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Biomedical subjects

C Chan

Publications and source records attributed to C Chan.

At least 19 recordsLinked to original sources

Quantitation of eosinophil Major Basic Protein cytotoxicity to rodent respiratory epithelium.

Eosinophil Major Basic Protein (MBP) may be a potent effector in damaging airway epithelium and inducing acute (2-3 h) hyperresponsiveness to agonists in primates. Accordingly, interactions between human eosinophil MBP and guinea-pig airway epithelium were quantitated biochemically. MBP was extracted from human eosinophils and purified by size-exclusion HPLC. This resulted in a single protein band on electrophoresis, which cross-reacted with antisera raised to peptides derived from the predicted sequence of human MBP. This human MBP caused modest, but statistically significant, damage to respiratory epithelium (16.4% increase in efflux of 51Cr from guinea-pig tracheal rings) after 3 h of incubation with 10(-4) M concentration, but not with lower concentrations. These data demonstrates that MBP cytotoxicity to intact epithelium can be rapidly measured in vitro, and suggests that rodent airway epithelium may be relatively resistant to the cytotoxic effects of MBP.

Animals

Improved myocardial ischemic response and enhanced collateral circulation with long repetitive coronary occlusion during angioplasty: a prospective study.

OBJECTIVES: The goal of the study was to evaluate the progressive increase in ischemic threshold with multiple sequential transient coronary occlusions and to assess the role of the collateral circulation in adaptation to ischemia. BACKGROUND: It has been observed that the duration of balloon inflations during coronary angioplasty can be gradually prolonged during subsequent dilations with a reduction in patient symptoms and diminished ischemic electrocardiographic (ECG) changes. Although the mechanism has not been fully explained, recruitment of coronary collateral circulation induced by repeated coronary occlusion has been reported. The stimuli for recruitment and the natural history of coronary collateral circulation are not understood. METHODS: Seventeen patients with isolated stenosis of the left anterior descending coronary artery and a normal left ventricle were enrolled. Angioplasty consisted of five successive prolonged inflations. Sequential changes in clinical, intracoronary ECG and left ventricular indexes of myocardial ischemia were examined. Coronary collateral channels were evaluated during balloon inflations by ipsilateral and contralateral injections of contrast medium and hemodynamically by occlusion pressure. RESULTS: An improved tolerance to myocardial ischemia with repetitive coronary occlusions was demonstrated by a significant reduction of angina, ST segment deviation, left ventricular filling pressure and less impairment of ejection fraction. Left ventricular wall motion abnormalities remained unchanged. Collateral angiographic grade did not change in 7 patients and increased in 10. CONCLUSIONS: This study confirms a progressive adaptation of myocardial ischemia to repetitive coronary occlusions and supports the concept that sequential episodes of myocardial ischemia are a stimulating factor for the recruitment of collateral channels in humans. These results also suggest that enhancement of recruitable collateral circulation might be an underlying mechanism of myocardial ischemic preconditioning.

Adult

The pain and discomfort experienced during orthodontic treatment: a randomized controlled clinical trial of two initial aligning arch wires.

A randomized controlled clinical trial was performed to compare the nature, prevalence, intensity, and duration of pain related to the use of a relatively recently developed superelastic arch wire and a more traditional multistranded steel arch wire. Other factors likely to influence the pain experience were also investigated. Forty-three subjects participated in the study, the pain response being assessed by each of the visual analogue scales, the questionnaires, and an analgesic consumption record. In 18 of the 43 subjects a standardized preliminary dental extraction procedure was used as a control. Subsequent to the random allocation of an initial arch wire in 43 patients, 22 of them underwent a second arch wire in the opposing arch, the wire again being determined by random allocation. It was found that the prevalence, intensity, and duration of pain after the insertion of the two types of wire was similar but much greater than in the postextraction control phase. The pain score peaked on the morning after the placement of the arch wire, lasting typically for 5 to 6 days. The pain and discomfort experienced after the insertion of the second arch wire was similar to that of the first, no conditioning response being evident. Overall a diurnal variation was found with a tendency to an increase in pain in the evenings and nights, although this did not greatly affect sleep. The pain response was found to be highly and consistently subjective, not related to the dental arch, crowding, sex, or social class; however, a statistically significant association was found between the age and the pain experienced.

Adolescent

Pharmacology of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)- indol-2-yl]-2,2-dimethyl propanoic acid), a potent, orally active leukotriene biosynthesis inhibitor.

MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)- indol-2-yl]-2,2-dimethyl propanoic acid, previously L-686,708) is a potent inhibitor of leukotriene (LT) biosynthesis in intact human and elicited rat polymorphonuclear leukocytes (PMNLs) (IC50 values 3.1 and 6.1 nM, respectively) and in human, squirrel monkey, and rat whole blood (IC50 values 510, 69, and 9 nM, respectively). MK-0591 had no effect on rat 5-lipoxygenase. MK-0591 has a high affinity for 5-lipoxygenase activating protein (FLAP) as evidenced by an IC50 value of 1.6 nM in a FLAP binding assay and inhibition of the photoaffinity labelling of FLAP by two different photoaffinity ligands. Inhibition of activation of 5-lipoxygenase was shown through inhibition of the translocation of the enzyme from the cytosol to the membrane in human PMNLs. MK-0591 was a potent inhibitor of LT biosynthesis in vivo, first, following ex vivo challenge of blood obtained from treated rats and squirrel monkeys, second, in a rat pleurisy model, and, third, as monitored by inhibition of the urinary excretion of LTE4 in antigen-challenged allergic sheep. Inhibition of antigen-induced bronchoconstriction by MK-0591 was observed in inbred rats pretreated with methysergide, Ascaris-challenged squirrel monkeys, and Ascaris-challenged sheep (early and late phase response). These results indicate that MK-0591 is a potent inhibitor of LT biosynthesis both in vitro and in vivo indicating that the compound will be suitable for assessing the role of leukotrienes in pathological situations.

5-Lipoxygenase-Activating Proteins

Reduced sensitivity to dexamethasone of pancreatic islets from obese (fa/fa) rats.

The direct effects of dexamethasone exposure on insulin secretion from islets of fa/fa rats and their lean littermates (Fa/?) were compared. After 72 h culture in 1 nM dexamethasone, glucose (27.5 mM)-stimulated insulin secretion over 90 min from islets of lean rats was significantly decreased compared with islets cultured without dexamethasone (12.9 +/- 1.4 vs. 5.7 +/- 1.0% of total islet content, p < 0.05). Higher doses of dexamethasone for 24-48 h culture produced similar effects. For islets of fa/fa rats, the minimum inhibitory concentration of dexamethasone was 10-fold higher, and islets required at least 48 h exposure for inhibitory effects to be observed. Dexamethasone also decreased the insulin response by islets to glybenclamide, indicating that dexamethasone effects were not specific to glucose transport or metabolism. The results suggest that islets of fa/fa rats may be less sensitive to direct inhibitory effects of glucocorticoids on glucose-stimulated insulin release than islets of lean animals.

Animals

The first oocyte donation pregnancy home-bred and delivered in Singapore to illustrate a simplified oocyte donation programme--no more embryo freezing, synchronisation or disruption of social life.

The wait for an oocyte donor is highly unpredictable and stressful. The recipients may have to remain contactable at all times. Even when a donor is present, their reproductive cycles may not be in synchrony to enable gamete or embryo replacement, and embryo freezing is required for the transfer of embryos in the subsequent cycle. After the release of the Guidelines for Assisted Reproductive Technique by the Ministry of Health we have established a simplified oocyte donation programme with which the need for synchronisation, embryo freezing and the disruption to the recipient couple's social life are eliminated. To illustrate, we report the first report of oocyte donation pregnancy home bred and delivered in Singapore.

Adult

Diagnosis of tuberculous meningitis by detection of tuberculostearic acid in cerebrospinal fluid.

Tuberculous meningitis still poses a major diagnostic problem. Recently, several new techniques for rapid diagnosis of tuberculous meningitis have been developed. One of these newer techniques is the detection of mycobacterial fatty acids, using gas chromatography--mass spectroscopy. In this study we evaluated the sensitivity and specificity of this recently reported method in a blind trial. The sensitivity was found to be 100%, specificity only 91%. The number of false positive results limits the value of this test in the primary diagnosis of tuberculous meningitis. Nonetheless, we consider this method to be a valuable tool for establishing the diagnosis in culture-negative patients presenting with signs and symptoms suggestive of tuberculous meningitis.

Diagnosis, Differential

The use of alternative therapies by Auckland general practitioners.

A survey of Auckland general practitioners was undertaken to explore their use of, and attitudes to, alternative medicines. Three hundred and seventy randomly selected doctors, from a total of about 700 doctors practising in Auckland, were posted questionnaires. Of 249 respondents, 75 (30%) practised one or more forms of alternative medicine. Acupuncture was the therapy most commonly used. Musculoskeletal disorders and chronic pain syndromes were the most frequently treated conditions. A total of 171 (68.7%) respondents referred patients to one or more forms of alternative treatment, and only 56 (32.7%) of these felt it necessary that the person referred to be medically qualified. Younger doctors were more inclined to refer and the most commonly cited reason for referral was failure of conventional medicine.

Acupuncture Therapy

Erythroid membrane-bound protein kinase binds to a membrane component and is regulated by phosphatidylinositol 4,5-bisphosphate.

In the erythrocyte, a membrane-bound serine/threonine protein kinase (a casein kinase) has been shown to phosphorylate a number of membrane proteins, modulating their function. Here we report that the membrane-bound protein kinase binds to membranes by an association with a minor membrane component contained in preparations of glycophorin (possibly a minor glycophorin). The binding of the kinase to glycophorins does not significantly modify kinase activity. However, upon binding, the kinase activity is potently inhibited by phosphatidylinositol 4,5-bisphosphate, and the affinity of the kinase for the glycophorins is increased. Other phospholipids or polyanions such as inositol 1,4,5-trisphosphate or 2,3-diphosphoglycerate do not affect protein kinase activity when the kinase is bound to membranes but do inhibit the solubilized membrane-bound kinase. In the erythrocyte, there is a cytosolic form of the casein kinase which is very similar, having the same molecular weight and substrate specificity as the membrane-bound casein kinase. The cytosolic casein kinase is inhibited by 2,3-diphosphoglycerate but much less so by glycophorin preparations containing phosphoinositol 4,5-bisphosphate. When the sequences of both casein kinases were compared by two-dimensional peptide mapping, it was found that the two kinases were very similar but not identical.

Casein Kinases

Breast epithelial antigen levels and breast tumor antigen content.

The relationship between the primary tumor expression of a breast epithelial antigen, called non-penetrating glycoprotein (NPGP) or breast epithelial mucin, and the same patient's serum level of this antigen at the time of relapse was studied in 23 cases. The expression of NPGP on breast tumors was measured by immunoperoxidase staining using monoclonal antibody Mc5, and quantitated by a histopathological index created for this purpose. Serum levels were measured by a competitive RIA using the same monoclonal antibody. An inverse correlation between these parameters was found, such that tumors having high NPGP levels in serum had a low index, while low NPGP serum levels had a high index. These results show that cellular events in breast tumors could participate in determining NPGP serum levels in breast cancer.

Antibodies, Monoclonal

Stability of solutions of histamine acid phosphate after sterilization by heating in an autoclave.

Histamine acid phosphate (HAP) solutions are used in tests for asthma and also as positive controls in general allergenic testing. Previously these solutions have been sterilized, if at all, by filtration, thus limiting the shelf-life of the preparation and introducing some degree of uncertainty in their use. It is shown here that HAP solutions can be sterilized successfully by heating in an autoclave with little degradation and that subsequent storage of autoclaved solutions indicates a minimum shelf-life of 4 months.

Chemical Phenomena

Psychotherapy training for the psychiatrist of the future.

There is uncertainty about the future role of psychodynamic psychotherapy in psychiatric practice and education. The Association for Academic Psychiatry and the American Association of Directors of Psychiatry Residency Training formed a joint task force to review the issue. It developed a rationale for continued training in expressive psychotherapy and a model curriculum for such training that is both effective and realistic in terms of the diverse demands and structures of modern residencies. A minimum curriculum was also designed for resource-poor programs.

Adult

[An in vitro study of the antimicrobial effectiveness of ultrasonic instrumentation].

Successful endodontic therapy is based upon the classic triad of diagnosis, adequate canal preparation, and obturation. Preparation for a root canal has two major components--debridement and shaping. Debridement, or cleaning, consists of removal of necrotic intracanal dentin and organic debris, and reduction of the bacteria inside the root canal. According to the research, the endontic ultrasonic system plays a valuable and significant and synergistic role in aiding the bacteriocidal mechanisms based on the cavitation and acoustic streaming effect. The purpose of this study was to compare the antimicrobial effectiveness of two newly developed endodontic ultrasonic devices and the conventional hand-filing techniques. Eighty single root canal teeth with deep caries or apical lesions were selected and evenly divided into 4 groups. The root canals were prepared using conventional hand filing or one of two newly developed ultrasonic filing systems, ENAC and CAVI-ENDO. The contents of the root canals before and after debridement were cultured in a thioglycolate culture tube. The results showed that in the ultrasonically prepared specimens irrigated with a normal saline solution, the microbial culture numbers were significantly reduced and obviously different from those prepared by the hand instrumentation technique. The above mentioned differences were statistically significant at the level of p less than 0.05 by the McNemar test and Chi-square test.

Bacteria

Toxoplasmic chorioretinitis and hepatic granulomas.

A 71-yr-old male presented with a 2-month history of fever, malaise, and weight loss. Physical exam revealed chorioretinitis. Laboratory studies were notable for elevated levels of alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate transaminase, and alanine transaminase. Immunoglobulin G antibody to Toxoplasma gondii was positive to a dilution of 1:4096, whereas serologic studies for hepatitis A virus, hepatitis B virus, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, Brucella, and Tularemia were negative. A percutaneous biopsy of the liver revealed hepatic granulomas. Culture of the biopsy specimen was negative for growth of mycobacteria or fungi. Spontaneous improvement in clinical and laboratory parameters occurred over a 4-month period.

Aged