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Biomedical subjects

S W Hwang

Publications and source records attributed to S W Hwang.

At least 37 records · Page 2Linked to original sources
PubMed1999

Capsaicin binds to the intracellular domain of the capsaicin-activated ion channel.

Capsaicin (CAP) excites small sensory neurons, causing pain, neurogenic inflammation, and other visceral reflexes. These effects have been proposed to be the result of CAP activation of a nonselective cation current. It is generally assumed that CAP binds to an extracellular domain of the membrane receptor. However, the exact binding site is not known because of the lipophilic nature of CAP. To determine whether the binding domain is extracellular or intracellular, we tested the effect of a synthetic water-soluble CAP analog, DA-5018.HCl, on current activation. CAP activated the 45 pS (at -60 mV) nonselective cation channel from either side of the membrane. However, DA-5018.HCl, which had a greater potency and efficacy than CAP, activated the channels only from the cytosolic side of the patch membrane in a capsazepine, a CAP receptor antagonist, reversible manner. When applied extracellularly, DA-5018. HCl did not, but CAP did, activate whole-cell currents in sensory neurons, as well as in oocytes expressing vanilloid receptor 1, a recently cloned CAP receptor. Hydrogen ions, reported as a possible endogenous activator of cation current, failed to elicit any current when acidic medium (pH 5.0-6.0) was applied intracellularly, indicating that H+ does not mediate the CAP effect. These results indicate that CAP and its analog bind to the cytosolic domain of the CAP receptor and suggest that an endogenous CAP-like substance other than H+ may be present in the cell.

Animals↗
PubMed1998

Identification of two major F2 isoprostanes, 8,12-iso- and 5-epi-8, 12-iso-isoprostane F2alpha-VI, in human urine.

Isoprostanes (iPs) are nonenzymatic, free radical-derived compounds isomeric with enzymatically formed eicosanoids such as prostaglandins, leukotrienes, and thromboxanes. One group formed by the auto-oxidation of arachidonic acid, the F2-iPs, consists of four classes of isomers of prostaglandin F2alpha (PGF2alpha). They are relatively abundant in human urine. This fact, along with their chemical stability and excellent characteristics for quantitation by gas chromatography/mass spectrometry, has made them attractive indices of oxidative stress in humans. We developed a specific assay using gas chromatography/mass spectrometry for the first identified F2-iP, iPF2alpha-III (previously called 8-iso-PGF2alpha or 8-epi-PGF2alpha), which demonstrated the utility of monitoring a specific isomer. Recently, we described an assay for another isomer, iPF2alpha-VI, which is present in urine in greater concentration than iPF2alpha-III and which is particularly amenable to quantitation. We now describe the identification in human urine of two more isomers, 8,12-iso-iPF2alpha-VI and 5-epi-8, 12-iso-iPF2alpha-VI, using high performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. These compounds are each present in approximately 5-fold greater concentrations than iPF2alpha-VI (approximately 20-fold greater than iPF2alpha-III). They share the unique chemical characteristics of class VI compounds, which make them attractive targets for quantitation by gas chromatography/mass spectrometry and immunoassay development.

Chromatography, High Pressure Liquid↗
PubMed1998

Risk factors for death in homeless adults in Boston.

BACKGROUND: Homeless individuals experience high mortality rates. Males, whites, and substance abusers are more likely to die, but other high-risk characteristics are unknown. OBJECTIVE: To identify demographic and clinical factors associated with an increased risk of death in homeless individuals. METHODS: We conducted a case-control study of 558 adults who were seen by a health care program for the homeless in Boston, Mass, and who died in 1988 to 1993. Age-matched paired controls were selected from among individuals seen by the program who were alive at the end of 1993. Predictive data were obtained by blinded review of medical records. Odds ratios (ORs) for death were calculated using logistic regression analysis models. RESULTS: In a multivariate analysis, the strongest risk factors for death were acquired immunodeficiency syndrome (OR, 55.8), symptomatic human immunodeficiency virus infection (OR, 17.7), asymptomatic human immunodeficiency virus infection (OR, 4.1), renal disease (OR, 18.4), a history of cold-related injury (OR, 8.0), liver disease (OR, 3.8), and arrhythmia (OR, 3.3). A history of substance abuse involving injection drugs (OR, 1.6) or alcohol (OR, 1.5) also increased the risk of mortality. Nonfluency in English was associated with a decreased risk of death (OR, 0.4). CONCLUSIONS: In a group of adults seen by a health care program for the homeless, specific medical illnesses were associated with the greatest risk of death. Substance abuse alone was less strongly associated with death. Interventions to reduce mortality among the homeless should focus on individuals with high-risk characteristics.

Adult↗
PubMed1998

IPF2alpha-I: an index of lipid peroxidation in humans.

Isoprostanes are prostaglandin isomers produced from arachidonic acid by a free radical-catalyzed mechanism. Urinary excretion of 8-iso-prostaglandin F2alpha, an isomer of the PGG/H synthase (cyclooxygenase or COX) enzyme product, prostaglandin F2alpha (PGF2alpha), has exhibited promise as an index of oxidant stress in vivo. We have developed a quantitative method to measure isoprostane F2alpha-I, (IPF2alpha-I) a class I isomer (8-iso-PGF2alpha is class IV), using gas chromatography/mass spectrometry. IPF2alpha-I is severalfold as abundant in human urine as 8-iso-PGF2alpha, with mean values of 737 +/- 20.6 pg/mg creatinine. Both isoprostanes are formed in a free radical-dependent manner in low density lipoprotein oxidized by copper in vitro. However, IPF2alpha-I, unlike 8-iso-PGF2alpha, is not formed in a COX-dependent manner by platelets activated by thrombin or collagen in vitro. Similarly, COX inhibition in vivo has no effect on IPF2alpha-I. Neither serum IPF2alpha-I, an index of cellular capacity to generate the isoprostane, nor urinary excretion of IPF2alpha-I, an index of actual generation in vivo, is depressed by aspirin or indomethacin. In contrast, both serum thromboxane B2 and urinary excretion of its 11-dehydro metabolite are depressed by the COX inhibitors. Although serum 8-iso-PGF2alpha formation is substantially depressed by COX inhibitors, urinary excretion of the compound is unaffected. Urinary IPF2alpha-I is elevated in cigarette smokers compared with controls (1525 +/- 180 versus 740 +/- 40 pg/mg creatinine; P < 0.01) and is highly correlated with urinary 8-iso-PGF2alpha (r = 0.9; P < 0.001). Urinary IPF2alpha-I is a novel index of lipid peroxidation in vivo, which can be measured with precision and sensitivity. It is an abundant F2-isoprostane formed in a free radical- but not COX-dependent manner. Although 8-iso-PGF2alpha may be formed as a minor product of COX, this pathway contributes trivially, if at all, to levels in urine. Urinary excretion of both isoprostanes is elevated in cigarette smokers.

Biomarkers↗
PubMed1998

A capsaicin-receptor antagonist, capsazepine, reduces inflammation-induced hyperalgesic responses in the rat: evidence for an endogenous capsaicin-like substance.

In the present study, the presence of an endogenous capsaicin-like substance and the role of capsaicin receptors in nociception during inflammation were assessed using Fos immunohistochemistry and the paw-withdrawal test in rats. Intradermal injection of carrageenan in the hind-paw produced inflammation in the foot pad, increased the number of cells exhibiting Fos-like immunoreactivity in the dorsal horn of the spinal cord, and decreased the paw-withdrawal latency. Intradermal injection of capsazepine, a capsaicin-receptor antagonist, significantly reduced the number of cells exhibiting Fos-like immunoreactivity, significantly increased the paw-withdrawal latency, but did not decrease inflammation induced by carrageenan injection. Intradermal injection of capsaicin or formalin also increased Fos-positive neurons. Capsaicin- or formalin-induced Fos expression was reduced in both cases by pretreatment of capsazepine, but to a much lesser extent for formalin. The capsazepine inhibition of carrageenan inflammation-induced hyperalgesic responses strongly suggests that an endogenous capsaicin-like substance is released in inflamed tissues and produces nociceptive neural impulses by acting on capsaicin receptors present on sensory neurons. Furthermore, our results indicate that capsaicin receptors take part only in generating nociceptive signals in sensory neurons, but not in activating the inflammation-promoting cells.

Animals↗
PubMed1997

Causes of death in homeless adults in Boston.

BACKGROUND: Homeless persons have high mortality rates. OBJECTIVE: To ascertain causes of death in a group of homeless persons. DESIGN: Cohort study. PATIENTS: 17,292 adults seen by the Boston Health Care for the Homeless Program from 1988 to 1993. MEASUREMENTS: Cause-specific mortality rates adjusted for race and rate ratios that compare mortality rates in homeless persons with those in the general population of Boston. RESULTS: Homicide was the leading cause of death among men who were 18 to 24 years of age (mortality rate, 242.7 per 100000 person-years; rate ratio, 4.1). The acquired immunodeficiency syndrome was the major cause of death in men (mortality rate, 336.5 per 100000 person-years; rate ratio, 2.0) and women (mortality rate, 116.0 per 100000 person-years; rate ratio, 5.0) who were 25 to 44 years of age. Heart disease and cancer were the leading causes of death in persons who were 45 to 64 years of age. CONCLUSIONS: The most common causes of death among homeless adults who have contact with clinicians vary by age group. Efforts to reduce the rate of death among homeless persons should focus on these causes.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The isoprostanes: a perspective.

The isoprostanes are a new class of natural products produced in vivo by a non-enzymatic free-radical-induced peroxidation of polyunsaturated fatty acid. In the case of arachidonic acid, for example, four classes of isoprostanes can be produced. Because of the specific structural features distinguishing them from other free-radical-generated products, e.g., HETEs, etc., the isoprostanes can provide an exclusive and selective index for the oxidant component of several inflammatory and degenerative diseases. The possible mechanisms of formation of the individual isoprostanes is discussed in detail. Class III products, such as 8-iso-PGF2 alpha and 8-iso-PGE2 have been shown to be vasoconstrictors and modulate platelet function. Several synthetic representatives from the four classes of arachidonic-acid-derived isoprostanes have already been prepared by total synthesis. These synthetic standards have been used for the identification and quantitation of these isoprostanes in biological fluids using gas chromatography/mass spectrometry methodology.

Animals↗
PubMed1997

Nomenclature of isoprostanes: a proposal.

We have proposed a nomenclature system for the isoprostanes, a new class of natural products formed in vivo by the free-radical peroxidation of polyunsaturated fatty acids. Our proposed nomenclature is based on the assignment of four isoprostanes, 1, 9, 17, and 25, as representatives of the four classes of isoprostanes derived from arachidonic acid (AA). We have attempted as much as possible to retain elements from the familiar prostaglandin nomenclature. In this proposal, we have used the abbreviation i.p. for isoprostane. We have classified isoprostane classes or types based on omega-carbon as being the starting reference. Roman numerals I-VI refer the six types of isoprostanes derived from eicosapentaenoic acid (EPA) and III-VI refer to the four types derived from AA. This nomenclature can be applied to isoprostanes derived from other PUFAs also.

Prostaglandins↗
PubMed1997

Aortic root abscess with fistula formation.

Aortic root abscess is a common complication of aortic valve endocarditis. However, aortic root abscess and formation of a fistula from the aortic root to the right ventricular outflow tract in the setting of a native aortic valve and previous repair of an aortic dissection with a Dacron graft is an uncommon event. Transesophageal echocardiography is superior to transthoracic echocardiography for the diagnosis of aortic root abscess. To our knowledge, no studies have compared the diagnostic value of cardiac MRI with transesophageal echocardiography for this condition.

Abscess↗
PubMed1996

D-arabinose dehydrogenase and biosynthesis of erythroascorbic acid in Candida albicans.

D-Arabinose dehydrogenase was purified 2750-fold from the cytosolic fraction of Candida albicans to apparent homogeneity, with an overall yield of 3%, by a purification procedure consisting of ammonium sulfate precipitation and DEAE-Sepharose A-50, Sephacryl S-200, Cibacron blue and phenyl-Sepharose CL-4B chromatographies. Gel-filtration chromatography gave an apparent molecular mass of 41 kDa and SDS-PAGE showed only one protein band corresponding to a molecular mass of 42 kDa, indicating that the enzyme is a single polypeptide. The enzyme was optimally active at pH 8.0 and the pI value of the enzyme was 5.0. The enzyme was relatively stable from pH 4.5 to 7.5. The optimal temperature for the enzyme activity was 30 degrees C. The activity of the enzyme was inhibited by Hg2+, Fe2+, Zn2+, Cu2+, Mg2+, Mn2+, N-ethylmaleimide and p-chloromercuribenzoic acid. The enzyme catalysed the oxidation of D-arabinose, L-fucose, L-xylose and L-galactose, which have the same configurations of hydroxyl groups at C2- and C3-positions, with apparent K(m) values of 29.2, 28.9, 37.1 and 91.3 mM at pH 8.0, respectively, with 50 microM NADP+. The enzyme used NADP+ as a coenzyme. Apparent K(m) value at 60 mM D-arabinose for NADP+ was 44.6 microM. NADPH inhibited the enzyme activity competitively with respect to NADP+ (Ki = 78.6 microM). The amino-terminal sequence of the enzyme was Met-Lys-Leu-Ala-Thr-Glu-Ile-Asp-Phe-X-Leu-Asn-Asn-Gly-. The reaction product was D-arabinono-1,4-lactone, judged from gas-liquid chromatography/mass spectrometry. In C. albicans, D-erythroascorbic acid was formed from D-arabinose by D-arabinose dehydrogenase and D-arabinono-1,4-lactone oxidase.

Amino Acid Sequence↗
PubMed1996

Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons.

Capsaicin (CAP), a neurotoxin, has been reported to activate a nonselective cation current in dorsal root ganglion (DRG) neurons. In this paper, we identify and describe the properties of CAP-activated single channels in cultured neonatal rat DRG neurons. We first identified CAP-sensitive whole-cell currents that reversed near 0 mV in physiological solution. In solution containing 140 mM Na+, extracellular application of CAP to outside-out patches caused activation of an ion channel in a concentration-dependent manner (EC50 = 1.1 microM). The channel was blocked by the CAP antagonist capsazepine (10 microM). The channel was also activated by 2-10 nM resiniferatoxin, a potent analog of CAP. In symmetrical 140 mM Na+, the single-channel slope conductances were 45.3 +/- 1.0 and 80.0 +/- 4.2 pS at -60 and +60 mV, respectively, showing outward rectification (n = 9). The reversal potential did not shift significantly when Na+ was replaced by K+, Cs+, Rb+, or Li+, showing that the channel discriminated poorly among cations. The channel was also permeable to Ca2+. Although acid (pH < 6.2) was suggested to be an endogenous activator of the CAP receptor, an acid solution (pH 5.9-6.0) failed to activate the channels in outside-out patches. This is the first clear demonstration of the presence of the CAP-activated ion channel in DRG neuron. Opening of these ligand-gated, cation-selective channels gives rise to the whole-cell CAP-activated current in DRG neurons and may underlie the neurotoxic effects of CAP.

Acids↗
PubMed1991

[Experimental life history of Echinostoma hortense].

The complete life cycle of Echinostoma hortense has been maintained in the laboratory, using Lymnaea pervia snails and Rana nigromaculata tadpoles as the first and second intermediate hosts. ICR mice was used as the definitive host. Within the egg of E. hortense, the miracidium was fully matured in 13 days of incubation at 29-30 degrees C. The miracidium was 93.8 x 53.6 microns in average size, covered with numerous cilia of 7-11 microns length. The epidermal plates were arranged in 6-8-4-2 formula. The first generation rediae (1.19 x 0.27 mm in average size) were observed in 14 days after miracidial challenge to the snails, and the second generation rediae (1.40 x 0.26 mm in average size) in 30 days. The average size of the cercaria was 295.5 x 145.0 microns. Their head crown was poorly developed, and collar spines were not yet observed. After a cercarial challenge to the tadpoles, all of the tadpoles became infected and the average worm recovery rate was 88.5%. The majority of the metacercariae (75.5%) were recovered from the muscle of the tadpole's posterior body and the rest (24.3%) from their gills. The metacercariae from the tadpoles were elliptical, and 167.7 x 129.9 microns in average size. The recovery rate of adults from the mice was different by the age of the metacercariae grown in the tadpoles. The metacercariae younger than 5 hrs could not infect mice whereas those older than 6 hrs could infect mice. The recovery rate became higher as the metacercaria matured, with the peak recovery rate of 90.0% at the metacercarial age of 9 days. Thereafter the recovery rate decreased to 55.0% at the age of 50 days. As shown by the above results, the whole life cycle of E. hortense has been completed in the laboratory. At least 55-58 days were required to maintain one egg-to-egg cycle of E. hortense.

Animals↗
PubMed1975

Plasma and hepatic binding of indocyanine green in guinea pigs of different ages.

Binding of indocyanine green (ICG) to the proteins in plasma and bile of guinea pigs ranging in age from 1 day old to adult was studied. The ICG in plasma was almost totally bound to the protein and there was no significant difference in the binding between newborn and adult animals. Binding of ICG to biliary protein was similar in all age groups. Particulate fractions of liver from adult guinea pigs had a higher ICG binding capacity than that from the newborn at all concentrations tested. The uptake of ICG by liver slices involved mostly active processes. The slice-to-medium (S/M) ratio of ICG was lowest in liver preparations from the newborn; however, the S/M ratio for adult animals was lower than that for 10-day-old animals. Liver slices from adult guinea pig showed the fastest ICG efflux rate, and the efflux rate with liver slices from the newborn was the slowest. Processes of hepatic uptake and release of ICG were incompletely developed in the newborn guinea pig.

Age Factors↗