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Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

At least 469 records · Page 26Linked to original sources
PubMed1987

Pharmacologic modulation of PAF-induced mortality in mice.

The effect of antiinflammatory drugs, phosphodiesterase inhibitors, leukotriene and mediator antagonists and other drug classes were evaluated in a PAF-induced mortality model in mice. By the oral route of administration (-1 hr), dapsone (ED50 = 25 mg/kg), BW 755C (ED50 = 29 mg/kg), theophylline (ED50 = 30 mg/kg) and LY-171,883 (ED50 = 50 mg/kg) protected against PAF-induced lethality in the mouse. Other drugs that afforded protection when given at various dosing schedules and routes were NDGA (100 mg/kg, -18 hr p.o.), diphenyldisulfide (100 mg/kg, -18 hr p.o.), diphenyldisulfide (200 mg/kg, -18 hr p.o.), dexamethasone (1 mg/kg, -3 hr p.o.), dipyridamole (2 mg/kg, -2 min i.v.) and kadsurenone (10 mg/kg, -2 min i.v.). Nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin were inactive and the combination of AA-861, a putative 5-LO inhibitor, and indomethacin also failed to prevent PAF-induced lethality. Therefore, our pharmacological data do not consistently support the notion that PAF-induced lethality is due unequivocally to leukotrienes derived from 5-lipoxygenase metabolism.

Animals↗
PubMed1987

Treatment of the Budd-Chiari syndrome with percutaneous transluminal angioplasty. Case report and review of the literature.

A patient with the Budd-Chiari syndrome due to membranous obstruction of the right hepatic vein and long segmental obstruction of the inferior vena cava who was successfully treated with percutaneous transluminal angioplasty is described. Review of the literature revealed 14 prior cases of balloon dilatation of the hepatic venous system: 10 of the hepatic portion of the inferior vena cava, three of the right hepatic vein, and one of the left hepatic vein. Follow-up ranged from six months to 37 months. No serious complications were reported. All attempts at dilatation were successful, but reocclusion occurred in six patients, three of whom had occlusion of the hepatic vein. All but one patient with reocclusion, however, underwent repeated angioplasty, which was successful in all cases attempted. Two patients who had repeated angioplasty required no further therapy, but two patients required a total of three angioplasties and two patients required four angioplasties. Successful angioplasty was accompanied by resolution of clinical symptoms in all patients described. It is concluded that percutaneous transluminal angioplasty is a safe and effective mode of therapy in the management of the Budd-Chiari syndrome due to membranous obstruction of the hepatic portion of the inferior vena cava or the hepatic veins.

Adult↗
PubMed1987

Immunological abnormalities in rats with adjuvant-induced arthritis--II. Effect of antiarthritic therapy on immune function in relation to disease development.

The effects of the experimental immunomodulatory agent tilomisole (Wy-18,251; (3-(p-chlorophenyl) thiazolo [3,2-a]benzimidazole-2-acetic acid) on disease development and immune function in rats with adjuvant-induced arthritis was assessed in comparison with indomethacin and levamisole. Daily p.o. administration of tilomisole (100-200 mg/kg/day) to M. butyricum-injected rats significantly reduced both edema and bone erosion in the uninjected paw. Moreover, tilomisole treatment restored to normal the diminished Con A-induced proliferative response and IL 2 synthesis observed in spleen cells from arthritic rats, but had no effect on macrophage IL 1 production. In contrast, levamisole treatment (25 mg/kg/day) of arthritic rats improved splenic immune function but did not influence paw edema or bone erosion. Conversely, indomethacin (1 mg/kg/day) significantly reduced paw edema and bone erosion but did not improve the deficient proliferative response or IL 2 synthesis by "arthritic" spleen cells. These results indicate that tilomisole possesses combined antiinflammatory and immunomodulatory activity in adjuvant-arthritic rats which is distinctly different from the effects of either indomethacin or levamisole. Moreover, these data suggest that tilomisole has potential disease-modifying activity in arthritis, which is currently being more closely examined in clinical trials.

Animals↗
PubMed1987

Leukotriene D4 antagonists and 5-lipoxygenase inhibitors. Synthesis of benzoheterocyclic [(methoxyphenyl)amino]oxoalkanoic acid esters.

A series of novel benzoheterocyclic [(methoxyphenyl)amino]oxoalkanoic acid esters has been prepared. These compounds were tested as inhibitors of rat polymorphonuclear leukocyte 5-lipoxgenase (LO) in vitro and as inhibitors of leukotriene D4 (LTD4) and ovalbumin (OA) induced bronchospasm in the guinea pig (GP) in vivo. In general, inhibitory activity against 5-LO, LTD4, and OA was broadest for benzthiazole-containing analogues (benzthiazole greater than benzimidazole much greater than benzoxazole, benzofuran). The most potent 5-LO inhibitor, 4-[[3-(2-benzthiazolylmethoxy)-phenyl]hydroxyamino]-4-oxobutanoic acid methyl ester (7), had an IC50 of 0.36 microM. Compound 7, however, was inactive vs. OA. The most potent compound in vivo, 4-[[3-[(1-methyl-2-benzimidazolyl)methoxy]phenyl]-amino] -4-oxobutanoic acid methyl ester 4, inhibited both LTD4- and OA-induced bronchospasm by 83% and 60%, respectively, at 50 mg/kg intraduodenally. Compound 4 was studied in the Ames assay employing five strains of bacteria (TA1535, TA1537, TA1538, TA98, and TA100) with and without S-9 rat liver enzyme metabolic activation, and there was no significant number of reversions noted.

Animals↗
PubMed1987

Phenylephrine derivatives as leukotriene D4 antagonists.

Two series of phenylephrine derivatives were prepared and tested as inhibitors of leukotriene D4 (LTD4) induced and ovalbumin-induced bronchospasm in the guinea pig. The most potent compound of the urea series, (R)-N,N-diethyl-N-[2-hydroxy-2-[3-(2-quinolinylmethoxy)phenyl]ethyl]-N- methylurea (3, Wy-47,120), was orally active with ED50's of 56 mg/kg vs. LTD4 and 55 mg/kg vs. ovalbumin. When tested as an antagonist of LTD4-induced contraction of isolated guinea pig tracheal strips, 3 was a competitive inhibitor with a p kappa B value of 5.22. In the second series, (R)-3-methyl-5-[3-(2-quinolinylmethoxy)phenyl]-2-oxazolidinone (26, Wy-47,674) had oral ED50's of 36 mg/kg against LTD4 and 95 mg/kg against ovalbumin. Compound 26 selectively antagonized contractile responses of guinea pig trachea evoked by LTD4 (p kappa B = 6.09). In the cat coronary artery, 3 dilated the preparation and blocked the coronary constrictor effect of LTD4. Compound 3 (0.13 mg/kg, iv) also preserved myocardial integrity in rats 48 h after coronary artery ligation. When tested in the rat alcohol-induced gastric lesion model, 3 and 26 manifested a dose-dependent mucosal protection against ethanol.

Animals↗
PubMed1987

Migration of leukaemic lymphocytes (chronic lymphocytic leukaemia) through a 3-D collagen gel: a possible prognostic factor.

Migratory properties of malignant lymphocytes in 27 patients with chronic lymphocytic leukaemia (CLL) were investigated using 3-D collagen gel. There was significant impairment of migration in malignant lymphocytes as compared with normal lymphocytes. Moreover there was an inverse correlation between Rai's staging and the migration index. Patients with progression of disease also showed a decrease in migration index. There was no correlation between kappa and lambda type in terms of migration index. The prognostic significance of the migratory properties of malignant lymphocytes is also discussed.

B-Lymphocytes↗
PubMed1987

Hemodynamic method to predict whether hunterian ligation of the basilar artery will lead to thrombosis of basilar bifurcation aneurysms.

In some cases, basilar artery aneurysms cannot be repaired surgically and the basilar artery is occluded near the neck of the aneurysm to stop flow into the aneurysm. After the operation, the aneurysm can fill only by flow through the posterior communicating arteries (PCoAs). Hemodynamically if the flow were the same in both PCoAs and there were no phase lag in the pressures, there would be no pressure gradient for flow to go across the neck of the aneurysm and therefore the aneurysm would thrombose. We have assumed that the diameter of the artery is roughly proportional to the flow that goes through it chronically. We measured the diameters of the PCoAs in 25 patients who had hunterian ligation of the basilar artery. We also measured the maximal width, height, and depth of the aneurysms on angiograms obtained before and after operation. Eleven aneurysms thrombosed completely and had a diameter ratio of greater than 0.6; 10 aneurysms thrombosed partially and had a diameter ratio of 0.46 approximately 1.0; 4 aneurysms did not change and had a diameter ratio of less than 0.45. The ratio of the sizes of the PCoAs pre- and postoperatively was comparable in most cases, so we believe that it is possible to predict reasonably accurately from this simple measurement whether the aneurysm is likely to thrombose if the basilar artery is ligated.

Basilar Artery↗
PubMed1987

Relationship between the result of preoperative pulmonary function test and postoperative pulmonary complications.

Good preoperative screening and evaluation of patients undergoing surgery is necessary because it serves to identify the individual who is at risk of increased intra-operative and postoperative morbidity and mortality. The retrospective study was done in an attempt to determine if abnormalities in preoperative pulmonary function, detected by routine pulmonary function tests, would predict which patients would suffer from pulmonary complications following surgery. Pulmonary complications in the postoperative period included fever, atelectasis and respiratory failure. The overall incidence of pulmonary complications from our 78 patients undergoing surgery was 37 percent based on clinical criteria. This incidence was high in patients with FEV1 less than 1.0 L/sec, MVV less than 40% of predicted value and PCO2 more than 45 mmHg.

Fever↗
PubMed1987

Altered aortic protease and antiprotease activity in patients with ruptured abdominal aortic aneurysms.

Aortic elastase, antiprotease (a-1-antitrypsin) and total protein were assayed in 37 patients who underwent an operation on the abdominal aorta for ruptured abdominal aortic aneurysms (AAA), an elective procedure for AAA or aortofemoral bypass for occlusive disease. Aortic elastase modified by local antiprotease activity (elastase/a-1-antitrypsin) was significantly higher in patients with a ruptured AAA compared with patients with an elective AAA or occlusive aortic disease: 241 nanograms per milligram of tissue in AAA-rupture versus 57 nanograms per milligram of tissue in AAA-elective versus 32 nanograms per milligram of tissue for occlusive (p less than 0.003). Patients with a ruptured AAA had the highest elastase activity (354 nanograms per milligram of tissue) and the lowest a-1-antitrypsin (1.07 nanograms per milligram of tissue) compared with patients with an elective AAA and occlusion (p less than 0.05). These data suggest that the homeostatic balance between elastase and antiprotease may be significantly altered in the aortic wall at the time of aneurysm rupture. Increased elastase unchecked by low antiprotease results in increased elastin breakdown which may be the inciting event for rupture of a compromised, thin aortic aneurysm wall.

Aorta, Abdominal↗
PubMed1987

Radioactive iodine exchange reaction of HIPDM: kinetics and mechanism.

In conjunction with single photon emission computed tomography (SPECT), iodine-123 (123I)-labeled N,N,N'-trimethyl-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3-propanediamine (HIPDM) has been used clinically as a regional cerebral perfusion imaging agent. The [123I]HIPDM can be prepared by a simple aqueous exchange reaction in a kit form. We synthesized unlabeled HIPDM by condensation of 2-hydroxy-3-methyl-5-iodobezaldehyde and N,N,N'-trimethyl-1,3-propanediamine, followed by a sodium borohydride reduction reaction. The kinetics of the radioactive iodine exchange reaction for the preparation of [123I]HIDM is controlled by the pH, the temperature, and the presence of reductant (sodium bisulfite), and oxidant (sodium iodate). The reaction is a second order iodine-iodine exchange with an activation energy of 30.6 kcal/mole. The mechanism of this reaction probably involves the formation of an active 1+ or iodine free radical, which is sensitive to the presence of a reductant, such as sodium bisulfite.

Drug Interactions↗
PubMed1986

Degradation of immunoreactive albumin in young and old conscious female rats.

The kinetics of inactivation of plasma albumin was studied in young (3-4 months) and old (25-28 months) Sprague-Dawley female rats. Conscious, free-moving animals carrying indwelling atrial and carotid cannulas received a single injection of [125I]-albumin (rat) via the carotid cannula. Sequential blood samples were removed at intervals during the following 120 min, and total (TR) and immunoprecipitable radioactivity (IPR) were determined in the corresponding plasmas. TR disappearance curves for young and old animals were almost identical but IPR disappearance curves showed a significantly faster decline in the young rats. The absolute plasma volumes for young and old rats were (mean +/- S.E.M.), 10.8 +/- 1.1 and 14.4 +/- 1.5 ml, respectively (P less than 0.05). The IPR/TR ratio, an estimate of albumin inactivation within the plasma space, showed a monoexponential decrease in vivo with a t 1/2 of 11.4 +/- 5.1 and 39.3 +/- 10.8 h (P less than 0.05) for young and old rats, respectively. The in vitro t 1/2s for albumin were 5.25 +/- 1.02 and 3.42 +/- 0.91 days (NS) for young and old rats, respectively. It is concluded that: the rate of albumin catabolism declines with age in the female rat; albumin is mainly inactivated in the extravascular space; and total plasma volume increases significantly with age in this species.

Aging↗
PubMed1986

Interleukin 1 activates phospholipase A2 in rabbit chondrocytes: a possible signal for IL 1 action.

We examined the effects of Interleukin 1 (IL 1) on rabbit articular chondrocytes with particular emphasis on arachidonic acid metabolism in these cells. Articular chondrocytes were isolated from the knee joints of normal New Zealand white rabbits and were cultured in vitro until confluent. Addition of 5 U/ml of purified IL 1 to chondrocytes led to an early increase in cell-associated phospholipase A2 (PLA2; measured by hydrolysis of [14C]arachidonic acid-labeled E. coli). Within 1 hr after IL 1 addition, cell-associated PLA2 activity was increased by more than threefold relative to basal PLA2 activity, and further increases in cellular enzyme activity were observed up to 48 hr of IL 1 treatment. IL 1 stimulation also led to a time- and dose-related release of extracellular PLA2 and PGE2, but IL 1-induced PLA2 and PGE2 secretion occurred after the initial burst of intracellular PLA2 activity. Similar PLA2 and PGE2 responses were also observed when purified human IL 1 or IL 1-containing conditioned medium from LPS-stimulated human monocytes were used, but recombinant IL 2 or IL 3 were inactive. IL 1-induced chondrocyte PLA2 did not release radiolabeled free fatty acid from phosphatidylethanolamine labeled at the C-1 position with [14C]stearic acid, confirming the identity of this enzyme as PLA2. These data, therefore, provide the first direct evidence that IL 1 activates cellular PLA2, and we propose that PLA2 activation may be an early signal that initiates the inflammatory actions of IL 1.

Animals↗
PubMed1986

Reconstitution of haemopoietic system with autologous marrow taken during relapse of acute myeloblastic leukaemia and grown in long-term culture.

In long-term cultures of bone marrow from a patient with acute myeloblastic leukaemia (AML) the leukaemic chromosome marker, which was present in a proportion of the marrow cells even during morphological remission, was not detectable after seven days of culture. After florid relapse of AML, large-scale bone marrow cultures were established while the patient received conditioning with cyclophosphamide and total body irradiation as for an allogeneic bone marrow transplant. Marrow cultured for ten days was reinfused and three and six months later the patient was in clinical remission with a normal karyotype.

Adolescent↗
PubMed1986

Correlation between mouse skin inflammation induced by arachidonic acid and eicosanoid synthesis.

We and others have shown that arachidonic acid (AA), when applied topically to ear surfaces, causes an intense acute inflammatory reaction within minutes (as measured by ear thickness). In this study, we have investigated the cellular and biochemical changes associated with this phenomenon and have attempted to correlate these changes with the induction of inflammation. Measurement of vascular permeability by the accumulation of [125I]albumin showed that significant plasma exudation was observed at 15 min in AA-treated ears. Furthermore, the increase in [125I]albumin was time related and was nearly 10-fold greater than control at 1 h. No time-related change in plasma exudation was observed with control ears. Measurement of LTC4 by radioimmunoassay showed that there was a significant increase in LTC4 synthesis at 15 min after AA treatment. Maximal LTC4 synthesis occurred at 15 min and subsequently decreased to 30% of peak level at 30 min. Histological examination and myeloperoxidase measurement indicated that few neutrophils were present at these early time points and suggested that cells other than neutrophils are contributing to LTC4 synthesis. Ear thickness, [125I]albumin accumulation and leukotriene C4 (LTC4) synthesis in AA-treated ears were reduced significantly by topically administered mixed lipoxygenase (LO) and cyclooxygenase inhibitors such as BW755C and phenidone. Therefore, we suggest that AA-induced ear inflammation is a suitable screen for detecting LO inhibitors in vivo.

Animals↗