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Biomedical subjects

W S Wong

Publications and source records attributed to W S Wong.

At least 19 recordsLinked to original sources

Contributory role of lung pleura to release of anaphylactic mediators from guinea pig lung in response to ovalbumin or A23187.

Previous findings revealed greater contractile responses of guinea pig lung pleural surface strips to antigen or A23187 challenge than denuded lung parenchymal strips (lung strip devoid of any pleura). Moreover, we have identified a high density of mast cells distributed throughout the lung pleura. The present study examined mediators released from guinea pig lung pleural surface and denuded lung parenchyma fragments in response to immunologic challenge with ovalbumin (OA) or non-immunologic challenge with the ionophore A23187. Histamine levels were measured radioenzymatically; leukotrienes (LTs), prostaglandins (PGs) and thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), were quantitated using an enzyme immunoassay. Histamine release reached a maximal level 3-5 min after OA challenge, whereas A23187-induced histamine release increased gradually in a time-dependent manner. Similar kinetics were observed in the release of LTs, PGs and TXA2. Pleural surface released a substantially (P < 0.05) greater amount of histamine to both challenges than denuded parenchyma. Moreover, histamine content in pleural surface was significantly (P < 0.05) higher than in denuded parenchyma. Pleural surface also released considerably (P < 0.05) more LTB4, LTC4, and LTE4 in response to OA and A23187 than denuded parenchyma. In contrast, pleural surface and denuded parenchyma released equivalent amounts of PGD2, PGE2, PGF2 alpha, and TXA2 in response to both challenges. The rank order of leukotriene release was LTC4 > LTE4 > LTB4, whereas that of prostanoid release was TXA2 >> PGD2 > or = PGF2 alpha >> PGE2. We conclude that pleural surface is the major source of histamine and leukotrienes released from guinea pig lung in vitro in response to OA and A23187, whereas both pleural surface and denuded parenchyma participate to the same extent in prostaglandin and TXA2 production after such challenges.

Animals

Malignant lymphocyst after Wertheim's operation.

Lymphocyst is a well-known complication after Wertheim's operation with an incidence varying from 2 to 20%. The majority are asymptomatic. However, when complications occur, the symptoms depend on the location and the pressure effects created. Most of the lymphocysts occur within 1 year after surgery and need to be differentiated from a hematoma or urinoma. At present, there is no standard management of early lymphocysts. Conservative management, ultrasound-guided needle aspiration, or percutaneous insertion of an indwelling catheter have been successfully employed. Intraperitoneal marsupilization with or without omental falp is also highly effective. When pelvic lymphocysts occur later than normal, the diagnostic dilemma is to differentiate benign collections from those involving recurrent tumor. Fine-needle biopsy of the cyst wall under ultrasound guidance is more effective in identifying recurrence than cytological evaluation of the fluid. Nonetheless, if such facility is not readily available, surgical drainage and excision of the cyst wall should be considered to ensure early diagnosis of recurrence.

Adult

Pharmacological and histological examinations of regional differences of guinea-pig lung: a role of pleural surface smooth muscle in lung strip contraction.

1. Parenchymal lung strip preparations have been widely used as an in vitro model of peripheral airway smooth muscle. The present study examined functional responses of 4 consecutive guinea-pig lung parenchymal strips isolated from the central region (segment 1) to the distal edge (segment 4) of the lower lung lobe. The middle two segments were designated as segments 2 and 3. 2. Lung segments 1 and 4 exhibited significantly greater contraction than the other 2 segments to KCl when responses were expressed as mg force per mg tissue weight. Contractile responses to bronchospastic agents including histamine, carbachol, endothelin-1, leukotrienes (LT) B4 and D4, and the thromboxane A2-mimetic U46619 demonstrated no significant difference in EC50 values among the 4 lung segments. 3. Contractile responses of segments 1 and 4 to antigen-challenge (ovalbumin), ionophore A23187 and substance P were significantly greater than the other 2 segments with respect to either sensitivity or maximum responsiveness. 4. U46619-induced contractions of the 4 lung segments were relaxed in similar manner by papaverine and theophylline up to 100%, salbutamol up to 80%, and sodium nitroprusside by only 20%. In contrast, sodium nitroprusside markedly reversed U46619-induced contraction of pulmonary arterial rings and bronchial rings. 5. Histological studies identified 2-4 layers of smooth muscle cells underlying the lung pleural surface. Mast cells were prominent in this area. Moreover, morphometric studies showed that segment 4 possessed the least amount of smooth muscle structures from bronchial/bronchiolar wall and vasculatures as compared to the other 3 segments, and a significant difference in this respect was evident between segment 1 and segment 4.6. Since lung segments 1 and 4 are covered with larger surface area of lung pleura, the present results suggest that the significantly greater intrinsic contractile responses of segments 1 and 4 are associated with the presence of increased lung pleural surface possibly together with more mast cells. Thus, a primary contribution to the net contraction of the lung parenchymal strips may be smooth muscle from the lung pleura, alveolar ducts and interstitial contractile cells rather than from bronchi/bronchioles and microvasculatures.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Pharmacologic evaluation of A23187-induced contractions of three distinct preparations of guinea pig lung parenchymal strips.

The present investigation examined the pharmacologic profiles of three distinct guinea pig lung parenchymal strips (LPS): intact LPS, denuded LPS (devoid of any lung pleura) and pleural surface strips. All three preparations responded similarly to increasing concentrations of KCl, whereas maximum contractile responses of the intact LPS and pleural surface strips to histamine, LTD4 and U46619, a thromboxane A2 mimetic, were significantly greater (P less than 0.001) than those elicited by the denuded LPS. Moreover, concentration-response curves for intact LPS and pleural surface strips to ovalbumin and ionophore A23187 challenges were equivalent to each other, which were significantly (P less than 0.001) higher in magnitude than that for the denuded LPS. The net contractile response of the denuded LPS to A23187 was significantly reduced by 35% in the presence of 1 x 10(-5) M A-64077, a 5-lipoxygenase inhibitor, and nearly abolished with the addition of 1 x 10(-6) M pyrilamine and 4 x 10(-6) M indomethacin. In contrast, the maximum contractile responses of the intact LPS and pleural surface strips were reduced by 40 and 30%, respectively, in the presence of all three inhibitors. On the other hand, morphometric analysis revealed that the density of mast cells in the smooth muscle of lung pleura was as high as that found in the bronchiolar area (2.35 +/- 0.31 vs. 2.62 +/- 0.28 per 0.05 mm2). In contrast, mast cells were scarcely identified in the alveolar parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Tumor growth fraction in cervical carcinoma.

Thirty-one cervical carcinomas have been studied immunohistochemically to determine tumor growth fraction by using the monoclonal antibody Ki-67, which reacts with a nuclear antigen expressed only by proliferating cells. The growth fraction of individual tumor is estimated as the percentage of stained nuclei in a population of 1000 tumor cells. There is a good correlation of the growth fraction measured by Ki-67 with mitotic index and high histological grade of cervical carcinoma. This study, together with that of D. C. Brown, D. Cole, K. C. Gatter, and D. Y. Mason [Brit. J. Cancer 57(2), 178-181 (1988)], shows the usefulness of Ki-67 in the evaluation of growth fraction in cervical carcinoma.

Adenocarcinoma

Diffuse aortitis complicating Behçet's disease leading to severe aortic regurgitation.

Cardiovascular complications are uncommon in Behçet's disease, but are frequently the cause of morbidity and mortality. Venous and peripheral arterial involvement have been well documented, but involvement of the proximal aorta has rarely been described. This report details a Chinese patient with Behçet's disease. Diffuse aortitis led to proximal aortic dilatation and severe aortic regurgitation necessitating aortic valve replacement. Histopathology of the aorta revealed features similar to those observed in other systemic diseases with aortic involvement.

Adult

Verrucous carcinoma of the cervix.

Verrucous carcinoma of the cervix is a very rare variant of squamous cell carcinoma at this site. We report such a case in an 80-year-old woman because it presented difficulties with diagnosis and was successfully treated by vaginal hysterectomy.

Aged

Purification and characterization of rat liver transglutaminase.

1. Transglutaminase (EC 2.3.2.13) was purified from rat liver. 2. The enzyme was stable at 25 degrees C in the pH range of 6.0-9.0, with the optimum at pH 9.0. 3. The enzyme was inactivated after incubation for 20, 4 and 1 min at 44 degrees C, 52 degrees C, and 60 degrees C, respectively. 4. Activation energies were 30.4 kcal/mol for denaturation and 19.9 kcal/mol for substrate conversion to products. 5. The enzyme was inactivated by sulfhydryl modification with hydroxymercuribenzoate (99.1%) and N-ethylmalemide (78.5%). 6. Calcium, required for the activity, was replaced to a lesser extent, by Mg2+, Sr2+, Zn2+ and Mn2+ (31.8, 27.0, 24.6 and 3.5%). 7. Steady-state kinetics showed: Vmax = 10 microM-min-1, Km = 0.05 mM (N-dimethylated casein), kcat = 31.9 min-1 kcat/Km = 560 min-1 mM-1.

Animals

Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene. IV. Effects on gastric lesions in rats induced by cold-restraint stress and thyrotropin-releasing hormone.

Propyl-methylenedioxyindene (pr-MDI; 30 mg/kg, i.p.), an intracellular calcium antagonist, significantly reduced the number and size of erosions per stomach induced by cold-restraint stress by 69% and 86%, respectively. Our previous findings indicate that the antiulcer activity of pr-MDI is highly correlated with its inhibitory effect on gastric motor activity. Since central TRH is suggested as the brain mediator responsible for cold-restraint stress gastric ulcers in rats, the inhibitory action of pr-MDI was evaluated in the TRH-induced gastric lesion model. Pr-MDI (30 mg/kg) did not reduce the gastric erosions induced by intracisternal administration of 100ng RX77368, a stable thyrotropin-releasing hormone (TRH) analogue, even though it abolished the RX77368-induced stimulation of gastric emptying, gastric acidity, and acid output. Since pr-MDI (30 mg/kg, i.p.) significantly inhibited the stimulation of gastric motility by both cold-restraint stress and TRH, but only cold-restraint stress-induced gastric erosions were effectively reduced by the drug, the present findings suggest a possible dissociation between the ulcerogenic mechanisms of cold-restraint stress and intracisternal administration of TRH.

Animals

Establishment and characterization of a new human cell line derived from ovarian clear cell carcinoma.

A new cell line, designated OCC1, was established from the ascitic fluid of a patient with a clear cell carcinoma of the ovary. The cell line grew well without interruption for over 12 months and over 80 passages. The doubling times of OCC1 were 36 and 38 hr at the 10th and 40th passages, respectively. Chromosomal analysis of the cell line showed hypertriploidy with modal number around 70-77. Several structural chromosomal abnormalities were consistently found. Electron microscopy revealed that OCC1 produced a basement membrane-like structure in vitro. Histological evaluation of xenografts from OCC1 in the 33th passage implanted and grown in nude (athymic) mice revealed a morphology identical to that of the original tumor.

Adenocarcinoma

Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene--I. Effect on cold/restraint stress-induced ulcers in rats.

1. Propyl-methylenedioxyindene (pr-MDI) is an intracellularly acting calcium antagonist with H2-receptor blocking properties. Stimulus-secretion coupling is inhibited by much lower concentrations of pr-MDI than is excitation-contraction coupling. 2. Since the processes leading to gastric ulceration are calcium-dependent, the aim of this study was to determine if pr-MDI could provide useful antiulcer activity at doses below those required to produce cardiovascular effects. 3. The antiulcer activity of pr-MDI (10-30 mg/kg) was examined in the cold (4 degree C)/restraint (3 hr) stress-induced ulcer model in male rats, and compared with the effects of the H2-blocker cimetidine (10-30 mg/kg) and the calcium channel blocker verapamil (11-32 mg/kg). The drugs were administered intraperitoneally 10 min prior to the cold/restraint stress. 4. All three drugs significantly reduced the number of ulcers and the cumulative length of ulcerated stomach surface in a roughly dose-dependent and equivalent manner. However, whereas the antiulcer doses of verapamil were extremely high, those of pr-MDI were one-sixth to one-half of its antiarrhythmic ED50 in rodents.

Animals

Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene--II. Effects on acid secretion and gastric emptying in rats.

1. Propyl-methylenedioxyindene (pr-MDI) is an intracellularly acting calcium antagonist which protects against cold/restraint-induced stress ulcers in rats. The doses of pr-MDI which produce antiulcer activity (10-30 mg/kg i.p.) are significantly lower than those which exhibit cardiovascular effects. 2. Two potential mechanisms for the antiulcer action of pr-MDI were investigated in this study: the effects on hydrochloric acid secretion and on gastric motility (gastric emptying). 3. Bethanechol-induced hydrochloric acid secretion in acutely pylorus-ligated rats was significantly obtunded by pr-MDI (30 mg/kg i.p.), but the effect was significantly weaker than that produced by verapamil (16 mg/kg i.p.) or cimetidine (10 mg/kg i.p.). Since 30 mg/kg pr-MDI produces greater antiulcer activity than the very high dose of 16 mg/kg verapamil, it is unlikely that inhibition of acid secretion plays more than a contributory role in the antiulcer mechanism of action of pr-MDI. 4. pr-MDI (10-30 mg/kg i.p.) produced a dose-dependent slowing of gastric emptying in rats fed a methylcellulose/Phenol Red test meal, and this effect correlated well with the antiulcer action. Verapamil (16 mg/kg i.p.) did not affect gastric emptying. 5. The results indicate that a reduction of gastric motility plays a major role in the mechanism of the antiulcer action of pr-MDI.

Animals

Bleeding duodenal ulcer. A prospective evaluation of risk factors for rebleeding and death.

There were 12 hospital deaths in 433 patients (2.8%, 1.6% at 30 days) presenting with bleeding duodenal ulcer. Excluding patients who underwent immediate operation or early elective surgery, where ulcer size was measured at initial endoscopy rebleeding was evident in 40/288 patients (13.9%) and was associated with an increased mortality (0.4% v 12.5%) (p less than 0.0001). Rebleeding rates for ulcers less than or equal to 1 cm and greater than 1 cm were respectively 28/239 (11.7%) and 12/49 (24.5%) (p less than 0.02). Rebleeding occurred in 13/186 patients (7.0%) in whom endoscopic stigmata of recent haemorrhage were absent and in 27/102 (26.5%) with such stigmata (p less than 0.0001). The mortality rate for patients without stigmata was 3/186 (1.6%) whilst mortality figures for patients with ulcers less than or equal to 1 cm and greater than 1 cm in size were respectively 0/77 and 3/25 (12.0%) when stigmata were identified. Ulcers greater than 1 cm were more frequent in the greater than 60 year age group, more likely to have stigmata and carried an increased risk of rebleeding and mortality.

Age Factors

Examination of the potential antiulcer activity of the calcium antagonist propyl-methylenedioxyindene. III. Lack of effect on cysteamine-induced duodenal ulcers in rats.

Since propyl-methylenedioxyindene (pr-MDI) exhibits significant protective effects against stress-induced ulcers in rats at subcardiovascular doses (10-30 mg/kg, i.p.), the aim of the present study was to explore the effect of this intracellular calcium antagonist on cysteamine-induced duodenal ulcers at the same low doses. Duodenal ulcers were induced in rats with a single dose of cysteamine (425 mg/kg, s.c.), which produced an 80% ulcer incidence within 24 h without affecting gastric acid concentration. Administration of pr-MDI (10 and 30 mg/kg, i.p.) at 0, 6 and 12 h post-cysteamine did not afford protection against ulceration. On the other hand, atropine (10 mg/kg, s.c., administered at 0, 6 and 12 h post-cysteamine) resulted in a 69% inhibition of ulceration, and the antacid Maalox (2 ml, administered p.o. at 0, 2, 4, 6 and 12 h post-cysteamine) completely prevented ulceration. The failure of pr-MDI to protect against duodenal ulceration is discussed in relation to its pharmacological mechanism of action and the pathogenetic mechanism of action of cysteamine.

Aluminum Hydroxide

Newcastle bone disease in Hong Kong: a study of aluminum associated osteomalacia.

We measured serum aluminum concentrations in 104 haemodialysis patients from 3 centres in Hong Kong. We found that the 52 patients dialyzed in unit A had much higher mean aluminium levels (100 micrograms/L) than those from the other two units (61 and 39 micrograms/L respectively). In unit A, where water treatment by reverse osmosis had been introduced only recently, 30.8% of patients had fractures/looser zones, 46.2% had rugger-jersey spine and 28.8% had skeletal erosions. When these patients were divided into two groups according to whether their serum aluminium concentration was below or above 100 micrograms/l, the latter patients had significantly lower alkaline phosphatase, serum phosphate, and higher total prescribed dose of aluminium hydroxide. It was concluded that both dialysate aluminium and oral aluminium intake seemed to have contributed to the high incidence of osteomalacic fractures among Unit A patients. In eight of these patients serum aluminium increased by more than 150 micrograms/L after four weeks of receiving 1.5 g desferrioxamine twice weekly. Serial X-rays showed that the mean time after dialysis for the appearance of fractures/Looser zones was 72 months. Three patients developed fractures/Looser zones after successful renal transplantation; and it was postulated that the prompt excretion of aluminium permitted increased osteoclastic activity, resulting in fractures in these patients.

Adult

Examination of the potential antiepileptic activity of calcium antagonists with different sites of action.

1. Calcium is proposed to play a role in the genesis of epileptic seizures, and a number of established antiepileptic drugs limit the transport of extracellular calcium into neuronal cells. 2. The aim of the present study was to explore the potential antiepileptic activity of three calcium antagonists: nifedipine (20 mg/kg i.p.), which blocks the calcium channel at its outer mouth; verapamil (30 mg/kg i.p.), which blocks the calcium channel at its inner mouth; and propyl-methylenedioxyindene (pr-MDI; 68, 100 and 120 mg/kg i.p.), which acts intracellularly to inhibit calcium mobilization from the endoplasmic reticulum. 3. In the maximal electroshock test, none of the calcium antagonists provided protection against tonic seizures in mice. Phenytoin (20 mg/kg i.p.), on the other hand, afforded complete protection. 4. In the pentylenetetrazol-induced seizure test, the order of effectiveness of the three calcium antagonists in attenuating the severity of the clonic and tonic seizures in mice was: nifedipine greater than verapamil greater than pr-MDI. All three calcium antagonists were less effective than ethosuximide (200 mg/kg i.p.). 5. These findings indicate that the calcium antagonists would be of no value in the treatment of grand mal epilepsy, while only those agents acting at the outer side of the membrane would have limited usefulness at best against petit mal seizures.

Animals

The reappraisal of dilute tissue thromboplastin inhibition test in the diagnosis of lupus anticoagulant.

The dilute tissue thromboplastin inhibition (DTTI) test (Schleider et al, 1976) is a sensitive but non-specific test for lupus anticoagulant (LA). False positive results are seen in patients with clotting factor deficiency involving the extrinsic pathway and also in some patients with specific factor inhibitors (Triplett et al, 1983; Rosove et al, 1986). Since the effect of LA is phospholipid dependent but those of factor deficiency and specific inhibitors are not, we analyse the test results by comparing the degree of inhibition using different dilutions of tissue thromboplastin and express it as the DTTI index. This is defined as the clotting time ratio with 0.2% tissue thromboplastin divided by the clotting time ratio with 2% tissue thromboplastin. We also perform a dilute tissue thromboplastin time with platelet substitution to see if this could neutralize the inhibition caused by LA. Both of these modifications can reliably distinguish LA from other conditions associated with prolonged APTT better than the original DTTI test.

Adolescent

Bleeding gastric ulcer: a prospective evaluation of rebleeding and mortality.

Clinical laboratory and endoscopic data were collected prospectively in 268 patients with bleeding gastric ulcer who were admitted between September 1985 and November 1987. There were 22 deaths, giving a hospital mortality rate of 8.2%. Surgery was undertaken in 68 patients (25.4%) with a mortality rate of 17.6% (11.8% at 30 days). There was one fatality in 104 (1.0%) patients less than or equal to 60 years compared with 21 deaths (12.8%) in patients greater than 60 years (P less than 0.001). Cirrhosis (P less than 0.01), malignant disease (P less than 0.03), chronic obstructive airways disease (P less than 0.02), congestive cardiac failure (P less than 0.02) and ischaemic heart disease (P less than 0.08) were each associated with an increased risk of mortality. Outcome in patients greater than 60 years was related to systolic blood pressure at admission (P less than 0.03), haemoglobin (P less than 0.02), serum bilirubin (P less than 0.02), and total transfusion requirements (P less than 0.001). For ulcers less than or equal to 1 cm, 1- less than or equal to 2 cm, greater than 2 cm in size, mortality rates were 1.9%, 11.4% and 18.0%, respectively. Initial endoscopy findings of a visible vessel, fresh blood, or active spurting/oozing haemorrhage were associated with rebleeding rates necessitating emergency surgery of 30.0%, 36.4% and 40.0%, respectively. There was no evidence of rebleeding in 187 patients (79.9%) managed conservatively and only five patients (2.7%) in this group succumbed, whereas rebleeding did occur in 47 patients (20.1%) with 13 subsequent deaths (27.7%; P less than 0.001). In patients greater than 60 years the presence of endoscopic stigmata of recent haemorrhage should lead to early consideration of therapeutic endoscopy and/or early surgery, particularly for ulcers greater than 1 cm in size.

Adolescent