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Biomedical subjects

W W Wong

Publications and source records attributed to W W Wong.

At least 19 recordsLinked to original sources

Mass spectrometric determination of dioxygen bond splitting in the "peroxy" intermediate of cytochrome c oxidase.

The "peroxy" intermediate (P form) of bovine cytochrome c oxidase was prepared by reaction of the two-electron reduced mixed-valence CO complex with (18)O(2) after photolytic removal of CO. The water present in the reaction mixture was recovered and analyzed for (18)O enrichment by mass spectrometry. It was found that approximately one oxygen atom ((18)O) per one equivalent of the P form was present in the bulk water. The data show that the oxygen-oxygen dioxygen bond is already broken in the P intermediate and that one oxygen atom can be readily released or exchanged with the oxygen of the solvent water.

Animals

Monitoring childhood obesity: assessment of the weight/height index.

The body mass index (BMI), defined as weight/height, is often used to monitor childhood obesity. BMI values for 979 children (438 White, 283 Black, and 258 Hispanic) aged 3-18 years living in the Houston, Texas, metropolitan area from 1994 to 1998 were compared with percentage of fat (%Fat) measurements obtained by using dual-energy x-ray absorptiometry. The associations between %Fat and BMI were statistically significant (r2 = 0.34-0.70, p < 0.0005) and were gender and ethnic dependent (p < 0.0005), indicating that BMI can provide a general description of the adiposity characteristics of a healthy pediatric population. However, BMI was a poor predictor for the individual child, with a standard error for %Fat of 4.7-7.3% of body weight. It is advantageous to identify accurately, as early as possible, those children who truly have excess adiposity, but this assessment should not be done at the risk of falsely mislabeling a significant number of healthy children as overweight or obese.

Absorptiometry, Photon

Nonspecific weak actomyosin interactions: relocation of charged residues in subdomain 1 of actin does not alter actomyosin function.

Yeast actin mutants with relocated charged residues within subdomain 1 were constructed so we could investigate the functional importance of individual clusters of acidic residues in mediating actomyosin weak-binding states in the cross-bridge cycle. Past studies have established a functional role for three distinct pairs of charged residues within this region of yeast actin (D2/E4, D24/D25, and E99/E100); the loss of any one of these pairs resulted in the same impairment in weak actomyosin interaction and in its function. However, the specificity of myosin interaction with these sites has not yet been addressed. To investigate this, we made and analyzed two new actin mutants, 4Ac/D24A/D25A and 4Ac/E99A/E100A. In these mutants, the acidic residues of the D24/D25 or E99/E100 sites were replaced with uncharged residues (alanines) and a pair of acidic residues was inserted at the N-terminus, maintaining the overall charge density of subdomain 1. Using the in vitro motility assays, we found that the sliding and force generation properties of these mutant actins were identical to those of wild-type actin. Similarly, actin-activated ATPase activities of the mutant and wild-type actins were also indistinguishable. Additionally, the binding of S1 to these mutant actins in the presence of ATP was similar to that of wild-type actin. These results show that relocation of charged residues in subdomain 1 of actin does not affect the weak actomyosin interactions and actomyosin function.

Actins

Serum concentrations of insulin, insulin-like growth factor-I and insulin-like growth factor binding proteins are different between white and African American girls.

OBJECTIVES: To determine whether serum insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP) concentrations are different between African American and white girls. STUDY DESIGN: Serum glucose and hormone concentrations were measured in blood samples collected after a 12-hour fast from 79 white and 57 African American healthy girls between 9 and 17 years of age. Tanner stages of pubic hair development were evaluated by physical examination, and body composition by dual energy x-ray absorptiometry. RESULTS: The African American girls were older and sexually more mature and had higher fat mass, higher serum insulin and free IGF-I concentrations, higher serum free IGF-I to total IGF-I ratio, but lower serum IGFBP-1 concentrations than the white girls. After controlling for sexual maturation and fat mass, the serum concentrations of total IGF-I, bound IGF-I, and IGFBP-3 in the white girls became significantly higher than those in the African American girls. The higher concentrations of total IGF-I in the white girls were due to a proportional increase in the concentrations of bound IGF-I that coincided with a similar increase in serum IGFBP-3 concentrations. CONCLUSIONS: Higher serum insulin concentrations in the African American girls are associated with lower serum IGFBP-1 concentrations and increased bioavailability of free IGF-I, which may contribute to their accelerated growth compared with their white counterparts.

Absorptiometry, Photon

Validity of self-assessment of pubertal maturation in African American and European American adolescents.

PURPOSE: To evaluate interobserver reliability of physician assessments of pubertal maturation and to evaluate the validity of self-assessment compared to physician assessments of pubertal maturation by girls in a multiethnic sample. METHODS: The study design is descriptive. A total of 107 8-17-year-old healthy volunteers from settings with large minority populations in the Houston metropolitan area were recruited for a study on adolescents' energy needs. The two outcome measures were interobserver reliability between two physicians' assessments of breast and pubic hair, and the self-assessment of breast and pubic hair maturation compared to physicians' assessments. RESULTS: The kappa coefficient for physician interobserver agreement for breast maturation was 0.5. The kappa coefficient for physician interobserver agreement for assessment of pubic hair was 0.79. The kappa coefficient for the validity of self-assessment of breast development was 0.34, and that for self-assessment of pubic hair was 0.37. CONCLUSION: Interobserver agreement for physician assessment of breast maturation was low and self-assessment of breast maturation was not reliable in this group of adolescent girls. However, whereas physician interobserver agreement for pubic hair was good, self-assessment of pubic hair maturation was not reliable in this group of adolescent girls.

Adolescent

Longitudinal assessment of energy balance in well-nourished, pregnant women.

BACKGROUND: Clinicians often recommend an additional energy intake of 1250 kJ/d to their pregnant patients. Previous studies have shown considerable variation in the metabolic response to pregnancy and thus in the additional energy required to support a pregnancy. OBJECTIVE: The purpose of this study was to assess how well-nourished women meet the energy demands of pregnancy and to identify factors that predict an individual's metabolic response. DESIGN: Resting metabolic rate (RMR), diet-induced thermogenesis (DIT), total energy expenditure (TEE), activity energy expenditure (AEE), energy intake (EI), and body fat mass (FM) were measured longitudinally in 10 women preconception; at 8-10, 24-26, and 34-36 wk of gestation; and 4-6 wk postpartum. RESULTS: Compared with preconception values, individual RMRs increased from 456 to 3389 kJ/d by late pregnancy. DIT varied from -266 to 110 kJ/meal, TEE from -105 to 3421 kJ/d, AEE from -2301 to 2929 kJ/d, EI from -259 to 2176 kJ/d, and FM from a 0.6-kg loss to a 10.6-kg gain. The only prepregnant factor that predicted FM gain was RMR (r = 0.65, P < 0.05). Women with the largest cumulative increase in RMR deposited the least FM (r = -0.64, P < 0.05). CONCLUSIONS: Well-nourished women use different strategies to meet the energy demands of pregnancy, including reductions in DIT or AEE, increases in EI, and deposition of less FM than anticipated. The combination of strategies used by individual women is not wholly predictable from prepregnant indexes. The use of a single recommendation for increased energy intake in all pregnant women is not justified.

Adult

Measurement of body water by multifrequency bioelectrical impedance spectroscopy in a multiethnic pediatric population.

BACKGROUND: Bioelectrical impedance spectroscopy (BIS) may provide a noninvasive, rapid method for the assessment of total body water (TBW), extracellular water (ECW), and intracellular water (ICW). Few studies, however, have examined the accuracy of BIS in pediatric populations. OBJECTIVE: Our objective was to evaluate the accuracy of BIS for the measurement of TBW, ECW, and ICW in healthy children. DESIGN: Dual-energy X-ray absorptiometry (DXA), total body potassium (TBK), and BIS measurements were performed in 347 children (202 males and 145 females aged 4-18 y). The reference values for TBW, ECW, and ICW were defined by using a DXA+TBK model. BIS values were evaluated by using the method of Bland and Altman. A randomly selected calibration group (n = 231) was used to derive new BIS constants that were tested in the remaining group (n = 116). RESULTS: BIS values were highly correlated with the reference values (r(2) = 0.94-0.97, P < 0.0001), but differences between the BIS and DXA+TBK models for individuals were significant (P < 0.001). Use of new BIS constants reduced the mean differences between the BIS and DXA+TBK models; the SDs of the mean differences were improved (1.8 L for TBW, 1.4 L for ICW, and 1.0 L for ECW) for the total population. CONCLUSIONS: On a population basis, BIS can be calibrated to replace the DXA+TBK model for the assessment of TBW, ECW, and ICW in healthy children. The accuracy of the BIS measurement in individual children may be refined further by using age- and sex-specific adjustments for the BIS calibration constants.

Absorptiometry, Photon

Fat mass deposition during pregnancy using a four-component model.

Estimates of body fat mass gained during human pregnancy are necessary to assess the composition of gestational weight gained and in studying energy requirements of reproduction. However, commonly used methods of measuring body composition are not valid during pregnancy. We used measurements of total body water (TBW), body density, and bone mineral content (BMC) to apply a four-component model to measure body fat gained in nine pregnant women. Measurements were made longitudinally from before conception; at 8-10, 24-26, and 34-36 wk gestation; and at 4-6 wk postpartum. TBW was measured by deuterium dilution, body density by hydrodensitometry, and BMC by dual-energy X-ray absorptiometry. Body protein was estimated by subtracting TBW and BMC from fat-free mass. By 36 wk of gestation, body weight increased 11.2 +/- 4.4 kg, TBW increased 5.6 +/- 3.3 kg, fat-free mass increased 6.5 +/- 3.4 kg, and fat mass increased 4.1 +/- 3.5 kg. The estimated energy cost of fat mass gained averaged 44,608 kcal (95% confidence interval, -31, 552-120,768 kcal). The large variability in the composition of gestational weight gained among the women was not explained by prepregnancy body composition or by energy intake. This variability makes it impossible to derive a single value for the energy cost of fat deposition to use in estimating the energy requirement of pregnancy.

Adipose Tissue

Pubertal African-American girls expend less energy at rest and during physical activity than Caucasian girls.

Between 1963 and 1991, the most dramatic increases in the prevalence of overweight in the United States have been reported in African-American girls. Lower basal energy expenditure and lack of physical activity are believed to be risk factors for excessive weight gain. We hypothesized that energy expenditure at rest and during physical activity are lower in pubertal African-American girls than in Caucasian girls. Basal metabolic rate and sleeping energy expenditure of 40 Caucasian and 41 African-American pubertal girls (matched for age, physical characteristics, body fat, and energy intake) were measured by whole-room calorimetry, energy expended for physical activity by the doubly labeled water method, sexual maturity by physical examination, body composition by dual-energy x-ray absorptiometry, physical fitness by treadmill testing, and energy intake by 3-day food record. After adjusting for soft lean tissue mass, the basal energy expenditure (1333 +/- 132 vs. 1412 +/- 132 kcal/day, P = 0.01) and energy expended for physical activity (809 +/- 637 vs. 1271 +/- 162 kcal/day, P < 0.01) were significantly lower in the African-American girls than in the Caucasian girls. The differences remained the same after controlling for differences in sexual maturity and/or physical fitness. The lower energy expenditure of the pubertal African-American girls suggests that they are at a higher risk of becoming overweight than their Caucasian counterparts.

Adolescent

Protein metabolism in insulin-treated gestational diabetes.

OBJECTIVE: To test the hypothesis that protein metabolism is not totally normalized in insulin treated gestational diabetes mellitus (GDM) patients compared with normal, pregnant control subjects. RESEARCH DESIGN AND METHODS: Protein metabolism in eight Hispanic women with insulin-treated GDM and eight healthy Hispanic control women was studied in late gestation and at 6 weeks postpartum. Nitrogen flux was assessed from the disposal rate of [15N]-labeled urea over 12 h after a dose of [15N]-labeled leucine. Plasma amino acid concentrations were determined in fasting and 2-h postprandial samples using an amino acid analyzer. RESULTS: Protein turnover was normalized in insulin-treated GDM; however, fasting and postprandial plasma amino acids were elevated antepartum and postpartum. Nitrogen flux was significantly lower during pregnancy (P = 0.04-0.001) and did not differ between groups. Fasting and postprandial plasma amino acids were elevated in GDM antepartum and postpartum, despite satisfactory glycemic control. Fasting levels of taurine, hydroxyproline, glutamic acid, glutamine, cystine, tyrosine, phenylalanine, tryptophan, and histidine were higher in GDM antepartum and postpartum (P < 0.05). Postprandial concentrations of taurine, hydroxyproline, valine, cystine, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, ornithine, lysine, histidine, and arginine were higher in GDM antepartum and postpartum (P < 0.05). With few exceptions, plasma amino acid concentrations were lower antepartum than postpartum (P < 0.05). CONCLUSIONS: Protein turnover was normalized in insulin-treated women with GDM; however, fasting and postprandial plasma concentrations of amino acids were elevated in the antepartum and postpartum periods, despite satisfactory maternal glycemic control.

Adolescent

Flavobacterium meningosepticum bacteremia: an analysis of 16 cases.

BACKGROUND: Flavobacterium meningosepticum is an uncommon pathogen causing nosocomial pneumonia and meningitis in newborns. It is usually resistant to antimicrobial agents used to treat gram-negative bacilli. While the pathogen often results in high mortality and serious sequelae in newborns, it is also found to cause to disease in adults. Therefore, it is necessary to know the full spectrum of the infection in adults and to identify effective antimicrobial agents. METHOD: Microbiology logbooks were reviewed for F meningosepticum isolated from January, 1992, to March, 1996. The medical records of these patients were reviewed. Special attention was paid to clinical manifestations, underlying diseases, risk factors, treatments, and prognosis. Twenty-four antimicrobial agents were tested using antimicrobial susceptibility tests. RESULTS: Eighteen isolates of F meningosepticum were identified from 16 patients. There were 10 men and six women, with a mean age of 63.7 years. The clinical features of infection included fever (> or = 38 degrees C) in 13 patients, chills in seven, shortness of breath in four, rales or rhonchi in four, shock in three and flank pain in two. All except one patient survived without sequelae. Fifteen patients contracted F meningosepticum from nosocomial sources. Of them, seven were suspected to have acquired the pathogen from diagnostic or therapeutic procedures. Bacteremia occurred in these patients within a mean period of 2.2 days. The other eight patients suffered nosocomial bacteremia within a mean period of 33.4 days after admission. The suspected infection route was not identified in only one patient. The organism was resistant to penicillins, cephalosporins, aztreonam, imipenem, aminoglycosides and macrolides. Testing with lomefloxacin, ciprofloxacin and ofloxacin yielded 72.2%, 83.3% and 94.4% susceptibility rates, respectively. Rifampin (61.1%) and trimethoprim-sulfamethoxazole (TMP-SMX) (88.9%) were effective. Vancomycin and minocycline were 100% effective. CONCLUSIONS: F meningosepticum is an opportunistic pathogen of low virulence and rarely causes serious infections in adults. Reducing the use of unnecessary residual devices and invasive procedures may help reduce the incidence of infection. Therapeutic options include vancomycin, TMP-SMX, minocycline, rifampin or fluoroquinolones.

Adult

Update in liver transplantation.

OBJECTIVE: To review recent developments in liver transplantation with particular emphasis on issues relevant to patient care before and after transplantation. QUALITY OF EVIDENCE: Preference was given to recent studies with well-designed cohort methods and large numbers of study subjects. Data on natural history are summarized from large databases in Canada and the United States. Due to the nature of the subjects involved, most treatment studies are open studies or consecutive series rather than randomized controlled trials. MAIN MESSAGE: Substantial advances in liver transplantation have established it as an effective treatment for most end-stage liver diseases, with 1-year survival rates higher than 85% in many centres. Early referral by family physicians and careful patient selection by transplant centres remain crucial to continued success. Managing these patients requires special care from family physicians because of post-transplantation immunosuppression, increased risk of opportunistic infection, and transplantation-associated medical problems. Other unresolved issues include recurrence of disease (hepatitis B and C, and malignancy) and an ongoing shortage of organs. CONCLUSIONS: Liver transplantation is an effective form of therapy for end-stage liver disease, improving both patients' likelihood of survival and their quality of life. Because medical care of liver transplant patients is so complex, coordinated efforts between primary care physicians and transplant teams are crucial.

Adult

Progression of cytomegalovirus retinitis in acquired immunodeficiency syndrome: a case report.

We report an AIDS patient with cytomegalovirus (CMV) retinitis that developed from an early minor lesion and progressed to extended involvement of the retina and severe deterioration of vision due to poor compliance with ganciclovir treatment. A 33-year-old man was known to have acquired immunodeficiency syndrome (AIDS) for eight months. The patient had no complaint of visual symptoms. A routine eye examination revealed his visual acuity to be 6/6 in both eyes. The dilated eye fundus examination using indirect ophthalmoscopy disclosed a localized white yellowish granular lesion in the peripheral retina of the right eye and a completely normal left eye. CMV retinitis with initial manifestation in the right eye was diagnosed. Due to incomplete treatment with ganciclovir, the retinal lesion rapidly enlarged and extended to the posterior pole, with eventual destruction of the nerve fiber layer and optic disc. The visual acuity of right eye dropped from 6/6 to 1/60 within six months. This case report indicates the importance of early, dilated eye fundus examination and recognition of early CMV retinitis in order to salvage visual function in AIDS patients. Completion of the anti-CMV treatment course in halting the progression of CMV retinitis is also emphasized.

AIDS-Related Opportunistic Infections

The results of radiotherapy for ependymomas: the Mayo Clinic experience.

PURPOSE: This analysis was performed to examine the outcome of patients with histologically confirmed ependymomas of the brain or spinal cord who received postoperative radiotherapy. METHODS AND MATERIALS: Eighty patients with histologically confirmed ependymomas were evaluated retrospectively. All were treated with various combinations of surgery, radiotherapy (RT), and chemotherapy. Follow-up ranged from 5 to 30 years (median 10.4 years). RESULTS: The 5- and 10-year survival rates for the entire study group were 79% and 73%, respectively. Patients with low-grade (1 and 2 of 4) tumors had a 5-year survival rate of 87% as compared to 27% for those with high-grade (3 and 4 of 4) tumors (p < 0.0001). Patients with tumors of the spine had a 5-year survival rate of 97% as compared to 68% for those with infratentorial tumors, and 62% for those with supratentorial tumors (p = 0.03). Patients with myxopapillary ependymomas of the spine had a 5-year survival rate of 100% as compared with 76% for patients with other histological subtypes of ependymoma (p = 0.02). Multivariate analysis revealed that the survival rate was independently associated with tumor grade (p = 0.0007) and histological subtype (p = 0.02). Twenty-eight patients (35%) experienced local failure and 10 patients (13%) developed leptomeningeal seeding. The 5-year leptomeningeal failure rate was 10% in patients with low-grade tumors as compared to 41% for patients with high grade tumors (p = 0.01). CONCLUSION: Patients with low-grade tumors, especially those with myxopapillary subtypes, have high 5-year survival rates when treated with post-operative radiotherapy. High grade ependymomas are associated with a much poorer outcome. New forms of therapy are required to improve the outcome of patients with high-grade ependymomas.

Adolescent

Malignant peripheral nerve sheath tumor: analysis of treatment outcome.

PURPOSE: To analyze the results of therapy for malignant peripheral nerve sheath tumor (MPNST) and to identify prognostic factors of survival, and of local and distant control of disease. METHODS AND MATERIALS: From 1975 through 1993, 134 MPNSTs were diagnosed and treated at our institution. Tumor sites included extremities in 36 (27%) cases and non-extremities in 98 (73%). Median follow-up for survivors was 53 months (range: 7-280). There were 14 tumors of histologic grade I disease (10%), 43 of grade II disease (32%), 43 of grade III disease (32%), and 32 of grade IV (24%). Seventy-three patients (54%) underwent radiation therapy (RT) as part of their initial treatment of the primary tumor, including 14 (10%) who had brachytherapy and 16 (12%) who had intraoperative electron irradiation (IOERT) as part of their radiation course. RESULTS: The 5- and 10-year survival rates were 52% and 34%, respectively. Local and distant failure rates at 5 years were both 49%. On univariate analysis, prognostic factors significantly related to survival (log-rank: p < 0.05) included tumor size, location of disease, history of neurofibromatosis type 1 (NF-1), history of prior irradiation, surgical margin status, use of IOERT or brachytherapy, disease stage, histologic grade and tumor subtype, as well as mitotic rate and the presence or absence of necrosis. On multivariate analysis, only history of prior irradiation (p = 0.023), and surgical margin status (p = 0.0044) remained significant. For local control of disease, univariate analysis showed location of disease, surgical margin status, history of NF-1, history of prior irradiation, mitotic rate, radiation dose > or = 60 Gy, and use of IOERT or brachytherapy to be significant prognostic factors. On multivariate analysis, only surgical margin status (p = 0.0024), RT dose (p = 0.021), and use of IOERT or brachytherapy (p = 0.016) remained significant. For distant control of disease, significant prognostic factors on univariate analysis included tumor size, stage, tumor grade, mitotic rate, presence or absence of necrosis, and histologic subtype. On multivariate analysis, tumor size (p = 0.0065), grade (p = 0.036), and histologic subtype (p = 0.001) remained significant. Patients with perineurial MPNSTs had a much lower rate of distant metastasis and a better overall survival as compared with other histologic subtypes. CONCLUSION: Management of patients with MPNST involves a multi-modality approach. The goal of surgery is complete resection with negative margins. Adjuvant irradiation to doses > or = 60 Gy and the inclusion of IOERT or brachytherapy are associated with improved local control of disease.

Adolescent

Regulation of protein phosphatase 2A activity by caspase-3 during apoptosis.

Although the available evidence suggests that whereas the caspase family plays a major role in apoptosis, they are not the sole stimulators of death. A random yeast two-hybrid screen of a lymphocyte cDNA library (using caspase-3 as the bait) found an interaction between caspase-3 and the regulatory subunit Aalpha of protein phosphatase 2A. This protein was found to be a substrate for caspase-3, but not caspase-1, and could compete effectively against either a protein or synthetic peptide substrate. In Jurkat cells induced to undergo apoptosis with anti-Fas antibody, protein phosphatase 2A (PP2A) activity increased 4.5-fold after 6 h. By 12 h, the regulatory Aalpha subunit could no longer be detected in cell lysates. There was no change in the amount of the catalytic subunit. The effects on PP2A could be prevented by the caspase family inhibitors acetyl-Asp-Glu-Val-Asp (DEVD) aldehyde or Ac-DEVD fluoromethyl ketone. The mitogen-activated protein (MAP) kinase pathway is regulated by PP2A. At 12 h after the addition of anti-Fas antibody, a decrease in the amount of the phosphorylated forms of MAP kinase was observed. Again, this loss of activated MAP kinase could be prevented by the addition of DEVD-cho or DEVD-fmk. These data are consistent with a pathway whereby induction of apoptosis activates caspase-3. This enzyme then cleaves the regulatory Aalpha subunit of PP2A, increasing its activity. These data show that the activated PP2A will then effect a change in the phosphorylation state of the cell. These data provide a link between the caspases and signal transduction pathways.

Apoptosis

ICE family proteases in inflammation and apoptosis.

The interleukin-1 beta converting enzyme (ICE) was first identified as a unique cysteine protease that processes the inactive precursor of the pro-inflammatory cytokine IL-1 beta to its mature active form. Subsequent revelation that a C. elegans cell death gene ced-3 bears sequence homology to ICE has led to rapid identification of at least nine other members of this gene family in humans, some of which are involved in apoptosis. Analyses of ICE-deficient mice generated by gene targeting technology reveal that this enzyme is important in maturation of several cytokines. The ICE deficient mice are resistant in several models of localized and systemic inflammation. ICE itself, however, is not required for Fas-mediated apoptosis, a physiological process for elimination of activated lymphocytes. Selective inhibitors of ICE would be novel therapeutic agents for treatment of diseases where excess inflammation contributes to pathological processes.

Animals