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Biomedical subjects

A Chung

Publications and source records attributed to A Chung.

At least 37 records · Page 2Linked to original sources
PubMed1998

The greatest dimension of prostate carcinoma is a simple, inexpensive predictor of prostate specific antigen failure in radical prostatectomy specimens.

BACKGROUND: Tumor volume in radical prostatectomies can be determined by several different techniques and appears to predict clinical progression. Greatest tumor dimension and area are easily obtained measures that are both correlated with tumor volume. The authors sought to determine whether greatest tumor dimension and/or area were predictors of prostate specific antigen (PSA) failure in men who underwent radical prostatectomy for adenocarcinoma of the prostate. METHODS: Fifty-seven men with prostate carcinoma who underwent surgical resection were followed for a median of 27.2 months (range, 1-112 months); 24 (42%) of these men had PSA failure. Preoperative PSA, Gleason grade, pathologic stage, margin status, and greatest tumor dimension and area were determined, and both univariate and multivariate analyses of the outcomes of PSA failure were performed. RESULTS: In the univariate analysis, larger values of greatest tumor dimension and area were strongly associated with increased incidence of PSA failure (P = 0.0001 and 0.0011, respectively). The forward stepwise multivariate analysis indicated that greatest tumor dimension had marginal statistical significance as a risk factor for PSA failure (P = 0.0577; risk ratio, 1.117). However, in this series, men with a greatest tumor dimension of less than 1 cm did not experience failure, whereas all patients with a greatest tumor dimension of more than 2 cm did. CONCLUSIONS: Measuring greatest tumor dimension is a simple, inexpensive predictor of PSA failure in men who have undergone radical prostatectomy.

Adenocarcinoma↗
PubMed1998

Differential rescue of visceral and cardiac defects in Drosophila by vertebrate tinman-related genes.

tinman, a mesodermal NK2-type homeobox gene, is absolutely required for the subdivision of the early Drosophila mesoderm and for the formation of the heart as well as the visceral muscle primordia. Several vertebrate relatives of tinman, many of which are predominately expressed in the very early cardiac progenitors (and pharyngeal endoderm), also seem to promote heart development. Here, we show that most of these vertebrate tinman-related genes can readily substitute for Drosophila tinman function in promoting visceral mesoderm-specific marker gene expression, but much less in promoting cardiac-specific gene expression indicative of heart development. In addition, another mesodermal NK2-type gene from Drosophila, bagpipe, which is normally only needed for visceral mesoderm but not heart development, cannot substitute for tinman at all. These data indicate that the functional equivalence of the tinman-related subclass of NK2-type genes (in activating markers of visceral mesoderm development in Drosophila) is specific to this subclass and distinct from other homeobox genes. Despite the apparent overall conservation of heart development between vertebrates and invertebrates, the differential rescue of visceral mesoderm versus heart development suggests that some of the molecular mechanisms of organ formation may have diverged during evolution.

Animals↗
PubMed1998

Assessment of outcome prediction models for patients with localized prostate carcinoma managed with radical prostatectomy or external beam radiation therapy.

BACKGROUND: A clinical staging system for localized prostate carcinoma that provides reliable information on which management decisions regarding an individual patient can be based is lacking. This study compared the abilities of all published proposed clinical staging systems to predict time to prostate specific antigen (PSA) failure after radical prostatectomy or external beam radiation therapy for clinically localized prostate carcinoma. METHODS: A total of 1441 clinically localized prostate carcinoma patients who were managed with radical prostatectomy at the University of Pennsylvania in Philadelphia (n = 688) or the Brigham and Women's Hospital in Boston (n = 288) or with external beam radiation therapy at the Joint Center for Radiation Therapy in Boston (n = 465) were entered into this study. Patients who received adjuvant or neoadjuvant hormonal or radiation therapy were excluded. Akaike's Information Criterion (AIC) and Schwartz Bayesian Criterion (SBC) estimates, which are comparative measures, were calculated for each clinical staging system. Pairwise comparisons of the AIC and SBC estimates for the most predictive clinical staging systems were performed using a formal bootstrap technique with 2000 replications. RESULTS: Both the staging system based on the risk score and the staging system based on the calculated volume of prostate carcinoma and PSA (cVCa-PSA) optimized the prediction of time to posttreatment PSA failure. The cVCa-PSA system, however, provided a more clinically useful stratification of outcome. CONCLUSIONS: Improved clinical staging for patients with localized prostate carcinoma may be possible with parameters obtained during routine evaluation. Validation by other investigators is underway.

Aged↗
PubMed1998

The feasibility of a syringe-needle-exchange program in Vietnam.

Since the beginning of the HIV/AIDS epidemic, syringe-exchange programs have been established in a number of developed countries and have proven effective in reducing the transmission of HIV. Very few similar programs have been established in developing countries. This study reports on the feasibility of establishing a syringe-exchange program in Vietnam. Process data collected since the beginning of the program indicate the feasibility of establishing such a program as well as highlight a number of important issues. These issues are: 1) Acceptability of the program in the community which has been achieved through workshops with key community people including the local police; 2) training and recruitment of ex-user outreach workers; 3) the distribution of clean syringes and needles through outreach services rather than at established exchange sites; 4) the establishment of appropriate methods for the collection of used injection equipment. Further research is needed to examine the efficacy of the program in reducing risks and acceptability of the program in the larger society.

Adult↗
PubMed1998

Juvenile dermatomyositis at diagnosis: clinical characteristics of 79 children.

OBJECTIVE: To evaluate demographic and clinical characteristics, duration of time between disease onset (date of first rash and/or weakness), and diagnosis/therapy, as well as socioeconomic status, of children with newly diagnosed juvenile dermatomyositis (JDM). METHODS: Structured telephone interview of families of a cohort of 79 children with JDM: interval between onset of symptoms to diagnosis, median of 3 months (range 0.5-20.0). RESULTS: At diagnosis, all the children had rash (100%) and proximal muscle weakness (100%); 58 (73%) had muscle pain; 51 (65%) fever; 35 (44%) dysphagia; 34 (43%) hoarseness; 29 (37%) abdominal pain; 28 (35%) arthritis; 18 (23%) calcinosis, and 10 (13%) melena. Muscle derived enzymes were normal in 10% of the children. Of the 43 children who had an electromyogram (EMG), 8 (19%) had normal results. Fifty-one children had a muscle biopsy; the results were normal/nondiagnostic in 10 (20%). Median time from disease onset to diagnosis was different between racial groups: Caucasians (n=59) 2.0 months: for minorities (n=20), 6.5 months, (p=0.0008). The median time from disease onset to therapy was: Caucasians. 3.0 months; minorities, 7.2 months (p=0.002). Report of calcinosis was associated with increased time to diagnosis and therapy (p=0.04). In the 33 children whose first symptom occurred in June-September, rash preceded or accompanied onset of muscle weakness in 83% (n=27). Ninety-one percent of the children were given steroid therapy and 9% received methotrexate as well. CONCLUSION: The results of an undirected site for muscle biopsy or EMG may not be diagnostic. Minority children had a longer interval between first JDM symptom and diagnosis/therapy than Caucasian children. Delay in diagnosis/therapy was associated with calcinosis.

Adolescent↗
PubMed1998

Assessment of outcome prediction models for localized prostate cancer in patients managed with external beam radiation therapy.

A comparison of the ability of all published proposed clinical staging systems to predict time to prostate-specific antigen (PSA) failure after external beam radiation therapy for clinically localized prostate cancer was performed using an independent radiation database. Cox regression multivariable analyses were used to assess the significance of the proposed staging systems to predict time to post-radiation PSA failure in 465 radiation managed patients. Significant staging systems identified using Cox regression were further tested using established comparative estimates to define the most predictive system. Both the Risk Score staging system and the staging system based on the calculated volume of prostate cancer (cV(Ca)) and PSA optimized the prediction of time to post-treatment PSA failure. The cV(Ca)-PSA system, however, provided a more clinically useful stratification of outcome. Many clinical staging systems for prostate cancer have been proposed. A single clinical staging system for patients with localized prostate cancer based on parameters obtained during the routine workup provided a statistically and clinically significant stratification of outcome after external beam radiation therapy.

Humans↗
PubMed1997

New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis.

OBJECTIVE: To determine, in a case-control study, if patients with new-onset juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset, exposure to certain environmental conditions, frequency of familial autoimmune diseases, or antibody titers, compared with 2 control groups. METHODS: A structured interview with the families of 80 children with juvenile DM, 40 children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from the same geographic area as the children with juvenile DM, was conducted. All children's sera were tested for antibody to Toxoplasma gondii, herpes simplex virus (HSV), or coxsackievirus B (CVB). RESULTS: A high proportion of children with juvenile DM had constitutional symptoms 3 months before the disease-onset date (P = 0.013 versus control children). Children with JRA had more relatives with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did children with juvenile DM or healthy children. Among children < or =7 years of age, elevated enteroviral titers were more frequent in those with juvenile DM (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a common environmental exposure. Titers to T gondii, HSV, or CVB 1-6 were normal. CONCLUSION: Frequencies of familial autoimmune disease, exposure to environmental factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months before the disease-onset date, and young patients have elevated enteroviral titers, as do young geographic controls.

Animals↗
PubMed1997

Interferon-alpha associated arthritis.

We describe a patient who developed progressive inflammatory polyarthritis after treatment with interferon-alpha (IFN-alpha) for chronic hepatitis C infection. Rechallenge with the drug caused worsening of the arthritis, but withdrawal did not result in remission. Preexisting autoantibodies and HLA-DR4 were detected in this serum and are thought to be relevant in the etiology of IFN-alpha associated autoimmune disease.

Adult↗
PubMed1996

Noninvasive arterial occlusion using MRI-guided focused ultrasound.

The purpose of this work was to test the hypothesis that reproducible and sustainable arterial occlusion can be induced by focused ultrasound energy deposition noninvasively within deep tissue. An MRI-compatible focused ultrasound transducer was used to sonicate a branch of the renal artery (diameter about 0.6 mm) in vivo (nine rabbits). An intravenous MRI contrast agent bolus was injected about 30 min and up to 7 days after the sonication. After follow-up, in vitro magnification x-ray angiograms were obtained and the kidneys were fixed in formaldehyde for histologic study. The ultrasound pulses resulted in complete cessation of blood flow, as shown by the gradient echo images. In seven of the nine rabbits, a wedge-shaped unenhanced area was seen at the part of the kidney that was perfused by the vessel after the contrast agent injection. This area extended laterally (outside of the sonicated volume) to the cortical surface of the kidney. The x-ray angiograms showed that the artery was completely occluded. Postmortem histologic evaluation showed an infarcted tissue volume corresponding to the wedge shape seen in the images. This study showed that appropriately focused ultrasound can be used to close arteries noninvasively. This finding has significant clinical potential.

Angiography↗
PubMed1996

Host cell invasion by trypanosomes requires lysosomes and microtubule/kinesin-mediated transport.

Invasion of mammalian cells by the protozoan parasite Trypanosoma cruzi occurs by an actin-independent mechanism distinct from phagocytosis. Clusters of host lysosomes are observed at the site of parasite attachment, and lysosomal markers are detected in the vacuolar membrane at early stages of the entry process. These observations led to the hypothesis that the trypanosomes recruit host lysosomes to their attachment site, and that lysosomal fusion serves as a source of membrane to form the parasitophorous vacuole. Here we directly demonstrate directional migration of lysosomes to the parasite entry site, using time-lapse video-enhanced microscopy of L6E9 myoblasts exposed to T. cruzi trypomastigotes. BSA-gold-loaded lysosomes moved towards the cell periphery, in the direction of the parasite attachment site, but only when their original position was less than 11-12 microns from the invasion site. Lysosomes more distant from the invasion area exhibited only the short multi-directional saltatory movements previously described for lysosomes, regardless of their proximity to the cell margins. Specific depletion of peripheral lysosomes was obtained by microinjection of NRK cells with antibodies against the cytoplasmic domain of lgp 120, a treatment that aggregated lysosomes in the perinuclear area and inhibited T. cruzi entry. The microtubule-binding drugs nocodazole, colchicine, vinblastine, and taxol also inhibited invasion, in both NRK and L6E9 cells. Furthermore, microinjection of antibodies to the heavy chain of kinesin blocked the acidification-induced, microtubule-dependent redistribution of lysosomes to the host cell periphery, and reduced trypomastigote entry. Our results therefore demonstrate that during T. cruzi invasion of host cells lysosomes are mobilized from the immediately surrounding area, and that availability of lysosomes at the cell periphery and microtubule/kinesin-mediated transport are requirements for parasite entry.

Amino Acid Sequence↗
PubMed1996

Treatment retention in women's residential chemical dependency treatment: the effect of admission with children.

In the United States there has been an increased interest in the development of treatment programs that admit chemically dependent women with their children. The Salvation Army Family Treatment Services in Honolulu, Hawaii has had a long history of admitting women both with and without their children to long-term residential treatment. This has provided an opportunity to study the differences in treatment retention between these two groups. Subjects were 130 females who participated in treatment between 1988 and 1993. Analyses were conducted to determine whether there were different outcomes for women with children in treatment and women without children in treatment, with regard to type of discharge and length of time in treatment. Results were significant and clearly indicated better retention rates for women who participated in treatment with their children.

Adolescent↗
PubMed1994

Surface-modified nanocrystalline ceramics for drug delivery applications.

Drug delivery systems comprised of various types of carriers have long been the object of pharmacological investigation. The search has been stimulated by the belief that carriers will lead to reduced drug toxicity, dosage requirements, enhanced cellular targeting and improved shelf-life. Among the carriers investigated are complex polymeric carbohydrates, synthetic proteins and liposomal structures. For the past four years, we have been experimenting with a radically new class of carriers comprised of surface-modified nanocrystalline ceramics. While the ceramics provide the structural stability of a largely immutable solid, the surface modification creates a glassy molecular stabilization film to which pharmacological agents may be bound non-covalently from an aqueous phase with minimal structural denaturation. As a consequence of maintained structural integrity and owing to concentration effects afforded by the surfaces of the nanocrystalline materials, drug activity following surface immobilization is preserved. We have used successfully surface-modified nanocrystalline ceramics to deliver viral antigens for the purpose of evoking an immune response, oxygenated haemoglobin for cell respiration and insulin for carbohydrate metabolism. The theoretical principles, technical details and experimental results are reviewed. Surface-modified nanocrystalline materials offer an exciting new approach to the well-recognized challenges of drug delivery.

Animals↗
PubMed1994

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): alternatively spliced, functionally distinct isoforms expressed during mammalian cardiovascular development.

The establishment of the cardiovascular system represents an early, critical event essential for normal embryonic development. An important component of vascular ontogeny is the differentiation and development of the endothelial and endocardial cell populations. This involves, at least in part, the expression and function of specific cell surface receptors required to mediate cell-cell and cell-matrix adhesion. Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) may well serve such a function. It is a member of the immunoglobulin superfamily expressed by the entire vascular endothelium in the adult. It is capable of mediating adhesion by a heterophilic mechanism requiring glycosaminoglycans, as well as by a homophilic, glycosaminoglycan independent, mechanism. It has been shown to regulate the expression of other adhesion molecules on naive T cells. This report documents by RT-PCR and immunohistochemical analysis the expression of PECAM-1 during early post implantation mouse embryo development. PECAM-1 was expressed by early endothelial precursors first within the yolk sac and subsequently within the embryo itself. Interestingly, embryonic PECAM-1 was expressed as multiple isoforms in which one or more clusters of polypeptides were missing from the cytoplasmic domain. The sequence and location of the deleted polypeptides corresponded to exons found in the human PECAM-1 gene. The alternatively spliced isoforms were capable of mediating cell-cell adhesion when transfected into L-cells. The isoforms differed, however, in their sensitivity to a panel of anti-PECAM-1 monoclonal antibodies. These data suggest that changes in the cytoplasmic domain of PECAM-1 may affect its function during cardiovascular development, and are consistent with our earlier report that systematic truncation of the cytoplasmic domain of human PECAM-1 resulted in changes in its ligand specificity, divalent cation and glycosaminoglycan dependence, as well as its susceptibility to adhesion blocking monoclonal antibodies. This is the first report of naturally occurring alternatively spliced forms of PECAM-1 having possible functional implications.

Amino Acid Sequence↗
PubMed1993

Membrane attachment sites for the membrane cytoskeletal protein 4.1 of the red blood cell.

The identity of the membrane binding sites for the membrane cytoskeletal protein 4.1 of the human red blood cell has been investigated. Exhaustive proteolysis of the membrane with a range of proteases led to the elimination of only some 60% of all binding sites. The predominant integral membrane protein, band 3, as well as glycophorin A, was totally digested at levels of proteolysis that were essentially without effect on the number of 4.1 binding sites. Proteolysis caused scission of the polypeptide chain of glycophorin C (together with the minor product, glycophorin D, of the same gene), but left a fragment from the region of the C-terminus still attached to the membrane. We have found a low-molecular weight protein, possessing an epitope (recognized by an antibody directed against the cytoplasmic domain of glycophorin C) in common with this proteolytic fragment, in cells of a Leach phenotype, which are characterized by lack of extracellular epitopes of glycophorin C. When these membranes were extracted at low ionic strength to dissociate the membrane cytoskeleton, approximately half the content of 4.1 was liberated, compared with only some 25% from normal membranes. Cells of a different variant of the Leach phenotype, which are totally devoid of glycophorin C, lost close to 70% of their 4.1 under these circumstances. The Rh(D) transmembrane protein, which interacts with the membrane cytoskeleton, is also resistant to proteolysis of the cytoplasmic membrane surface, but Rhnull cells, devoid of this protein, showed no decreased retention of 4.1. The results suggest that glycophorin C (with D) may contain two types of binding site for 4.1, which would be sufficient in number to account for all the strong binding of 4.1 on normal membranes; modulation of binding at one of the sites by another protein or by lipid is not excluded. A possible site for reinitiation of translation overlapping the premature stop codon in the mutant expressing the truncated glycophorin C can be discerned.

Binding Sites↗
PubMed1993

Severe hemophilia A in a female by cryptic translocation: order and orientation of factor VIII within Xq28.

We report studies of a female with severe hemophilia A resulting from a complex de novo translocation of chromosomes X and 17 (46,X,t(X;17)). Somatic cell hybrids containing the normal X, the der(X), or the der(17) were analyzed for coagulation factor VIII (F8C) sequences using Southern blots and polymerase chain reaction. The normal X, always late replicating, contains a normal F8C gene, whereas the der(X) has no F8C sequences. The der(17) chromosome containing Xq24-Xq28 carries a functional G6PD locus and a deleted F8C allele that lacks exons 1-15. Also, it lacks the DXYS64-X locus, situated between the F8C locus and the Xq telomere. These results indicate that a cryptic breakpoint within Xq28 deleted the 5' end of F8C, but left the more proximal G6PD locus intact on the der(17) chromosome. As the deleted segment includes the 5' half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5' region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD-3'F8C-5'F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the proband, revealing a more complex rearrangement (three chromosomes involved) than that expected from cytogenetic analysis, chromosome painting, and Southern blots. A 900-kb segment within Xq28 has been translocated to another autosome. Hemophilia A in this heterozygous female is due to the decapitation of the F8C gene on the der(17) and inactivation of the intact allele on the normal X.

Child↗