Identification of two monohydroxyeicosatetraenoic acids synthesized by human pulmonary macrophages.
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Biomedical subjects
Publications and source records attributed to J Chang.
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Mycoplasma mycoides subspecies mycoides (large-colony type) was isolated from the lungs of a goat with pneumonia. Clinical signs included inappetence, weakness, listlessness, coughing, dyspnea, pyrexia, slight nasal discharge, and lameness. Tylosin (4 mg/kg of body weight) was administered each day for 4 days, resulting in slow recovery. Three weeks later, the clinical signs recurred and the kid was anemic. It was given a single blood transfusion and tylosin was administered daily. The kid's health status was steadily declined and it died after 6 days' treatment. At necropsy, the lungs were edematous and congested. Histopathologic findings were those of septicemia and pneumonia.
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A systematic series of methyl (2 and 3) and dimethyl (4) analogues of trimetoquinol (1) were synthesized and evaluated for their beta 1 (atria) and beta 2 (trachea) and adrenoceptor activities. Structural assignments for the erythro (2) and the threo (3) diastereoisomers of 1-(3,4,5-trimethoxy-alpha-methylbenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline were based on NMR spectra of the 6,7-dibenzyl precursors 15 and 16, respectively, and on the synthetic derivatives of cis- and trans-13-methyl-2,3-bis(benzyloxy)-9,10,11-trimethoxytetrahydroprotoberberine (18 and 17). The rank order of beta 2-agonist activity for these compounds was 3 greater than 1 greater than 2 greater than 4. The rank order of activity as beta 1 agonists on the guinea pig atria is 1 greater than 3 greater than 2, and 4 was inactive. The methylated analogues show selectivity for beta 2 receptors in our preliminary pharmacological studies. The threo isomer 3 is the most potent and selective beta 2 stimulant reported to date in the tetrahydroisoquinoline class.
Human pulmonary macrophages (PAM) recovered from young cigarette smokers and from age- and sex-matched subjects who had never smoked were used to investigate arachidonic acid metabolism. The uptake of radiolabeled arachidonic acid by PAM obtained from smokers and nonsmokers was not significantly different. The phagocytic indexes of the smoker and nonsmoker macrophages were 17.4 X 3.9% and 18.5 +/- 5.0%, respectively. Both smoker and nonsmoker macrophages produced prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and prostaglandin F2 alpha (PGF2 alpha). A significant decrease in PGE2 and TXB2 synthesis but not in PGF2 alpha synthesis by the smoker PAM compared PAM compared with the nonsmoker PAM was observed using 2 different assays to measure prostaglandin production. Nonsmoker macrophages produced 644 +/- 128,239 +/- 53, and 29 +/- 12 ng/1.5 X 10(6) cells of PGE2, TXB2, and PGF2 alpha, respectively, whereas smoker macrophages synthesized 168 +/- 20, 41 +/- 3, and 17 +/- 1 ng/1.5 X 10(6) cells, as measured by radioimmunoassay. Similar differences were observed using isotopic assays. A cigarette-smoke-induced lesion in phospholipid hydrolysis or the mechanism regulating phospholipid hydrolysis seem most consistent with these findings.
Fatal Yersinia pseudotuberculosis infection was diagnosed in 3 bushbabies (Galago crassicaudatus) in a large prosimian colony. The clinical signs were diarrhea, dyspnea, hyperthermia, dehydration, and lethargy. Histologically, the disease was characterized by lesions of ulcerative enterocolitis, necrotizing hepatitis, splenitis, lymphadenitis, and nonsuppurative pneumonitis.
The level of anti-T antibodies directed towards the precursor T antigen of the MN blood group system was measured in the sera of 55 patients with disseminated melanoma, before and during chemoimmunotherapy. The anti-T titer was subnormal in patients before therapy; patients who responded to therapy had significantly higher titers than did nonresponders in sera taken before therapy, at regression/progression of disease, and during the last pulse of treatment. Higher pretreatment titers were associated with a significntly longer survival time. A single infusion of Corynebacterium parvum was given to 14 other melanoma patients and significant elevation of preimmunization titers was observed on days 14, 21, and 28 after infusion; Bacillus Calmette-Guerin, vaccination of 9 patients did not significantly alter the anti-T titer. The expression of the normally cryptic T antigen on melanoma cells would absorb naturally circulating anti-T antibodies. Less dense expression of T antigen on melanoma cells that were responsive to therapy, i.e., less "malignant," would explain the better prognosis for patients with higher titers. The increase in anti-T antibodies following administration of C parvum but not of BCG is of possible clinical relevance when C parvum is used as an immunotherapeutic agent.
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A patient with an accessory bile duct originating from the left common hepatic duct and emptying into the stomach along the lesser curvature presented with periodic symptomatic bile gastritis. Reimplantation of the accessory duct into the duodenum relieved his symptoms.
We observed that the treatment of murine macrophages with proteolytic enzymes can activate the synthesis and release of arachidonic acid (ARA) metabolites. Murine peritoneal macrophage monolayers prelabeled with [14C]ARA were incubated with neutral proteases. Specific bacterial and mammalian proteases from various sources provoke the synthesis and release of prostaglandin E2 (PGE2) and other radiolabeled metabolites. However, cells treated with the neutral proteases thrombin and trypsin did not release significant amounts of PGE2. Neutral protease treatment did not decrease cell viability (> 90%) and boiled protease preparations did not activate prostaglandin synthesis. Protease-activated PGE2 synthesis was inhibited by a variety of protease inhibitors and synthetic substrates for neutral proteases. An inflammatory agent that induces macrophage neutral protease activity, 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated synthesis and release of PGE2 in a dose- and time-dependent manner. TPA-activated PGE2 synthesis was also blocked by a variety of protease inhibitors. These results suggest that neutral proteases have the capacity to activate ARA metabolism and imply that neutral proteases found in inflammatory reactions may infuence prostaglandin production.
An inhibitor of two ribopolymer-transcribing DNA polymerases can be isolated from MOPC-21 myeloma tumors, from the sera of mice bearing these tumors, or from MCDV-12 ascitic leukemia. The peritoneal fluid of mice bearing the latter neoplasm is also a source of the inhibitor. The inhibitor is a small DNA molecule which displays inhibitory activity in both double- and single-stranded form.
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A study was carried out on 779 hospital patients in the Orthopaedic and Paediatric Unit of Queen Mary Hospital, Hong Kong. Patients who had no clinical evidence of liver disease, previous history of transfusion with blood or blood products and no major surgery in the past were entered into the study. Markers of previous exposure to Hepatitis B virus (HBV) were HBsAg, anti-HBc and anti-HBs (radioimmunoassay) were done. The results showed that (a) Chinese living in Hong Kong are exposed to HBV infection throughout life (b) horizontal transmission is the dominant mode of transmission and (c) cpronic HBsAg carriers probably do not carry HBV for life but may clear HBs antigenaemia with age.
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