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Biomedical subjects

D Chan

Publications and source records attributed to D Chan.

At least 91 records · Page 5Linked to original sources
PubMed1998

Reversal of anticancer multidrug resistance by the ardeemins.

Two "reverse prenyl" hexahydropyrroloindole alkaloids, 5-N-acetylardeemin and 5-N-acetyl-8-demethylardeemin, were evaluated as reversal agents in cells exhibiting a multidrug resistant (MDR) phenotype. These ardeemins (i) reversed drug resistance to vinblastine (VBL) or to taxol as much as 700-fold at relatively noncytotoxic concentrations in vitro; (ii) as a single agent at high concentrations killed MDR cells more efficaciously than the respective parent wild-type cells; and (iii) exhibited strong synergistic effects with doxorubicin (DX) and VBL against the growth of MDR neoplastic cells, and to a lesser extent, of the parent wild-type cells. Mechanistic studies showed that photoaffinity labeling of P-glycoprotein (Pgp) with [3H] azidopine was competitively inhibited by the ardeemins. Resistance to DX in MDR-[Pgp+ and MDR-associated protein (MRP)+], MDR-Pgp+, lung resistance protein (LRP)+-expressing, and wild-type lung cancer cells were reversed 110- to 200-fold, 50- to 66-fold, 7- to 15-fold, and 0.9- to 3-fold, respectively, by 20 microM of the ardeemins. Moreover, these compounds increased the intracellular accumulation of VBL and markedly decreased its efflux. Finally, in vivo combination studies demonstrated that nontoxic doses of the ardeemins with DX significantly improved the chemotherapeutic effects in B6D2F1 mice bearing DX-resistant P388 leukemia, and nude mice bearing human MX-1 mammary carcinoma xenografts. The above features indicate that the ardeemins may have utility in the therapy of cancer.

Alkaloids↗
PubMed1998

General transducing phages like Salmonella phage P22 isolated using a smooth strain of Escherichia coli as host.

A smooth colony strain, resistant to phages lambda and P22, was isolated from sewage and identified as Escherichia coli (strain H). Four temperate phages plaquing on strain H were isolated from sewage. The archetype, HK620, does not plaque on strains C and K12 of E. coli nor on the LT2 strain of Salmonella enterica. Bacterial mutants resistant to a clear plaque mutant of HK620 produce rough colonies. Some are also galactose-negative, a few are histidine auxotrophs, and most show sensitivity to lambda. HK620 can transduce a wide variety of auxotrophic mutants of E. coli H to prototrophy. It can recombine with lambda but its virions resemble those of P22.

Escherichia coli↗
PubMed1998

A nonsense mutation in the carboxyl-terminal domain of type X collagen causes haploinsufficiency in schmid metaphyseal chondrodysplasia.

Type X collagen is a short-chain homotrimeric collagen expressed in the hypertrophic zone of calcifying cartilage. The clustering of mutations in the carboxyl-terminal NC1 domain in Schmid metaphyseal chondrodysplasia (SMCD) suggested a critical role for this type X collagen domain, but since no direct analysis of cartilage has been conducted in SMCD patients, the mechanisms of type X collagen dysfunction remain controversial. To resolve this problem, we obtained SMCD growth plate cartilage, determined the type X collagen mutation, and analyzed the expression of mutant and normal type X collagen mRNA and protein. The mutation was a single nucleotide substitution that changed the Tyr632 codon (TAC) to a stop codon (TAA). However, analysis of the expression of the normal and mutant allele transcripts in growth plate cartilage by reverse transcription PCR, restriction enzyme mapping, and a single nucleotide primer extension assay, demonstrated that only normal mRNA was present. The lack of mutant mRNA is most likely the result of nonsense-mediated mRNA decay, a common fate for transcripts carrying premature termination mutations. Furthermore, no mutant protein was detected by immunoblotting cartilage extracts. Our data indicates that a functionally null allele leading to type X collagen haploinsufficiency is the molecular basis of SMCD in this patient.

Animals↗
PubMed1998

Rarity of debrisoquine hydroxylase gene polymorphism in Chinese patients with Parkinson's disease.

Impaired debrisoquine metabolism resulting from defects in the cytochrome P450 CYP2D6-debrisoquine hydroxylase gene has been shown to be associated with the development of Parkinson's disease (PD). We studied two polymorphisms in this gene in 207 Chinese PD patients and 227 control subjects by polymerase chain reaction and restriction analysis. The G to A substitution at position 1934 in the junction of intron 3/exon 4 was detected in one sporadic PD patient and two control subjects, all of whom were heterozygous. The single base deletion at position 2637 in exon 5 was not detected in any of the study subjects. Such rarity of CYP2D6 polymorphism indicates PD in the Chinese population is associated with some other gene defects.

Aged↗
PubMed1998

Evaluation and management of men whose radical prostatectomies failed: results of an international survey.

OBJECTIVES: To determine how urologists evaluate and treat men who develop recurrent prostate cancer after radical prostatectomy. METHODS: Surveys were mailed to 4467 American Urological Association members comprising 3205 U.S. and 1262 non-U.S. urologists randomly selected from a total membership of approximately 12,000. One thousand four hundred sixteen were returned and 1050 (760 U.S. and 290 non-U.S.) surveys were evaluable. RESULTS: To evaluate men with an elevated or rising prostate-specific antigen (PSA) level more than 1 year after radical prostatectomy, 98% of respondents use digital rectal examination, 68% use bone scan, 54% use transrectal ultrasound with biopsy, 36% use abdominal or pelvic computed tomography scan, 31% use transrectal ultrasound without biopsy, 25% use prostatic acid phosphatase, 11% use monoclonal antibody scan, and 5% use abdominal or pelvic magnetic resonance imaging. Respondents evaluate men with an elevated or rising PSA within 1 year of radical prostatectomy similarly. To treat documented local recurrence, 81% of respondents recommend radiation therapy, 7% recommend orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonists, 6% recommend observation only, and 5% recommend combined androgen ablation. To treat documented distant recurrence, 50% recommend combined androgen ablation, 42% recommend orchiectomy or LHRH agonists, and 7% recommend observation only. To treat PSA-only recurrence, 54% recommend observation only, 16% recommend combined androgen ablation, 15% recommend orchiectomy or LHRH agonists, and 13% recommend radiation therapy. CONCLUSIONS: The evaluation of men whose radical prostatectomy failed varies among urologists and does not depend on time of recurrence. Radiation therapy is used by most urologists to treat local recurrence. Hormonal manipulation is used by more than 90% of urologists to treat distant recurrence. More than 50% of urologists recommend observation for men with biochemical-only recurrence.

Adult↗
PubMed1998

Echocardiography in thoracic trauma.

The availability of bedside ultrasonography can dramatically impact the care of patients with cardiac or aortic injuries. A focused, limited echocardiographic examination in the initial evaluation of victims with thoracic injuries can provide vital information the clinician needs to expedite the management of these patients. This article reviews the current use of transthoracic and transesophageal echocardiography in patients with thoracic trauma.

Cardiac Tamponade↗
PubMed1998

Phenotypic and biochemical consequences of collagen X mutations in mice and humans.

Skeletal biology has entered an exciting period with the technological advances in murine transgenesis and human genetics. This review focuses on how these two approaches are being used to address the role of collagen X, the major extracellular matrix component of the focal zone of endochondral ossification, the hypertrophic cartilage zone. The hypothesized role of this unique collagen in skeletal morphogenesis and the phenotypic and biochemical consequences resulting from the disruption of its function are discussed. Specifically, data from three murine models, including transgenic mice with a dominant interference phenotype for collagen X, and two sets of mice with an inactivated collagen X gene through gene targeting and homologous recombination, as well as the human disorder of Schmid metaphyseal chondrodysplasia resulting from mutations in collagen X, are summarized and compared. Several inconsistencies and unresolved issues regarding the murine and human phenotypes and the function of collagen X are discussed.

Animals↗
PubMed1998

Understanding pretest and posttest reactions to cognitive ability and personality tests.

To understand the nature of test reactions and their relationship to test performance, the relationships among belief in tests, pretest reactions, test performance, and posttest reactions were modeled for cognitive ability and personality tests. Results from structural equation models that were fitted to responses from 197 undergraduate examinees supported the hypothesized relationships. On the cognitive ability test, pretest reactions affected test performance and mediated the relationship between belief in tests and test performance. Test performance affected posttest reactions even after taking into account the effect of pretest reactions. On the personality test, belief in tests affected pretest and posttest reactions, but the three variables were unrelated to test performance (Conscientiousness scores). Conceptual, methodological, and practical implications of the findings are discussed in the context of research on test reactions and test performance.

Cognition↗
PubMed1998

ATM associates with and phosphorylates p53: mapping the region of interaction.

The human genetic disorder ataxia-telangiectasia (AT) is characterized by immunodeficiency, progressive cerebellar ataxia, radiosensitivity, cell cycle checkpoint defects and cancer predisposition. The gene mutated in this syndrome, ATM (for AT mutated), encodes a protein containing a phosphatidyl-inositol 3-kinase (PI-3 kinase)-like domain. ATM also contains a proline-rich region and a leucine zipper, both of which implicate this protein in signal transduction. The proline-rich region has been shown to bind to the SH3 domain of c-Abl, which facilitates its phosphorylation and activation by ATM. Previous results have demonstrated that AT cells are defective in the G1/S checkpoint activated after radiation damage and that this defect is attributable to a defective p53 signal transduction pathway. We report here direct interaction between ATM and p53 involving two regions in ATM, one at the amino terminus and the other at the carboxy terminus, corresponding to the PI-3 kinase domain. Recombinant ATM protein phosphorylates p53 on serine 15 near the N terminus. Furthermore, ectopic expression of ATM in AT cells restores normal ionizing radiation (IR)-induced phosphorylation of p53, whereas expression of ATM antisense RNA in control cells abrogates the rapid IR-induced phosphorylation of p53 on serine 15. These results demonstrate that ATM can bind p53 directly and is responsible for its serine 15 phosphorylation, thereby contributing to the activation and stabilization of p53 during the IR-induced DNA damage response.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1998

Minilaparotomy radical retropubic prostatectomy: technique and results.

PURPOSE: A small incision (minilaparotomy) radical retropubic prostatectomy is described and evaluated. A newly designed self-retaining retractor was used as a robot and functioned as a second operative assistant. MATERIALS AND METHODS: A total of 522 consecutive patients underwent minilaparotomy radical prostatectomy by a single surgeon (F. F. M.) between 1991 and 1997. The technique of minilaparotomy radical retropubic prostatectomy (a 7 to 8 cm. midline incision) is described in detail. RESULTS: A questionnaire was mailed to all 522 patients and there were 265 responses. Satisfactory continence was achieved in the short term in 85% of patients (0 to 1 pad). Of the patients 83% had a prostate specific antigen of less than 0.2 ng./ml. at average followup of 2.6 years. There was no operative mortality and the overall complication rates were similar to other patients treated by the same department staff with a larger incision. The typical patient was discharged home 3 days postoperatively. CONCLUSIONS: Minilaparotomy radical retropubic prostatectomy compares favorably with standard radical retropubic prostatectomy.

Equipment Design↗
PubMed1998

Cigarette smoking and age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (ARMD) is one of the leading causes of severe visual impairment among older Americans. Several hypotheses have been proposed regarding the pathogenesis of ARMD. The possible association of cigarette smoking and ARMD remains controversial. METHODS: Studies concerning the relationship between cigarette smoking and ARMD are identified through the use of Vision Articles Online and PubMed. Articles published since 1970 are reviewed. RESULTS: The literature reviewed strongly supports a link between smoking and ARMD. CONCLUSIONS: The identification of smoking as a risk factor can lead to early intervention. Such intervention may lessen visual loss from this disease, which has limited medical treatment options.

Fundus Oculi↗
PubMed1998

Bedside emergency department ultrasonography plus radiography of the kidneys, ureters, and bladder vs intravenous pyelography in the evaluation of suspected ureteral colic.

OBJECTIVE: To determine the role of bedside renal ultrasonography (US) and plain radiography of the kidneys, ureters, and bladder (KUB) as the initial investigative modality for those patients presenting to the ED with unilateral flank pain and hematuria. The hypothesis was that the renal US + KUB may obviate the need for emergent i.v. pyelography (i.v.P) in a majority of patients. METHODS: Prospective study over an 8-month period of all consecutive adult patients between the ages of 18 and 65 years presenting with unilateral flank pain and hematuria to the ED at LAC + USC Medical Center. Patients received KUB followed by a 500-mL bolus of normal saline. Bedside US was then performed by emergency physicians (EPs). Hydronephrosis of the kidney was graded as mild, moderate, or severe. All patients then underwent i.v.P. The results of the bedside US + KUB were then compared with those of i.v.P (the criterion standard). RESULTS: Of a total of 139 eligible patients, 108 were enrolled. The combination of US and KUB correctly identified pathology consistent with nephroureterolithiasis with a sensitivity of 97.1% (95% CI = 93.1-100%) when compared with i.v.P. The KUB + US results were falsely positive in 16 patients, resulting in a specificity of 58.9% (95% CI = 43.5-74.3%). The positive predictive value of the combined modality was 80.7%, the negative predictive value was 92.0%, and the overall accuracy was 83.3%. CONCLUSION: The bedside US + KUB has a high sensitivity and can be performed rapidly at the bedside by the EP when compared with i.v.P. This combined modality is an effective screening tool in the initial evaluation of ureteral colic.

Abdominal Pain↗
PubMed1998

Streptococcus iniae, a human and animal pathogen: specific identification by the chaperonin 60 gene identification method.

It was recently reported that Streptococcus iniae, a bacterial pathogen of aquatic animals, can cause serious disease in humans. Using the chaperonin 60 (Cpn60) gene identification method with reverse checkerboard hybridization and chemiluminescent detection, we identified correctly each of 12 S. iniae samples among 34 aerobic gram-positive isolates from animal and clinical human sources.

Animals↗
PubMed1998

The epidemiology of Parkinson's disease in an Australian population.

A prevalence study of Parkinson's disease (PD) was conducted in the rural town of Nambour, Australia. There were 5 cases of PD in a study population of 1207, yielding a crude prevalence ratio of 414 per 100,000 (95% confidence interval; 53-775). We performed a separate case-control study involving 224 patients with PD and 310 controls from South East Queensland and Central West New South Wales, to determine which factors increase the risk for PD in Australia. A positive family history of PD was the strongest risk factor for the development of the disease (odds ratio = 3.4; p < 0.001). In addition, rural residency was a significant risk factor for PD (odds ratio = 1.8, p < 0.001). Hypertension, stroke and well water ingestion were inversely correlated with the development of PD. There was no significant difference between patients and controls for exposure to herbicides and pesticides, head injury, smoking or depression. The high prevalence of PD in Nambour may be explained by rural residency. However, the most significant risk factor for PD was a positive family hisotry. This demonstrates the need for improved understanding of the genetic nature of the disease.

Age of Onset↗
PubMed1998

The prevalence and effect of alcohol and drug abuse on cohort-matched critically injured patients.

A prospective study was undertaken at a Level I trauma center to evaluate the prevalence of substance use among victims of major trauma, along with the impact on clinical outcome. Five hundred sixteen patients had urine toxicology and blood alcohol screens performed and correlated with pattern and severity of injury, hospital course, and outcome. Three hundred seventy-one patients (71%) screened positive for alcohol or drugs, or both. Fifty-two per cent had positive alcohol screens, and 42 per cent had positive drug screens (cocaine and opiates represented 91% of positive drug screens). Univariate analysis revealed patterns of alcohol/drug use varied among subgroups according to demographics (less use among patients older than 55 years, females and Asians; more drug use in blacks; more alcohol use in Hispanics), mechanism of injury (non-use in blunt trauma patients and use of both in penetrating trauma patients) and body region injured (non-use in head-injured patients). Septic complications and mortality were more correlative with severity of injury, but not with use or non-use of alcohol or drugs. We conclude that alcohol and drug use remains a major comorbid factor in major trauma, and that injury prevention efforts should include a strong focus on counseling regarding these lifestyle choices.

Adolescent↗
PubMed1998

Elecsys TSH, FT4, T4, T-uptake, FT3 and T3. Clinical results of a multicentre study.

6 assays for the assessment of thyroid function (TSH, FT4, T4, T-uptake, FT3 and T3) were targets of the International Multicenter Study on the random access analyzer Elecsys 2010. The aim of the study was to characterize the clinical performance of the assay in method comparison and reference range studies. The assays under evaluation were compared to a broad variety of radio isotopic and non-radio isotopic assays. They are suitable for serum and plasma samples. In case of TSH the study include 2nd and 3rd generation TSH procedures. In general, good to excellent correlations were found between the Elecsys and the respective routine methods. Systematic deviations were extraordinary low in case of TSH, FT4 and T4. Regarding the analysis of T3 and FT3 some systematic deviations in terms of standardization have been observed. Results of Elecsys T4 and Elecsys FT4 were independent of the serum total protein or serum albumin concentrations. In T3 and FT3 Elecsys the results of samples from NTI (non-thyroidal-illness) patients were decreased, reflecting the physiological situation in these patients. Studies using samples from healthy euthyroid as well as untreated hypo- and hyperthyroid individuals enabled us to assess the assays reference ranges.

Humans↗