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Biomedical subjects

A Chen

Publications and source records attributed to A Chen.

At least 325 records · Page 18Linked to original sources
PubMed1994

Falciparum malaria treated with a chloroquine suspension administered rectally in Trinidad.

A new mode of administering malaria chemotherapy to patients unable to tolerate oral medication is described. A patient with Plasmodium falciparum malaria, severe hyponatremia and hypokalaemia who regurgitated oral treatment of chloroquine phosphate and pyrimethamine and sulfadoxine (Fansidar) is presented. But neither chloroquine nor quinine intravenous formulations were available locally. As the patient was deteriorating, a suspension of chloroquine phosphate was prepared and administered rectally, resulting in a decline in the level of parasitaemia from ++++ to ++ within 48 hours. The patient improved, and further clinical management was uncomplicated.

Administration, Rectal↗
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↗
PubMed1994

Experimental IgA nephropathy. Enhanced deposition of glomerular IgA immune complex in proteinuric states.

BACKGROUND: IgA nephropathy is induced by the IgA-immune complex (IC). IgA nephropathy associated with heavy proteinuria is considered a more progressive form of the disease. To elucidate the mechanism by which the latter condition occurs, we investigated the effect of proteinuria on the glomerular deposition of IgA-IC. EXPERIMENTAL DESIGN: BALB/c female mice that had been made proteinuric by adriamycin or bovine serum albumin (BSA) were injected with TEPC-15 hybridoma-derived IgA anti-phosphorylcholine (PC) and individual specific antigens. The 6-hour clearance kinetics of IgA were measured, and the accumulation of IgA deposits and the third complement component (C3) in the glomerulus were analyzed. RESULTS: The clearance kinetics of 125I-IgA injected together with a specific antigen, PC-conjugated BSA (BSA-PC), showed only a minimal distinction between the experimental (proteinuric) and the control (nonproteinuric) groups of mice. However, analysis of renal tissue by immunofluorescence and light microscopic autoradiography revealed markedly enhanced mesangial IgA-IC deposition in the proteinuric mice receiving IgA and one of three specific antigens, BSA-PC, PC-conjugated cytochrome-c, and a pneumococcal C-polysaccharide. Immunofluorescence also showed augmented mesangial C3 deposition in proteinuric mice that received IgA/PC-conjugated cytochrome-c or IgA/pneumococcal C-polysaccharide. In addition, adriamycin or BSA per se did not influence glomerular IgA-IC localization. CONCLUSIONS: Glomerular localization of nephritogenic IgA-IC was comparably enhanced in mice with proteinuria induced by various methods. Thus, a vicious cycle for the progression of IgA nephropathy might ensue in proteinuric states.

Animals↗
PubMed1993

Systematic HRAS amplification in ovary-independent mammary tumors: correlation with progressively anaplastic phenotypes.

Progression of well differentiated rat mammary adenocarcinomas to very anaplastic phenotypes was found to correlate with a systematic and significant amplification of a mutant HRAS allele. Tumors with high amplification levels of this oncogene were analyzed by chromosomal in situ hybridization; in four of the cases the amplified sequences did not reside at the native chromosome 1 locus but were localized in a novel marker chromosome. The model described has potential as a reproducible system for the study of the chromosomal and cellular mechanisms operative "in vivo" for oncogene amplification.

Adenocarcinoma↗
PubMed1993

(S)-geranylgeranylglyceryl phosphate synthase. Purification and characterization of the first pathway-specific enzyme in archaebacterial membrane lipid biosynthesis.

The first pathway-specific step in the biosynthesis of the core membrane diether lipids in archaebacteria is the alkylation of the primary hydroxyl group in (S)-glyceryl phosphate by geranylgeranyl diphosphate. The reaction is catalyzed by (S)-3-O-geranylgeranylglyceryl phosphate ((S)-GGGP) synthase. The cytosolic enzyme was purified to homogeneity from the moderately thermophilic archaebacterium Methanobacterium thermoautotrophicum by a combination of ammonium sulfate precipitation, four chromatographic steps (DE52, Q-Sepharose, phenyl-Superose, and Protein Pak), and native polyacrylamide gel electrophoresis. SDS-polyacrylamide gel electrophoresis of gel-purified GGGP synthase gave a single band at 29 kDa. The enzyme requires Mg2+ for optimal activity, although prenyltransfer is also seen in buffers containing Mn2+ or Zn2+. A well defined pH optimum occurs between 6.0 and 7.5. Maximal activity is seen at 50-65 degrees C. The Michaelis constants for GGGP synthase are Vmax = 4.1 +/- 0.5 mumol min-1 mg-1, KMGGPP = 4.1 +/- 1.1 microM, and KMGP = 41 +/- 5 microM.

Alkyl and Aryl Transferases↗
PubMed1993

DNA topoisomerase I is essential in Drosophila melanogaster.

Both biochemical and genetic experiments suggest that the type I DNA topoisomerase may participate in DNA replication, recombination, transcription, and other aspects of DNA metabolism. Despite its apparent importance, genetic studies in unicellular organisms including eubacteria and yeasts indicate that topoisomerase I is not essential for viability. We have previously isolated the cDNA clone encoding DNA topoisomerase I from Drosophila melanogaster. We report here the cytogenetic mapping of top1 to the X chromosome at 13C1 and isolation of top1 genomic DNA. Using P-element mutagenesis, we have isolated a mutant deficient in Drosophila topoisomerase I functions. Genetic studies of this mutant show that topoisomerase I is essential for the growth and development of the fruit fly, a multicellular organism. The biological functions of topoisomerase I are inferred from our analysis of the regulation of topoisomerase I expression during Drosophila development.

Animals↗
PubMed1993

A homopurine:homopyrimidine sequence derived from the rat neuronal cell adhesion molecule-encoding gene alters expression in transient transfections.

A 178-bp homopurine-homopyrimidine (R:Y) sequence is located upstream from the transcription start point (tsp) of the rat neuronal cell adhesion molecule-encoding gene (NCAM). This R:Y sequence contains several mirror repeats. Such sequences have been proposed to regulate gene expression. To determine its effect on gene transcription, a DNA fragment containing the R:Y sequence was cloned into a luciferase-encoding (luc) expression vector. Transient transfection assays with the R:Y-luc constructs were performed in cell lines which constitutively express (B104 rat neuronal cells and C6 rat glial cells) or lack (H411E rat liver cells and L mouse fibroblast cells) NCAMs. In its natural orientation, the R:Y sequence caused a 2.5-fold reduction in luc expression in B104 and H411E cells, but had a statistically insignificant effect in C6 and L cells. The magnitude of the R:Y sequence reduction in luc expression was position and orientation dependent (varying from 2- to 5.5-fold). To determine if nuclear protein(s) specifically bind the sequence, gel retardation assays of a DNA fragment containing the R:Y sequence were carried out with nuclear extracts from these four cell lines. Specific DNA-protein interaction was found with B104 and H411E nuclear extracts, but not with C6 and L cell nuclear extracts. Competition experiments indicate that the (AGG):(TCC) repeat segment within the rat R:Y sequence may constitute the protein-binding domain. These results indicate that the R:Y sequence may have a negative effect on gene transcription in certain cell lines. In correlation with this negative effect, these same cell lines also contain nuclear proteins which bind the sequence.

Animals↗
PubMed1993

Purification and characterization of farnesyl diphosphate/geranylgeranyl diphosphate synthase. A thermostable bifunctional enzyme from Methanobacterium thermoautotrophicum.

Farnesyl diphosphate (FPP)/geranylgeranyl diphosphate (GGPP) synthase, a bifunctional enzyme that synthesizes C15 and C20 isoprenoid diphosphates from isopentenyl diphosphate and dimethylallyl diphosphate, was purified to homogeneity from the archaebacterium Methanobacterium thermoautotrophicum. The only activities detected from synthesis of FPP and GGPP copurified through (NH4)2SO4 precipitation and four chromatographic steps. The pure enzyme was a 79-kDa homodimer that catalyzed the sequential addition of isopentenyl diphosphate to dimethylallyl diphosphate, geranyl diphosphate, and FPP by a non-processive mechanism which allowed substantial amounts of FPP to accumulate during turnover, creating a pool for further elongation to GGPP or for synthesis of squalene. The bifunctional enzyme required Mg2+ or Mn2+ and was optimally active at 65 degrees C. Catalysis of chain elongation in M. thermoautotrophicum differs from related reactions in eubacteria and eukaryotes, where distinct FPP synthases and GGPP synthases are found.

Alkyl and Aryl Transferases↗
PubMed1993

A nonrandom interneuronal pattern in the developing frog spinal cord.

In the developing spinal cord of the frog, Xenopus laevis, a population of interneurons assumes a pattern that represents a previously undescribed level of organization. Glyoxylic acid treatment and immunocytochemistry show that the neurons contain catecholamines and their synthetic enzyme, tyrosine hydroxylase. Cells are located within the ependymal layer of the floor plate region of the larval spinal cord. The cells have several processes including a long one that projects toward the brain without fasciculating with other labeled processes. In addition, the cytoplasm of the catecholaminergic cells extends into the central canal, showing that they are a population of cerebrospinal fluid-contacting neurons. The spatial domain of catecholaminergic neurons starts abruptly at the boundary between the hindbrain and spinal cord and continues to the tip of the tail. The neurons occupy two longitudinal columns within the sheet of floor plate cells, which includes cells that do not exhibit the catecholaminergic phenotype. Unlabeled cells are intercalated between catecholaminergic cells in each column, giving the labeled cells the appearance of being spaced along the length of the spinal cord. This general arrangement is evident at the time of hatching. Spatial analysis showed that the position of cells along a column is not random. The nonrandom behavior is due to cells being excluded from the area immediately surrounding other catecholaminergic cells. Further analysis showed that the cellular pattern lacks segmental or other periodic repeats. Ultimately, the location of a cell within a column depends upon the position of its closest catecholaminergic neighbor.

Animals↗
PubMed1993

Spastic paraparesis associated with human T-lymphotropic virus type I: a clinical, serological, and genomic study in Iranian-born Mashhadi Jews.

The Mashhadi-Jewish community originating in Iran is a closed and ethnically segregated population with a unique history and a high rate of intrafamilial marriage among its members. A high risk of infection by human T-lymphotropic virus type I (HTLV-I) and of adult T-cell leukemia associated with such infection was found in this population. HTLV-I is also associated with a syndrome of progressive spastic paraparesis. We therefore evaluated the occurrence of HTLV-I infection and spastic paraparesis in Mashhadi-born Iranian Jews who immigrated to Israel. We examined 83 Mashhadi-born subjects (52 women, 31 men; mean age, 61 +/- 15.5 years) and 73 age-matched non-Mashhadi Iranian-born Jews. Blood samples were tested for HTLV-I antibodies by particle agglutination test. The polymerase chain reaction (PCR) was used to detect HTLV-I proviral DNA sequences from peripheral blood mononuclear cells. Fifteen Mashhadi-born Jews (18%) were both seropositive and PCR-positive for HTLV-I. Four HTLV-I-seronegative subjects were found to be positive for HTLV-I proviral DNA by PCR. Of the 19 HTLV-I-infected subjects (11 women, 8 men; mean age, 59 +/- 16 years), 13 (68%) had spastic paraparesis of varying severity. There were no signs of myelopathy in the Mashhadi-born subjects who were negative for HTLV-I proviral DNA by PCR. None of the non-Mashhadi Iranian Jews was seropositive or PCR-positive for HTLV-I proviral DNA, or had clinical signs of spastic paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia.

We have identified a unique case of acute promyelocytic leukaemia (APL) with a t(11;17) reciprocal chromosomal translocation involving the retinoic acid receptor alpha (RAR alpha) and a previously uncharacterized zinc finger gene. As a result of this translocation, mRNAs containing the coding sequences of the new gene, fused in-frame either upstream of the RAR alpha B region or downstream from the unique A1 and A2 regions of the two major RAR alpha isoforms, are expressed from the rearranged alleles. The above gene, which we have termed PLZF (for promyelocytic leukaemia zinc finger), encodes a potential transcription factor containing nine zinc finger motifs related to the Drosophila gap gene Krüppel and is expressed as at least two isoforms which differ in the sequences encoding the N-terminal region of the protein. Within the haematopoietic system the PLZF mRNAs were detected in the bone marrow, early myeloid cell lines and peripheral blood mononuclear cells, but not in lymphoid cell lines or tissues. In addition, the PLZF mRNA levels were down-regulated in NB-4 and HL-60 promyelocytic cell lines in response to retinoic acid-induced granulocytic differentiation and were very low in mature granulocytes. Our results demonstrate for the first time the association of a variant chromosomal translocation involving the RAR alpha gene with APL, further implicating the RAR alpha in leukaemogenesis and also suggesting an important role for PLZF as well as retinoic acid and its receptors in myeloid maturation.

Amino Acid Sequence↗
PubMed1993

Down-regulation of retinoic acid receptor activity associated with decreased alpha and gamma isoforms expression in F9 embryonal carcinoma cells differentiated by retinoic acid.

F9 embryonal carcinoma cells differentiate in response to retinoic acid (RA). To investigate the regulation of RA receptors (RARs) expression during this process, cDNA probes specific for the major RAR isoforms were used. In contrast to the level of RAR beta 2 mRNA which was high in cells treated 5 days with RA and below detection in untreated cells, as previously described, the steady state levels of RAR alpha 1, alpha 2, gamma 1, and gamma 2 mRNAs were markedly decreased in the RA-differentiated cells as compared to untreated cells. The down-regulation of the RA-responsive system in differentiated cells was also evident in gel shift assays as a marked decrease in binding capacity to a retinoid acid response element (beta 2RARE), as well as in chloramphenicol acetyltransferase (CAT) assays as a sixfold decrease in RA-mediated transacting activity via this element. The down-regulation of RAR DNA-binding and transacting activity coincided with the burst in tissue plasminogen activator secretion and thus, occurred at the hinge between early and late differentiation. The down-regulation of RA responsiveness may constitute an important event in the transition between early and late differentiation stage in F9 cells.

Animals↗
PubMed1993

A novel human macrophage-derived intestinal mucin secretagogue: implications for the pathogenesis of inflammatory bowel disease.

BACKGROUND: A novel 68-kilodalton macrophage-derived protein (MMS-68) stimulating mucin release from respiratory epithelial cells has previously been described. In this study, the effect of MMS-68 on mucin release from intestinal epithelial cells was determined. METHODS: Colonic epithelial cells isolated from normal colon, ulcerative colitis, Crohn's colitis, and cells from three colon cancer cell lines were labeled with [3H]-glucosamine and stimulated with MMS-68. High molecular weight glycoproteins were precipitated and counted. RESULTS: In all of the cells tested, MMS-68 enhanced mucin secretion by 1.46-2.0-fold above control values, comparable to the level achieved with carbachol (10(-5) mol/L). Coincubation with anti-MMS-68 monoclonal antibody 1D-10 blocked this bioactivity. Freshly isolated intestinal macrophages reacted with monoclonal antibody 1D-10. Immunofluorescent staining of frozen sections revealed the presence of MMS-68-producing cells (macrophages) in the lamina propria of normal colon and Crohn's colitis, with weaker expression in ulcerative colitis mucosa. CONCLUSIONS: Intestinal macrophages produce a novel mucin secretagogue, which is as potent as carbachol for stimulating mucin secretion from colonic epithelial cells. This factor may explain, in part, the alterations in mucin secretion often seen in inflammatory bowel disease.

Antibodies, Monoclonal↗
PubMed1993

Domain specifications and content representativeness of the revised Value Orientation Inventory.

Value orientations represent theoretical belief systems that guide teachers' curricular decision making. Research using the Value Orientation Inventory (VOI) to examine physical educators' value orientations in school settings found inconsistencies between the inventory findings, descriptions of class environments, and teachers' self-reports of their curricular goals. This article reports the VOI revision process that included (a) literature and research reviews resulting in domain specifications and new VOI item development and (b) item ratings that provide evidence of content representativeness for the revised items. The reviews supported four of five orientations that formed the original theoretical framework for the VOI: disciplinary mastery, learning process, self-actualization, and ecological integration. The fifth orientation, social reconstruction, was not supported by school-based research. Findings were more consistent with a social responsibility orientation. New items (K = 150) were written based on the literature reviews. The new items were sent to university and public school teachers (N = 298) to assess content representativeness. Eighty-one percent of the item means were > 4.0 on a 5-point scale. The social responsibility items were found to be domain representative and were included in the revised inventory.

Achievement↗
PubMed1993

Interaction of human beta 1 thyroid hormone receptor and its mutants with DNA and retinoid X receptor beta. T3 response element-dependent dominant negative potency.

Mutations in the human beta thyroid hormone receptor (h-TR beta) gene are associated with the syndrome of generalized resistance to thyroid hormone. We investigated the interaction of three h-TR beta 1 mutants representing different types of functional impairment (kindreds ED, OK, and PV) with different response elements for 3,3',5-triiodothyronine (T3) and with retinoid X receptor beta (RXR beta). The mutant receptors showed an increased tendency to form homodimers on a palindromic T3-response element (TREpal), a direct repeat (DR + 4), and an inverted palindrome (TRElap). On TRElap, wild type TR binding was decreased by T3, while the mutant receptors showed a variably decreased degree of dissociation from TRElap in response to T3. The extent of dissociation was proportional to their T3 binding affinities. RXR beta induced the formation of h-TR beta 1:RXR beta heterodimers equally well for mutants and the wild type h-TR beta 1 on these T3 response elements. However, the T3-dependent increase in heterodimerization with RXR beta was absent or reduced for the mutant TRs. Transient transfection studies indicated that the dominant negative potency was several-fold more pronounced on the TRElap as compared to TREpal or DR + 4. In CV-1 and HeLa cells, transfection of RXR beta could not reverse the dominant negative action. These results demonstrate that the binding of mutant h-TRs to DNA, as well as their dominant negative potency, are TRE dependent. In addition, competition for DNA binding, rather than for limiting amounts of RXR beta, is likely to mediate the dominant negative action.

Animals↗
PubMed1993

Nemesis revisited: tuberculosis infection in a New York City men's shelter.

In November 1990, a screening was conducted to determine the point prevalence of tuberculosis infection in a volunteer sample of homeless men (n = 161) living in a congregate shelter in New York City. Of those for whom we have results (n = 134), 79% were positive for tuberculosis. The mean length of shelter stay from date of shelter entry was 31.8 months and was significantly associated with the tuberculosis infection rate. The findings suggest that crowded living conditions and the presence of a stable resident pool in crowded congregate shelters may be associated with transmission of tuberculosis infection.

Adult↗