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Biomedical subjects

L S Wong

Publications and source records attributed to L S Wong.

At least 19 recordsLinked to original sources

Detection of circulating tumour cells with the magnetic activated cell sorter.

A technique has been developed for the detection of tumour cells in blood with the magnetic activated cell sorter (MACS). Colonic carcinoma cell lines and disaggregated primary tumours were used to establish optimal conditions of separation. A murine monoclonal antibody specific for epithelial cells was added to the suspension of leucocytes and tumour cells, followed by magnetic labelled goat antimouse antibody. The labelled tumour cells were retrieved by passing this suspension through a MACS separation column in a strong magnetic field. Tumour cells were detected at a dilution of 10 cells per ml blood. Tumour cells were identified in mesenteric blood in three of 24 patients undergoing surgery for colorectal cancer. This study supports the use of the MACS to detect circulating tumour cells.

Aged

Lymphocytes infiltrating colorectal cancer have low proliferative capacity but can secrete normal levels of interferon gamma.

Significant numbers of infiltrating mononuclear cells are commonly observed in solid tumours, although their role in restricting tumour growth is not clear. Tumour-infiltrating lymphocytes (TIL) from 38 patients with colorectal cancer, in parallel with peripheral blood lymphocytes (PBL), were assayed to determine their ability to proliferate in response to concanavalin A (ConA), interleukin-2 (IL-2), ConA+IL-2, phorbol 12-myristate 13-acetate (PMA)+ionomycin ionomycin (IOM), and staphylococcal enterotoxin B(SEB). These reagents were selected to give a range of weak to strong proliferative responses either via or independent of the T cell receptor. Proliferation of TIL was significantly lower than that of PBL in all cultures: ConA (P < 0.001), IL-2 (P = 0.002), ConA+IL-2 (P < 0.001), PMA+IOM (P < 0.001), SEB (P = 0.002). In addition to the low proliferative capacity of TIL, production of cytokines by TIL may also play a role in control of tumour growth. We have assayed IFN gamma production in the supernatants from 16 paired TIL and PBL cultures, and tumour necrosis factor alpha (TNF alpha) in 6 paired cultures. TNF alpha concentrations were significantly lower in TIL cultures than in PBL cultures stimulated with ConA (P < 0.05), but no different in control or IL-2 stimulated cultures. IFN gamma levels did not significantly differ between PBL and TIL cultures, indicating that despite the restricted proliferative capacity of TIL, these cells remain capable of secreting significant amounts of IFN gamma.

Adenocarcinoma

Aggressive angiomyxoma in males. A report of four cases.

Aggressive angiomyxoma (AAM) is a rare, locally infiltrative but nonmetastasizing tumor of the pelvic and perineal soft tissues that occurs almost exclusively in adult females. The authors describe four cases of AAM in adult males that arose in the scrotum. There was some histologic variation among the tumors. One case was focally hypercellular around the blood vessels, two were more densely cellular throughout, and one had cystic degeneration. Three of the tumors were widely infiltrative, and one of the four tumors recurred locally. The clinicopathologic features of these cases are similar to those of AAM occurring in females. In either sex, AAM should be distinguished from benign myxoid tumors with a low risk of local recurrence and fully malignant myxoid tumors with distant metastatic potential.

Adolescent

Role of methylation in aerotaxis in Bacillus subtilis.

Taxis to oxygen (aerotaxis) in Bacillus subtilis was characterized in a capillary assay and in a temporal assay in which the concentration of oxygen in a flow chamber was changed abruptly. A strong aerophilic response was present, but there was no aerophobic response to high concentrations of oxygen. Adaptation to a step increase in oxygen concentration was impaired when B. subtilis cells were depleted of methionine to prevent methylation of the methyl-accepting chemotaxis proteins. There was a transient increase in methanol release when wild-type B. subtilis, but not a cheR mutant that was deficient in methyltransferase activity, was stimulated by a step increase or a step decrease in oxygen concentration. The methanol released was quantitatively correlated with demethylation of methyl-accepting chemotaxis proteins. This indicated that methylation is involved in aerotaxis in B. subtilis in contrast to aerotaxis in Escherichia coli and Salmonella typhimurium, which is methylation independent.

Aerobiosis

Amino acid efflux in response to chemotactic and osmotic signals in Bacillus subtilis.

We observed a large efflux of nonvolatile radioactivity from Bacillus subtilis in response to the addition of 31 mM butyrate or the withdrawal of 0.1 M aspartate in a flow assay. The major nonvolatile components effluxed were methionine, proline, histidine, and lysine. In studies of the release of volatile radioactivity in chemotaxis by B. subtilis cells that had been labeled with [3H]methionine, the breakdown of methionine to methanethiol can contribute substantially to the volatile radioactivity in fractions following addition of 0.1 M aspartate. However, methanol was confirmed to be released after aspartate addition and, in lesser quantities, after aspartate withdrawal. Methanol and methanethiol were positively identified by derivitization with 3,5-dinitro-benzoylchloride. Amino acid efflux but not methanol release was observed in response to 0.1 M aspartate stimulation of a cheR mutant of B. subtilis that lacks the chemotaxis methylesterase. The amino acid efflux could be reproduced by withdrawal of 0.1 M NaCl, 0.2 M sucrose, or 0.2 M xylitol and is probably the result of changes in osmolarity. Chemotaxis to 10 mM alanine or 10 mM proline resulted in methanol release but not efflux of amino acids. In behavioral studies, B. subtilis tumbled for 16 to 18 s in response to a 200 mosM upshift and for 14 s after a 20 mosM downshift in osmolarity when the bacteria were in perfusion buffer (40 mosM). The pattern of methanol release was similar to that observed in chemotaxis. This is consistent with osmotaxis in B. subtilis away from an increase or decrease in the osmolarity of the incubation medium. The release of methanol suggests that osmotaxis is correlated with methylation of a methyl-accepting chemotaxis protein.

Amino Acids

The influence of preload on post-systolic shortening in ischaemic myocardium.

Post-systolic shortening is a wall motion abnormality defined as shortening of cardiac muscle after the end of ejection and usually regarded as a manifestation of ischaemia. This study was designed to determine whether changes in preload may alter the magnitude of ischaemia-induced post-systolic shortening. Eleven beagles were anaesthetized (halothane 0.8%) and instrumented for measurement of pressures, flows and dimensions in the apical subendocardium supplied by the left anterior descending coronary artery. Myocardial ischaemia was obtained by tightening a micrometer-controlled snare around the left anterior descending coronary artery. Post-systolic shortening, calculated as end-systolic length minus minimum length divided by end-systolic length, was measured at different levels of preload. Increasing the preload from 4 to 17 mmHg caused a significant reduction in post-systolic shortening (8.9% vs. 12.9%, P < 0.05, Student's paired t-test); post-systolic shortening was negatively correlated with coronary perfusion pressure (r = 0.35, P < 0.01) and positively correlated with systolic bulging. This study demonstrates that the amount of post-systolic shortening depends on the volume status, which therefore has to be taken into account in interpreting regional wall motion abnormalities, such as those detected by echocardiography.

Animals

Post-ischemic diastolic dysfunction.

Though a sustained post-ischemic decrease in contractile function has been clearly established, post-ischemic diastolic function has not been thoroughly investigated. Accordingly, 11 anesthetized (isoflurane 1%) open-chest beagles were instrumented to measure left ventricular pressure and dimensions (circumferential length and wall thickness) in an apicoanterior area supplied by the left anterior descending coronary artery (LAD). Pressure-dimension relations were modified by stepwise infusion and withdrawal of 200 mL of the animals' own blood during baseline, 45 minutes partial occlusion of the LAD (systolic bulging), and 60 minutes after the onset of reperfusion. Stiffness constants were derived from the end-diastolic pressure-length and stress-strain relations, respectively. Myocardial ischemia was associated with significant (P < 0.05) alterations of the following parameters of diastolic function: (1) 47% increase in end-diastolic pressure; (2) 22% decrease in peak negative dP/dt; (3) 9% increase in the time constant of isovolumic relaxation (tau); (4) postcystolic contraction; (5) 6% increase in end-diastolic length and 10% decrease in end-diastolic thickness; (6) 12% increase in unstressed length (creep) and 13% decrease in unstressed thickness; (7) 51% increase in chamber stiffness and a 63% increase in myocardial stiffness; and (8) 40% decrease in the peak lengthening rate. After 60 minutes of reperfusion, only end-diastolic pressure and tau had returned to baseline values whereas systolic shortening fraction, postsystolic contraction, and end-diastolic and unstressed dimensions had only partially recovered. No recovery occurred in peak negative dP/dt, chamber stiffness, myocardial stiffness, and peak lengthening rate. Thus, both myocardial ischemia and reperfusion are associated with complex changes in global and regional left ventricular diastolic function.

Anesthesia, Inhalation

Graded myocardial ischemia is associated with a decrease in diastolic distensibility of the remote nonischemic myocardium in the anesthetized dog.

OBJECTIVES: This study was designed to investigate the changes in regional distensibility of the ischemic segment and of a remote nonischemic segment brought about by graded myocardial ischemia. BACKGROUND: Ventricular distensibility is a major determinant of left ventricular end-diastolic pressure. The effects of graded myocardial ischemia on the regional distensibility of the ischemic area have not been studied. Moreover, there are few data on the effects of myocardial ischemia on the regional distensibility of the nonischemic myocardium. METHODS: Nine anesthetized open chest mongrel dogs were fitted with instruments to measure left ventricular pressure and circumferential length (sonomicrometry) in the ischemic segment and in a nonischemic segment. The pressure-length relation was modified by stepwise infusion and withdrawal of 200 ml of each dog's own blood over 30 min in five consecutive stages of regional ischemia. Unstressed dimensions were obtained by repeated inferior vena cava occlusions. In both segments, regional distensibility was assessed at end-diastole by means of the constants of the pressure-length (chamber stiffness), the pressure-strain and the force-strain (myocardial stiffness) relations. RESULTS: In the ischemic segment, partial and complete coronary occlusions were associated with a twofold increase in the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant, whereas in the nonischemic segment the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant increased by 50%. CONCLUSIONS: Regional myocardial ischemia is associated with a decrease in distensibility of both the ischemic and the remote nonischemic myocardium.

Analysis of Variance

Effect of isoflurane and halothane on regional cardiac stiffness.

To investigate the possibility of regional differences in cardiac stiffness which may relate to the known regional differences in systolic left ventricular function, seven mongrel dogs were acutely instrumented and regional cardiac stiffness was measured at both apical and basal region under two different concentrations of isoflurane (1.08% and 1.9%) as well as equipotent concentrations of halothane (0.9% and 1.58%). Cardiac stiffness was determined in terms of distensibility, chamber stiffness (derived from pressure-length relationships), and an elastic stiffness constant (derived from stress-strain relationships). Regional differences in cardiac stiffness were observed for all three indices and for each anaesthetic setting except for the elastic stiffness constant under 1.9% of isoflurane. The data indicate that regional differences in cardiac stiffness exist between the apex and the base of the heart. These regional differences do not depend on the anaesthetic agent or its concentration and may contribute to the differences in systolic function.

Anesthesia, Inhalation

Antioxidant activity of propylthiouracil.

Propylthiouracil (PTU) has been demonstrated to reduce alcohol-induced hepatocyte damage and severe alcoholic liver disease. Although the mechanism by which the drug operates is yet to be elucidated, there is evidence that PTU may act as an antioxidant. The present study examines the reaction of PTU with oxygen free radicals and the ability of PTU to directly inhibit peroxidation of a model membrane system. PTU reacted directly with hydroxyl radicals produced by gamma-radiolysis. The rate constant for the PTU/hydroxyl radical reaction as determined by steady state competition kinetics with p-nitrosodimethylaniline was 8 x 10(9) L/mol/sec. PTU was less reactive towards superoxide generated by the xanthine/xanthine oxidase system, having a small but significant inhibitory effect on superoxide-induced reduction of cytochrome c only at a concentration of 200 microM. The ability of PTU to protect lipids from peroxidative changes was tested in membranes prepared from linoleic acid. The rate of peroxidation induced by 40 degrees heat decreased from 0.078 to 0.024 mM hydroperoxide/hr in the presence of 0-50 microM PTU. However, this trend was reversed at PTU concentrations above 50 microM. These data suggest that the protective effects of PTU against liver damage may be due to scavenging reactions with hydroxyl radicals in particular and/or its antioxidant potential.

Animals

A controlled trial of interferon with or without prednisone priming for chronic hepatitis B.

In a randomized, controlled trial of recombinant interferon alfa-2b with or without prednisone priming in Chinese adults with chronic hepatitis B virus infection, stratified randomization for pretreatment serum alanine aminotransferase levels was done. Partial or complete antiviral responses were achieved in 17 (21.5%) of 79 treated patients and 3 (8.3%) of 36 controls (P = 0.14). The response to interferon treatment was significantly better in those who had elevated pretreatment transaminase levels and comparable to that reported in white patients [15 (38.5%) of 39 patients compared with 2 (5%) of 40 who had normal pretreatment transaminase levels (P = 0.0005)]. The spontaneous seroconversion rate was also higher among the controls with elevated transaminase levels [3 (18.8%) of 16 compared with 0 of 20 with normal transaminase levels], but this difference was not statistically significant (P = 0.16). Among the interferon-treated patients, prednisone priming appeared to have a marginal benefit over treatment with interferon alone in patients with elevated transaminase levels (43% vs. 33%), but not in those with normal transaminase levels (0% vs. 9.5%). It was confirmed that Chinese patients with normal transaminase levels respond very poorly to interferon alfa therapy. However, the response was significantly better in patients with elevated transaminase levels.

Adult

Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases.

Three-hundred forty-one HBsAg-positive family members of 152 patients with chronic hepatitis B virus infection (47 asymptomatic carriers, 59 with chronic hepatitis, 17 with cirrhosis and 29 with hepatocellular carcinoma) were prospectively studied to determine the morbidity and mortality from chronic hepatitis B virus infection in the family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases. Most of the family members had no history of acute hepatitis, were asymptomatic and were unaware of their carrier status. However, 5.3% had stigmata of chronic liver disease, 6% had serum ALT levels that exceeded two times the upper limit of normal and 78% of those who had biopsies had chronic hepatitis with or without cirrhosis. During a follow-up period of 12 to 90 mo (median = 39 mo), 3% had symptoms of chronic liver disease; 24% had transient, recurrent or persistent elevation in serum ALT levels, 1.4% had cirrhosis and 1% had hepatocellular carcinoma. Neither hepatocellular carcinoma in the index patient nor a previous history of hepatocellular carcinoma in the family was associated with an increase in the morbidity and mortality from chronic hepatitis B virus infection in the HBsAg-positive family members.

Adolescent

Current seroepidemiology of hepatitis A in Hong Kong.

The current seroepidemiology of hepatitis A in Hong Kong was examined by testing stored sera from 702 healthy subjects, collected between 1987-1989, for antibody to hepatitis A virus (anti-HAV). The overall prevalence of anti-HAV antibody was 45.6%. There were significant increases in prevalence of anti-HAV antibody with every 10-year increase in age up to age 40. The prevalence of anti-HAV antibody was 24% for subjects below age 30 and 89.2% for those above age 30 (P less than 0.0001). Socioeconomic factors did not appear to have any influence on the prevalence of anti-HAV antibody. In comparison with another study conducted in Hong Kong 10 years ago, the prevalence of anti-HAV antibody in the current study was significantly lower in every age group from 0 to 30 years. In summary, it was shown that HAV infection is no longer highly endemic in Hong Kong. In view of the changing epidemiology, postexposure prophylaxis will be necessary for young adults and children, and hepatitis A vaccine may be indicated for high risk groups when it is generally available.

Adolescent

Role of dopamine and GABA in the control of motor activity elicited from the rat nucleus accumbens.

The application of 1.2 and 12.0 micrograms/side of the GABAA receptor agonist 3-aminopropane sulphonic acid bilaterally into the nucleus accumbens (Acb) of rats nonsignificantly depressed locomotor activity as assessed in automated Animex activity cages, while the highest dose (60 micrograms/side) significantly stimulated activity. The GABAA receptor antagonists picrotoxinin (0.0625 and 0.125 micrograms/saide) and bicuculline (0.895 micrograms/side) produced forward locomotion around the cage accompanied by a number of other behaviours. The GABAB agonist baclofen (0.023 and 0.092 micrograms/side) induced a short-lasting (18 min) locomotor depression. None of the GABAB antagonists tested (2-hydroxysaclofen 2.6 micrograms/side, two novel beta-(benzo[b]furan) analogues of baclofen 9G or 9H each 6.8 micrograms/side, 4-aminobutylphosphonic acid 1.32 micrograms/side and phaclofen 0.535 and 2 micrograms/side) significantly affected locomotor activity. In rats pretreated with reserpine and alpha-methyl-p-tyrosine, picrotoxinin (0.0625 and 0.125 micrograms/side) did not significantly alter locomotor activity. Furthermore, when picrotoxinin (0.0625 micrograms/side) was combined with either the selective dopamine (DA) D1 agonist SKF38393 or the selective D2 agonist quinpirole, no significant alteration in locomotor function occurred. When SKF38393 and quinpirole were coadministered, significant stimulation occurred which was further enhanced by the addition of picrotoxinin. It is concluded that GABAA receptors, together with D1 and D2 receptors, play a major role in modulating the control of motor function by the Acb of rats.

Animals

Pulsatile LH secretion in streptozotocin-induced diabetes in the rat.

This study aimed to determine the effect of streptozotocin (STZ)-induced diabetes on pulsatile LH secretion in the mature male rat. LH pulse frequency was reduced by 56% and pulse amplitude by 54%, with a consequential decrease of 72% in mean LH levels 8 days after i.v. administration of STZ (55 mg/kg) to castrated Wistar rats compared with castrated non-diabetic controls. Twice daily insulin treatment completely reversed all parameters of pulsatile LH secretion to control values. Food-restricted non-diabetic controls, studied to distinguish the metabolic effect of diabetes from that of concurrent weight loss, demonstrated a 34% reduction in LH pulse frequency but no significant changes in LH pulse amplitude or mean LH levels compared with non-diabetic controls given free access to food. To distinguish whether the decreased LH pulse amplitude in diabetes was due to a reduction in either the quantity of hypothalamic gonadotrophin-releasing hormone (GnRH) released per secretory episode or to decreased pituitary responsiveness to GnRH, the responsiveness of the pituitary to exogenous GnRH (1-1000 ng/kg body weight) was tested in diabetic rats after castration, using a full Latin square experimental design. The net LH response (total area under response curve over 40 min following GnRH) was decreased by 33% (P = 0.001) in diabetic compared with control rats. The decreased LH pulse frequency in STZ-induced diabetes therefore suggests that the metabolic effect of diabetes is to decelerate directly the firing rate of the hypothalamic GnRH pulse generator independent of testicular feedback. These effects were fully reversed by insulin treatment and were only partly due to the associated weight loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Alpha-interferon treatment in Chinese patients with chronic hepatitis B.

alpha-Interferon has been shown to be the most promising antiviral agent in the treatment of chronic hepatitis B virus infection in Caucasian patients. The experience with recombinant interferon alfa-2a and alfa-2b in four randomized controlled trials in Chinese adults and children is reviewed here. alpha-Interferon alone has little long-term benefit in the treatment of Chinese patients with chronic hepatitis B virus infection, especially in patients who have normal or near normal serum aminotransferase levels. The response in patients with elevated aminotransferase levels appears to be better. The poor antiviral response in patients with normal aminotransferase levels is probably due to immunological tolerance to HBV induced by exposure to the virus in early life. Prednisone pretreatment does not seem to have any additional benefit to using interferon alone in these patients, while the effect in patients with elevated aminotransferase levels remains to be proven.

Adult

Neurochemical studies on quinolone antibiotics: effects on glutamate, GABA and adenosine systems in mammalian CNS.

Quinolone antibiotics, which can be proconvulsant in susceptible patients, were found to inhibit the specific binding of the adenosine receptor ligands L-3H-N6-phenylisopropyladenosine (L-3H-PIA) and 3H-N-ethylcarboxamidoadenosine (3H-NECA) to rat brain synaptic membranes. The inhibitions were concentration dependent, and for both ligands the order of potency was rosoxacin greater than nalidixic acid greater than oxolinic acid greater than or equal to ciprofloxacin greater than norfloxacin greater than enoxacin: IC20 values (concentrations causing a 20% inhibition of specific binding) ranged from 30-35 microM to 1-3 mM. Hill coefficients were approximately 0.5, suggesting that the compounds are probably antagonists at these sites. Most of the compounds did not alter 3H-diazepam binding directly, although rosoxacin showed relatively strong, and enoxacin weak, concentration-dependent inhibition. At 50 microM the compounds enhanced the maximal gamma-aminobutyric acid (GABA) activation of 3H-diazepam binding to varying degrees, without altering the EC50 of activation, whereas at 200 microM they tended to reduce GABA activation. Most noteworthy was the large increase in GABA-stimulated 3H-diazepam binding caused by 50 microM nalidixic acid. The compounds did not alter the Ca2+/Cl- -dependent binding of 3H-glutamate, nor of the binding of the glutamate site-selective ligands 3H-kainate and alpha-3H-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (3H-AMPA); the uptake of the non-metabolized glutamate analogue D-3H-aspartate by cortical homogenates was also unaffected. The CNS side effects of these antibiotics may result, in part, from interaction with sites which mediate the inhibitory neurotransmission of adenosine and, possibly, GABA.

4-Quinolones