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A Chiu

Publications and source records attributed to A Chiu.

At least 19 recordsLinked to original sources

Laminin isoforms 8 and 10 are primary components of the subendothelial basement membrane promoting interaction with neoplastic lymphocytes.

To determine whether subendothelial laminins (LNs) could be implicated in the extravasation of neoplastic lymphocytes, we have examined the distribution of a number of LN isoforms in human vascular structures of adult individuals and have assayed the ability of the isolated LN molecules to promote adhesion of lymphoma and leukemic cells in vitro using a novel cell adhesion assay, CAFCA, Centrifugal Assay for Fluorescence-based Cell Adhesion (E. Giacomello et al., Biotechniques, 26: 758-762, 1999; P. Spessotto et al., Methods Mol. Biol., 139: 321-343, 2000). The use of previously characterized LN chain-specific antibodies showed that the vast majority of the smaller vascular compartments, known to correspond to sites of lymphocyte transmigration, expressed the subunits involved in the structuring of 9 of the 12 LN isoforms known to date. Eight LN isoforms (i.e., LN-1, -2, -4, -5, -8, -9, -10, and -11) and four naturally occurring LN complexes were isolated from various tissues and cultured cells by combined gel filtration, ion exchange, and immunoaffinity chromatographies, and the identity/composition of the isolated LNs/LN complexes was asserted by immunochemical means and amino-acid sequencing. Notwithstanding the widespread colocalization of LN isoforms, a panel of neoplastic B- and T-cell lines and lymphocytes isolated from patients affected by chronic lymphocytic B-cell leukemia attached preferentially and with high avidity to purified LN-8, purified LN-10, and LN-10-containing protein complexes, whereas lymphocytes derived from patients diagnosed with acute lymphocytic leukemia failed to bind to these LNs. All of the tested neoplastic lymphocytes failed to adhere to the isolated LN-1, LN-4, LN-9, and LN-11 and attached moderately well to purified LN-2 and LN-5. The interaction of transformed lymphocytes with LNs was cation-dependent and interchangeably mediated by the alpha3beta1 and alpha6beta1 integrins. The degree of engagement of the two LN receptors was dependent upon their relative levels of cell surface expression, whereas, irrespective of the phenotype, lymphocytes deprived of either of these receptors were incapable of LN binding. The findings suggest that LN-8 and LN-10 may act in an independent or complementary fashion as primary components of the endothelial basement membrane favoring the interaction of extravasating neoplastic lymphocytes. Thus, our results would demonstrate that different LN isoforms may evoke diverse cellular responses in different cell types and that this divergence may be the basis for the redundancy of LN distribution in a number of vascular structures.

Animals↗

Rib pain in a 23-year-old woman with severe asthma.

This case illustrates the importance of considering a wide range of diagnoses in patients complaining of rib, flank, and pleuritic pain. Further, additional evaluation is warranted when "pneumonia" does not respond to conventional treatment.

Adult↗

Combining Drosophila melanogaster somatic-mutation-recombination and electron-spin-resonance-spectroscopy data to interpret epidemiologic observations on chromium carcinogenicity.

Lung cancers are significantly increased among workers exposed to chromate (Cr6+, Cr3+), chromium pigments (Cr6+) and chromium plating (Cr6+). Chromium lung burdens and cancer risk increase proportionately with duration of employment at long latencies. However, this epidemiologic information alone is insufficient in determining whether Cr6+ or Cr3+ are equally important in causing cancer. We have attempted to combine epidemiologic data with data from the Drosophila melanogaster somatic-mutation-recombination-test and from the in vitro electron-spin-resonance spectroscopy study to demonstrate that following somatic recombination plays a more important role than somatic mutation in chromium carcinogenesis. Cr4+ is more important than Cr5+ or Cr6+ in inducing somatic recombination while Cr6+ produces more and bigger clones than Cr4+ in somatic mutation. Cr3+ produces negative results in this fruit-fly wing-spot-assay. When the larvae and flies exposed to Cr6+ and Cr4+ are examined by ESR, only Cr5+ and Cr3+ are found. Thermodynamic parameters deltaE, deltaH, and deltaS are also estimated from these latter experiments to explain the relative importance of Cr6+, Cr4+, Cr3+ in chromium carcinogenesis among exposed industrial workers.

Animals↗

Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients undergoing echocardiography to determine left ventricular dysfunction.

BACKGROUND: Although echocardiography is an important tool for making the diagnosis of left ventricular (LV) dysfunction, the cost of this procedure limits its use as a routine screening tool for this purpose. Brain natriuretic peptide (BNP) accurately reflects ventricular pressure, and preliminary studies have found it to be highly sensitive and highly specific in diagnosing congestive heart failure in the emergency department. We hypothesized that BNP might therefore be useful as a screening tool before echocardiography in patients with suspected LV dysfunction. METHODS: Subjects included patients referred for echocardiography to evaluate the presence or absence of LV dysfunction. Patients with known LV dysfunction were excluded from analysis. BNP was measured by a point-of-care immunoassay (Biosite Diagnostics, San Diego, Calif). The results of BNP levels were blinded from cardiologists making the assessment of LV function. Patients were divided into those with normal ventricular function, abnormal systolic ventricular function, abnormal diastolic function, and evidence of both systolic and diastolic dysfunction. RESULTS: Two hundred patients in whom LV function was unknown were studied. In the 105 patients (53%) whose ventricular function was subsequently determined to be normal by echocardiography, BNP levels averaged 37 +/- 6 pg/mL. This was significantly less than in those patients with either ultimate diastolic dysfunction (BNP 391 +/- 89 pg/mL (P <.001) or systolic dysfunction (BNP 572 +/- 115 pg/mL (P <.001). A receiver-operator characteristic curve showing the sensitivity and specificity of BNP against the echocardiography diagnosis revealed the area under the curve (accuracy) was 0.95. At a BNP level of 75 pg/mL was 98% specific for detecting the presence or absence of LV dysfunction by echocardiography. CONCLUSIONS: A simple, rapid test for BNP, which can be performed at the bedside or in the clinic, can reliably predict the presence or absence of LV dysfunction on echocardiogram. The data indicate that BNP may be an excellent screening tool for LV dysfunction and may, in fact, preclude the need for echocardiography in many patients.

Aged↗

A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients.

High-dose recombinant human GH (rhGH) has been shown to improve the nutritional status of malnourished older adults. It is uncertain whether low-dose rhGH is effective and whether its effect on nutritional status will lead to any improvement in physical function. There is also no data on the outcome after a short course of rhGH treatment. The objectives of this study were to determine the efficacy of low-dose rhGH treatment for 4 weeks in malnourished elderly patients, its effect on physical functions, and the intermediate term outcome after a 4-week rhGH treatment. The study design was a randomized, placebo-controlled, double-blind trial conducted in a university teaching hospital. The patients were 19 medically stable malnourished elderly subjects. Intervention in the rhGH group was as follows: rhGH (Saizen, Serono, Switzerland) 0.09 IU/kg body weight (BW) 3 times weekly were given together with appropriate dietary intervention as prescribed by the dietitian. In the placebo group, equal volumes of normal saline per kilogram BW were given 3 times weekly together with the dietary intervention. The baseline demographic, anthropometric, nutritional, and hematological variables, measures of physical function, and insulin-like growth factor I levels in both groups were comparable. Compared with the placebo group, the GH-treated group showed a more rapid gain in BW (after 3 weeks, +1.27 +/- 0.36 vs. -0.28 +/- 0.37 kg; P = 0.008), total lean body mass (change after 3 weeks by bio-impedance analysis, +1.45 +/- 0.36 vs. -0.37 +/- 0.48 kg; P = 0.009) and a faster improvement in 5-m walking time (decrease after 4 weeks, 23.79 +/- 9.41 vs. 0.45 +/- 4.62 sec; P = 0.047). The hemoglobin level rose more in the rhGH than the placebo groups (change at 8 weeks, +0.84 +/- 0.34 vs. -0.42 +/- 0.29 g/dL; P = 0.012). Serum albumin level also showed a greater delayed increase in the rhGH group than in the placebo group (change at 8 weeks, +5.1 +/- 0.8 vs. 1.6 +/- 1.2 g/dL; P = 0.023). There was no statistically significant difference for other nutritional variables. There was a greater rise in the mean serum insulin-like growth factor I level at 4 weeks in the GH than in the placebo groups (197 +/- 58 vs. 54 +/- 26 U/L; P = 0.034). The improvement in the rhGH group gradually diminished on follow-up and became statistically insignificant 8 weeks after stopping rhGH treatment. There were no GH-related adverse effects. Low-dose rhGH was an effective and safe adjuvant to dietary augmentation for stable malnourished elderly subjects. It led to a faster gain in total lean body mass, which was associated with greater improvement in walking speed when compared with dietary intervention alone. There were no apparent side effects.

Aged↗

Synchronous water-clear cell double parathyroid adenomas a hitherto uncharacterized entity?

Water-clear cell hyperplasia is a rare but well-documented cause of primary hyperparathyroidism. Parathyroid adenomas of the water-clear cell type are exceptionally rare, and only 2 cases have been reported. We describe a patient with synchronous water-clear cell double parathyroid adenomas, an entity that has not previously been reported. In our case, the enlarged superior parathyroid glands were completely replaced by water-clear cells, with only a minute rim of extracapsular, histologically unremarkable parathyroid tissue. The inferior parathyroid glands were grossly unremarkable, and incisional biopsy specimens were histologically normal (no foci of water-clear cells were identified). The findings in this case are most consistent with the diagnosis of double adenomas of the water-clear cell type. We acknowledge that despite molecular proof of monoclonality of the 2 lesions, it is not possible to entirely exclude the possibility that this unusual case could be due to asymmetric hyperplasia.

Adenoma↗

A potential source of false-positive sentinel nodes: immunostain misadventure.

The clinical and pathologic aspects of sentinel lymph node biopsy have generated much attention. Pitfalls in the pathologic handling of sentinel lymph node specimens have received little attention. We report a case in which a false-positive diagnosis might have been rendered on a sentinel lymph node because of an inadvertent immunostaining error. Attention was drawn to the problem by an unusual pattern of distribution of immunoreactive cells-which proved to be plasma cells rather than metastatic carcinoma cells.

Antibodies↗

Are microinvasion and micrometastasis in breast cancer mountains or molehills?

BACKGROUND: The increased rate of early detection of breast cancer due to widespread mammographic screening has led to an increased incidence of in situ as well as microinvasive carcinoma. The enhanced pathological examination to which sentinel lymph nodes are subjected has led to an increased rate of detection of micrometastatic carcinoma. Despite the augmented rate of diagnoses of both diseases, the pathological diagnoses as well as clinical management of these entities continue to be controversial. DATA SOURCES: A computerized literature search was performed on the Medline and PubMed database from 1990 to date. Relevant earlier publications were also perused. The database of the Department of Pathology at New York Presbyterian Hospital-Well Medical College of Cornell University were also accessed. CONCLUSIONS: Based on cumulative data, patients diagnosed with either microinvasive or micrometastatic carcinoma of breast have a relatively favorable, albeit guarded, prognosis. Treatment recommendations for both of these disease entities continue to be controversial, and may remain so until additional refined clinicopathological data becomes available.

Axilla↗

Effects of carbohydrate ingestion before and during exercise on glucose kinetics and performance.

We investigated the effect of carbohydrate (CHO) ingestion before and during exercise and in combination on glucose kinetics, metabolism and performance in seven trained men, who cycled for 120 min (SS) at approximately 63% of peak power output, followed by a 7 kJ/kg body wt time trial (TT). On four separate occasions, subjects received either a placebo beverage before and during SS (PP); placebo 30 min before and 2 g/kg body wt of CHO in a 6.4% CHO solution throughout SS (PC); 2 g/kg body wt of CHO in a 25.7% CHO beverage 30 min before and placebo throughout SS (CP); or 2 g/kg body wt of CHO in a 25.7% CHO beverage 30 min before and 2 g/kg of CHO in a 6.4% CHO solution throughout SS (CC). Ingestion of CC and CP markedly (>8 mM) increased plasma glucose concentration ([glucose]) compared with PP and PC (5 mM). However, plasma [glucose] fell rapidly at the onset of SS so that after 80 min it was similar (6 mM) between all treatments. After this time, plasma [glucose] declined in both PP and CP (P < 0.05) but was well maintained in both CC and PC. Ingestion of CC and CP increased rates of glucose appearance (R(a)) and disappearance (R(d)) compared with PP and PC at the onset of, and early during, SS (P < 0.05). However, late in SS, both glucose R(a) and R(d) were higher in CC and PC compared with other trials (P < 0.05). Although calculated rates of glucose oxidation were different when comparing the four trials (P < 0.05), total CHO oxidation and total fat oxidation were similar. Despite this, TT was improved in CC and PC compared with PP (P < 0.05). We conclude that 1) preexercise ingestion of CHO improves performance only when CHO ingestion is maintained throughout exercise, and 2) ingestion of CHO during 120 min of cycling improves subsequent TT performance.

Adult↗

Cr(IV) causes activation of nuclear transcription factor-kappa B, DNA strand breaks and dG hydroxylation via free radical reactions.

Electrophoretic mobility shift, DNA strand breakage assays and electron spin resonance (ESR) spin trapping were used to investigate the activation of nuclear transcription factor (NF)-kappa B, DNA strand breakage and 2'-deoxyguanosine hydroxylation induced by Cr(IV), as well the role of free radical reactions in these processes. Incubation of synthesized Cr(IV)-glutathione complex with cultured Jurkat cells resulted in activation of DNA binding activity of NF-kappa B. Cr(VI) is also able to induce NF-kappa B activation through Cr(V) and Cr(IV) intermediates generated during the reduction of Cr(VI) by the cells. Cr(III) did not cause observable NF-kappa B activation due to its inability to cross cell membranes. Cr(IV)-induced NF-kappa B activation is dose-dependent. Catalase inhibited the activation while superoxide dismutase enhanced it. The metal chelator, deferoxamine, and hydroxyl (.OH) radical scavengers, sodium formate and aspirin, also inhibited the NF-kappa B activation. Electrophoretic assays using lambda Hind III linear DNA showed that, in the presence of H2O2, Cr(IV) is capable of causing DNA strand breaks. Deferoxamine, sodium formate and aspirin inhibited the DNA strand breaks. HPLC measurements also show that .OH radical generated by the Cr(IV)-mediated reaction with H2O2 was capable of causing 2'-deoxyguanosine (dG) hydroxylation to generate 8-hydroxyguanosine (8-OHdG). The relative magnitude of 8-OHdG formation correlated with the generation of .OH radicals. ESR spin trapping measurements showed that reaction of Cr(IV) with H2O2 generated .OH radicals, which were inhibited by deferoxamine, sodium formate and aspirin. The results show that Cr(IV) can cause NF-kappa B activation, DNA strand breaks and dG hydroxylation through .OH radical-initiated reactions. This reactive chromium intermediate may play an important role in the mechanism of Cr(VI)-induced carcinogenesis. The results also suggest that the Cr(IV)-glutathione complex may be used as a model compound to study the role of Cr(IV) in Cr(VI) carcinogenicity.

Antioxidants↗

Risk factors for falls in hospitalized older medical patients.

BACKGROUND: The incidence of falls among older hospitalized patients is higher than that of community-dwelling older persons. Prevention is important, but factors associated with these falls are less well studied than falls occurring in the community or nursing homes. METHODS: This study was conducted in an acute-care general hospital in Hong Kong. During November 1995 to March 1997, all older inpatients who fell during hospitalization were assessed by a geriatrician, a physiotherapist, and an occupational therapist. A standardized protocol to study the clinical and performance-oriented functional factors was employed. A sex- and age-matched hospital control was recruited for each case. In total, 51 cases and controls (mean ages 77.8 +/- 7.3 years and 77.5 +/- 7.0 years, respectively) were studied. RESULTS: Among the multiple clinical and functional risk factors for falls identified, lower limb weakness (i.e., power less than MRC grade 4 in one or both lower limbs) and poor tandem walk ability emerged as two significant predictive factors for falls in the hospital. The overall classification accuracy of fallers and nonfallers was 79%. The sensitivity was 84% and specificity was 75%. Clinical factors were the underlying causes for the lower limb weakness and poor tandem walk performance. CONCLUSIONS: Among clinical and functional risk factors for falls in the older medical patient, lower limb weakness and poor tandem walk ability were most predictive. Falls prevention programs in hospitals should employ these two tests as screening instruments.

Accidental Falls↗

Troponin-I, myoglobin, and mass concentration of creatine kinase-MB in acute myocardial infarction.

Myoglobin, creatine kinase-MB (CKMB) mass concentration and troponin-I are newer biochemical markers for the diagnosis of acute myocardial infarction (AMI). We conducted a prospective study to formulate a model for the collective interpretation of these three markers in the diagnosis of AMI. Eighty-seven patients with AMI had serial serum samples taken to establish the time-frame sensitivity of individual markers. None of the markers had a good sensitivity within the first 4 h of infarction. Myoglobin and CKMB (mass) had sensitivities of 92.3% and 96.2%, respectively, at 4-8 h post infarct. CKMB (mass) and troponin-I had sensitivities >92% at 8-24 h. Troponin-I maintained sensitivity >93% until 72 h. A guideline was formulated based on the results. Our data suggest that troponin-I, myoglobin and CKMB (mass) yield satisfactory diagnostic sensitivity when used with reference to specific time frames. The combined use of these markers can provide valuable information for clinicians in managing AMI patients.

Adult↗

Inhaled nitric oxide protects against hyperoxia-induced apoptosis in rat lungs.

Inhaled nitric oxide (NO), frequently administered in combination with hyperoxic gas mixtures, was recently shown to protect against the injurious consequences of prolonged hyperoxia. We investigated the possibility that this protective effect is attributable to the ability of NO to block pulmonary apoptosis. We show that rats exposed to 100% O2 for 60 h develop severe lung injury consisting of pronounced vascular leak and alveolar apoptosis as inferred from the presence of positive terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and DNA ladders in agarose gels and a decrease in constitutive procaspase-3 levels. However, the inclusion of NO (20 parts/million) in the hyperoxic gas mixture significantly attenuated both the vascular leak and apoptosis. NO reversed the hyperoxia-associated changes in the activity of the redox-sensitive transcription factors nuclear factor-kappaB, activator protein-1, and Sp1 after 24 h, lowered intercellular adhesion molecule-1 levels, and increased glutathione content. We therefore show, for the first time, that NO can protect against both hyperoxia-induced apoptosis and inflammation. The data suggest that this protection may occur at the transcriptional and caspase-activation levels.

Administration, Inhalation↗

Ten-year cardiovascular risk in a Hong Kong population.

BACKGROUND: Cardiovascular disease is a major health issue in Hong Kong. We conducted a screening program to assess the 10-year risk for the population and to assess the potential benefit of large-scale screening in Hong Kong. METHOD: A local screening program for cardiovascular risk was carried out in a health service network with a total of 17,716 participants. Retrospective data analysis for the prevalence and distribution of the various risk factors was performed. The data were then applied to calculate the 10-year risk of each individual, according to the European Task Force coronary risk chart. RESULTS: Of the participants, 54.2% had total cholesterol levels > 5.2 mmol/l; 28.7% had body mass index > 25 kg/m2; 18.5% were hypertensive; 15.1% were smokers; and 3.7% had diabetes mellitus. There were 35.5% of the screened population who had at least two risk factors and 10.9% had at least three risk factors. A total of 9049 individuals satisfied the criteria for the European Task Force guidelines and were selected for 10-year cardiovascular risk analysis. We calculated that 68.0% of the male population had at least 10% risk and 41.5% had at least 20% risk of developing a coronary heart event within 10 years. Among women, 48.2% of the population carried at least 10% risk and 2.8% carried at least 20% risk. CONCLUSION: The calculated 10-year risk of the population, particularly for men, is significant. Our study demonstrated that mass screening is feasible, and has the benefit of early identification of high-risk individuals, which could be a reasonable strategy for cost-effective medicine.

Adolescent↗