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Biomedical subjects

L C Chang

Publications and source records attributed to L C Chang.

87 records · Page 5Linked to original sources

Serological studies on systemic lupus erythematosus.

Serum samples from 73 cases of Systemic lupus erythematosus (SLE) were studied for proteins, immunoglobulins, complement components and anti-nuclear antibodies. In fresh cases of SLE, low serum albumin, high alpha-1, alpha-2, and gamma-globulins were found. Marked elevation of serum levels of IgG was found at the time of diagnosis, but this returned to normal after regular treatment. Over 71% of SLE had serum levels of C3 and C4 lower than normal (mean - 2SD). The more severe the disease, the lower the serum levels of these two components of complement. Fluorescent anti-nuclear antibody (FANA) was found in 98.6% of the cases studied. Most (85.1%) cases and anti-double stranded deoxyribonucleic acid (anti-ds DNA) antibody levels higher than normal control (mean + 2 SD). We may conclude that FANA, C3, C4 and anti-ds DNA anatibody are immunological parameters sensitive in the early diagnosis of SLE. FANA is the most sensitive, and can be used as a screening test in SLE. The serum C3 and C4 levels correlate well with the severity of the disease.

Adolescent↗

L-Asparagainases from Citrobacter freundii.

Three enzymes which catalyze the hydrolysis of L-asparagine have been identified in extracts of Citrobacter freundii. One of these (asparaginase-glutaminase (EC 3.5.1.1) also shows substantial glutaminase activity. This enzyme is extremely labile, is sensitive to inactivation by p-chloromercuribenzoate, and is not protected by dithiothreitol. A second enzyme (asparaginase B) is also sensitive to mercurials but is protected from inactivation by dithiothreitol. This enzyme has a relatively low affinity for L-asparagine (Km = 1.7-10(-3) M). The third enzyme (asparaginase A) is insensitive to inactivation by mercurials, is stable upon long term storage and has a relatively high affinity for L-asparagine (Km = 2.9-10(-5) M). This enzyme has been purified to homogeneity and has a molecular weight of approx. 140 000; the subunit weight being approx. 33 000. The C. freundii asparaginase A produced significant increases in the survival time of C3H/HE mice carrying the 6C3HED lymphoma tumor.

Amino Acids↗

Alteration of canine renal vascular response to hemorrhage by inhibitors of prostaglandin synthesis.

The involvement of prostaglandins in the redistribution of renal cortical blood flow to inner cortical nephrons during hemorrhagic hypotension was studied in the pentobarbital-anesthetized dog. Total renal blood flow and distribution of renal cortical flow were determined with the radioactive microsphere technique by dividing the cortex into four zones of equal thickness, zone 1 being outermost and zone 4 being juxtamedullary. Two inhibitors of prostaglandin synthesis were used: indomethacin 8 mg/kg and aspirin 100 mg/kg. The inhibitor or the vehicle was given intravenously prior to a control period which was followed by a hemorrhage sufficient to decrease arterial pressure by about one-third. The distribution of cortical flow was determined before hemorrhage, during hemorrhagic hypotension, and after transfusion. In the vehicle-treated dogs, total renal blood flow was well maintained, but flow redistributed to favor the inner cortical nephrons. This vasodilation in the inner cortex was blocked by both inhibitors of prostaglandin synthesis resulting in a decrease in total renal blood flow and relative ischemia of the juxtamedullary nephrons. Salicylate levels required to accomplish blockage of inner cortical vasodilaton were less than 7 mg/100 ml. These studies indicate that prostaglandins are responsible for the decreased vascular resistance of the inner cortical nephrons which results in the redistribution of blood flow during hemorrhage, and when prostaglandin synthesis is blocked, the kidney vasculature constricts during hemorrhage.

Animals↗

Synthesis of prostaglandins by the rat renal papilla in vitro. Mechanism of stimulation by angiotensin II.

1. The biosynthesis of prostaglandins in the rat renal papilla was studied in a whole-cell preparation in vitro. Prostaglandins recovered from the incubation medium were identified by gas chromatography-mass spectrometry as prostaglandin E2 and prostaglandin F2alpha. Quantitative estimates of prostaglandin output were obtained by bioassay and confirmed by selected ion monitoring. 2. Prostaglandin biosynthesis was enhanced by exogenous arachidonic acid and also by triglyceride lipase, indicating that arachidonic acid released from papillary triglycerides is readily available for prostaglandin biosynthesis. 3. Angiotensin II (10--100 ng/ml) stimulated the biosynthesis of both prostaglandin E2 and prostaglandin F2alpha, thus increasing prostaglandin levels in both the incubation medium and the tissues. 4. The mechanism whereby angiotensin II stimulates prostaglandin biosynthesis was investigated using the isotope dilution technique. In the presence of [14-C]-arachidonic acid, angiotensin II stimulated the output of more prostaglandin that had a significantly lower specific activity than the controls. Angiotensin II therefore increased the availability of endogenous, non-labelled substrate for prostaglandin biosynthesis. This conclusion was supported by experiments in which enough arachidonic acid was added to make the kinetics of prostaglandin synthesis zero order. Under such conditions angiotensin II failed to cause any further increase in prostaglandin synthesis. 5. It is concluded that angiotensin II controls prostaglandin biosynthesis in the renal papilla by regulating the availability of free precursor. Possible mechanisms for increased levels of free arachidonic acid could be the activation of a tissue acyl hydrolase or decreased utilization of fatty acids.

Angiotensin II↗

Enhanced renal prostaglandin production in the dog. II. Effects on intrarenal hemodynamics.

The effects of enhanced endogenous production of prostaglandins by the kidney on the distribution of blood flow in the renal cortex were assessed by infusing sodium arachidonate, the precursor of the renal prostaglandins, into one renal artery of the dog. The changes produced with arachidonate (3 times 10--6 g/kg min-1 and 10--5 g/kg min--1) were compared with those produced by infusions of prostaglandin (PG) E2 (10--7 g/kg min--1) and PGF2alpha (3 times 10--7 g/kg min--1) into one renal artery. Distribution of renal blood flow was measured by the radioactive microsphere technique. Sodium arachidonate caused an increase in blood flow to the inner cortical zones with no change in flow to the nephrons in the outermost quarter of the cortex. PGE2 increased flow to all cortical zones, and PGF2alpha produced no change in flow. Since arterial blood pressure did not change, changes in vascular resistance were reciprocal to changes in flow. Thus, vascular resistance fell in the inner cortical regions but not in the outer regions, with arachidonate infusions and in all regions of the cortex with PGE2 infusions; no changes were seen with PGF2alpha infusions. These data indicate that prostaglandin formed endogenously in the kidney affects the vascular resistance of only the inner cortical nephrons; the data thus support the hypothesis that renal prostaglandins are one mediator of renal autoregulation of blood flow.

Animals↗

The effect of vaccination with a live attenuated strain of Japanese encephalitis virus on stillbirths in swine in Taiwan.

Since an excellent candidate strain (M) for live virus vaccination of swine against Japanese encephalitis was developed, a number of large vaccination programmes have been implemented in Japan with the aim of controlling Japanese encephalitis epidemics in man by reducing the population size of nonimmune swine. Encouraging results have been obtained but no studies have been made on the benefits of live-virus vaccination to the industry. In order to determine the effect of vaccination upon the number of stillbirths occurring in the Japanese encephalitis post-emergence season, a total of 74 vaccinated, and subsequently mated, gilts at a large breeding farm in subtropical Taiwan were subjected to follow-up observations in comparison with a control group. The total incidence of litter stillbirths in the vaccinated group (1/74) was significantly lower than that in the control group (21/68). Over 92% of the newborn piglets from the vaccinated gilts were healthy, while 31.6-54.1% of the newborn piglets in the control groups were stillborn. The litter size of vaccinated gilts was larger than that of the control gilts. The vaccine was shown by tests in 22 swine to have an adequate degree of safety. Four weeks after vaccination with either 10(5.6) or 10(8.0) smicLD(50) of virus, all the swine developed an adequate level of antibody. The results indicate that live virus vaccination could benefit the industry in addition to achieving the main aim of controlling Japanese encephalitis viraemia in swine.

Animals↗

Low molecular weight protamine: a potent but nontoxic antagonist to heparin/low molecular weight protamine.

To avoid bleeding complications, protamine is routinely used after cardiovascular surgery to neutralize the anticoagulant function of heparin. However, its clinical use is associated with adverse and sometimes fatal reactions. Based on literature review of the mechanism of heparin neutralization and protamine induced immunologic toxicity, we propose the following hypothesis: If a chain shortened low molecular weight protamine (LMWP) containing the heparin neutralizing domain could be derived from native protamine, it could be a potent and yet nontoxic heparin antagonist. In this study, we present results to validate this hypothesis. LMWP fragments containing an intact arginine sequence and an average molecular weight of approximately 1,100 daltons were successfully prepared by enzymatic digestion of protamine with thermolysin. In vitro studies show that such LMWP fragments completely neutralized the anticoagulant functions of heparin and LMWH, based on the anti-Xa chromogenic and aPTT clotting time assays. In vivo results reveal that although injection of protamine to mice led to obvious production of anti-protamine antibodies, injection of LMWP did not elicit any detectable immunogenic responses. In addition, these LMWP fragments exhibited a markedly reduced antigenicity and cross-reactivity toward the mice anti-protamine antibodies.

Animals↗

A study of the interaction of practolol with acetylcholine, histamine, serotonin and bradykinin in the guinea-pig, and with bean-sprout juice in the mouse.

1. The interactions of practolol with acetylcholine, histamine, serotonin and bradykinin were studied on the trachea and lung of the guinea-pig, an animal whose sensitivity to bronchoactive endogens is known to be similar to that of human asthmatic bronchi. 2. Practolol, like propranolol, potentiated the action of the first three agonists mentioned above, but, unlike propranolol, it did not potentiate the bronchospastic effect of bradykinin. 3. Practolol, in fact, antagonized the action of bradykinin, but this effect was unlike that produced by nonsteroidal anti-inflammatory drugs. 4. The possibility that beta-adrenoreceptor antagonists might show adverse interactions with certain foodstuffs was investigated, an is discussed. 5. It is suggested that the feasibility of the continued use of practolol (or the newer cardioselective beta-blockers) in asthmatics necessarily depends on the type of allergic reaction involved, and so it is not possible to generalize. Any drug or food that might cause a bronchospastic effect synergistically in the presence of a beta- adrenoreceptor antagonist, even a cardioselective one, should be regarded with suspicion.

Acetylcholine↗