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Biomedical subjects

J Chen

Publications and source records attributed to J Chen.

At least 1,189 records · Page 66Linked to original sources

Visual field responses to a hand vibration stimulus.

Two short visual field tests were performed on 106 subjects approximately 5 minutes apart with or without a hand vibration stimulus between the field tests. There were 31 eyes in the control group (10 without glaucoma, eight glaucoma suspects, 10 with primary open-angle glaucoma, and three with secondary open-angle glaucoma). There were 75 eyes in the hand vibration group (16 without glaucoma, 20 glaucoma suspects, 25 with primary open-angle glaucoma, eight with secondary open-angle glaucoma, three with normal-tension glaucoma, and three with other forms of glaucoma). Average visual field sensitivities were significantly reduced in the arcuate zones after a hand vibration stimulus (-0.42 dB; SD, 1.26 dB) when compared with sensitivities in the arcuate zones in subjects without the hand vibration stimulus (+0.38 dB; SD, 1.53 dB; P = 0.01). Multivariate analysis demonstrated a significant reduction in this response in the arcuate zone associated with use of betaxolol (P = 0.021) and timolol (P = 0.047). Betaxolol was associated with significantly smaller reductions in visual field sensitivities in the paracentral zone (P = 0.01). Reductions in visual field sensitivities that may be related to ocular vasospasm occurred after a hand vibration stimulus. This response may be able to be modified pharmacologically with topical beta-blockers, particularly betaxolol.

Adolescent↗

The Hettinger hand vibration test, vasospasm, and glaucoma.

Ocular vasospasm in response to local and/or systemic stimuli may contribute to ischemia of the optic nerve. The Hettinger hand vibration test was applied to patients with and without glaucoma to identify subgroups with a high systemic vasospastic tendency. A total of 580 subjects were tested (113 controls, 86 glaucoma suspects, 270 with primary open-angle glaucoma, 71 with secondary open-angle glaucoma, 30 with normal-tension glaucoma, and 10 with angle-closure glaucoma). The frequency distribution curve of Hettinger scores (HS) was bimodal, suggesting two distinct groups. Within each diagnostic group, a subpopulation with a high HS could be identified. Multivariate analysis demonstrated a significant association between the nonselective topical beta-blocker timolol and higher mean HS (P = 0.04) and a significantly higher proportion of subjects with HS of 1.5 or more (P = 0.01). Although subjects taking systemic beta1-selective blockers had significantly lower mean HS (P = 0.04), the proportion of patients with HS of 1.5 or more was not affected significantly by topical and systemic beta1-selective blocker use. Whereas topical nonselective beta-blockers may have an adverse effect on vasospastic tendency, systemic beta1-selective blockers may be partially protective against this effect.

Adrenergic beta-Antagonists↗

Does preoperative nephrostomy increase the incidence of wound infection after nephrectomy?

OBJECTIVES: To determine whether patients with nephrostomy after simple nephrectomy more often had postoperative wound complication than did matched patients without nephrostomy. METHODS: The hospital records of patients who underwent retroperitoneal simple nephrectomy were evaluated, and the following data were retrieved: age, indication for nephrectomy and nephrostomy insertion, medical history, urine culture, antibiotic regimen, time elapsed from nephrostomy insertion to nephrectomy, surgical technique, type of complication, time elapsed from surgery to complication, treatment, and outcome of complications. RESULTS: Thirty-one patients (mean age 57.9 years, +/-SE 3.0) were evaluated. Seven (31.8%) of the 22 patients without nephrostomy (group 1 ) had wound infection compared with 7 (77.7%) of the 9 patients with nephrostomy (group 2) (P <0.05). All 9 group 2 patients had infected urine compared with 11 of the 22 in group 1 (P <0.05). Complications were apparent within a median time of 1 month (+/-SD 0.9) from surgery in group 2, whereas the median time to complication was 4.5 months (+/-SD 3.7, P <0.05) in group 1. Two patients in group 2 died of wound infection and sepsis. Both groups were similarly matched for age, indication for nephrostomy and nephrectomy, perioperative and operative techniques, and histologic findings of the removed kidneys. All patients received antibiotic agents at the time of surgery. CONCLUSIONS: Patients with nephrostomy inserted because of pyonephrosis or to relieve obstruction who underwent simple nephrectomy because of unrecoverable renal damage had earlier and more frequent wound infections than patients who underwent the identical procedure without nephrostomy. UROLOGY

Humans↗

Posterior corneal surface topographic changes after laser in situ keratomileusis are related to residual corneal bed thickness.

OBJECTIVE: To determine whether ectasia after laser in situ keratomileusis (LASIK) is related to residual corneal bed thickness. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Thirty-two eyes of 16 patients with refractive errors of -4.00 to -18.00 diopters were examined. INTERVENTION: LASIK was performed. The topography of the posterior corneal surface was examined with the Orbscan slit scanning corneal topography/pachymetry system. MAIN OUTCOME MEASURES: The difference in the elevation of posterior corneal surface regarding the best-fit sphere was measured. RESULTS: After surgery, mean bulge of 17.2 +/- 7.2 microns was found in eyes with residual corneal bed of 250 microns or greater, whereas 41.0 +/- 22.1 microns was seen in eyes with bed thickness less than 250 microns (t = 4.29; P = 0.000). CONCLUSION: Posterior corneal bulge is correlated with the residual corneal bed thickness. The risk of ectasia may be increased if the residual corneal bed is thinner than 250 microns.

Cornea↗

Molecular analysis of barley yellow mosaic virus isolates from China.

The complete sequences of both RNAs of an isolate of barley yellow mosaic virus from Yancheng, Jiangsu province, China, were determined. The sequences resembled those of an isolate from Japan (96.8% identical nucleotides for RNA1; 95.7% for RNA2) more closely than one from Germany (93.9 and 91.0%, respectively). The greatest differences between the Chinese and Japanese isolates were in the 5'-UTRs of RNAs 1 and 2 (88.9 and 91.6% identical nucleotides, respectively) and there were also some other regions of difference in P1 (RNA2) and P3, CI, NIa and the 5' end of the coat protein (CP) (RNA1). Molecular differences between isolates from ten sites widely distributed in Eastern China were studied by sequencing RNA regions coding for the CP (RNA1) and the N-terminus of the P2 protein (RNA2). The P2 fragment was more variable than the CP, and phylogenetic analysis of both regions showed that Asian and European isolates formed distinct clusters. Differences between isolates were also revealed by single-strand conformation polymorphism of reverse transcription-polymerase chain reaction products, spanning the full lengths of both RNA1 and RNA2. However, molecular variations between isolates could not be linked to earlier results showing differences in cultivar response.

Base Sequence↗

SZF1: a novel KRAB-zinc finger gene expressed in CD34+ stem/progenitor cells.

The identification and study of genes expressed in hematopoietic stem/progenitor cells should further our understanding of hematopoiesis. Transcription factors in particular are likely to play important roles in maintaining the set of genes that define the stem/progenitor cell. We report here the identification of a putative KRAB-zinc finger gene (SZF1) from a cDNA library prepared from human bone marrow CD34+ cells. Characterization of SZF1 implicates its role in hematopoiesis. The predicted protein contains a highly conserved KRAB domain at the NH2 terminus and four zinc fingers of the C2H2 type at the COOH terminus. Two alternatively spliced products of SZF1 were isolated, which predict proteins of 421 (SZF1-1) and 361 (SZF1-2) amino acids, differing from each other only at the carboxy terminus. The two transcripts of SZF1 have different expression patterns. SZF1-2 is ubiquitously expressed, as indicated by Northern blot, RNase protection, and reverse transcriptase polymerase chain reaction. SZF1-1 expression, in contrast, was detected only in CD34+ cells. We recently isolated the promoter region for the stem/progenitor cell expressed FLT3/FLK-2/STK-1 gene and used this region to generate a reporter construct to test the effect of SZF1 expression. Cotransfection of the reporter construct with SZF1 constructs showed that SZF1-2 repressed transcription three- to fourfold, whereas SZF1-1 showed a lower level of repression. The expression pattern of SZF1 transcripts and the transcriptional repression of a CD34+-specific promoter demonstrate a possible role for SZF1 in hematopoietic stem/progenitor cell differentiation.

Alternative Splicing↗

Development and aging of primitive hematopoietic stem cells in BALB/cBy mice.

Evaluating the function of an individual hematopoietic stem cell (HSC) is a difficult and important problem. The functional ability per HSC, as well as the HSC concentration, was measured with minimal disruption to the cells in vivo using the new competitive dilution assay. Distribution of HSC into recipients was modeled based on Poisson probabilities. Predictions of donor contributions from models assuming different levels of donor HSC functional ability and concentration were compared to actual observations. The model with the least difference between predictions and observations was accepted. In BALB/ cBy (BALB) mice, models assuming equal functional ability of HSC from the same donor fit extremely well with actual observations, suggesting that all HSC are functionally homogeneous at any particular time point during development or aging. Relative HSC functional ability per cell declined during development, so that a fetal HSC had 1.6 to 3.0 times the functional ability of a young adult HSC. The decline continued with age, so that a young adult HSC had 1.6 to 2.0 times the functional ability of an old HSC. Concentrations of HSC that engrafted and functioned were similar among 16-day fetal liver cells and bone marrow cells (BMC) from 3-month and 25 to 28-month-old adult mice. They were either 10 or 4 HSC per million cells when tested in BALB or CByB6F1 recipients, respectively. All HSC were pluripotent and produced lymphoid and myeloid descendants proportionally (r = 0.80 to 0.98, p < 0.01). Fetal and young HSC in both types of recipients maintained clonal stability long term so that percentages of donor cells at 6 and 9 months were strongly correlated (r = 0.72 to 0.93, p < 0.01). Although HSC from aged donors in BALB recipients maintained clonal stability, HSC from the same aged donors failed to show clonal stability in CByB6F1 recipients, perhaps due to the less suitable host environment. All HSC from BALB mice seemed to have equal functional levels at a given stage of life and were gradually exhausted simultaneously through development and aging.

Aging↗

Primary hyperalgesia to mechanical and heat stimuli following subcutaneous bee venom injection into the plantar surface of hindpaw in the conscious rat: a comparative study with the formalin test.

To elucidate the underlying mechanisms of pathological pain, it is important and necessary to develop an animal model characterized by both spontaneous tonic pain and hyperalgesia with a prolonged duration post-tissue injury. In this report, we investigated whether the two animal models of spontaneous tonic pain (the formalin test and the bee venom test) could develop a hyperalgesia to mechanical and thermal stimuli in the injured area following subcutaneous (s.c. ) administration of the two chemical agents into the plantar surface of one hindpaw in the conscious rats. It was found that the persistent nociceptive response (flinching and lifting/licking the injected hindpaw) was monophasic and lasted for 1-2 h followed by a 72-96 h period of reduction in mechanical threshold and heat latency of withdrawal reflex in the bee venom injection area; however, in contrast, the spontaneous pain-related response was biphasic followed by a permanent hypoalgesia or analgesia in the formalin injection area although the duration and response intensity of spontaneous pain was comparable with those following bee venom treatment. Subcutaneous. bee venom injection also produced a distinct reduction of heat latency on the contralateral hindpaw, while s.c. formalin did not. On the other hand, s.c. bee venom injection produced a striking edema and redness of the plantar surface for nearly the same period as the development of hyperalgesia, while the edema and redness could not be obviously observed after the formalin treatment. In the control study, repetitive suprathreshold mechanical or heat stimuli applied to the plantar surface with or without saline treatment did not significantly influence the mechanical threshold or heat latency, suggesting that the phenomena of mechanical and heat hyperalgesia were not the effects of vehicle treatment or those of the stimulus modalities themselves. Taken together, our present results showed that in contrast to s.c. formalin injection, subcutaneous. bee venom injection produced little tissue damage but a striking inflammation accompanied by a prolonged spontaneous pain and a pronounced primary hyperalgesia to mechanical and heat stimuli in the treated hindpaw and a heat, but not mechanical, hyperalgesia in the contralateral hindpaw, implicating that bee venom model may have more advantages over the formalin test and probably other chemoirritants to study the neural mechanisms underlying pathological pain and, especially, the relationship between spontaneous pain and development of hyperalgesia.

Animals↗

Assay for the determination of low dosage form of formoterol dry syrup by capillary electrophoresis with head-column field-amplified sample stacking.

The development of a capillary zone electrophoresis method with head-column field-amplified sample stacking injection for the determination of formoterol (FMTR) in a low dosage dry syrup form was described. To obtain the highest sensitivity, the sample solution was prepared by high content of organic solvent with the presence of a small amount of H+ (60-100 microM) and the capillary inlet end was dipped in water before electroinjection. This method was fully validated in terms of repeatability (RSDs for migration time, peak area of FMTR and peak area ratio between FMTR and I.S. at 1 microg/ml of FMTR was 0.76, 1.10 and 0.55% respectively), reproducibility (RSDs from different capillaries, analytes, days and instruments were 1.52%, 1.04%, 1.16% and 1.93% respectively), linearity (y = 0.827x - 0.085, r = 0.9993 (n = 6) over the range of 0.25-2.0 microg/ml), limits of quantitation, ruggedness and robustness. The method was applied to the determination of the drug in commercial dry syrup preparation (recovery was 100.9%, RSD = 1.5%, n = 5) and proved to be fast and reliable for the quantitation analysis of FMTR in the pharmaceutical form.

Bronchodilator Agents↗

Expression of core binding factor Osf2/Cbfa-1 and bone sialoprotein in tooth development.

The transcription factor Osf2/Cbfa1 is a key regulator of osteogenic differentiation while BSP, a major non-collagenous protein, is a marker of osteoblastic differentiation. To determine the relationship between Osf2/Cbfa1 and the formation of mineralized tissues in tooth development we have studied the temporal expression of Osf2/Cbfa1 and BSP mRNA using in situ hybridization. These studies show that Osf2/Cbfa1 is expressed early in mesenchymal and epithelial tissues destined to form the mineralized tissues of the tooth and periodontal tissues, whereas BSP provides a specific marker for the differentiated cells in each of these tissues. Expression of Osf2/Cbfa1, but not BSP, was observed in the periodontal ligament indicating that expression of Osf2/Cbfa1 is not restricted to mineralizing tissues.

Age Factors↗

In vivo evaluation of 99mTc/188Re-labeled linear alpha-melanocyte stimulating hormone analogs for specific melanoma targeting.

Radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analogs were examined in melanoma-bearing mice to determine the effects of peptide length, structure, and radiometal chelation chemistry on tumor targeting and in vivo biodistribution. The linear alpha-MSH analogs [Nle4,D-Phe7]alpha-MSH (NDPMSH) and [D-Phe7]alpha-MSH(5-10) (DPMSH) were radiolabeled with 99mTc and 188Re via the addition of tetrafluorophenyl mercapto-acetylglycylglycyl-gamma-aminobutyrate (MAG2) or tetrapeptide Ac-Cys-Gly-Cys-Gly (CGCG) chelation moieties. 125I-Tyr2-NDPMSH was obtained by direct iodination of the Tyr2 residue. Tumor uptake of 99mTc-labeled CGCG- and MAG2-NDPMSH analogs at 30 min postinjection were 6.52 +/- 1.11 %ID/g and 4.17 +/- 1.34 %ID/g, respectively, resulting in a significantly higher tumor-to-blood uptake ratio than that of 125I-NDPMSH or a shorter alpha-MSH analog, 99mTc-CGCG-DPMSH. The combination of radiolabeling efficacy and in vivo tumor uptake highlights the potential of 99mTc-CGCG-NDPMSH as a melanoma imaging agent.

Animals↗

Control of V(D)J recombinational accessibility of the D beta 1 gene segment at the TCR beta locus by a germline promoter.

The germline promoter region upstream of the D beta 1 gene segment in the murine TCR beta locus was deleted to assess its role in controlling V(D)J recombination. Associated with diminished D beta 1 region germline transcription, rearrangement of the D beta 1 but not the D beta 2 gene segment was reduced 10- to 20-fold. A corresponding reduction in RAG-mediated cleavage at the D beta 1 and J beta 1 signal sequences was apparent only when purified CD4- CD8- thymocytes were analyzed because, as we demonstrate, cleavage at these gene segments also occurred in CD4+ CD8+ thymocytes. These findings suggest that germline promoters regulate localized accessibility of gene segments for recombination and that in CD4+ CD8+ thymocytes TCR beta allelic exclusion does not result from inaccessibility of D beta gene segments.

Animals↗

Interpolation algorithms for digital mammography systems with multiple detectors.

RATIONALE AND OBJECTIVES: In some full-field digital mammography systems, multiple detectors are abutted together, and the physical gaps between adjacent detectors produce seams between the resultant subimages. In this study, a variety of interpolation algorithms for estimating the missing information in the seams were compared, and their effect on image quality was evaluated. MATERIALS AND METHODS: Eight representative interpolation algorithms were selected, including nearest neighbor, one-dimensional and two-dimensional weighting, mean value, one-dimensional and two-dimensional polynomial, and one-dimensional and two-dimensional cubic spline interpolation methods. These methods were applied to digital mammograms and phantom images. The effectiveness of each algorithm was evaluated for accuracy and geometric distortion. RESULTS: These interpolation algorithms offered similar accuracy in estimating missing image information. The weighting, polynomial, and cubic spline interpolation algorithms introduced less geometric distortion than the nearest neighbor and mean value interpolation algorithms. All algorithms were more effective in estimating larger, lower-contrast features (such as breast masses) than in estimating smaller, higher-contrast features (such as breast microcalcifications). Small microcalcifications within the seams cannot be recovered with interpolation. The probability of a microcalcification in a seam is small, however, and the failure to image a few microcalcifications of a cluster generally does not substantially alter diagnostic performance. CONCLUSION: In the development of full-field digital breast imaging systems, appropriate interpolation algorithms can satisfactorily fill in narrow gaps between adjacent detectors. The one-dimensional weighting interpolation method seems an effective and efficient choice.

Algorithms↗

Genetic analysis of BRCA1 function in a defined tumor cell line.

Retrovirally expressed, wild-type BRCA1 decreased the gamma radiation (IR) sensitivity and increased the efficiency of double-strand DNA break repair (DSBR) of the BRCA1-/- human breast cancer line, HCC1937. It also reduced its susceptibility to DSB generation by IR. By contrast, multiple, clinically validated, missense mutant BRCA1 products were nonfunctional in these assays. These data constitute the basis for a BRCA1 functional assay and suggest that efficient repair of double-strand DNA breaks is linked to BRCA1 tumor suppression function.

BRCA1 Protein↗

Endogenous bile acids are ligands for the nuclear receptor FXR/BAR.

The major metabolic pathway for elimination of cholesterol is via conversion to bile acids. In addition to this metabolic function, bile acids also act as signaling molecules that negatively regulate their own biosynthesis. However, the precise nature of this signaling pathway has been elusive. We have isolated an endogenous biliary component (chenodeoxycholic acid) that selectively activates the orphan nuclear receptor, FXR. Structure-activity analysis defined a subset of related bile acid ligands that activate FXR and promote coactivator recruitment. Finally, we show that ligand-occupied FXR inhibits transactivation from the oxysterol receptor LXR alpha, a positive regulator of cholesterol degradation. We suggest that FXR (BAR) is the endogenous bile acid sensor and thus an important regulator of cholesterol homeostasis.

Animals↗

Cloning and characterization of a mammalian pseudouridine synthase.

This report describes the cloning and characterization of a pseudouridine (psi) synthase from mouse that we have named mouse pseudouridine synthase 1 (mpus1p). The cDNA is approximately 1.5 kb and when used as a probe on a Northern blot of mouse RNA from tissues and cultured cells, several bands were detected. The open reading frame is 393 amino acids and has 35% identity over its length with yeast psi synthase 1 (pus1p). The recombinant protein was expressed in Escherichia coli and the purified protein converted specific uridines to psi in a number of tRNA substrates. The positions modified in stoichiometric amounts in vitro were 27/28 in the anticodon stem and also positions 34 and 36 in the anticodon of an intron containing tRNA. A human cDNA was also cloned and the smaller open reading frame (348 amino acids) was 92% identical over its length with mpus1p but is shorter by 45 amino acids at the amino terminus. The expressed recombinant human protein has no activity on any of the tRNA substrates, most probably the result of the truncated open reading frame.

Amino Acid Sequence↗