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Biomedical subjects

A Chen

Publications and source records attributed to A Chen.

At least 343 records · Page 19Linked to original sources
PubMed1993

Cell adhesion receptors and early mammalian heart development: an overview.

Cardiovascular development is the end result of a complex genetic program subject to regulation by signals transmitted between a cell and its extracellular environment. As cells encounter new extracellular matrices or establish new cell-cell interactions, new genes must be activated to accommodate the altered developmental situation within which the cell finds itself. This is likely reflected in a program of adhesion receptor and counter receptor expression on the surface of cells engaged in the morphogenesis. To understand the molecular basis of development, it is necessary to first determine if such a program exists and then to establish the role of various receptors and counter receptors in the particular morphogenetic process under investigation. To this end, we have initiated an investigation into expression of specific adhesion receptors during cardiovascular development in the mouse. Here, we demonstrate that platelet endothelial cell adhesion molecule (PECAM)-1 is an excellent marker for following vascular formation in the mammalian embryo. It is expressed during development in several alternatively spliced forms involving the cytoplasmic domain of the molecule. These forms differ in their ligand binding properties. Thus, a change in the cytoplasmic domain affects the folding of the molecule in such a way as to structurally alter the extracellular domain. Further, several receptors including the laminin receptor, the fibronectin receptor and a hyaluronic acid receptor, display specific expression patterns during heart development. These include differential expression in the endocardium and myocardium, down regulation during endocardial and myocardium, down regulation during endocardial cushion formation and cessation of expression in particular regions of the heart upon maturation. Interference with the function of one of these receptors (the fibronectin receptor) results in aberrant heart formation. These observations strongly support the concept that morphogenesis requires specific cell adhesion molecules that are expressed in precisely choreographed programs.

Animals↗
PubMed1993

Epithelioid leiomyosarcoma of the breast: report of a case.

A 36-year-old female presented with a palpable mass in the right breast. She received a modified radical mastectomy after admission. Brain and multiple bony metastases were noted 10 months later. Microscopically, the tumor was composed of nodules of small spindle and large round cells showing abundant eosinophilic, vacuolated cytoplasm and prominent nucleoli. No glandular or ductular differentiation could be identified. By immunohistochemistry, the tumor cells were positive for vimentin and desmin in focal areas, but negative for cytokeratin, S-100, epithelial membrane antigen, actin, myoglobin, or alpha-1-antichymotrypsin. Electron microscopy showed focally cohesive large cells maintained together by poorly-defined intercellular junctions and surrounded segmentally by thin basal laminae. Intracytoplasmic filaments were identified in some tumor cells, diffusely arranged in the cytoplasm. These findings indicate that this was a case of epithelioid leiomyosarcoma of the breast. The literature concerning this rare neoplasm is reviewed.

Adult↗
PubMed1993

Lupus nephritis, emphasizing tubulointerstitial lesions: a clinico-pathological analysis.

Tubulointerstitial lesions (TIL) such as interstitial inflammation, fibrosis and tubular atrophy are frequently found in classes of lupus nephritis. A retrospective study evaluate lupus nephritis, the relationship between TIL and glomerular lesions, and the significance of TIL in assessing the severity and prognosis for cases of lupus nephritis. Between June 1983 and Jan 1990, 492 renal biopsies were performed. Lupus nephritis was diagnosed in 37 patients who fulfilled the American Rheumatology Association (ARA) criteria for Systemic lupus erythematosus (SLE). The results showed a significant correlation between degree of TIL and impairment of renal function. Degree of TIL and severity of glomerular lesions must be considered simultaneously to predict renal function of patients with lupus nephritis.

Adolescent↗
PubMed1992

Poisson sampling-based inference for single ion channel data with time interval omission.

Patch-clamp recording allows investigations of the gating kinetics of single ion channels. Statistical analysis of kinetic data can enhance our understanding of channel gating at a molecular level. Experimental channel records suffer from time interval omission, i.e. failure to detect brief channel openings and closings. It is important to incorporate this phenomenon into statistical analyses of ion channel data. When time interval omission is ignored, the method of maximum likelihood can usually be used to estimate gating parameters from a single channel record. However, it is far more difficult to apply this method when time interval omission is incorporated. We present an alternative approach to parameter estimation based on Poisson sampling. A simulated homogeneous Poisson process is superimposed onto the channel record and inference is based on the numbers of points in successive open and closed sojourns, rather than on the sojourn times themselves. We describe the method for the two-state Markov model C<-->O, although it is applicable to more general models. Computer-simulated data are used to demonstrate the efficacy of the method. Modifications of the method are discussed briefly.

Animals↗
PubMed1992

Mucin gene expression in colonic tissues and cell lines.

Complementary DNA clones encoding four different mucin core peptides have been isolated. However, the expression of these mucin genes in the colon has not been systematically studied. The present investigation used Northern blot analysis to study the expression of MUC1, MUC2, MUC3, and MUC4 mRNA in paired normal and cancerous colonic tissues, and nine colon cancer cell lines. Results were correlated with the clinicopathological features of the tumors and with the immunohistochemical expression of several carbohydrate tumor-associated antigens that may reside on mucins. MUC1 mRNA was expressed in all colonic tissues, and levels in paired normal and cancer tissues were similar in most cases. MUC2 and MUC3 mRNAs were expressed in both normal and cancer tissues, but levels were often decreased in the cancers. MUC4 mRNA was present in normal mucosa with comparable or sometimes greater expression in cancers. There was no apparent correlation between the expression of any particular mucin gene or pattern of mucin genes and the site, stage, or histological type of tumor. In addition, the expression of mucin-associated carbohydrate antigens did not correlate with any individual mucin gene or group of mucin genes. In colon cancer cell lines all four MUC genes were expressed rather weakly or not at all. These results indicate that the human colon expresses a broad repertoire of mucin genes which are differentially regulated in malignancy. Whether this differential regulation of mucin genes affect the behavior of the tumor and results in the altered glycosylation commonly seen in these requires further investigation.

Aged↗
PubMed1992

Nonrandom abnormalities involving chromosome 1 and Harvey-ras-1 alleles in rat mammary tumor progression.

Little is known about the role of chromosomal abnormalities in the widely used models of rat mammary carcinogenesis. In this study, we cytogenetically analyzed nitrosomethylurea-induced rat mammary adenocarcinomas at different time points of development. As tools to study more advanced stages of malignant progression, we also analyzed the cytogenetic progression of tumors transplanted into younger syngeneic hosts, and of tumors that did not regress or that developed after host ovariectomy. Our results indicate that rat mammary adenocarcinomas appear to start development as diploid lesions with cytogenetically "normal" karyotypes. However, upon progression, tumors showed coexistence of normal diploid clones with abnormal clones bearing specific abnormalities affecting mainly chromosomes 1 and 15. Almost every ovary-independent tumor presented stem lines with specific nonrandom chromosomal abnormalities. Numerical chromosomal abnormalities such as specific trisomies started to develop mainly after subsequent in vivo transplantations. The abnormalities affecting chromosome 1 observed in many tumors were: (a) interstitial deletions and breakpoints for translocation in region 1q22; and (b) partial or complete overrepresentation of chromosome 1 in the form of direct duplication of region 1q22q43 or as trisomy 1. Interestingly, Harvey-ras-1 gene maps to rat chromosome 1, and by Southern analysis we observed that 4 of 8 primary tumors and 6 of 9 ovary-independent tumors showed considerable loss of Harvey-ras-1 signal indicating probable allele loss. However, analyses of some tumor transplants in more advanced stages of progression showed, paradoxically, an increased copy number of the Harvey-ras-1 oncogene coinciding with the presence of the direct duplication observed in chromosome 1 or with trisomy 1 as possible mechanisms for gene amplification. Interestingly, rat chromosome 1 is the homologue to human chromosome 11, and in numerous cases of human breast cancer loss of heterozygosity of several genes in chromosome 11p15.5 has been reported. Some of the rat chromosome 1 abnormalities observed may be equivalent to those affecting 11p15 in human tumors. We also observed 8 tumors with abnormalities affecting chromosome 15. At least 3 genes of interest in breast cancer have been previously mapped to that rat chromosome. The similarities observed with human breast cancer may point to common mechanisms of tumor progression in both species.

Adenocarcinoma↗
PubMed1992

Anti-idiotype monoclonal antibody elicits broadly neutralizing anti-gp120 antibodies in monkeys.

Murine monoclonal antibodies (mAbs) were raised against human, polyclonal, anti-gp120 antibodies (Ab1) and were selected for binding to broadly neutralizing anti-gp120 antibodies in sera positive for human immunodeficiency virus (HIV). One anti-idiotype mAb (Ab2), 3C9, was found to be specific for human anti-gp120 antibodies directed against an epitope around the conserved CD4 attachment site of gp120. The 3C9 reactive human anti-gp120 antibodies (3C9+ Ab) neutralized MN, IIIB, RF, and four primary isolates of HIV type 1 (HIV-1). Cynomolgus monkeys were immunized with 3C9 in adjuvant to test whether this anti-idiotype mAb could induce neutralizing anti-gp120 antibodies. The results show that purified anti-anti-idiotype antibodies (Ab3) from 3C9 immune sera bind to an epitope around the CD4 attachment site of gp120SF and gp120IIIB. Furthermore, purified gp120-specific Ab3 neutralize MN, IIIB, and RF isolates. These results demonstrate that primates immunized with an anti-idiotype mAb produce broadly neutralizing anti-HIV-1 antibodies. Since this anti-idiotype mAb was selected by identifying a clonotypic marker, its biological activity can be explained as the results of clonotypic B-cell stimulation.

Animals↗
PubMed1992

Extrarenal cytokines modulate the glomerular response to IgA immune complexes.

Clinical episodes of IgA nephropathy coincide recurrently with microbial infections. Cytokines produced during such infections may play a role in the pathogenesis of IgA-associated glomerulonephritis. To test this hypothesis, we examined the influence of passively administered proinflammatory cytokines (IL-1, IFN-gamma and IL-6) on the development of glomerulonephritis in an experimental model of IgA nephropathy. Glomerular IgA immune deposits were induced in mice by administration of IgA anti-phosphorylcholine (PC) with either a PC-containing carbohydrate antigen of Pneumococcal C polysaccharide (PnC) or a protein antigen of PC-conjugated bovine serum albumin (PC-BSA). The effect of IL-1 on the IgA-PC-BSA induced glomerular changes resulted in an increase of mesangial hypercellularity that was associated with mild proteinuria and hematuria. Mice treated with IL-1 and IgA-PnC developed diffuse proliferative glomerulonephritis with proteinuria and hematuria. In contrast, IL-6 treatment with IgA-PC-BSA of IgA-PnC failed to exert any significant renal effect. The combination of IL-6 and IL-1, however, intensified the mesangial hypercellularity of the IgA-PC-BSA, and induced severe proliferative glomerulonephritis with inflammatory monocytes and neutrophils infiltrates in the IgA-PnC treated mice. These glomerular changes were also accompanied by increased proteinuria and hematuria. Similarly, the combination of IFN with IL-1 produced histologic changes and compromised renal function more than IFN or IL-1 exerted independently. These results suggest that extrarenal cytokines influence the renal response to IgA immune deposits. We also conclude that a synergy of multiple cytokines and nephritogenic antigens immobilized in glomerular IgA immune deposits may lead to rapid progression of IgA-associated glomerulonephritis.

Animals↗
PubMed1992

The role of value orientations in curricular decision making: a rationale for teachers' goals and expectations.

This research examined the role of value orientations in curricular decision making from the perspective of high school physical education teachers and students. Educational value orientations served as the theoretical base for the research. Teachers who exhibited one of two paired orientations, disciplinary mastery/learning process (DM/LP) or ecological integration/social reconstruction (EI/SR), were interviewed to examine the extent to which their value orientations influenced their stated (a) goals for student learning, and (b) expectations for academic performance and behavior. Students were also interviewed to investigate the extent to which they acknowledged these goals and expectations. Data were analyzed using constant comparison. Results suggested that goals and expectations of DM/LP and EI/SR teachers were distinctly different and that comments from students in the EI/SR teachers' classes did not reflect their teachers' goals and expectations. Dynamical system theory was used to conceptualize value orientations as attractors within the educational ecosystem. Teachers working from weak EI/SR value attractors may be limited by learner, instructional, and contextual constraints.

Curriculum↗
PubMed1992

Recombinant human acid alpha-glucosidase generated in bacteria: antigenic, but enzymatically inactive.

Genetic deficiency of acid alpha-glucosidase (GAA) results in glycogen storage disease type II. To investigate whether we could generate a functional recombinant human GAA protein for future enzyme replacement therapy, we subcloned the GAA cDNA into the bacterial expression plasmid pMaI and analyzed the recombinant protein produced. This nonglycosylated recombinant human GAA was found to be antigenic by reacting with polyclonal rabbit antibody to human placental GAA using ELISA and Western techniques. However, the protein was not enzymatically active, suggesting that glycosylation may play a role in enzymatic function.

Amino Acid Sequence↗
PubMed1992

The application of the Screening Cerebral Assessment of Neppe (BROCAS SCAN) to a neuropsychiatric population.

Assessments of higher cortical functioning are often neglected in patients with possible coarse neurobehavioral psychiatric disease, such as dementia, stroke, or focal cerebral lesions. When performed, the short Folstein Mini-Mental State Exam (MMSE) is typically used. The authors' research on 45 neuropsychiatric patients compared the MMSE with a new 20-30-minute bedside examination, the Screening Cerebral Assessment of Neppe (BROCAS SCAN). This screens 10 areas: recall, recognition, orientation, organization of thought, concentration, calculation, agnosia, apraxia, speech, and sensory-motor-reflex phenomena. The BROCAS SCAN (total) correlated extremely well with neuropsychiatric prediction, MRI changes, and neuropsychological testing, and distinguished diagnoses, demonstrating construct and face validity. It also accounted for a larger proportion of variance than the MMSE in correlating with these parameters and was more sensitive in mildly cognitive impaired patients. The briefer first section of the BROCAS SCAN, the core SCAN, also showed statistically relevant relationships to age, diagnosis, MRI, and neuropsychiatric prediction.

Adolescent↗
PubMed1992

[Synthesis and radiosensitizing activity of benzimidazoles].

In search for effective radiosensitizer with low neurotoxicity, benzimidazole compounds were synthesized. Reaction of 2-nitrobenzimidazole with ethyl chloroformate yielded ethyl alpha-(2-nitrobenzimidazolyl-1)-formate(1) or ethyl alpha-(2-hydroxybenzimidazolyl-1)-formate(2), depending upon the solvents used. Reaction of 2-nitrobenzimidazole with 1,2-epoxy-3-chloropropane gave a cyclized compound which was confirmed to be benzimidazo(1,2b)-5'-chloromethyl-oxazolidine(3). In attempt to increase hydrophilicity, 1-substituted 2(3'-pyridyl)-5-nitrobenzimidazoles were prepared by reaction of 2-(3'-pyridyl)-5(6)-nitrobenzimidazole(4) with alkyl epoxides or ethyl chloroacetate. Some of the compounds synthesized were tested for radiosensitizing activity in Ehrlich ascites carcinoma-bearing mice. Preliminary results showed that some compounds have radiosensitizing activity. The radiosensitizing enhancement ratio (SER) of compounds 3, 5 and 6 were found to be 1.50, 1.52 and 1.65 respectively.

Animals↗
PubMed1992

Occurrence of distinct PML-RAR-alpha fusion gene isoforms in patients with acute promyelocytic leukemia detected by reverse transcriptase/polymerase chain reaction.

A specific 'nested' reverse transcriptase/polymerase chain reaction (RT/PCR) procedure was used to characterize the expression patterns of PML-RAR-alpha chimeric mRNAs in 32 patients with acute promyelocytic leukemia (APL). The sensitivity of the technique was such that the fusion gene transcript could be detected from as little as 2.5 pg of total leukemic cell RNA against a background of 1 microgram of cellular RNA lacking the PML-RAR-alpha fusion gene transcript(s). In 19 cases the PML-RAR-alpha isoform referred to here as long was identified. A short isoform, which in comparison with the long form lacks three PML exons, was detected in 11 other cases. A third PML-RAR-alpha mRNA isoform, in which the most 3' PML exon present in the long-type isoform was truncated in its sequences lying immediately upstream of RAR-alpha B region, was found and characterized in a single patient. In one APL patient with a variant translocation t(11;17), the PCR product corresponding to PML-RAR-alpha chimeric mRNAs could not be amplified despite the presence of RAR-alpha gene rearrangement. Genomic and PCR analysis showed that the different PML-RAR-alpha isoforms found in APL patients arise as a result of distinct translocation breakpoints. In each case the exons encoding the B-F regions of RAR-alpha are expressed and are spliced downstream from variable PML gene exons. The 'nested' RT/PCR analysis of the PML-RAR-alpha fusion gene proved to be a rapid and sensitive tool for the diagnosis of the APL and for monitoring the residual APL chimeric mRNA expression during complete remission.

Adolescent↗
PubMed1992

Carcinoid tumor localized in the liver--two cases report: immunohistochemical and ultrastructural studies.

Two cases of carcinoid tumors, considered to be probably hepatic in origin, occurring in a 53-year-old man and a 69-year-old woman are reported. In both cases no endocrine syndrome appeared, and an alternative primary source of the tumor was not found in case two, despite an intensive search at operation. The neoplasms in both cases were soft, firm, brown-pink and well-encapsulated. They were composed of small uniform cells, that had distinct borders and grew in insular, nests, trabeculae and strands that were separated by a delicate fibrous stroma. Stains of argentaffin and argyrophil showed strong positivity in both cases. The immunohistochemical and ultrastructural studies all demonstrated characteristics of a carcinoid. The postoperative recovery was good. They have remained well 5 years later in case 1 and 3 years in case 2 after surgical treatment. Literature concerning this rare condition is also reviewed.

Aged↗
PubMed1992

Glomerular localization of nephritogenic protein complexes on a nonimmunologic basis.

BACKGROUND: In a preliminary study, we have found that a group of charge-distinct protein molecules can react with each other to form protein complexes in vitro. The present study was conducted to determine the nephritogenic effect and the mode of action of these proteins in vivo. EXPERIMENTAL DESIGN: To demonstrate the precipitating interactions, a phosphorylcholine (PC)-conjugated, cationized bovine serum albumin (BSA(+)-PC) was applied to react with dinitrophenyl (DNP)-protein conjugates by double diffusion test. The types of forces involved in binding actions were determined. The experimental groups of CDF1 mice were injected simultaneously with BSA(+)-PC and individual DNP-protein conjugates through the tail vein. Both clearance kinetics and renal tissue studies were performed. RESULTS: BSA(+)-PC was able to form precipitin lines with respective DNP-protein conjugates in the agarose gel without any antigen-antibody interactions. These precipitating reactions were partially prevented by the presence of either NaCl, urea, or trifluoroacetate, suggesting that electrostatic force, hydrogen bond, and/or hydrophobic force are involved in the precipitation of these modified protein molecules. The clearance kinetics of BSA(+)-PC/BSA-DNP, and BSA(+)-PC/DNP-apoferritin showed a significant acceleration of the rapid phase of elimination. All of the experimental mice had hematuria and systemic thrombotic microangiopathic changes 1 hour later. By immunofluorescence, both the BSA(+)-PC and the DNP-protein conjugate injected were present in the renal glomerular tufts of experimental groups, although these protein molecules failed to deposit in the glomerulus when injected alone. Concomitant fibrinogen deposition was noted in almost all of the glomeruli affected. Moreover, 10 to 50% of the glomeruli examined 4 hours after injection had deposition of the third component of complement (C3). CONCLUSIONS: These data strongly support a hypothesis that nondeposited nephritogenic protein molecules in a fashion of heterogeneous complexes can localize in the glomerulus, thereby initiating renal injury, with the lack of antibody involvement.

Animals↗
PubMed1991

Alpha-helix stabilization by natural and unnatural amino acids with alkyl side chains.

Knowledge of the role of individual side chains in forming different secondary structures such as the alpha-helix would be useful for prediction of protein structure from sequence or de novo protein design. Experimental and theoretical studies on natural and synthetic peptides and proteins indicate that individual side chains differ in their helix-forming potential. Four aliphatic side chains occur in the standard complement of amino acids: alanine and leucine are helix stabilizing, whereas isoleucine and valine are weakly destabilizing. We have synthesized a series of helical peptides containing unnatural aliphatic side chains having two to four carbons to explore some of the factors involved in alpha-helix stabilization and the basis for selection of the natural set. We find that linear side chains with two, three, or four carbons are as strongly helix stabilizing as the single methyl in alanine and that all linear side chains are stronger helix promoters than leucine. In addition, a t-butyl side chain is significantly more helix destabilizing than the sec-butyl side chain of isoleucine, the isopropyl side chain of valine, or even the unrestricted side chain of glycine. These results provide experimental evidence that restriction in conformational freedom of a side chain imposed by alpha-helix formation is a major component of the role of a side chain in stabilizing helical structure.

Amino Acids↗