanoma cells. Using autologous fibroblasts as target cells, we detected no increase in cytotoxicity when autologous lymphocytes were incubated with RNA from animals immunized either with melanoma tissue or normal skin tissue from the autochthonous host. By contrast, when allogeneic lymphocytes were used as effector cells, RNA extracted from animals immunized either with melanoma tissue or normal skin mediated cytotoxic immune reactions against melanoma target cells and normal fibroblast target cells derived from the same patient.

Antigens, Neoplasm↗

Mediation of cytotoxic immune responses against human tumor-associated antigens by allogeneic immune RNA.

Allogeneic immune RNA (I-RNA), extracted from the peripheral blood lymphocytes of patients putatively cured of cancer, mediated cytotoxic immune reactions that apparently were directed specifically against human tumor-associated antigens. I-RNA was extracted from the peripheral blood lymphocytes of patients with various types of cancer. Patients selected had not been previously sensitized to HL-A or other normal transplantation antigens or to blood group antigens. Normal human peripheral blood lymphocytes were incubated with these allogeneic I-RNA preparations and tested for cytotoxicity against human target cells in vitro. Allogeneic I-RNA mediated cytotoxic immune reactions only against tumor target cells of the same histologic type as the I-RNA donor. I-RNA's extracted from peripheral blood lymphocytes of melanoma patients mediated cytotoxic immune reactions only against melanoma cells. Similarly, only I-RNA's extracted from the lymphocytes of patients with colon cancer mediated cytotoxic immune reactions against colon carcinoma cells, and only I-RNA's from the lymphocytes of breast cancer patients mediated immune reactions against breast cancer target cells. Allogeneic I-RNA extracted from peripheral blood lymphocytes of cancer patients possibly mediated specific cytotoxic immune reactions that were directed against common tumor-associated antigens shared by human tumors of similar histologic type.

Antigens, Neoplasm↗