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Biomedical subjects

A Chen

Publications and source records attributed to A Chen.

At least 271 records · Page 15Linked to original sources

Routine use of unilateral and bilateral radial arteries for coronary artery bypass graft surgery.

OBJECTIVES: This study sought to evaluate the routine use of radial artery (RA) grafts in patients undergoing coronary artery revascularization. BACKGROUND: Previous long-term studies have documented poor patency of saphenous vein grafts compared with internal thoracic artery (ITA) grafts. METHODS: We performed a prospective review of 175 of 249 consecutive patients. RESULTS: Fifty-four patients had bilateral RAs harvested. Mean number (+/- SD) of grafts/patient was 3.27 +/- 0.93, with 2.76 +/- 0.97 arterial grafts; a mean of 1.53 +/- 0.68 grafts were performed with the RA. The operative mortality rate was 1.6%. No deaths were related to RA grafts, and there were no RA harvest site hematomas or infections. Transient dysesthesia 1 day to 4 weeks in duration occurred in the distribution of the lateral antebrachial cutaneous nerve in six extremities (2.6%). Elective cardiac catheterization in 60 patients at 12 weeks postoperatively demonstrated a 95.7% patency rate. CONCLUSIONS: Because of potential benefit of long-term patency associated with arterial grafts, minimal morbidity and mortality associated with use of the RA and excellent short-term patency rates, we cautiously recommend use of one or both RAs as additional conduits to be used concomitantly with the ITA for arterial revascularization of the coronary arteries.

Adolescent↗

Sialosyl-Tn antigen is prevalent and precedes dysplasia in ulcerative colitis: a retrospective case-control study.

BACKGROUND & AIMS: Expression of the carbohydrate-associated sialosyl-Tn (STn) antigen has been correlated with carcinogenesis in sporadic colon cancer. This retrospective study analyzed surveillance colonoscopy biopsy specimens to determine whether STn antigen could serve as a marker for neoplasia risk in patients with long-standing ulcerative colitis. METHODS: Eleven patients who developed dysplasia or cancer and who had undergone at least three surveillance colonoscopies were matched with 11 controls who had not developed neoplasia. Sections from 969 available surveillance biopsy specimens were stained immunohistochemically with monoclonal antibody TKH2 and were interpreted blindly. RESULTS: Compared with controls, patients expressed STn antigen more frequently in their biopsy specimens (44% patient biopsy specimens vs. 11% control biopsy specimens). Patients were also more likely to undergo colonoscopies with two or more colonic segments expressing STn antigen (73% vs. 22%), repeated STn antigen expression in two or more consecutive colonoscopies (91% vs. 27%), and STn antigen expression proximal to the hepatic flexure (64% vs. 0%). STn antigen appearance preceded the detection of neoplasia by 7 or fewer years, and its preferential expression in patients was not confounded by the degree of active inflammation. CONCLUSIONS: Repeated STn antigen expression in nondysplastic colonic mucosa may presage the development of neoplasia in long-standing ulcerative colitis and may be a useful adjunct to dysplasia during colonoscopic surveillance.

Adult↗

Student interest in activities in a secondary physical education curriculum: an analysis of student subjectivity.

Situational interest is defined as a student's perception of interest inherent in an activity. Holding interest is conceptualized as a specific situational interest perceived by a student based on his or her subjective understanding of the activity's meaningfulness. It motivates the student to continuously participate in that activity. This research was designed to examine the patterns of holding interest for physical activities in a state physical education curriculum for secondary schools. A group of college students (N = 35) who completed their entire secondary education in the state was invited to construct their perceptions of interest in the activities selected from their secondary physical education curriculum. Q methodology was used to determine and analyze patterns of the interest. Four patterns of holding interest were determined: fitness, socialization, activity variation, and self-expression. Specific activities associated with each pattern were identified, and relationships among the four patterns were described. Findings (a) support the notion that holding interest is based on students' subjective understanding and valuing of the unique meanings in physical activities and (b) suggest that holding interest is person- and activity-specific, implying that physical educators should focus on student-activity matching when making curricular decisions.

Adult↗

A gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6.

Late-onset non-syndromic hearing impairment is the most common type of neurological dysfunction in the elderly. It can be either acquired or inherited, although the relative impact of heredity on this type of loss is not known. To date, nine different genes have been localized, but none has been cloned. Using an extended American family in which a gene for autosomal dominant late-onset non-syndromic hearing impairment is segregating, we have identified a new locus, DFNA10, on chromosome 6.

Chromosome Mapping↗

Genetic and physiological analysis of the lethal effect of L-(+)-lactate dehydrogenase deficiency in Streptococcus mutans: complementation by alcohol dehydrogenase from Zymomonas mobilis.

CH4ts is a previously isolated recombinant mutant of Streptococcus mutans NG8 which produces a thermolabile L-(+)-lactate dehydrogenase (LDH) activity. It does not grow at 42 degrees C under a variety of cultivation conditions. In this study, we show that a batch culture of CH4ts shifted from 30 to 42 degrees C underwent rapid cessation of growth and accelerated cell death. The mutant grew at 42 degrees C in continuous culture under glucose-limiting conditions. Under these conditions, lactate production was replaced by production of ethanol and, to a smaller extent, acetoin. The cloned Zymomonas mobilis gene for alcohol dehydrogenase II, placed under the control of the S. mutans spaP regulatory signals, complemented LDH deficiency. The alcohol dehydrogenase-complemented mutant grew as well or better than NG8 on a variety of carbon sources at 42 degrees C and produced significant amounts of ethanol in place of lactic acid. These results are in accord with other approaches indicating that S. mutans has other enzymatic activities, including pyruvate formate-lyase and pyruvate dehydrogenase, for pyruvate metabolism. However, at high glucose concentrations, the levels of activity of these enzymes are apparently insufficient to compensate for the absence of LDH.

Alcohol Dehydrogenase↗

Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues.

MUC2 and MUC3 are prominent mucin genes expressed in the human intestine. Using in situ hybridization with RNA probes, we examined the cellular distribution of MUC2 and MUC3 mRNA in normal, malignant, and inflammatory human intestinal tissues. In normal small intestine and colon, MUC2 mRNA was expressed exclusively in goblet cells and occurred throughout the entire height of the mucosa. MUC3 mRNA was expressed by goblet and columnar cells but was restricted to the villous compartment of the small intestine and the surface epithelium of the colon. Expression of MUC2 and MUC3 mRNA were both markedly decreased in poorly, moderately, and well-differentiated colon cancers but were preserved in mucinous colon cancers. In ulcerative colitis and Crohn's colitis tissues, MUC2 and MUC3 mRNA expression displayed a normal pattern regardless of whether the mucosa manifested active or quiescent inflammation. These findings indicate that MUC2 is goblet cell-specific, whereas MUC3 is related to maturation of intestinal epithelial cells. In colon cancers, the genetic regulation of MUC2 and MUC3 is different depending on the histological type of tumor. The constitutive expression of MUC2 and MUC3 mRNA in inflammatory bowel diseases suggests that these genes may be necessary for maintenance of normal epithelial cell function during inflammation.

Colitis, Ulcerative↗

Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients.

PURPOSE: To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). PATIENTS AND MATERIALS: A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 microg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 microg/m2/h with G-CSF. RESULTS: Without G-CSF, two of eight patients who received 47 microg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 microg/m2/h (with a platelet count < 25,000/microL in one). With G-CSF, zero of seven patients treated with 47 microg/m2/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/microL in five) entered at 59 microg/m2/h. Among 39 patients entered at > or = 25 microg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicities of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia ( r = .85). CONCLUSION: The recommended phase II dose of 9-AC given by 72-hour infusion every 2 weeks is 35 microg/m2/h without G-CSF or 47 microg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance.

Adult↗

Monomeric immunoglobulin A protects glomerulus against polymeric immunoglobulin A immune complex in experimental immunoglobulin A nephropathy.

Polymeric (p) IgA constitutes 13% of total serum IgA, whereas monomeric (m) IgA represents the other 87%. pIgA tends to form complexes in the circulation that eventually localize in the glomerulus. mIgA is a nonprecipitable antibody. When complexed with an antigen in vivo, the circulating mIgA immune complex (IC) thus formed does not deposit in the glomerulus. The purpose of the present study was to evaluate the influence of mIgA on the formation of pIgA-lC and subsequent glomerular deposition of the IC in an experimental model of IgA nephropathy. The influence of mIgA anti-dinitrophenyl (DNP) on pIgA anti-DNP/DNP-conjugated BSA (BSA-DNP) IC formation was assessed by double diffusion test and competition PAGE in combination with autoradiography. Only the BSA-DNP, a model antigen of relatively low molecular mass, was radiolabeled and monitored throughout the latter experiment. An analysis of clearance kinetics (1 and 6 hours) of the antigen using 4-week-old female BALB/c mice, and a series of renal studies were performed after intravenous injection with a single dose of combined pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP. As demonstrated by the double diffusion test, addition of mIgA anti-DNP resulted in suppression of the precipitating reaction of pIgA anti-DNP and BSA-DNP. This effect was confirmed by PAGE for size determination of the BSA-DNP which had been complexed with either pIgA anti-DNP or a mixture of pIgA anti-DNP and mIgA anti-DNP. The clearance kinetics studies showed that the elimination of BSA-DNP injected with pIgA anti-DNP was prolonged in the presence of mIgA anti-DNP in a partially dose-dependent manner. The experimental mice receiving pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP showed less hematuria (p < 0.005) than mice receiving pIgA anti-DNP and BSA-DNP (positive control) when examined 1 hour after injection. Immunofluorescence study of the renal tissue of mice receiving pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP showed a suppressed glomerular localization of IgA and third component of complement, as compared with those injected with pIgA anti-DNP and BSA-DNP alone. Similarly, a significant decrease of glomerular BSA-DNP deposits was observed in mice receiving pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP compared with those receiving pIgA anti-DNP and BSA-DNP alone, as demonstrated by light microscopic autoradiography. These findings indicate that a high dose of specific mIgA was capable of modulating glomerular deposition of the pIgA-IC in this animal model of IgAN.

Animals↗

[Cloning and sequencing of VH and VL genes of an anti-human lung adenocarcinoma monoclonal antibody].

By comparing the conserved regions at each end of the nucleotide sequences of murine germ-line genes encoding FR1 and FR4 regions of immunoglobulin heavy and light chain variable regions, we designed two sets of primer for amplification of VH and VL genes. Hybridoma cell WLA-2C4, secreting an antihuman lung adenocarcinoma McAb, was cultured and the genome DNA was extracted and used as template for PCR. After PCR the desired VH and VL fragments were amplified. The PCR products were then cloned into pUC19 vector. By screening and identification, several recombinants that had been inserted with the target fragments were obtained. Then they were sequenced with Sanger's method. It was confirmed by computer-assisted comparative sequence analysis that clones of full-length and potentially functional VH and VL genes from the hybridoma cell line WLA-2C4 were ob-tained.

Adenocarcinoma↗

[L-arginine nitric oxide pathway in acute renal ischemia reperfusion injury of the aged rats].

OBJECTIVE: To gain further insights into the greater susceptibility to acute ischemic renal injury (ARF, 45 minutes of renal arteries clamping) of old rats (O, 24-26 months) as against young ones (Y, 3-4 months), and the possible role of endothelium derived relaxing factor (EDRF) and its influence on ischemic renal function. METHODS: Basal renal dynamics was compared between O and Y. RESULTS: Two hours after ischemia, the decrease of GFR RPF, and UV was more severe in O than in Y. Urine cGMP was significantly dropped in both groups. Intravenous administration of L-arginine increasld urine cGMP of the O as well as the Y, with that of the Y higher than that in O. GFR, RPF, UV were elevated significantly in the O. Simultaneous administration of L-NNA, the analogue of L-Arginine could partially antagonize its effect on elevating RPF. RT-PCR technique was used to detect renal inducible nitric oxide synthase (iNOS) expression. Although the ischemic kidney was capable of expressing iNOS mRNA in the presence of L-arginine after ischemia, the production of NO in the old may not be regulated at the transcriptional level, other factors such as NOS enzyme activity, availability of L-arginine and O2, metabolism of NO after its production were suspected to be involved.

Aging↗

Phenotypic manifestations of branchio-oto-renal syndrome.

Branchiootorenal (BOR) syndrome is a variable, autosomal-dominant disorder of the first and second embryonic branchial arches, kidneys, and urinary tract. We describe the phenotype in 45 individuals, highlighting differences and similarities reported in other studies. Characteristic temporal bone findings include cochlear hypoplasia (4/5 of normal size with only 2 turns), dilation of the vestibular aqueduct, bulbous internal auditory canals, deep posterior fossae, and acutely-angled promontories.

Abnormalities, Multiple↗

Structural requirements regulate endoproteolytic release of the L-selectin (CD62L) adhesion receptor from the cell surface of leukocytes.

L-selectin mediates leukocyte rolling on vascular endothelium at sites of inflammation and lymphocyte migration to peripheral lymph nodes. L-selectin is rapidly shed from the cell surface after leukocyte activation by a proteolytic mechanism that cleaves the receptor in a membrane proximal extracellular region. This process may allow rapid leukocyte detachment from the endothelial surface before entry into tissues. In this study, the structural requirements for regulation of human L-selectin endoproteolytic release were examined through analysis of chimeric selectin molecules and mutant L-selectin receptors. The use of chimeric selectins and a cytoplasmic tail truncation mutant demonstrated that the extracellular membrane-proximal 15-amino acid region of L-selectin is required for endoproteolytic release. The introduction of alanine-scanning mutations within this membrane-proximal region did not prevent endoproteolytic release, indicating that a specific amino acid motif was not an absolute requirement for cleavage. Furthermore, alterations within the putative primary cleavage site (K283-S284) resulted in either constitutive endoproteolytic release of the receptor or inhibition of cell activation-induced shedding to variable extents. The length of the membrane-proximal region was also critical since truncations of this region completely abolished endoproteolytic release. Thus, release of L-selectin is likely to be regulated by the generation of an appropriate tertiary conformation within the membrane-proximal region of the receptor which allows recognition by a membrane-bound endoprotease with relaxed sequence specificity that cleaves the receptor at a specific distance from the plasma membrane. These observations suggest a generalized protein-processing pathway involved in the endoproteolytic release of specific transmembrane proteins which harbor widely differing primary sequences at or neighboring their cleavage sites.

Amino Acid Sequence↗

Validity of the three-column theory of thoracolumbar fractures. A biomechanic investigation.

STUDY DESIGN: This study validated the three-column theory of fractures by correlating the multidirectional instabilities and the vertebral injuries to each of the three columns, using a biomechanic trauma model. OBJECTIVES: The objective was to validate the three-column theory as applied to the thoracolumbar fractures. SUMMARY OF BACKGROUND DATA: The widely used three-column theory of fractures for classification and evaluation was based on retrospective analysis of radiographs. No biomechanic study, using realistic spinal fractures and multidirectional instability measurements, was available. METHODS: Using 16 fresh cadaveric thoracolumbar human spine specimens, two groups of burst fractures were produced by either simple axial compression or flexion-compression, using a high-speed trauma model. Multidirectional flexibility was measured before and after the trauma, thus quantifying the instability of the burst fracture. Computed tomography scans were taken after the fracture, and a newly developed injury scoring scheme quantified the injuries to the anterior, middle, and posterior columns. Statistical correlations were obtained between the flexibility parameters and injuries to each of the three columns. RESULTS: In the axial compression group, the middle column injury, compared with the other two columns, showed the highest correlations to eight of the nine flexibility parameters (average R2 = 0.77). In the flexion-compression group, again the middle column injury showed the highest correlations to eight of the nine flexibility parameters (average R2 = 0.85). CONCLUSIONS: The results of this study supported the three-column theory of the thoracolumbar fractures and bolstered the concept of the middle column being the primary determinant of mechanical stability of this region of the spine.

Adult↗

Tumor-associated sialylated antigens are constitutively expressed in normal human colonic mucosa.

Immunohistochemical studies have indicated that sialylated carbohydrate antigens such as sialyl-Tn, sialyl-Le(a), and sialyl-Le(x) are expressed in a tumor-associated fashion in human colon. Since sialic acid residues are O-acetylated more extensively in normal colonic epithelium than in colon cancer cells, we examined whether deacetylation of colonic tissues might enable monoclonal antibodies to recognize these tumor-associated sialylated antigens. In normal colon, deacetylation turned most cases (82%) positive with anti-sialyl-Tn mAb TKH2; and in colon cancers, it increased the number of TKH2-positive cells. Sialyl-Le(a) and sialyl-Le(x) detection was also increased after deacetylation of normal and malignant colonic tissues so that the frequency of positive cases in normal tissues was similar to that in the cancers. However, in the stomach and pancreas, the same treatment rarely increased the detection of the sialylated epitopes in normal or cancerous tissues. Thus, the same sialylated epitopes can be expressed in a tumor-associated fashion by different mechanisms in different gastrointestinal organs; in the colon, these antigens are constitutively expressed and O-acetylated, whereas in the upper gastrointestinal tract, they are rarely O-acetylated, suggesting that other mechanisms such as differences in glycosylation account for the cancer-associated expression.

Adenocarcinoma↗

Tyrosine 27 of the specificity polypeptide of EcoKI can be UV crosslinked to a bromodeoxyuridine-substituted DNA target sequence.

The specificity (S) subunit of the restriction enzyme EcoKI imparts specificity for the sequence AAC(N6)GTGC. Substitution of thymine with bromodeoxyuridine in a 25 bp DNA duplex containing this sequence stimulated UV light-induced covalent crosslinking to the S subunit. Crosslinking occurred only at the residue complementary to the first adenine in the AAC sequence, demonstrating a close contact between the major groove at this sequence and the S subunit. Peptide sequencing of a proteolytically-digested, crosslinked complex identified tyrosine 27 in the S subunit as the site of crosslinking. This is consistent with the role of the N-terminal domain of the S subunit in recognizing the AAC sequence. Tyrosine 27 is conserved in the S subunits of the three type I enzymes that share the sequence AA in the trinucleotide component of their target sequence. This suggests that tyrosine 27 may make a similar DNA contact in these other enzymes.

Amino Acid Sequence↗

E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle.

The E2F transcription factors play a role in regulating the expression of genes required for cell proliferation. Their activity appears to be regulated by association with the retinoblastoma protein (pRb) and the pRb-related proteins p107 and p130. In vivo, pRb is found in complex with a subset of E2F components--namely, E2F-1, E2F-2, and E2F-3. Here we describe the characterization of cDNAs encoding two unusual E2Fs, E2F-4 and E2F-5, each identified by the ability of their gene product to interact with p130 in a yeast two-hybrid system. E2F-4 and -5 share common sequences with E2F-1, E2F-2, and E2F-3 and, like these other E2Fs, the ability to heterodimerize with DP-1, thereby acquiring the ability to bind an E2F DNA recognition sequence with high affinity. However, in contrast to E2F-1, E2F-4 and E2F-5 fail to bind pRb in a two-hybrid assay. Moreover, they show a unique pattern of expression in synchronized human keratinocytes: E2F-4 and E2F-5 mRNA expression is maximal in mid-G1 phase before E2F-1 expression is detectable. These findings suggest that E2F-4 and E2F-5 may contribute to the regulation of early G1 events including the G0/G1 transition.

Amino Acid Sequence↗