Biomedical subjects

M L Chang

Publications and source records attributed to M L Chang.

At least 37 records · Page 2Linked to original sources

PubMed1997

The effects of oxidative stress on in vivo brain GSH turnover in young and mature mice.

Glutathione (GSH) synthetase activities and GSH turnover rates were examined during severe oxidative stress in the mouse brain as induced by t-butylhydroperoxide (t-BuOOH). Brain GSH synthetase activities in 8-mo-old mice in the cortex, striatum, thalamus, hippocampus, midbrain, and cerebellum were found to increase following t-BuOOH treatment. The effect of GSH synthesis on brain GSH turnover rates for 2- and 8-mo-old mice were determined after intracerebroventricular (icv) injection of [35S]cysteine. Rate constants for GSH turnover were determined by least-squares iterative minimization from the specific activity data from 20 min to 108 h after [35S]cysteine administration. GSH and glutathione disulfide (GSSG) specific activities were determined after separation by high-pressure liquid chromatography (HPLC). The half-life of GSH in the 2-mo-old mouse was 59.5 h and in the 8-mo-old mouse was 79.1 h. In summary, defense mechanisms against oxidative stress in the brain differ with age. Young mice can increase the cellular availability of GSH, whereas mature mice can increase GSH synthetase activity during oxidative stress. These differences make mature mice more susceptible to brain oxidative damage.

Aging↗

PubMed1997

Pharmacokinetics of intracerebroventricular tBuOOH in young adult and mature mice.

This in vivo study compared the pharmacokinetics of intracerebroventricularly administered tertiary butylhydroperoxide (tBuOOH) (109.7 mg/kg) among six different brain regions in two age groups of mice (2- and 8-mo-old mice). Brains were dissected at 11 time-points ranging from 0.5-60 min. Pharmacokinetics parameters did not differ between the two age groups. This demonstrates that previously reported age-related differences in tBuOOH toxicity may not be owing to pharmacokinetic differences between the two age groups. Differences were found when comparing the pharmacokinetics of tBuOOH among the various brain regions. Area under the curve (AUC) values were highest in the striatum and thalamus, and lowest in the cerebellum. The half-life of tBuOOH varied widely among the regions with the longest half-lives in the cortex and hippocampus, and the shortest in the striatum and cerebellum. The oxidation of glutathione and the induction of DNA damage are critical aspects of tBuOOH toxicity. These data show that region-dependent differences in toxicity reported previously may result from factors, such as tBuOOH-induced glutathione oxidation and DNA damage.

Aging↗

PubMed1997

The effects of traditional antirheumatic herbal medicines on immune response cells.

OBJECTIVE: Clinically, some traditional Chinese herbal medicines have been thought to be effective in treating rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. To examine the mechanism by which such herbal remedies might be effective, we investigated the ability of Tripterygium wilfordii Hook-f (TWHf) and tetrandrine (TTD) to affect human immune responsiveness in vitro. METHODS: We measured the ability of these agents to affect cytokine secretion from monocytes or T cells, prostaglandin E2 (PGE2) secretion from monocytes, IgG production from B cells, and the phagocytosis of bacteria by neutrophils. RESULTS: These studies revealed that both TWHf and TTD significantly inhibited interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 secretion from monocytes, IgG secretion from B cells, and phagocytosis of bacteria by neutrophils; however, only TWHf inhibited IL-2 and IL-4 production from lymphocytes, and PGE2 secretion from monocytes. CONCLUSION: TWHf and TTD exert a powerful suppressive effect on human immune responses. This action might account for their therapeutic effectiveness in rheumatic diseases, and might support broader and more rigorous clinical trials.

Alkaloids↗

PubMed1996

Apoptosis and oxidative stress in the aging brain.

DNA is a primary site of damage during oxidative stress in the brain. DNA fragmentation occurs within minutes of induction of oxidative stress. This DNA fragmentation probably results from the attack of free radicals on DNA and from the activation of endonucleases. Oxidative stress was induced by intracerebroventricular injection of t-butylhydroperoxide. This results in a very rapid flux of t-butylhydroperoxide, which is cleared from the brain within minutes. This flux of t-butylhydroperoxide results in the formation of hydroxyl radical in the brain and probably in the nuclei of brain cells. Necrosis results from extensive DNA fragmentation caused by massive oxidative stress. Cresyl violet stained brain sections demonstrated necrosis in many brain regions. In addition, previous electron microscopy studies showed degradation of cellular nuclei caused by tBuOOH toxicity. Low doses of t-butylhydroperoxide can induce apoptosis, which is a delayed form of cell death. Apoptosis was found in brains stained to visualize apoptotic DNA fragments. Experiments performed in mice aged 2, 8 or 24 months will be discussed. We have also found that apoptosis and DNA fragmentation can be prevented by pretreating mice with the vitamin micotinamide. Nicotinamide is a precursor for NAD. DNA repair requires high levels of NAD in the nucleus for the activity of poly(ADP-ribose) polymerase. Oxidative stress in the brain produces both necrosis and apoptosis, probably as the result of DNA fragmentation. Senescence is associated with an increase in the production of DNA fragments during brain oxidative stress, which probably leads to more necrosis and apoptosis than in younger mice.

Aging↗

PubMed1996

Pulmonary edema induced by phorbol myristate acetate is attenuated by compounds that increase intracellular cAMP.

We have investigated the effect of terbutaline, aminophylline and dibutyryl cyclic AMP (DBcAMP) on phorbol myristate acetate (PMA)-induced acute lung injury in isolated, blood-perfused rabbit lungs. Pulmonary arterial pressure and lung weight were measured for 30 min after a bolus injection of PMA (10 mu g/kg). In the group exposed to PMA alone, the mean pulmonary arterial pressure (PAP) increased from 16.33 + or - 1.28 to 77.30 + or - 6.40 mmHg (P <0.001), and lung weight increased by 70.69 + or - 10.94 g during the 30 min after PMA challenge (P<0.001). Pretreatment with terbutaline, aminophylline or DBcAMP prevented the increases in both PAP and lung weight (P <0.001). Each of the three drugs also prevented the increase in pulmonary vascular permeability induced by PMA: terbutaline, aminophylline, and DBcAMP all significantly reduced the pulmonary capillary filtration coefficient (KfC) as well as the albumin concentration in the lung lavage fluid after PMA exposure. Post-treatment with terbutaline 5 min after PMA administration also had a protective effect. The mechanisms responsible for these protectivp3 effects may all involve an increase in intracellular cAMP, since all three drugs increase cAMP in the lung (though by different mechanisms). Our data further indicate that the inhibition of tumor necrosis factor production may likewise play an important role in the protective effect exerted by these drugs.

Adrenergic beta-Agonists↗

PubMed1995

Age-dependent effects of t-BuOOH on glutathione disulfide reductase, glutathione peroxidase, and malondialdehyde in the brain.

Intracerebroventricular t-butyl hydroperoxide has been reported to induce damage to many types of brain cells. t-Butyl hydroperoxide administration increases glutathione disulfide levels and decreases levels of glutathione. Young adult mice may be more protected from t-butyl hydroperoxide than mature mice due to their higher glutathione levels, even after the administration of t-butyl hydroperoxide. This leads to our current study, investigating glutathione peroxidase and glutathione disulfide reductase in 2-mo-old and 8-mo-old mice. Furthermore, malondialdehyde levels were measured with the thiobarbituric acid assay and compared between the two age groups. Mature mice detoxify glutathione disulfide less readily than young adult mice. Glutathione disulfide reductase activity increases in young adult mice after t-butyl hydroperoxide administration, but not in mature mice. Glutathione peroxidase activity is significantly lower in 8-mo-old than 2-mo-old mouse striatum after t-butyl hydroperoxide administration. Furthermore, malondialdehyde levels in the 8-mo-old striatum increase significantly 20 min after t-butyl hydroperoxide administration. This suggests that age plays a factor in protective mechanisms that are involved in oxidative stress in the brain.

Aging↗

PubMed1995

Three genes that encode human beta-galactoside alpha 2,3-sialyltransferases. Structural analysis and chromosomal mapping studies.

The synthesis of alpha 2,3-linked sialic acid to Gal(beta 1,3)GalNAc is mediated by at least three beta-galactoside alpha 2,3-sialyltransferases (EC 2.4.99.4, SiaT-4) that are encoded by three distinct genes. In contrast, only a single gene encodes the beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1, SiaT-1). This report assesses the relationship and nature of the SiaT-4 genes. Analysis of human-mouse somatic cell hybrids demonstrates that the sialyltransferase genes are dispersed in the human genome. The gene for SiaT-4 resides in chromosome 8, that for SiaT-4b resides in p21-p34 of chromosome 1 and that for SiaT-4c in q23.3-qter of chromosome 11. The gene symbols for these genes have been designated SIAT4A, SIAT4B and SIAT4C, respectively. To assess the structural organization of one of the SiaT-4 genes, a human SiaT-4a cDNA from submaxillary glands was isolated and characterized. Rapid amplification of cDNA 5' ends (5'-RACE) analysis indicates an unusually long 1 kb 5'-untranslated leader. The catalytic domain of the cloned sequence was expressed in transfected cells and was shown to be competent in mediating the specific synthesis of sialic acid alpha 2,3 to Gal(beta 1,3)GalNAc-R. Genomic sequences for SiaT-4a were also isolated and examined. The data demonstrate that coding information for SiaT-4a protein is dispersed into seven discrete exon segments in a manner reminiscent of the SiaT-1 gene. Furthermore, as in the SiaT-1 gene, intervening sequences interrupt both sialylmotif domains, regions that are conserved among all known sialyltransferases.

Amino Acid Sequence↗

PubMed1995

Protective effect of mepacrine on hypoxia-reoxygenation-induced acute lung injury in rats.

Mepacrine, a cell membrane stabilizer and inhibitor of phospholipase A2 (PLA2), exerts a protective effect on ischemia-reperfusion injury in heart; however, its effect in lungs has not been examined. This study aimed to determine whether mepacrine pretreatment attenuates ischemia-reperfusion lung injury simulated by hypoxia reoxygenation and to identify possible mechanisms for such protection. Acute lung injury was induced in Sprague-Dawley rats by ventilation with 5% CO2-95% N2 and 5% CO2-95% air. Pretreatment with 0.06 mM mepacrine significantly attenuated the acute lung injury. Capillary filtration coefficient, lung weight gain, and protein concentration of lung lavage fluid were significantly lower in mepacrine-treated rats than in rats exposed to hypoxia reoxygenation alone. Steroid dexamethasone, another potential PLA2 inhibitor, had almost no protective effect. Mepacrine but not dexamethasone caused dose-dependent attenuation of the increase in leukocyte chemiluminescence produced by exposure to phorbol myristate acetate. Mepacrine also dose-dependently inhibited production of tumor necrosis factor-alpha (TNF-alpha) by human monocytes; dexamethasone was much less effective in decreasing TNF-alpha production. We conclude that mepacrine but not dexamethasone can significantly attenuate a hypoxia-reoxygenation-induced injury of the lung. This protective effect of mepacrine may not be the result of its inhibition of PLA2 but rather of its downregulation of oxygen radical production by circulating or resident leukocytes or its attenuation of TNF-alpha production by macrophages.

Animals↗

PubMed1995

Acquired immunodeficiency syndrome with CNS toxoplasmosis: a case report.

Central nervous system (CNS) toxoplasmosis is an important infectious complication of acquired immunodeficiency syndrome (AIDS) which appears to result from reactivation of a previously acquired infection and requires prolonged treatment. A 31-year-old male presented in a drowsy mental state and with an unstable gait. Computerized tomographic (CT) scan and magnetic resonance imaging (MRI) showed multiple nodular lesions in the cerebrum and cerebellum; the seropositivity for the human immunodeficiency virus (HIV-1) and high serum IgG toxoplasma titers were also demonstrated. A presumptive diagnosis of CNS toxoplasmosis was based on neurological signs and neuroradiological findings. This was confirmed by improvement in both clinical and neuroradiological pictures during treatment with pyrimethamine and clindamycin. Four months later, however the patient died of intracranial hemorrhage and massive upper GI bleeding.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Lupus in Chinese male: a retrospective study of 61 patients.

BACKGROUND: Systemic lupus erythematosus (SLE) has traditionally been considered a disease of women, and is uncommon in men. In recent years, several large clinical series of male lupus patients have been reported. As no known data are available for lupus in males from Taiwan, a retrospective analysis of data from male lupus patients was done to determine whether these patients differed from other series of male or female SLE patients in the literature. METHODS: Sixty-one male lupus patients, diagnosed and followed in Tri-Service General Hospital, between 1983 and 1993, were studied and their data analyzed, retrospectively. RESULTS: The mean age of diagnosis was 30 +/- 17 (mean +/- SD, range: 13-81) years. The peak age of diagnosis was between 13 and 40 years. The mean duration of follow-up was 36 +/- 36 (range: 2-256) months. The 1-, 5- and 10-year survival rates were 84%, 76% and 75%, respectively. The frequency of clinical manifestations were renal disease, 75%; malar rash, 70%; arthritis, 60%; fever, 56%; photosensitivity, 48%; pleuritis, 39%; pericarditis, 31%; alopecia, 31%; mucosal ulcers, 29%; neuropsychiatric disease, 26%; discoid lupus, 21%; vasculitis, 15%; Raynaud's phenomenon, 10%; and lymphadenopathy, 2%. The frequency of abnormal laboratory findings were antinuclear antibodies (ANA), 95%; hypocomplementemia, 77%; antibodies to double-stranded DNA (anti-dsDNA), 57%; leukopenia, 44%; lupus erythematosus (LE) cells, 39%; anti-Ro, 39%; anti-Smith antibodies (anti-Sm), 19%; thrombocytopenia, 18%; rheumatoid factor, 17%; anti-ribonucleoprotein antibody (anti-RNP), 14%; autoimmune hemolytic anemia, 8%; false-positive venereal disease research laboratory test (VDRL), 6% and anti-La, 4%. CONCLUSIONS: In a review of the 61 ethnic Chinese male lupus patients, a higher frequency of renal disease, malar rash and photosensitivity, but a lower frequency of arthritis and lymphadenopathy, compared to previous reports of Caucasians. There were no significant immunological differences from other series of male lupus, except a lower frequency of anti-dsDNA. In general, poor prognosis was noted for male lupus patients here.

Adolescent↗

PubMed1995

X-linked agammaglobulinemia: a case report.

A 20-year-old male was admitted with fever and hemoptysis. Agammaglobulinemia was found, with bronchiectasis and sinusitis. Clinical and laboratory evidence included immunological examinations, bone marrow and small intestinal biopsies. Results suggested a diagnosis of X-linked agammaglobulinemia. After treatment with antibiotics and intravenous human immunoglobuline, the clinical symptoms demonstrated progressive improvement. The case is reported along with a review of the literature.

Adult↗

PubMed1994

An experimental model of osteoarthritis in rabbit.

BACKGROUND: From both a microscopic and a metabolic view, experimental animal models are very important for study of the pathogenesis of osteoarthritis. A new, different operative procedure was used in rabbit models, and the pathologic findings were evaluated. METHODS: Twelve New Zealand white rabbits were divided into six groups; eight were used as animal models and four, for drug efficacy study. Transection of the anterior cruciate and medial collateral ligaments on the left knee joint, and sham-operation were performed on the right knee joint. Rabbits were sacrificed post surgery from 4, 6, 8 and 12 weeks. Eight parameters from gross to microscopic findings were used in order to evaluate osteoarthritic changes. Indomethacin and aspirin were chosen for the drug efficacy experiment; the two rabbits of each group were sacrificed at the end of the sixth week post-surgery. RESULTS: According to pathological findings, this operative procedure can produce osteoarthritic changes, visible both microscopically and macroscopically. There were osteoarthritic changes in the fourth week post-surgery group and, obviously, in the eighth week; these persisted until 12th weeks post-surgery. Neither indomethacin nor aspirin showed any effect in preventing osteoarthritis progression. CONCLUSIONS: Transection of the anterior cruciate and medial collateral ligament rabbit model can produce osteoarthritic lesions in the knee joint. This model can be used for further biochemical and metabolic studies.

Animals↗

PubMed1994

Intermittent intravenous treatment of lupus nephritis with cyclophosphamide: a four-year experience with twenty-four patients.

BACKGROUND: Renal involvement in systemic lupus erythematosus commonly leads to renal failure and death. We conducted a study to evaluate the efficacy and side effects of intermittent intravenous treatment with cyclophosphamide of patients with lupus nephritis. METHODS: Twenty-four patients with lupus nephritis were recruited at Tri-Service General Hospital from 1988 to 1992. Cyclophosphamide was administered intravenously monthly for three months, and then every three months. 24-hour urinary protein, creatinine clearance, serum creatinine, blood urea nitrogen, C3 and C4 levels, serum albumin, hemoglobin, and dosage of prednisolone were recorded before each treatment. During treatment, the side effects were monitored. RESULTS: Two patients progressed to renal failure within one year and one patient after three years. Fifteen patients completed therapy for one year. Among these 15 patients, the levels of hemoglobin, serum albumin, and C3 significantly increased at six months, then became stable; the level of C4 increased at 12 months. In contrast, the dosage of prednisolone decreased significantly at six months. There was no significant difference of creatinine clearance, 24-hour urinary protein, serum creatinine, and blood urea nitrogen before and after treatment. The most common side effects were nausea and vomiting. No severe side effect necessitated discontinuing therapy with cyclophosphamide. CONCLUSIONS: Intermittent intravenous therapy in lupus nephritis with cyclophosphamide can significantly increase levels of hemoglobin, serum albumin, C3 and C4, and keep renal function stable. Poor response was found in a subset of patients. The side effects were mild in the present study.

Adult↗

PubMed1994

Lupus nephritis: an analysis of 70 cases.

BACKGROUND: The influence of renal morphology and clinical factors at biopsy on the development of renal failure in patients with lupus nephritis remain controversial. We investigated the relation between renal histologic finding and clinical manifestations, and evaluated prognostic factors and short-term prognosis among patients with lupus nephritis. METHODS: Seventy patients with lupus nephritis were enrolled in the study from 1982 to 1992 at the Tri-Service General Hospital. Renal biopsy specimens from these patients were assessed according to the World Health Organization (WHO) classification, activity and chronicity indices, and clinical parameters. Survival was analyzed by using the day of renal biopsy as the starting point. The end point of renal survival was the date when patient started to receive regular hemodialysis. RESULTS: In pathological finding, one patient was grouped as Class I (1.4%); 14, as Class II (20%); 15, as Class III (21.4%); 29, as Class IV (41.4%); 9, as Class V (12.9%), and 2, as Class VI (2.9%). The scores of activity indices were highest in Class IV. The blood levels of C3 and C4 in Class V were significantly higher than Class IV. The values of BUN and 24-hour urine protein in Class II were significant lower than Class IV. Patients who progressed to renal failure had significantly higher numbers of death, higher serum creatinine and chronicity index, less creatinine clearance, and higher numbers of hypertension at the time of biopsy. Nephrotic syndrome was not associated with renal failure. Patient and renal survivals did not differ among WHO classifications. The patient and renal survivals were 84%, 60% and 85%, 72% at one and five years, respectively. Seventeen patients (24.2%) progressed to end-stage renal disease and 21 patients (30%) died during the study period. The leading causes of death were sepsis and renal failure. CONCLUSIONS: WHO classification had little correlation with clinical and renal information. At the time of biopsy the elevated serum creatinine and hypertension were good predictors for end-stage renal disease. Poor patient and renal survivals were found in this study.

Adolescent↗

PubMed1993

Efficacy and possible mechanisms of the Chinese herbs suching-huo-hsuei-tang in the treatment of adjuvant-induced arthritis in rats.

The Chinese herbal formula suching-huo-hsuei-tang (SHT) was studied to evaluate its efficacy and possible mechanism on adjuvant-induced arthritis (AIA) in rats. SHT was extracted with water, butanol and chloroform into 5 different layers. The top 3 layers of SHT showed a significant suppression of AIA and writhing reaction; the top 2 layers suppressed neutrophil chemotaxis and platelet aggregation. The results suggest that SHT is very promising in the treatment of rheumatoid arthritis (RA) by way of its anti-inflammatory and analgesic action. The possible mechanisms for arthritis are multifactorial.

Animals↗

PubMed1993

[The influence of Chinese traditional medicine on the production and activity of interleukin 1 (IL-1)].

Interleukin 1 (IL-1) is a cytokine closely related to the pathogenesis of inflammation and chronic destructive changes in rheumatoid arthritis (RA). Analysis of the effect of antirheumatic drugs on IL-1 production and activity is of great importance in exploring the therapeutic mechanism of RA. The purpose of the present study was to investigate the effect of Chinese herbs (10 prescription and 15 single drugs), which was often used in the treatment of RA, on the production and activity of IL-1. The production of IL-1 was tested through human monocytes stimulated with zymosan and measured by ELISA method; the activity of IL-1 was measured by its effect on the proliferation of murine thymocytes. The results showed that Tripterygium Wilfordii Hook, Tripterygil Hyhoglauci Tetrandrine significantly inhibited both of IL-1 production and IL-1 activity; while Aconiti Tuber, Ephedrae Herba, Atractyloidis Rhizoma, Atractyloidis Lanceae Rhizoma, Ledebouiellae Radix slightly inhibited IL-1 activity but not affecting IL-1 production. The ten prescriptions had no inhibitory effect on both of IL-1 production and IL-1 activity.

Animals↗

PubMed1993

Human triosephosphate isomerase deficiency resulting from mutation of Phe-240.

Triosephosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketolisomerase [E.C.5.3.1.1]) deficiency is an autosomal recessive disorder that typically results in chronic, nonspherocytic hemolytic anemia and in neuromuscular impairment. The molecular basis of this disease was analyzed for one Hungarian family and for two Australian families by localizing the defects in TPI cDNA and by determining how each defect affects TPI gene expression. The Hungarian family is noteworthy in having the first reported case of an individual, A. Jó., who harbors two defective TPI alleles but who does not manifest neuromuscular disabilities. This family was characterized by two mutations that have never been described. One is a missense mutation within codon 240 (TTC [Phe]-->CTC [Leu]), which creates a thermolabile protein, as indicated by the results of enzyme activity assays using cell extracts. This substitution, which changes a phylogenetically conserved amino acid, may affect enzyme activity by disrupting intersubunit contacts or substrate binding, as deduced from enzyme structural studies. The other mutation has yet to be localized but reduces the abundance of TPI mRNA 10-20-fold. Each of the Australian families was characterized by a previously described mutation within codon 104 (GAG [Glu]-->GAC [Asp]), which also results in thermolabile protein.

Adolescent↗

PubMed1991

Neutrophil chemiluminescence and superoxide production in patients with rheumatoid arthritis: the effect of zymosan, phorbol myristate acetate and platelet-activating factor.

Previous study demonstrated that platelet activating factor (PAF) was a potent inducer of polymorphonuclear leukocyte (PMN) activation. This study used a luminometer to measure the chemiluminescence (CL) of peripheral blood (PB) PMNs in 15 patients with rheumatoid arthritis (RA). Superoxide production from PB and synovial fluid (SF) PMNs was also determined by inhibiting reduction of ferricytochrome C with superoxide dismutase. Neutrophils obtained from 12 age- and sex-matched healthy subjects (HS) were used as controls. The results showed that PAF at both 1 microM and 10 microM significantly increased neutrophil CL in both RA (1.40 +/- 0.90 mv, 1.87 +/- 1.18 vs control 0.66 +/- 0.18) and HS (1.70 +/- 0.72, 2.22 +/- 1.25 vs control 0.67 +/- 0.13), with no significant difference between the two groups. Both PMA and zymosan also significantly enhanced PMN CL in both RA (41.51 +/- 17.42, 40.0 +/- 26.51) and HS (43.42 +/- 17.28, 39.91 +/- 27.24), and those values were much higher than those of controls or via PAF stimulation, but, again, there was no difference between RA and HS groups. Lipopolysaccharide (LPS)-stimulated mononuclear cell supernatant can induce neutrophil activity, too. Like CL, PAF had a weak effect on the generation of superoxide from PMNs. Neutrophils from seven RA SF stimulated with PMA or PAF showed a significant increase in superoxide production (76.05 +/- 2.14, 2.83 +/- 0.18) and these were higher than in PB of either RA patients (54.35 +/- 12.46, 1.03 +/- 0.74) and HS (55.70 +/- 17.9; 1.08 +/- 1.12) (p less than 0.05). These findings demonstrated the PMNs were more activated in SF than those in PB of RA patients and HS, suggesting some unidentified factors in SF provoked PMNs activation.

Arthritis, Rheumatoid↗