Low dose thiazide diuretic. May not lower blood pressure effectively.
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Biomedical subjects
Publications and source records attributed to L Chang.
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Gamma-aminobutyric acid (GABA) is thought to be one of the classic neurotransmitters acting as a developmental signal. To understand the role for GABA in development, we investigated the expression of transcripts encoding two forms of the GABA-synthesizing enzyme glutamate decarboxylase (GAD65 and GAD67) in the cervical enlargement of the rat spinal cord at successive postnatal days--P0, P7, P14, P21, and P90 (adult)--by using in situ hybridization histochemistry. Cells hybridized with two oligonucleotide probes designed to detect GAD65 and GAD67 mRNAs were widely distributed in all laminae, except in motoneurons of the spinal cord. The integrated densities of hybridization signals were measured across all layers of the gray matter. The relative number of GAD mRNA-labeled cells was determined within each of four regions: laminae I-III, laminae IV-VI, laminae VII and VIII, and lamina X. There was a transient increase in both the integrated density and the relative number of hybridized cells between P7 and P14, after which there was a marked decline to adult levels (lowest). An overall decrease in the number of GAD mRNA-labeled cells was evident in all layers, but a dramatic drop occurred in a subpopulation of cells within ventral portions of the spinal cord. The distribution patterns and postnatal changes in expression of the mRNAs encoding GAD65 and GAD67 were similar and closely paralleled reported changes in the abundance of GAD65 and GAD67 proteins and their product, GABA. Transient increases in GAD mRNA expression during the early postnatal period coincide with, and may be linked to, synapse formation and synapse elimination of the developing spinal cord.
The role of naturally produced antibody in discordant xenograft rejection is still uncertain. Twelve orthotopic pig-to-baboon heart transplants (HTx) were performed. In 2 baboons, no antibody adsorption (AbA) was performed. In 5 baboons, AbA with a pig lung was performed during circulatory arrest. In 5 baboons, AbA and blood exsanguination at the beginning of cardiopulmonary bypass (CPB) were performed. Baboons were divided into 2 groups; group 1 (n = 4) died within 24 hr of HTx and group 2 (n = 8) survived more than 24 hr. Mean survival period was 9.8 +/- 3.0 hr in group 1 and 151 +/- 33 hr in group 2. Baboon anti-pig antibody (Ab) was measured before CPB, before circulatory arrest, during AbA, at the end of CPB, and daily after HTx. Anti-RBC Ab was measured by the titration method at temperatures of 4 degrees C and 37 degrees C (RAb-4 and RAb-37). Anti-endothelial cell Ab (EAb) and anti-white blood cell Ab (WAb) titers were measured with ELISA. RAb titration > or = 1/4 and EAB and WAb > or = 1/256 were determined to be seropositive (S(+)). S(+) rate of RAb-37 at the end of CPB (endCPB) in group 2 was significantly higher than that in group 1 (8/8 vs. 1/4; P < 0.05). The seronegative (S(-)) rates of RBC-4 and EAb (endCPB) in group 2 were higher than those in group 1 (7/8 vs. 1/4 and 6/8 vs. 1/4, respectively), but not significantly. There was no difference in S(-) rate of WAb (endCPB) between group 1 and group 2. More than 4-fold decrease in RAb-4 and RAb-37 by AbA with a pig lung was observed in 5 and 7 of 8 baboons, while EAb and WAb did not change by AbA. In all of group 2, RAb-4 reverted to S(+) within 3 days after HTx. One baboon had no rejection episode and died of infection 16 days after HTx (baboon 16); however, it also became S(+) for RAb-4 a day after HTx until death. In 4 of group 2, RAb-37 became S(+) 1 or 2 days before death by rejection. Baboon 16, however, became S(+) for RAb-37 7 days after HTx and S(-) again 9 days after HTx until death. EAb became S(+) in all of group 2, but 5 of them survived more than 5 days after seroconversion.(ABSTRACT TRUNCATED AT 400 WORDS)
OBJECTIVES: To evaluate the efficacy of endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy in patients with gallstone pancreatitis and to determine criteria predictive of common bile duct stones (CBDS). DESIGN: Retrospective chart review. PATIENTS: Seventy-one consecutive patients with gallstone pancreatitis. MAIN OUTCOME MEASURES: Identification and endoscopic management of CBDS, complications, and mortality. RESULTS: Preoperatively, ERCP revealed CBDS in seven of 22 patients and postoperatively, in five of six patients. All stones were successfully removed. Laboratory values and common bile duct dilatation on admission did not predict CBDS. Persistent hyperamylasemia (> 150 U/L) and persistent hyperbilirubinemia (> 29.07 mumol/L [1.7 mg/dL]) were associated with CBDS on ERCP or intraoperative cholangiography. All five patients with cholangitis underwent ERCP, and CBDS were found and removed in four. There were no deaths and there was a 7% complication rate. CONCLUSIONS: Gallstone pancreatitis can be effectively managed by selective ERCP, endoscopic sphincterotomy, and laparoscopic cholecystectomy. Preoperative ERCP can be restricted to patients with cholangitis, persistent hyperbilirubinemia, or persistent hyperamylasemia.
Recombinant human activin A, a member of the transforming growth factor-beta superfamily, induced significant cell loss in rodent livers and in primary hepatocyte cultures. Histologically and biochemically the hepatocyte death was mediated by apoptosis, a form of programmed cell death. Male mice were treated with 200 or 500 micrograms recombinant human activin A/kg body wt/day for up to 3 days by means of a subcutaneously implanted minipump. Livers were taken for light and electron microscopy, DNA isolation and in situ nick end-labeling. Primary cultures of rat hepatocytes were treated with 10 ng/ml recombinant human activin A for 24 hr before being harvested for electron microscopy and DNA isolation. Infusion of activin A evoked dose-dependent loss of liver mass due to the atrophy and death of hepatocytes around the central vein. Morphologically, the dying cells demonstrated all the characteristic nuclear and cytoplasmic features of apoptosis. Low molecular weight DNA isolated activin A-treated intact livers and primary cultures exhibited the typical oligosomal ladder. Nick end-labeling of DNA in situ confirmed that virtually all topographical apoptotic hepatocytes had fragmented DNA. The currently accepted criteria for apoptosis (i.e., specific morphological alterations and internucleosomal clipping of DNA) were evident in activin A-treated hepatocytes both in vitro and in vivo, leading to the conclusion that cell loss occurs mainly through apoptosis. These observations suggest that activin A may be important in hepatic homeostasis.
To determine the relationships between clinical and brain function in persons with a familial risk for Alzheimer's disease, the authors assessed subjective and objective cognitive abilities, mood state, and cerebral glucose metabolism (using positron emission tomography) in 43 persons with age-associated memory impairment, with and without first-degree relatives with a clinical diagnosis of Alzheimer's disease. Subjective complaints of memory loss, mood state ratings, and objective memory measures were similar in persons with a family history of Alzheimer's disease (n = 29) compared to those without such a history (n = 14). Metabolic ratios in the frontal regions correlated with a decrease in a specific type of subjective memory complaint (mnemonics usage; p < .001) and some mood state ratings. These results indicate that parietal and temporal hypometabolism is not evident in persons with mild age-related memory complaints, even when such subjects have a familial risk for Alzheimer's disease. Moreover, self-reports of mnemonics usage may be sensitive indicators of decreased frontal lobe function. Longitudinal study will determine whether such clinical and metabolic measures will predict eventual disease progression.
Neuropsychological functioning was compared between 7 myotonic dystrophy (MD) patients with maternal inheritance (mMD), 14 MD patients with paternal (pMD) inheritance, and 10 normal controls. Both groups evidenced slowed performance on a measure of information processing speed. However, the pMD group had an otherwise normal neuropsychological profile. In contrast, the mMD group exhibited abnormal scores on measures of intelligence, visual-construction, and some, albeit not all, measures of frontal functioning. No significant differences between the three groups were detected on measures of verbal or visual memory, or on measures of visual-perception. Overall, these findings suggest that inheritance pattern is one important moderating variable in determining the impact of the MD gene on cognitive functioning. Personality assessment revealed a relatively high incidence of dependent tendencies and depressive symptoms, even among pMDs. Given the generally normal cognitive functioning among pMDs, personality/emotional disturbance observed among MD patients may largely reflect their adjustment to having a progressively disabling medical condition, rather than being a direct expression of MD related brain dysfunction.
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Surgical treatment of type II odontoid fractures (OFs) has usually entailed C1-2 arthrodesis rather than fracture fixation. An alternative treatment of direct screw fixation is used to treat the fractures for preservation of atlantoaxial rotation. Type II OFs that cannot be completely reduced by close means are generally believed to be a contraindication for anterior screw fixation. Seven patients (group I) with displaced type II OFs that could be completely reduced were treated with fracture fixation by one 4.5-mm double-threaded compression screw and five patients (group II) with displaced type II OFs that could only be partially reduced were treated with fracture fixation by one 3.0-mm double-threaded compression screw. All patients had a minimum of 1-year follow-up. No major complications occurred. No loss of reduction occurred in group I patients. Group II patients had an average loss of reduction of 0.8 mm anterior displacement and 5 degrees anterior angulation. The overall rate of fracture union was 100%, and fracture resolution averaged 4.1 months. Ten patients had a normal range of cervical rotation, and there was no difference in preservation of cervical rotation between the two groups. Our results suggest that close reduction and compressive osteosynthesis by one double-threaded compression screw is an optimal method of treatment for displaced type II OFs that can be completely reduced and for some cases that can only be partially reduced. A 100% rate of fracture union and preservation of cervical rotation are the major advantages of this method. However, significant complications have been reported by other investigators. (ABSTRACT TRUNCATED AT 250 WORDS)
Anti-proteinase 3 antibodies are a subgroup of anti-neutrophil cytoplasmic antibodies (ANCA), and we have established an ELISA for their detection using high performance liquid chromatography (HPLC)-purified protein. This assay is sensitive and specific: inhibition studies have shown that despite the homology between proteinase 3 and elastase there is no cross-reactivity between the corresponding antibodies for their targets. Anti-proteinase 3 antibodies were associated most often with cytoplasmic fluorescence (17/22, 77%), but occasionally with a perinuclear (3/22, 14%) or atypical pattern (1/2). These antibodies were found in 23 out of 76 sera (30%) that were positive in an ELISA based on a crude neutrophil cytoplasmic extract, and they were associated with both 29 and 55 kD bands on Western blots. Anti-proteinase 3 antibodies were found in most individuals with active Wegener's granulomatosis (10/13, 77%), but less often in individuals with microscopic polyarteritis (2/10, 20%) or segmental necrotizing glomerulonephritis (3/6, 50%). However, anti-proteinase 3 antibodies were not detected in any of 32 sera from individuals with rheumatoid arthritis or systemic lupus erythematosus (SLE). Occasionally anti-proteinase 3 antibodies were associated with anti-glomerular basement membrane antibodies (1/11, 9%) or with anti-myeloperoxidase antibodies (1/11, 9%). IgM anti-proteinase 3 antibodies were uncommon (2/22 sera, 9%), and no IgA antibodies were demonstrated in any of 22 sera from patients with active systemic vasculitis. Significantly more individuals presented with anti-proteinase 3 antibodies in April-May-June, suggesting that an infective agent prevalent in Autumn might have a causative role in the associated diseases. Anti-proteinase 3 antibodies are the most common target antigen associated with Wegener's granulomatosis and cytoplasmic fluorescence.
BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) are typically associated with small vessel vasculitides. They are also found in situations where other autoantibodies are common, sometimes after infections and possibly in individuals who have received multiple blood transfusions. AIMS: The aim of this study was to determine the incidence of ANCA in a variety of haematological disorders, where these predisposing factors may be at work. METHODS: Sera from patients with myelodysplasia (n = 26), acute myeloid leukaemia (AML) (n = 3), and myeloproliferative (n = 25) or lymphoproliferative syndromes (n = 16) were screened for ANCA using a crude neutrophil cytoplasmic extract ELISA and indirect immunofluorescent examination of normal peripheral blood neutrophils. Positive results were confirmed by ELISAs for anti-proteinase 3, anti-myeloperoxidase or anti-elastase antibodies. RESULTS: ANCA were demonstrated in two patients with myelodysplasia, both with chronic myelomonocytic leukaemia and greater than 5% blasts in the bone marrow. Both of these individuals were infected at the time that ANCA were demonstrated and other autoantibodies were present. One of these individuals had never had evidence of any vasculitis; the other probably developed myelodysplasia after treatment with cyclophosphamide for Wegener's granulomatosis. ANCA were demonstrated in one individual with AML secondary to myelodysplasia. ANCA were also found in a patient with lymphoma in whom autoantibodies against red cells and platelets were already noted. ANCA were demonstrated in one further individual with lymphomatoid granulomatosis, a condition that resembles Wegener's granulomatosis clinically and histologically, but which is treated as a lymphoma. No ANCA were present in any of the patients with myeloproliferative syndromes. DISCUSSION: ANCA probably occur secondary to immune dysregulation in myelodysplasia and the lymphoproliferative conditions and they are not necessarily associated with the presence of a vasculitis.
The chemical characteristics of 10 neoplastic and 11 infectious brain masses were studied by in vivo 1H magnetic resonance spectroscopy. In tumors, peak height ratios of n-acetyl-L-aspartate to choline were decreased compared to those in normal brain tissue and infectious masses (p < 0.02), but the ratios in normal brains and those with infections did not differ. N-acetyl-L-aspartate-to-creatine/phosphocreatine ratios were significantly lower in infectious masses and tumors compared to normal brain tissue (p = 0.003). However, in progressive multifocal leukoencephalopathy, N-acetyl-L-aspartate appeared relatively unchanged. Lactate was greater than choline in 9 of 11 brains with infection, 0 of 14 control brains, and 1 of 10 tumors. Lactate-to-choline ratios were significantly elevated in infectious masses compared with tumors (p < 0.01). 1H magnetic resonance spectroscopy is promising for the noninvasive diagnosis of focal brain masses.
Antioxidant enzymes located in the bronchial epithelium can be expected to be important in protecting these cells against both endogenous and exogenous oxidants. In this study, human bronchial epithelial cells were isolated and cultured from specimens obtained from donors for lung transplantation. The levels and relative importance of different antioxidant enzymes were also assessed using an immortalized human bronchial epithelial cell line (BEAS 2B cells). Immunocytochemical studies showed a similar pattern of intracellular localization with the moderate degrees of labeling for Mn superoxide dismutase (SOD), CuZn SOD, and catalase in freshly isolated bronchial epithelial cells, bronchial epithelial cells in primary culture, and BEAS 2B cells. CuZn SOD and catalase decreased in labeling density whereas Mn SOD was unchanged when bronchial epithelial cells were placed in primary cultures. In contrast, Mn SOD and catalase were decreased in BEAS 2B cells compared with primary cultures. Although Mn SOD was low in BEAS 2B cells, it could be significantly induced by tumor necrosis factor treatment. Biochemical analysis showed remarkably similar catalase and glutathione reductase activities in primary cultured epithelial cells and BEAS 2B cells.(ABSTRACT TRUNCATED AT 250 WORDS)
This study investigated the correlation between in vivo serial T2-weighted magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na+), and potassium ion (K+) contents measured in vitro using rat brain following right middle cerebral artery occlusion in conjunction with bilateral common carotid artery (CCA) occlusion. One hour later the left CCA was released. Serial MR images showed edema developed from the outer cortex towards the center. The T2 signal intensity of the injured right cortex increased with time compared to that of the contralateral cortex. Increased Na+ and water and decreased K+ contents occurred in the injured cortex, indicating that serial T2-weighted MR imaging reflects the changes in water content and Na+ and K+ concentrations determined by biochemical techniques. GSH-Px activity was little changed. Total SOD in the injured cortex decreased 1 hour after ischemia and remained low throughout the experiment. In contrast, SOD activity in the noninfarcted left cortex also decreased after 1 hour but returned to normal after 2 hours of ischemia. Our results suggest that oxygen free radicals are important in developing ischemic brain edema and cerebral infarction.
Many autoantibodies have been described in HIV-infected individuals. We have examined the incidence, associations and prognostic significance of anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies in individuals with HIV infections. One hundred and five patients, with asymptomatic infections (n = 37), AIDS-related complex (n = 32) or AIDS (n = 36) were studied. Plasma from 24 of these (23%) were positive for ANA: most demonstrated speckled fluorescence (n = 21) and were of low titre (1+ in 18). ANCA were demonstrated by IIF in 18 individuals (17%) and all fluorescent patterns were seen; 6 of these plasma were also positive in the ELISAs for antibodies to proteinase 3, myeloperoxidase or elastase. Thirteen plasma were positive for ANCA in the neutrophil cytoplasm ELISA; 10 of these were also positive in the specific ELISAs. A total of 30 plasma bound to proteinase 3, myeloperoxidase or elastase in specific ELISAs, in 6 cases with 2 specificities. Finally, 18 plasma (17%) contained anti-GBM antibodies by ELISA, but none of 4 plasma tested in inhibition assays was specific. ANA, ANCA and anti-GBM antibodies were not uncommon in HIV-infected individuals but the presence of these antibodies was not associated with the clinical manifestations of the corresponding autoimmune diseases. In addition, there was no correlation between the demonstration of these antibodies and the immunological status of the individual (apart from a correlation between CD4 counts less than 400/microliters with anti-GBM antibodies), the presence of an opportunistic infection, the development of malignancy or reduced survival. Some of these antibodies may arise from polyclonal activation, or be due to "sticky" serum since we have shown that the presence of anti-GBM antibodies correlated with the demonstration of ANCA by ELISA. These antibodies are not more common in hypergammaglobulinemic plasma but some may be due to heat-treatment of the plasma. The clinician caring for HIV-infected individuals needs to be aware of these "false-positive" antibody results.
A strain S-1231 isolated from specimen of soil around Beijing area is gram-negative, non-sporing, motile by peritrichous flagella. It produces exopolysaccharide succinoglycan from carbohydrates as its carbon source but not starch and cellulose. Acid is produced during fermentation of glucose. Growing for 12-24 hr, the cells are rods 0.7-0.8 x 1.3-1.5 microns, round ended, single or in pairs. Colonies on nutrient agar plate are unpigmented, circular, raised, smooth and moist-glistening, edge entire. The organism produces 3-ketolactose and is unable to invade sunflower tissue. The G+C content of DNA is 62.8-63.4 mol%. The organism is referred to as Agrobacterium radiobacter. Moreover, the strain is oxidase-positive, catalase-positive, H2S-produce and can grow at 35 degrees C and 2% NaCl also. Litmus milk is alkalified. Thus, the organism was renamed Agrobacterium radiobacter biovar I. Component analyses showed that the exopolysaccharide (Agran-S) from A. radiobacter biovar I S-1231 consisted of D-glucose (69.1%), D-galactose (8.6%), pyruvic acid (9.5%) and succinic acid (10.5%). Methylation analyses revealed that the polysaccharide Agran-S contained following main structural units: (1-->3)-linked D-glucose (21.2%), (1-->3)-linked D-galactose (11.4%), (1-->6)-linked D-glucose (10.5%), (1-->4)-linked D-glucose (30.4%), (1-->4, 1-->6)-linked D-glucose (22.2%) and terminal D-glucose (4.3%). The -1H-NMR spectrum of the polysaccharide indicated that the linkages in the polymer are all beta-glycosidic. The IR spectra of the polysaccharide revealed the presence of ester linkage in polysaccharide Agran-S.
An 18 months old Akita-Inu was presented with granulomatous panuveitis, ulcerative blepharitis and dermal depigmentation, ulceration and crusting, involving lips, nasal planum, prepuce, scrotum and perineum. Histologic examination of the affected skin demonstrated lichenoid dermatitis with infiltration of histiocytes and neutrophils. The diagnosis is based on the typical clinical and histological lesions.
The construction of live recombinant bacterial vaccines requires a reasonably sophisticated genetic system for the introduction, stabilization and expression of foreign antigen genes. Bacteriophages offer a rich collection of tools that can be used for vaccine construction, including site-specific integration-proficient vectors, non-antibiotic selectable markers and signals for efficient transcription and translation of foreign genes. We describe the characterization of a temperate phage of the mycobacteria, mycobacteriophage L5, and application of these phage studies for the construction of recombinant BCG vaccines.