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Biomedical subjects

A L Chen

Publications and source records attributed to A L Chen.

At least 19 recordsLinked to original sources

The RNA binding protein YB-1 binds A/C-rich exon enhancers and stimulates splicing of the CD44 alternative exon v4.

Exon enhancers are accessory pre-mRNA splicing signals that stimulate exon splicing. One class of proteins, the serine-arginine-rich (SR) proteins, have been demonstrated to bind enhancers and activate splicing. Here we report that A/C-rich exon enhancers (ACE elements) are recognized by the human YB-1 protein, a non-SR protein. Sequence-specific binding of YB-1 was observed both to an ACE derived from an in vivo iterative selection protocol and to ACE elements in an alternative exon (v4) from the human CD44 gene. The ACE element that was the predominant YB-1 binding site in CD44 exon v4 was required for maximal in vivo splicing and in vitro spliceosome assembly. Expression of wild-type YB-1 increased inclusion of exon v4, whereas a truncated form of YB-1 did not. Stimulation of exon v4 inclusion by wild-type YB-1 required the ACE necessary for YB-1 binding in vitro, suggesting that YB-1 stimulated exon inclusion in vivo by binding to an exonic ACE element. These observations identify a protein in addition to SR proteins that participates in the recognition of exon enhancers.

Alternative Splicing↗

Arthroscopic diagnosis and management of ochronotic arthropathy of the knee.

Ochronotic arthropathy is a progressive joint disorder resulting from the deposition of a derivative of homogentisic acid into connective tissues, especially meniscal and articular cartilage. Patients may present with symptoms, physical examination results, and radiographic changes consistent with degenerative joint disease. We present a case in which an operative arthroscopy of the knee was highly suggestive of ochronotic arthropathy. The definitive diagnosis of ochronosis was subsequently confirmed by laboratory and pathologic evaluation.

Arthralgia↗

Efficacy of combined technetium-99m sulfur colloid/indium-111 leukocyte scans to detect infected total hip and knee arthroplasties.

The reliability of combined indium-111 leukocyte/technetium-99m sulfur colloid scans, with and without the addition of blood pooling and blood flow studies, in the diagnosis of infected total joint arthroplasty was investigated. Both scans were performed on 58 patients before reoperation of total hip or knee arthroplasty in the period 1996-1999. Results for imaging alone included 100% specificity, 46% sensitivity, 100% positive predictive value, 84% negative predictive value, and 88% accuracy. Inclusion of blood pooling and flow phase data improved results to 66% sensitivity, 89% negative predictive value, and 90% accuracy, with reductions in specificity (98%) and positive predictive value (91%). Routine use of these radionuclide scans is not supported by these data.

Adult↗

Midterm clinical and radiographic results with the genesis I total knee prosthesis.

The midterm results of primary posterior cruciate ligament-retaining, minimally conforming, cemented modular total knee arthroplasties using the Genesis I prosthesis in 110 knees in 72 patients were reviewed. Patients were evaluated at a mean follow-up of 7.3 years by Knee Society pain and functional scores, radiographic and survivorship analysis, and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) health status questionnaire. Range of motion increased from an average of 96.3 degrees to 112.5 degrees. Knee Society pain and functional scores increased from preoperative averages of 55 and 44 to 92 and 88, respectively. There were 91 excellent, 16 good, 1 fair, and 2 poor results. WOMAC scores were increased significantly in each subcategory examined (pain, stiffness, and physical function). Kaplan-Meier survivorship was 97% at 10 years. An increase in loosening as a result of eccentric stress concentration secondary to the nonconforming design of this prosthesis, theoretically a matter of some clinical concern, was not shown in this investigation.

Aged↗

Vibrio aerogenes sp. nov., a facultatively anaerobic marine bacterium that ferments glucose with gas production.

A mesophilic, facultatively anaerobic, marine bacterium, designated strain FG1T, was isolated from a seagrass bed sediment sample collected from Nanwan Bay, Kenting National Park, Taiwan. Cells grown in broth cultures were motile, Gram-negative rods; motility was normally achieved by two sheathed flagella at one pole of the cell. Strain FG1T required Na+ for growth, and exhibited optimal growth at 30-35 degrees C, pH 6-7 and about 4% NaCl. It grew anaerobically by fermenting glucose and other carbohydrates with production of various organic acids, including acetate, lactate, formate, malate, oxaloacetate, propionate, pyruvate and succinate, and the gases CO2 and H2. The strain did not require either vitamins or other organic growth factors for growth. Its DNA G+C content was 45.9 mol%. It contained C12:0 as the most abundant cellular fatty acid. Characterization data, together with the results of a 16S rDNA-based phylogenetic analysis, indicate that strain FG1T represents a new species of the genus Vibrio. Thus, the name Vibrio aerogenes sp. nov. is proposed for this new bacterium. The type strain is FG1T (= ATCC 700797T = CCRC 17041T).

Anaerobiosis↗

Minimal stimulation achieves pregnancy rates comparable to human menopausal gonadotropins in the treatment of infertility.

OBJECTIVE: To examine the effectiveness of a novel clomiphene citrate (CC) and hMG combination protocol ("minimal stimulation") for controlled ovarian hyperstimulation. Minimal stimulation consists of administering 100 mg/d CC for 5 days followed by a single dose of 150 IU hMG. The results of this analysis are compared with those of an hMG-alone protocol. In vitro fertilization-embryo transfer and donor insemination patients are excluded from this analysis. DESIGN: Retrospective review of minimal stimulation and hMG cycles from January 1, 1989 to December 31, 1992. SETTING: Tertiary care center reproductive endocrinology and infertility clinic. PATIENTS: Two hundred thirty-two women who underwent 549 treatment cycles. MAIN OUTCOME MEASURES: Clinical and multiple pregnancy rates (PRs) and medication costs. RESULTS: Sixty-one women received 106 cycles of minimal stimulation and 183 received 443 cycles of hMG. Although subject groups were not assigned randomly, multivariate analysis detected no significant differences between the treatment groups. The total ampules of hMG required differed significantly (2.0 for minimal stimulation versus 16.8 +/- 8.5 [mean +/- SD] for hMG). Pregnancy rates and multiple gestation rates were similar. Medication expense of minimal stimulation is 21% that of the hMG protocol. CONCLUSIONS: Minimal stimulation is as effective as hMG in the population examined. The comparable PRs and decreased medication costs of minimal stimulation justifies further evaluation of its role in the treatment of infertility.

Adult↗

Historical total and respirable silica dust exposure levels in mines and pottery factories in China.

Historical exposure estimates of total dust and respirable silica were made in a recent nested case-referent study of lung cancer among mine and pottery workers in China. Exposure to total dust and respirable silica was assessed in 20 mines and 9 pottery factories. The average total dust concentration was 7.26 mg center dot m-3, with a range from 17.68 mg center dot m-3 in the 1950s to 3.85 mg center dot m-3 in the 1980s, while the average respirable silica dust was 1.22 mg center dot m-3, with a range from 3.89 mg center dot m-3 in the 1950s to 0.43 mg center dot m-3 in the 1980s. The highest respirable silica dust occurred in the underground mining operations (1.43 mg center dot m-3), particularly for manual drillers (9.03 mg center dot m-3). Among all facility types, tungsten mines had the highest respirable silica dust exposure (1.75 mg center dot m-3), while the lowest exposure occurred in copper-iron mines (0.32 mg center dot m-3).

Ceramics↗

Indirect validation of a retrospective method of exposure assessment used in a nested case-control study of lung cancer and silica exposure.

Validations of retrospective methods of assessment used in occupational epidemiological studies have rarely been published. This study is an indirect validation of a quantitative retrospective assessment of exposure to silica used in a nested case-control study of lung cancer among workers at 29 metal mines and pottery factories in China. Indices of cumulative total dust and cumulative respirable dust were calculated by merging work histories with the historical exposure profile for each subject. To validate indirectly the methods of exposure assessment used in the study of lung cancer, trends for exposure response relation between the two indices of exposure to silica and risk of silicosis were evaluated with 376 patients with silicosis from the study population as the cases, and 1262 controls without silicosis for comparison. Age adjusted odds ratios (ORs) as a measure of risk of silicosis showed striking trends with both indices of exposure to silica. For cumulative respirable dust, the OR (95% confidence interval) rose from 7.6 (5.1-11.4) for low exposure to 20.0 (13.2-30.6) for medium exposure, and to 51.7 (31.0-86.8) for high exposure. The strength of the association between exposure to silica and risk of silicosis suggests that the retrospective assessment of exposure used in the case-control study of lung cancer would accurately reflect an exposure response relation between silica and lung cancer, if it existed.

Case-Control Studies↗

Estimating historical exposure to silica among mine and pottery workers in the People's Republic of China.

A quantitative retrospective exposure assessment method was developed for use in a nested case-control study of lung cancer among mine and pottery workers exposed to silica dust in the People's Republic of China. Exposure assessment was carried out in 20 mines (10 tungsten, 6 iron/copper, and 4 tin) and nine pottery factories. A job title dictionary was developed and used in both the collection of historical exposure information and work histories of 1,668 (316 cases and 1,352 controls) study subjects. Several data abstraction forms were developed to collect historical and current exposure information and employees' work histories, starting in 1950. A retrospective exposure matrix was developed on the basis of facility/job title/calendar year combinations using available historical exposure information and current exposure profiles. Information on the amount of respirable, thoracic, and free silica content in total dust was used in estimating exposure to silica. Starting in 1950, 6,805 historical estimates had been carried out for 14 calendar-year periods. We estimated the average total dust concentration to be 9 mg/M3, with a range from 28 mg/M3 in earlier years to 3 mg/M3 in recent years. Several exposure indices [such as cumulative dust, average dust, cumulative respirable (< 5 mu in particle size) and thoracic (< 10 mu in particle size) silica dust, average respirable and thoracic silica dust, exposure-weighted duration, and the highest/longest exposure] were calculated for individuals by merging work history and historical exposure matrix for each study subject. We developed these various measures of exposure to allow investigators to compare and contrast different indices of historical exposure to silica.

Case-Control Studies↗

Patient acceptance of two health status measures: the Medical Outcomes Study Short-form General Health Survey and the Duke Health Profile.

BACKGROUND: The Medical Outcomes Study Short-Form General Health Survey (MOS-SF) and the Duke Health Profile (DUKE) are brief, reliable, valid, and practical health status measures with potential applications in clinical research. We compared patient acceptance, ease of completion, and adequacy of capture (of the patient's self-perception of health) of these instruments in a primary care setting. METHODS: The MOS-SF, DUKE, and assessment questionnaires were administered to 79 patients in a university-based family practice. Patient acceptance of each instrument was assessed with Likert scale questions. Patients then compared the two instruments for relative ease of completion, preference, and completeness of capture. RESULTS: Both forms assessed each item well, but the DUKE scored statistically significantly better than the MOS-SF on four of six patient acceptance questions and both ease of completion items. There were no significant differences for capture items. CONCLUSIONS: Although both instruments are well accepted, investigators may favor the DUKE over the MOS-SF for situations in which patient acceptance or ease of completion is a key issue.

Adult↗

Associations among family support, family stress, and personal functional health status.

The self-reported family support and stress of 249 ambulatory adult patients, aged 18-49 years, were studied relative to their self-reported functional health. Support from family members was found to be related positively with emotional function. Stress from family members was associated negatively with symptom status, physical function, and emotional function. Patients' severity of illness was related negatively to their symptom status, physical function, and social function, but not to their emotional function. During the study a new self-report instrument, the Duke Social Support and Stress Scale (DUSOCS), was developed to measure family and non-family support and stress. Also, a new chart audit methodology, the Duke Severity of Illness Scale (DUSOI), was designed to assess severity in the ambulatory setting. Reliability and validity of the DUSOCS and the DUSOI were supported. The importance of the patient's perception of health and its family determinants is emphasized.

Adolescent↗

Species differences in the effects of prostaglandins on inositol trisphosphate accumulation, phosphatidic acid formation, myosin light chain phosphorylation and contraction in iris sphincter of the mammalian eye: interaction with the cyclic AMP system.

Comparative studies on the effects of prostaglandins (PGs) on 1,2-diacylglycerol, measured as phosphatidic acid (PA), and inositol trisphosphate (IP3) production, cyclic AMP (cAMP) formation, myosin light chain (MLC) phosphorylation and contraction in the iris sphincter smooth muscle of rabbit, bovine and other mammalian species were undertaken and functional and biochemical relationships between the IP3-Ca++ and cAMP second messenger systems were demonstrated. The findings obtained from these studies can be summarized as follows: 1) all PGs investigated, including PGE2, PGF2 alpha, PGF2 alpha-ester, PGE1 and PGA2 increased IP3 accumulation and PA formation, and the extent of stimulation was dependent on the animal species. Thus, PGF2 alpha-ester (1 microM), the most potent of the PGs, increased IP3 accumulation in rabbit and bovine sphincters by 33 and 58%, respectively, and increased PA formation by 67 and 56%, respectively. The PG increased IP3 accumulation in both rabbit and bovine sphincters very rapidly (T1/2 values about 26 sec) and in a dose-dependent manner. 2) The PG had no effect on MLC phosphorylation in the rabbit sphincter, but it increased that of the bovine by 36%. 3) The PG increased cAMP formation by 75% in the rabbit sphincter but it had no effect on that of the bovine. 4) The PG induced a maximal contractile response in the bovine sphincter but it had no effect on that of the rabbit. 5) In the bovine, PGA2 induced IP3 accumulation and contraction, without an effect on cAMP formation; however, in the rabbit, cat and dog it increased cAMP formation and had no effect on IP3 accumulation and contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Heparin metabolism and heparin-release lipase activity during long-term estrogen-progestin treatment.

Short-term oral contraceptive therapy has been reported to decrease postheparin lipolytic activity (PHLA). Resistance to heparin has been held responsible for this effect. To test several alternative explanations, we studied both PHLA and heparin concentrations in nine control women and nine women receiving long-term estrogen-progestin therapy after they were given heparin intravenously (10 units/kg). There were no significant differences in the concentration of heparin, its rate of disappearance, or calculated space of distribution between control and treated groups. PHLA was depressed (p less than 0.05) by approximately 50% during long-term estrongen-progestin therapy. PHLA disappearance was similar in both groups. Thus, reduced PHLA in women receiving long-term oral contraceptive therapy cannot be related to altered heparin metabolism or to accelerated enzyme disappearance from plasma. Long-term estrogen-progestin administration may decrease the heparin-facilitated release of individual triglyceride hydrolase activities or enhance the affinity of enzyme binding to tissues.

Contraceptives, Oral↗

One-stage assay of heparin.

A simple and rapid one-stage plasma heparin assay based on the heparin-dependent neutralization of activated factor X (Xa) is described. Factor Xa is prepared in a concentration adjusted to produce a clotting time of 18 to 20 seconds when heparin-free plasma is tested in the system. The assay incubation mixture contains "standard human plasma", the heparinized test plasma, cephalin, and factor Xa. Clotting times are measured automatically after incugation and calcium addition. A linear relationship was found between the log of the clotting time and the heparin concentration for the standard curve from which the heparin level is determined. The lower limit of sensitivity is about 0.05 unit heparin per milliliter. Dilution of test plasma is required to bring the heparin level to between 0.05 and 0.2 unit per milliliter. The standard curve is reproducible with a coefficient of variation of 2 to 4 per cent. Ten different, nonheparinized samples had clotting times of 18.9 plus or minus 1.0 (plus or minus 2 S.D.) seconds. Theoretically calculated and experimentally determined heparin levels after pulse injection of heparin agreed well in 5 volunteer subjects with r values between 0.93 and 0.99. This assay is not affected by normal variation in the plasma levels of fibrinogen, prothrombin, and factor V or by the plasma defects induced by coumadin.

Blood Coagulation↗