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Biomedical subjects

S K Lo

Publications and source records attributed to S K Lo.

At least 55 records · Page 3Linked to original sources
PubMed1998

In vivo expression of neutrophil inhibitory factor via gene transfer prevents lipopolysaccharide-induced lung neutrophil infiltration and injury by a beta2 integrin-dependent mechanism.

The binding of beta2 (CD18) integrins on PMN cell membrane to intercellular adhesion molecule (ICAM) counter-receptors on the surface of vascular endothelial cells mediates PMN adhesion to endothelial cells. Neutrophil inhibitory factor (NIF), a 41-kD glycoprotein isolated from the canine hookworm (Ancylostoma caninum), is a beta2 integrin antagonist that inhibits PMN adhesion to endothelial cells. We transferred the NIF gene into CD1 mouse lungs by intravenous injection of cationic liposomes to study the effects of in vivo NIF expression on LPS-induced lung PMN sequestration and the development of lung injury. RT-PCR and Northern blot analysis indicated the lung-selective expression of the NIF transgene, and immunocytochemistry showed prominent NIF expression in pulmonary microvessel endothelial cells. NIF staining was also observed in intraluminal leukocytes present in pulmonary microvessels. This may be the result of NIF binding to leukocytes after its secretion from the transduced lung cells, since there was no evidence of NIF gene expression in circulating leukocytes. Pulmonary vascular NIF expression abrogated the lung tissue PMN uptake and airspace migration of PMN and prevented lung vascular injury (as measured by the lung tissue uptake of [125I]labeled albumin) after the intraperitoneal LPS challenge (200 microg/mouse). Expression of a control protein, chloramphenicol acetyltransferase (CAT), by the same strategy, had no effect on these responses. In vitro studies showed that NIF prevented mouse PMN adhesion consistent with the inhibition of lung uptake after LPS challenge in NIF transgene-expressing mice. We conclude that pulmonary vascular expression of NIF, a specific beta2 integrin- binding protein, is a potentially useful gene transfer strategy in modulating the infiltration of PMN across the alveolar-capillary epithelial barrier and in preventing lung vascular endothelial injury.

Animals↗
PubMed1998

Predictors of systemic embolism in patients with mitral stenosis. A prospective study.

BACKGROUND: Most studies of the predictors of systemic embolism in patients with mitral stenosis have been retrospective. OBJECTIVE: To prospectively study factors associated with systemic embolism in mitral stenosis. DESIGN: Prospective cohort study. SETTING: University-affiliated medical institution with 3000 beds. PATIENTS: 534 consecutive patients with a mitral valve area of 2.0 cm2 or less; 132 patients were in sinus rhythm, and 402 were in atrial fibrillation. MEASUREMENTS: Nine clinical and 10 echocardiographic variables were assessed for prediction of systemic embolism over a mean (+/- SD) follow-up of 36.9 +/- 22.5 months. Diagnosis of systemic embolism was based on symptoms and signs (sudden onset of peripheral arterial ischemic or neurologic manifestations without prodromes) and on findings on computed tomography, angiography, and surgery. RESULTS: For patients in sinus rhythm, age (relative risk [RR], 1.12 [95% CI, 1.04 to 1.21]), the presence of a left atrial thrombus (RR, 37.1 [CI, 2.82 to 487.8]), mitral valve area (RR, 16.9 [CI, 1.53 to 187.0]), and the presence of significant aortic regurgitation (RR, 22.4 [CI, 2.72 to 184.8]) were positively associated with embolism. For patients in atrial fibrillation, previous embolism (RR, 3.11 [CI, 1.66 to 5.85]) was positively associated with embolism; percutaneous balloon mitral commissurotomy (RR, 0.37 [CI, 0.18 to 0.79]) was a negative predictor. CONCLUSIONS: It may be prudent to give anticoagulants not only to patients in atrial fibrillation and patients with previous systemic embolism but also to those showing a left atrial thrombus or significant aortic regurgitation on echocardiography. Early percutaneous balloon mitral commissurotomy may also help prevent systemic embolism in patients with mitral stenosis.

Adult↗
PubMed1998

Leishmania lipophosphoglycan reduces monocyte transendothelial migration: modulation of cell adhesion molecules, intercellular junctional proteins, and chemoattractants.

We previously identified the structural requirement for the inhibitory activity of Leishmania lipophosphoglycan (LPG) to block endothelial adhesion to monocytes. Here we showed that LPG reduces transendothelial migration of monocytes. LPG pretreatment of endothelial cells (2 microM, 1 h) reduced monocyte migration across endothelial cells activated by bacterial endotoxin (LPS) or IL-1beta (60 and 46%, respectively). A fragment of LPG (i.e., repeating phosphodisaccharide (consisting of galactosyl-mannose)) and LPG coincubated with LPG-neutralizing mAb lacks inhibitory activity on monocyte migration. Pretreatment of monocytes with LPG (2 microM, 1 h) also did not affect monocyte migration through control or LPS-activated endothelial cells. FACS analysis reveals that LPG treatment blocked the LPS-mediated expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 on endothelial cells and monocyte adhesion without altering the integrity of the endothelial monolayer. LPG (2 microM, 1 h) alone was capable of altering the expression and distribution of two junctional adhesion molecules, CD31 and vascular endothelium cadherin, as well as reversing the effects of LPS on these proteins. The induction of endothelial cells by LPS to transcribe and release monocyte chemoattractant protein-1 (MCP-1) was significantly reduced by LPG (40-65%). LPG treatment of nonactivated endothelial cells also suppressed by 55 to 75% the monocyte migration triggered by a MCP-1 chemoattractant gradient, and coincubation of LPG with neutralizing mAb abrogated the inhibitory activity. Together, these data point to a novel anti-inflammatory function of LPG in reducing monocyte migration across endothelial cells via a mechanism of inhibition of endothelial expression of cell adhesion molecules, modulation of intercellular junctional proteins, and synthesis of MCP-1.

Animals↗
PubMed1998

A randomized study comparing ribavirin and interferon alfa monotherapy for hepatitis C recurrence after liver transplantation.

Hepatitis C virus (HCV) infection usually recurs after orthotopic liver transplantation (OLT), and most patients develop graft damage. This study compared the efficacy of interferon alfa (IFN-alpha) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft. Thirty OLT recipients with chronic hepatitis C were randomized to receive either IFN-alpha (3 MU three times a week) or ribavirin (up to 1.2 g daily) for 24 weeks. Virological, biochemical, and histological responses to treatment were assessed. Twenty-eight patients completed the treatment regimen, two ribavirin-treated patients being withdrawn because of severe hemolysis. Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin (93%) and 6 of 14 patients receiving IFN-alpha (43%; P=.01). Lobular inflammation was reduced in 9/14 ribavirin-treated (64%) and 3 of 14 IFN-alpha-treated patients (21%; P=.05), each of whom had a biochemical response. However, the total histological activity index did not improve in either the interferon (P=.43) or the ribavirin (P=.96) group. Posttreatment viremia levels were significantly reduced in IFN-alpha-treated (P=.05) but not in ribavirin-treated (P=.88) patients. Hemolysis occurred in all ribavirin-treated patients, with serum hemoglobin decreasing to < 10 g/dL in 50%. Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment (P=.02 and P=.004, respectively). We concluded that in patients with chronic hepatitis C after OLT, IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation, but not the total histological activity index. These findings provide a rationale for combination therapy in the post-OLT setting, although patients must be carefully monitored for hemolysis.

Adult↗
PubMed1998

Predictors of outcome in emphysematous pyelonephritis.

PURPOSE: We identified and quantified prognostic factors for emphysematous pyelonephritis. MATERIALS AND METHODS: The clinical information, laboratory data and radiological findings from 38 patients with emphysematous pyelonephritis were retrospectively analyzed. RESULTS: There were no significant differences between the nonsurvivor and survivor groups with respect to age, gender, diabetes mellitus history, presence of bacteremia, identity of infecting organisms, blood glucose level, leukocyte count, urinary white blood count, presence or absence of urinary tract obstruction or urolithiasis, and modes of treatment. There were significant differences between the nonsurvivor and survivor groups, however, with respect to platelet count (84,300 +/- 119,500 versus 220,400 +/- 161,800/mm.3, p = 0.001), serum creatinine level (3.61 +/- 1.25 versus 2.19 +/- 1.32 mg./dl., p = 0.003) and urinary red blood counts (56.47 +/- 41.86 versus 27.65 +/- 36.14, p = 0.028). Patients with radiological type I emphysematous pyelonephritis were significantly more likely to die than those with type II (69 versus 18%, p = 0.002). CONCLUSIONS: Serum creatinine level is the most reliable predictor of outcome in patients with emphysematous pyelonephritis. By calculating likelihood ratios, patients with creatinine levels greater than 1.4 mg./dl. and platelet counts 60,000/mm.3 or less were at high risk. The posttest probability of death increased from 69 and 18% to 92 and 53% for type I and II emphysematous pyelonephritis, respectively. Patients with creatinine levels 1.4 mg./dl. or less and platelet counts greater than 60,000/mm.3 were at much lower risk. Posttest mortality risk in these patients dropped from 69 and 18% to 27 and 4% for type I and II emphysematous pyelonephritis, respectively.

Adult↗
PubMed1998

The prognostic factors of lung cancer patients with brain metastases treated with radiotherapy.

PURPOSE: To analyze the prognostic factors of lung cancer with brain metastases (BM) and evaluate the role of cranial irradiation on survival. METHODS AND MATERIALS: From 1987 to 1994, 159 lung cancer patients with CT scan documented BM were reviewed. All of them underwent cranial irradiation (median radiation dose: 30 Gy). Chemotherapy and surgery of BM were performed in 21 and 10 cases, respectively. RESULTS: Overall median survival was 3.5 months and one year survival rate was 10.69%. Univariate analysis showed that the significant factors were performance status, age, total radiation dose to brain, BM as the first metastasis, neurosurgery, symptoms of urine/stool incontinence, and synchronous BM. Multivariate analysis indicated that (1) performance status (p = 0.0002), (2) total radiation dose (p = 0.0032), (3) BM as the first metastasis (p = 0.0449), (4) neurosurgery (p = 0.0233), (5) symptoms of urine/stool incontinence (p = 0.0002), and (6) the presence of a midline shift on cranial CT scans (p = 0.0063) were significant prognostic factors. CONCLUSION: The prognosis of BM in lung cancer patients is extremely poor. Radiotherapy appears as an effective means of palliation with 75% overall symptomatic response rate. Higher radiation dose (> or = 30 Gy) and neurosurgery are associated with longer survival. Good performance status, BM as the first metastasis, absence of sphincter dysfunction, and midline shift on CT scans are favorable prognostic predictors. The role of midline shift is very interesting and needs to be explored further.

Adult↗
PubMed1998

The use of serum CA-125 as a marker for endometriosis in patients with dysmenorrhea for monitoring therapy and for recurrence of endometriosis.

BACKGROUND: To estimate the value of CA-125 for the diagnosis of endometriosis in women with dysmenorrhea, as well as its significance in monitoring therapy and follow-up. METHODS: One hundred and fifty-seven women undergoing laparoscopy for dysmenorrhea were prospectively studied for serum CA-125 concentration. For those with advanced endometriosis receiving danazol treatment after conservative surgery, CA-125 was also determined every month during medication and once every 12 months after treatment. RESULTS: The sensitivity and specificity of serum CA-125 for the diagnosis of endometriosis were 61.1% and 87.5% respectively. Elevated CA-125 (>35 U/ml) was noted in 65/75 cases (86.70%) with advanced endometriosis, but in only 15/56 patients (26.8%) with minimal and mild endometriosis. Although there were significantly higher CA-125 levels in unmarried women, and a negative correlation (r=-0.1970, p=0.0284) between CA-125 and parity, there was no statistical difference in incidence of endometriosis by the status of marriage or parity. Ten women with advanced endometriosis were found with persistent endometriosis by laparoscopy during danazol treatment, even though they tested with normal CA-125 levels (<35 U/ml) at that time. Fifteen patients had elevated CA-125 levels before and one year after therapy, and were confirmed with recurrence of endometriosis by laparoscopy. Nine women with elevated CA-125 levels before treatment, were found without recurrence of endometriosis and had normal CA-125 levels one year after therapy. CONCLUSION: For endometriosis, CA-125 is a valuable adjuvant in the follow-up of recurrence in patients with advanced endometriosis and initially elevated CA-125 levels. It is not an effective screening tool for patients with dysmenorrhea, or for monitoring therapy. There was no significant correlation between the development of endometriosis and reproductive factors.

Adolescent↗
PubMed1998

Gallstone pancreatitis: a prospective study on the incidence of cholangitis and clinical predictors of retained common bile duct stones.

OBJECTIVE: The aim of this study was to define the incidence of cholangitis in gallstone pancreatitis, in the absence of cholangitis, to identify the clinical predictors of persistent common bile duct (CBD) stones at endoscopic retrograde cholangiography (ERCP) or at intraoperative cholangiography (IOC). METHODS: A total of 122 consecutive patients with acute gallstone pancreatitis were prospectively evaluated for the presence of CBD stones as determined by elective ERCP or IOC. Urgent ERCP was restricted to patients with concomitant cholangitis. APACHE II scores and serial laboratory data were obtained. RESULTS: Four (3%) patients had cholangitis and all underwent urgent ERCP successfully. Eighteen (15%) patients without cholangiogram were excluded. The remaining 100 patients underwent elective ERCP or IOC on a mean of hospital day 6.8. Twenty-one (21%) patients had persistent CBD stones. Univariate analysis detected significant differences in serum total bilirubin, ALT, and alkaline phosphatase levels between patients with and without persistent CBD stones. On multivariate analysis, serum total bilirubin on hospital day 2 was the best predictor of CBD stones. A serum total bilirubin level > 1.35 mg/dl had a sensitivity of 90.5% and specificity of 63%. Age, gender, mean APACHE II score, amylase, and presence of CBD dilation on ultrasound were not predictive of CBD stones. CONCLUSION: In patients with gallstone pancreatitis, 1) cholangitis is uncommon, and 2) the best clinical predictor of persistent CBD stones is serum total bilirubin on hospital day 2.

APACHE↗
PubMed1998

Endoscopic measurement of pancreatic blood flow.

A reduction of pancreatic blood flow has been observed in acute and chronic pancreatitis in animal models. Most available blood flow techniques are either too invasive or impractical to carry out in humans. Since the arrival of endoscopic retrograde cholangiopancreatography (ERCP), our understanding and management of pancreatic disorders has gradually improved. It may now be utilized to investigate what is believed to be a very important factor in the pathogenesis of pancreatic disease and symptoms: pancreatic tissue perfusion.

Acute Disease↗
PubMed1998

Liver transplant in Singapore--coming of age.

BACKGROUND/AIM OF STUDY: Liver transplantation was first performed in 1967, and has become an accepted form of treatment worldwide for chronic liver diseases, acute liver failure and certain metabolic diseases. We document our experience in Singapore over the last 7 years since the first transplant was performed in 1990. METHOD: Retrospective study at National University Hospital, Singapore. RESULTS: Twenty-two operations (10 paediatric and 12 adults) have been performed with the last 17 having been performed in the last 17 months. Currently, there are 15 survivors (68%) since 1990, and percentage survival is even better if one considers the cases from the last 17 months when the majority of cases (17 transplants-77%) were performed (77% survival). The most common indication for transplant was biliary atresia for the paediatric group, while the adults were transplanted for hepatitis B and C cirrhosis, primary biliary cirrhosis, and fulminant liver failure. Tacrolimus is the main immunosuppression (10 patients), with the remaining 5 patients on cyclosporine. Various surgical techniques (living donor, graft reduction) have been employed successfully to provide a complete transplant service. Hospital and ICU stays are within normal limits and the hospital charges range from a low of S$30,000 to S$141,000. CONCLUSION: Liver transplantation has become a reality in Singapore with outcomes comparable to other transplant centres. The shortage of donors remains the greatest stumbling block for further expansion.

Adolescent↗
PubMed1998

Halothane-induced acute liver failure: continuing occurrence and use of liver transplantation.

BACKGROUND/AIMS: This study was aimed at determining if the frequency and pattern of acute liver failure (ALF) following halothane anaesthesia had decreased during the last 11 years in comparison with a previous series of 48 patients referred between 1965 and 1984 and whether clinical outcome had been altered by the introduction of liver transplantation. METHODS: Between January 1985 and December 1995, all patients with halothane-induced ALF admitted to the Liver Failure Unit at King's College Hospital were identified. Four other European liver transplant centres with a known interest in acute liver failure also provided data. RESULTS: Of the 18 patients admitted, the clinical data were complete in 15. Ten of these patients had at least one previous halothane anaesthesia with documented clinical complications following the earlier exposure in six. Four patients had been re-exposed to halothane within 1 month of the penultimate halothane anaesthesia. Of the 15 patients four survived with medical management alone and 11 patients fulfilled transplant criteria. Four of the latter group were not listed because of rapidly deteriorating medical state and died, and of the seven patients who were listed, three died without a liver becoming available and four were transplanted, one of whom survived. No patient who had grade 4 encephalopathy and a prothrombin time > 50 s survived without a transplant. The survey of the other European liver centres recorded a total of 19 patients with halothane-induced ALF including three cases reported in the literature. Of those, 13 patients had been transplanted with nine survivors. CONCLUSION: Cases of halothane-induced acute liver failure still occur, albeit at a lower frequency than previously, and the Committee on Safety of Medicines guidelines are not being followed. The results of transplantation in these patients are encouraging.

Adult↗
PubMed1997

Elastance of the pleural space: a predictor for the outcome of pleurodesis in patients with malignant pleural effusion.

BACKGROUND: In patients who have malignant pleural effusion, it is difficult to diagnose trapped lung before thoracoscopy, thoracostomy, and drainage of the effusion. Predicting the outcome of pleurodesis in patients who have malignant pleural effusion without trapped lung is also difficult. OBJECTIVE: To investigate the factors that may be useful in diagnosing trapped lung and predicting the outcome of pleurodesis. DESIGN: Prospective cohort study. SETTING: University medical center. PATIENTS: 65 patients with symptomatic malignant pleural effusion. INTERVENTION: A chest tube was inserted for drainage of the effusion, and pleurodesis was done using bleomycin as the sclerosant. MEASUREMENTS: The pH and glucose levels of the effusion and the elastance of the pleural space (defined as the decline in pleural fluid pressure in cm H2O after removal of 500 mL of effusion) were measured. The outcome of pleurodesis was evaluated 1 month after the chest tube was removed. RESULTS: Patients with an elastance of 19 cm H2O or more had a higher incidence of trapped lung (11 of 14 patients) than did those with an elastance less than 19 cm H2O (3 of 51 patients) (P < 0.001). None of the 14 patients with an elastance of 19 cm H2O or more and none of the 14 patients with a trapped lung had successful pleurodesis. Forty-two of 43 patients with an elastance less than 19 cm H2O who did not have a trapped lung had successful pleurodesis. Elastance seemed to be the best predictor for trapped lung and outcome of pleurodesis, although outcome was also correlated with pH and glucose levels of the effusion. Low-dose bleomycin (30 mg) is as effective as the usual dose of bleomycin (60 mg) for pleurodesis. CONCLUSION: In patients with symptomatic malignant pleural effusion, measurement of the elastance of the pleural space is a simple and effective method for the diagnosis of trapped lung and prediction of the outcome of chemical pleurodesis with bleomycin.

Adult↗
PubMed1997

Engagement of the Lewis X antigen (CD15) results in monocyte activation.

We previously reported that monocyte adhesion to tumor necrosis factor-alpha (TNF-alpha)-treated endothelial cells increased expression of tissue factor and CD36 on monocytes. Using immunological cross-linking to mimic receptor engagement by natural ligands, we now show that CD15 (Lewis X), a monocyte counter-receptor for endothelial selectins may participate in this response. We used cytokine production as a readout for monocyte activation and found that CD15 cross-linking induced TNF-alpha release from peripheral blood monocytes and cells from the monocytic cell line MM6. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in steady-state TNF-alpha mRNA after 3 to 4 hours of cross-linking. CD15 cross-linking also concomitantly increased interleukin-1 beta (IL-1 beta) mRNA, while no apparent change was observed in the levels of beta-actin mRNA, indicating specificity. To examine transcriptional regulation of cytokine genes by CD15 engagement, a CAT plasmid reporter construct containing IL-1 beta promoter/enhancer sequences was introduced into MM6. Subsequent cross-linking of CD15 increased CAT activity. CD15 engagement by monoclonal antibody also attenuated IL-1 beta transcript degradation, demonstrating that signaling via CD15 also had posttranscriptional effects. Nuclear extracts of anti-CD15 cross-linked cells demonstrated enhanced levels of the transcriptional factor activator protein-1, minimally changed nuclear factor-kappa B, and did not affect SV40 promoter specific protein-1. We conclude that engagement of CD15 on monocytes results in monocyte activation. In addition to its well-recognized adhesive role, CD15 may function as an important signaling molecule capable of initiating proinflammatory events in monocytes that come into contact with activated endothelium.

Antibodies, Monoclonal↗
PubMed1997

Human herpesvirus-6 and human herpesvirus-7 infections in bone marrow transplant recipients.

Human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6), and human herpesvirus-7 (HHV-7) DNA in peripheral blood leukocytes (PBL) of 61 bone marrow transplant recipients was monitored weekly during the first 12 weeks post-transplantation by a nested polymerase chain reaction (PCR). Thirty-seven (61%), 17 (28%), and 32 (53%) of patients had one or more PBL specimens positive for HCMV, HHV-6 or HHV-7 DNA, respectively. HHV-7 DNA in PBL during the early post-transplant period was associated with a longer time to neutrophil engraftment (mean 28.8 days vs 19.8 days; P = 0.01). In two patients who failed to engraft, HHV-6 DNA and HHV-7 DNA was detected in plasma and PBL, respectively, early in their post-transplant period. Patients with HCMV disease were more likely to have concurrent HHV-7 DNA in PBL prior to onset of disease than were patients with asymptomatic HCMV infection, suggesting that HHV-7 may be a cofactor in the progression from HCMV infection to HCMV disease. In the 17 patients (179 specimens) in whom viral DNA in plasma was studied (in addition to PBL), a positive result was found only in 3. In each, viral DNA in plasma appeared to correlate with clinically significant disease. HHV-7 DNA in plasma was associated with encephalitis in an allograft recipient.

Acyclovir↗
PubMed1997

Effect of MMA-g-UHMWPE grafted fiber on mechanical properties of acrylic bone cement.

Ultrahigh molecular weight polyethylene (UHMWPE) fibers were treated with argon plasma for 5 min, followed by uv irradiation in methyl methacrylate (MMA)-chloroform solution for 5 h to obtain MMA-g-UHMWPE grafted fiber. The grafting content was estimated by the titration of esterification method. The grafting amount of 5280 nmol/g was the largest for the MMA concentration at 18.75 vol%. To improve the mechanical properties of acrylic bone cement, pure UHMWPE fiber and MMA-g-UHMWPE fiber were added to the surgical Simplex. P radiopaque bone cement. The mechanical properties including tensile strength, tensile modulus, compressive strength, bending strength, and bending stiffness were measured. Dynamic mechanical analysis was also performed. By comparing the effect of the pure UHMWPE fiber and MMA-g-UHMWPE grafted fiber on the mechanical properties of acrylic bone cement, it was found that the acrylic bone cement with MMA-g-UHMWPE grafted fiber had a more significant reinforcing effect than that with untreated UHMWPE fiber. This might be due to the improvement of the interfacial bonding between the grafted fibers and the acrylic bone cement matrix.

Acrylates↗
PubMed1997

Anticardiolipin IgG subclasses: association of IgG2 with arterial and/or venous thrombosis.

OBJECTIVE: To determine whether the presence of anticardiolipin antibodies (aCL) of a specific IgG subclass is associated with clinical complications of the antiphospholipid antibody syndrome (APS) and whether polymorphisms of Fc receptors for IgG (FcgammaR) with differential binding preferences contribute to an increased risk of thrombotic complications. METHODS: In 60 patients with IgG aCL, we assessed clinical complications of the APS, measured the level of antibody activity, and determined the IgG subclass distribution of aCL by a modified enzyme-linked immunosorbent assay (ELISA) with murine anti-human IgG subclass monoclonal antibodies. Selective IgG subclass adsorption studies were performed to determine the relative contribution of specific IgG subclasses to overall aCL activity. Fcgamma receptor IIA (FcgammaRIIA) genotypes of aCL patients with thrombosis and of non-systemic lupus erythematosus controls were determined by polymerase chain reaction amplification of genomic DNA and allele-specific probes. RESULTS: IgG2 aCL, detected in 75% of the patients, was the major subclass of aCL. Selective adsorption studies demonstrated that IgG2, in contrast to IgG1, was the predominant subclass responsible for aCL reactivity. IgG2 aCL was the only subclass associated with clinical complications, specifically, arterial and/or venous thrombosis (P < 0.04). The presence of FcgammaRIIA-H131, a receptor expressed on platelets, monocytes, and endothelial cells and the only human FcgammaR which efficiently recognizes IgG2, was associated with thrombosis in aCL patients. Among 45 high-titer (>40 GPL [IgG phospholipid] units) aCL patients with thrombosis, 40% were homozygous for FcgammaRIIA-H131, compared with 25% of disease-free controls (P = 0.042). CONCLUSION: While all 4 IgG subclasses are found in autoimmune aCL, only the presence of IgG2 is significantly associated with thrombotic complications. Reactivity in aCL ELISA is largely due to the presence of IgG2 in high-titer patients. The presence of IgG2 aCL, particularly in association with FcgammaRIIA-H131, may be a useful clinical predictor of increased thrombotic risk in patients with autoimmune IgG aCL. Allelic variants of FcgammaRIIA with distinct capacities to interact with IgG subclasses provide a mechanism for genetic susceptibility to an autoantibody-induced prothrombotic state.

Alleles↗
PubMed1997

p53 expression and proliferative activity in Bowen's disease with or without chronic arsenic exposure.

A comparative study of Bowen's disease (BD) with or without chronic arsenic exposure may contribute to understanding arsenic carcinogenesis. We compared the p53 overexpression and proliferative activity of 26 cases of BD with chronic arsenic exposure (group I) and 22 comparable cases of BD without chronic arsenic exposure (group II) by immunohistochemical method on formalin-fixed, paraffin-embedded tissues with antibodies PAb1801 and MIB-1, respectively. We also included in this study two squamous cell carcinomas that developed from BD in group I and one in group II. Two paired BD lesions in the same individual of one patient in group I and of three patients in group II were also studied. The significant p53(+) (>10% stained cells) rates were 42.3% (11 of 26) and 9.1% (2 of 22) for groups I and II, respectively, and the difference was statistically significant (P = .01). The p53 expression in different lesions of the same individual remained consistently the same. Squamous cell carcinomas that developed in 2 cases of p53(+) BD in group I were also positive, but the one in 1 case of p53(-) BD in group II was negative. No significant statistical difference in proliferative activity was found between group I BD and group II BD (P= .769), nor between p53(+) cases (>10% stained cells) and p53(-) cases (<10% stained cells) in group I BD (P = .519). This study showed that significant overexpression of p53 protein was higher in BD with chronic arsenic exposure. Therefore, arsenic carcinogenesis of BD might be different from that of BD unrelated to arsenic, and alteration of p53 plays a more important role in the pathogenesis of BD with chronic arsenic exposure. Overexpression of p53 was not a prerequisite for developing squamous cell carcinoma and was not affected by proliferative activity.

Adult↗