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Biomedical subjects

T Chung

Publications and source records attributed to T Chung.

At least 37 records · Page 2Linked to original sources
PubMed2000

Expression of human choline kinase in NIH 3T3 fibroblasts increases the mitogenic potential of insulin and insulin-like growth factor I.

In mammalian cells, growth factors, oncogenes, and carcinogens stimulate phosphocholine (PCho) synthesis by choline kinase (CK), suggesting that PCho may regulate cell growth. To validate the role of PCho in mitogenesis, we determined the effects of insulin, insulin-like growth factor I (IGF-I), and other growth factors on DNA synthesis in NIH 3T3 fibroblast sublines highly expressing human choline kinase (CK) without increasing phosphatidylcholine synthesis. In serum-starved CK expressor cells, insulin and IGF-I stimulated DNA synthesis, p70 S6 kinase (p70 S6K) activity, phosphatidylinositol 3-kinase (PI3K) activity, and activating phosphorylation of p42/p44 mitogen-activated protein kinases (MAPK) to greater extents than in the corresponding vector control cells. Furthermore, the CK inhibitor hemicholinium-3 (HC-3) inhibited insulin- and IGF-I-induced DNA synthesis in the CK overexpressors, but not in the vector control cells. The results indicate that high cellular levels of PCho potentiate insulin- and IGF-I-induced DNA synthesis by MAPK- and p70 S6K-regulated mechanisms.

3T3 Cells↗
PubMed2000

Placental alkaline phosphatase, insulin, and adenine nucleotides or adenosine synergistically promote long-term survival of serum-starved mouse embryo and human fetus fibroblasts.

Earlier we showed that in serum-starved fibroblasts placental alkaline phosphatase (PALP) can exert growth factor-like effects. Here we report that in mouse embryo (NIH 3T3) and human fetus (HTB-157) fibroblasts, PALP (200 nM) alone provided full protection against serum starvation-induced cell death for 5 days. After 12 days, substantial effects of PALP on cell survival required the copresence of insulin (500 nM) and ATP or adenosine (100 microM). In serum-starved NIH 3T3 cells, PALP induced activating phosphorylation of p42/p44 mitogen-activated protein (MAP) kinases; insulin, but not ATP, had small additional effects. PALP also stimulated the expression of various cyclins; ATP both prolonged and enhanced PALP-induced expression of cyclins A and E. Finally, ATP/adenosine enhanced activation of Akt kinase by insulin. The results suggest that PALP may be a regulator of growth and remodeling of fetal tissues during the second and third trimester of pregnancy when it is expressed.

3T3 Cells↗
PubMed2000

Accuracy of MRI evaluation of pulmonary blood supply in patients with complex pulmonary stenosis or atresia.

Detailed imaging of pulmonary artery (PA) anatomy and significant aorto-pulmonary collaterals (APCs) is crucial for surgical planning and follow-up in patients with complex congenital heart disease (CHD) and pulmonary stenosis or atresia. Because examination by echocardiography is often technically limited and catheterization is invasive, this study evaluated the diagnostic accuracy of magnetic resonance imaging (MRI) as an alternate non-invasive tool. Thirteen patients (median age 28 years, range: 1-44 years) underwent both cardiac catheterization and MRI within a median of two months (range 0.1-8 months). Diagnoses included tetralogy of Fallot (TOF) with pulmonary atresia (n = 8), TOF with pulmonary stenosis (n = 2), single left ventricle with pulmonary stenosis (n = 2), and complex heterotaxy with pulmonary stenosis (n = 1). The MRI sequences used in this study were ECG-gated spin echo and gradient echo sequences acquired in multiple planes. Compared to catheterization, MRI had 100% sensitivity and specificity for the diagnosis of main PA (n = 6) and branch PA (n = 13) hypoplasia or stenosis, as well as discontinuous (n = 4) or absent (n = 10) branch PAs. There was complete agreement between catheterization and MRI identification of significant APCs (n = 18). Main PA atresia was noted by MRI in four patients but was not definitively seen by catheterization in any. MRI but not catheterization precisely defined the distance between discontinuous PAs and their relationship to other mediastinal structures. In conclusion, cardiac MRI is a reliable non-invasive imaging modality to define PA and APC anatomy in patients with complex pulmonary stenosis or atresia.

Adolescent↗
PubMed2000

Is osteitis pubis associated with the use of bone anchors in urinary continence operations?

We studied 130 patients who underwent either a vaginal needle suspension procedure or a pubofascial sling procedure with Mitek titanium bone anchors to determine the association of osteitis pubis with bone anchoring in these procedures. Fifteen patients complained of postoperative suprapubic pain; five cases were due to wound infections and another five were associated with tying the suspension sutures too tightly. We suggest the use of the term 'periostitis pubis' to describe the remaining five patients who suffered suprapubic pain. We found no radiological evidence of osteitis pubis in any patients.

Journal Article↗
PubMed2000

Screening adolescents for problem drinking: performance of brief screens against DSM-IV alcohol diagnoses.

OBJECTIVE: The performance of three brief screens, the CAGE, TWEAK and Alcohol Use Disorders Identification Test (AUDIT), was evaluated against a DSM-IV diagnosis of alcohol abuse or dependence in an adolescent sample. METHOD: Adolescents (13-19 years old) who presented to an emergency department for treatment of an injury, and who tested negative for blood alcohol concentration at time of admission, were administered a structured diagnostic interview and modified versions of the CAGE, TWEAK and AUDIT. RESULTS: Of the 415 adolescents for whom complete data were available, 18% met criteria for a DSM-IV alcohol use disorder according to the Diagnostic Interview Schedule for Children (version 2.3). Teens who reported alcohol use in the last year (n = 261, 58% male, 71% white) were included in analyses that compared the performance of the three screening instruments. Receiver Operating Characteristic analysis indicated that the AUDIT demonstrated the best performance across the range of its cut-scores, with optimal performance at a cut-score of 4. The TWEAK performed optimally at a cut-score of 2 and the CAGE at a cut-score of 1. CONCLUSIONS: Routine alcohol screening among adolescents seen in a hospital setting is indicated. Two important directions for future research include the identification of adolescent-specific alcohol screening items, and the validation of an adolescent-specific definition of problem drinking that addresses limitations of DSM-IV alcohol diagnoses when applied to adolescents.

Adolescent↗
PubMed1999

Ex vivo expansion and genetic marking of primitive human and baboon hematopoietic cells.

The achievement of positive outcomes in many clinical protocols involving hematopoietic stem cells (HSCs) has been handicapped by the limited numbers of marrow repopulating cells available to actually bring about therapy. This insufficiency has been especially problematic in stem cell transplantation and gene therapy. A number of studies have been initiated to attempt expansion of HSCs, mainly by manipulation of key cytokines in cell suspension cultures. Unfortunately, these expansion methods usually lead to altered properties in the amplified cells, mainly by reducing their self-renewal and multi-lineage differentiative potentials. Here we discuss our ongoing work, utilizing a unique endothelial cell line that supports primitive hematopoiesis, to attempt to generate expansion of primate HSCs that retain their elementary properties. Genetic marking of early hematopoietic cells to facilitate tracking will be mentioned as will the development and employment of assay systems designed to evaluate the long-term functional attributes of the expanded cells.

Animals↗
PubMed1999

In vitro evaluation of calphostin C as a novel agent for photodynamic therapy of bladder cancer.

OBJECTIVES: Calphostin C, a highly specific protein kinase C inhibitor, induces apoptosis in the presence of visible light. We report the photoactivatable cytotoxicity of calphostin C in a series of well-characterized human bladder cancer cell lines: RT4, UM-UC-3, and 5637. METHODS: The human bladder cancer cell lines RT4, UM-UC-3, and 5637 were chosen on the basis of their p53, pRb and 9p21 deletion status. Using standard tissue culture techniques, the cytotoxicity of 10 to 100 nM calphostin C in combination with increasing exposures of visible light was examined. Controls consisted of cells treated with calphostin C without visible light and cells exposed to visible light without calphostin C treatment. Cell viability was determined by MTT assay. The induction of apoptosis by activated calphostin C was determined by 4,6-diamidino-2-phenylindole (DAPI) staining/fluorescence microscopy of nuclei. RESULTS: In the absence of light, calphostin C did not demonstrate a cytotoxic effect on any of the cell lines tested. Increasing the duration of light exposure resulted in a concomitant decrease in cell viability. Significant cell death was seen with calphostin C concentrations as low as 10 nM. These studies also demonstrated that calphostin C induced apoptosis by a mechanism independent of p53 and pRb status and the presence or absence of 9p21 deletions. CONCLUSIONS: We demonstrated the ability of activated calphostin C to induce apoptosis in a light-dependent and concentration-dependent fashion in a bladder cancer model system. Activated calphostin C cytotoxicity is independent of tumor genetic background and the status of p53 and pRb. Further development of calphostin C as a photosensitizer for photodynamic therapy of superficial bladder cancer may be warranted.

Antibiotics, Antineoplastic↗
PubMed1999

Extracellular calcium stimulates DNA synthesis in synergism with zinc, insulin and insulin-like growth factor I in fibroblasts.

In serum-starved mouse NIH 3T3 fibroblasts cultured in 1.8 mM Ca2+-containing medium, addition of 0.75-2 mM extra Ca2+ stimulated DNA synthesis in synergism with zinc (15-60 microM), insulin and insulin-like growth factor I. Extra Ca2+ stimulated phosphorylation/activation of p42/p44 mitogen-activated protein kinases by an initially (10 min) zinc-independent mechanism; however, insulin, and particularly zinc, significantly prolonged Ca2+-induced mitogen-activated protein kinase phosphorylation. In addition, extra Ca2+ activated p70 S6 kinase by a zinc-dependent mechanism and enhanced the stimulatory effect of zinc on choline kinase activity. Insulin and insulin-like growth factor I also commonly increased both p70 S6 kinase and choline kinase activities. In support of the role of the choline kinase product phosphocholine in the mediation of mitogenic Ca2+ effects, cotreatments with the choline kinase substrate choline (250 microM) and the choline kinase inhibitor hemicholinium-3 (2 mM) enhanced and inhibited, respectively, the combined stimulatory effect of extra Ca2+ (3.8 mM total) and zinc on DNA synthesis. In various human skin fibroblast lines, 1-2 mM extra Ca2+ also stimulated DNA synthesis in synergism with zinc and insulin. The results show that in various fibroblast cultures, high concentrations of extracellular Ca2+ can collaborate with zinc and certain growth factors to stimulate DNA synthesis. Considering the high concentration of extracellular Ca2+ in the dermal layer, Ca2+ may promote fibroblast growth during wound healing in concert with zinc, insulin growth factor-I insulin, and perhaps other growth factors.

3T3 Cells↗
PubMed1999

The pubofascial anchor sling procedure for recurrent genuine urinary stress incontinence.

OBJECTIVE: To evaluate, in a preliminary study, the outcome of a modified pubovaginal sling operation with titanium bone anchors for recurrent genuine stress urinary incontinence (GSI) in women. PATIENTS AND METHODS: This prospective study included 13 consecutive women who underwent the modified sling procedure between September 1994 and August 1996. The subjective and objective cure of urinary stress incontinence, and the occurrence of postoperative osteitis pubis, were assessed. RESULTS: All 13 patients subjectively claimed complete urinary continence and 12 were objectively cured (12 patients agreed to undergo a repeat urodynamic study) during a median (range) follow-up of 26 (19-38) months. There were no cases of postoperative osteitis pubis, bladder injury or major complications. Mild suprapubic pain was a frequent and self-limiting complication. CONCLUSIONS: This innovative modified sling procedure is effective for recurrent urinary stress incontinence, with no complication of osteitis pubis. We suggest that this procedure should be considered as a treatment for recurrent GSI and perhaps for primary GSI. A study incorporating a longer follow-up and more patients has been planned.

Aged↗
PubMed1998

Evaluation of regional differences in right ventricular systolic function by acoustic quantification echocardiography and cine magnetic resonance imaging.

BACKGROUND: Accurate quantitative evaluation of right ventricular (RV) function has been limited by its complex structural geometry. Although embryological and anatomic observations suggest that the RV is composed of 2 distinct components, the RV sinus and infundibulum, most studies on RV dimensions and function viewed it as a single chamber. This study was designed to determine the volumes, relative contribution to global systolic function, and temporal course of contraction and relaxation of the RV sinus and infundibulum. METHODS AND RESULTS: Thirty-one individuals without heart disease (aged 1 month to 17 years, 16 boys and 15 girls) participated in this study. Instantaneous area over time, its derivatives, and the temporal course of contraction and relaxation were studied by acoustic quantification echocardiography and phonocardiography in 20 individuals. Global and regional RV volumes and ejection fraction were determined by cine MRI in 11 individuals. The RV sinus made up 81+/-6% of the combined RV end-diastolic volume and 87+/-4% of the combined stroke volume. The infundibulum accounted for the remaining 19+/-6% and 13+/-4%, respectively (P<0.0001). Compared with the infundibulum, the extent of RV sinus fiber shortening was significantly greater: for ejection fraction (56+/-11% versus 38+/-13%, P<0.001), fractional area change (42+/-14% versus 28+/-9%, P<0.0001), and dA/dt (27+/-17% versus 13+/-6%, P<0.0001). Analysis of temporal course of contraction and relaxation (expressed as percentage of the cardiac cycle to adjust for differences in heart rate) showed that the infundibulum follows the RV sinus: onset of contraction 53%+/-14 versus 19+/-11% of systole, time to peak systole 115+/-16% versus 97+/-19% (P< or =0.01), indicating a peristalsis-like pattern of contraction and relaxation. CONCLUSIONS: The results of this study demonstrate significant regional differences between the sinus and infundibulum components of the RV with regard to contribution to stroke volume, extent of fiber shortening, and sequence of mechanical activation. These data from normal individuals can be used in future research on RV function in pathological conditions.

Adolescent↗
PubMed1998

Stimulation of DNA synthesis in untransformed cells by the antiviral and antitumoral compound tricyclodecan-9-yl-xanthogenate (D609).

The antiviral and antitumor xanthate compound tricyclodecan-9-yl-xanthogenate (D609) is best known for its inhibitory effect on phosphatidylcholine-specific phospholipase C activity. Now we report that in NIH 3T3 cells, but not in several transformed cell types tested, D609 stimulated DNA synthesis when phosphocholine (PCho), insulin, or ATP was also present. Maximal co-mitogenic effects of D609 were observed at 5 microg/mL, a concentration 4-6 times lower than that required to inhibit phospholipase C activity. The synergistic mitogenic effects of D609 and PCho, but not of D609 and insulin, were associated with activation of p42 and, to a lesser extent, p44 mitogen-activated protein (MAP) kinases. The results raise the possibility that the mitogenic activity of D609 in untransformed cells may contribute to its antiviral and antitumor effects.

3T3 Cells↗
PubMed1998

Ossifying renal tumor of infancy presenting as a palpable abdominal mass.

We report a case of ossifying renal tumor of infancy, which presented as a palpable abdominal mass in an otherwise asymptomatic 10-month-old girl. The tumor was partially calcified and occupied the renal pelvis, causing severe hydronephrosis. The differential diagnosis for a patient this age included Wilms tumor, extra-adrenal neuroblastoma, infection, calculus, calcified hematoma and ossifying renal tumor of infancy. The child underwent heminephrectomy and is currently doing well.

Abdominal Neoplasms↗
PubMed1998

A population study of face and brow presentation.

This was a retrospective review of the experience of face and brow presentation deliveries in South Glamorgan between 1990 and 1996. The incidence of face and brow presentation was 1 in 994 and 1 in 755 deliveries respectively (no cases of cranial vault anomalies in this series). There was a higher incidence of prematurity and very low birthweight among infants delivered by face presentation and higher incidence of postmaturity among those delivered by brow when compared with the vertex population in the same period. Over half of malpresentations were diagnosed in the second stage. Most fetuses presenting by the brow were delivered by caesarean section and 56% of fetuses presenting by face presentation achieved a vaginal delivery. The reported incidence of these forms of deflexed cephalic attitudes has gradually changed over the last century especially over the past decade when the incidence of face is no longer more common than brow presentation.

Journal Article↗
PubMed1998

Techniques, coils, pulse sequences, and contrast enhancement in pediatric musculoskeletal MR imaging.

The first half of this article emphasizes the basic techniques involved in performing MR imaging of the pediatric musculoskeletal system. These include patient preparation, sedation issues, immobilization, coil selection, and pulse sequences. The second half of this article provides a detailed discussion of the use of Gadolinium and its enhancement characteristics in the normal developing musculoskeletal system, and its pathologic states are given.

Adolescent↗
PubMed1998

Activated calphostin C cytotoxicity is independent of p53 status and in vivo metastatic potential.

The development of novel therapeutic agents to modulate programmed cell death independent of genetic background or malignant potential is a primary goal of modern cancer therapy. In this report, the light activation- and concentration-dependent cytotoxicity of calphostin C, a photoactivatable perylenequinone, is carefully evaluated using a series of nine well-characterized human and rodent prostate cancer cell lines representing the spectrum of disease progression (e.g., variations in metastatic ability, ploidy, and tumor suppressor gene status). Treatment of these cancer cell lines with nanomolar concentrations of calphostin C in combination with increasing amounts of light exposure established a relationship between light and dose dependence of calphostin C cytotoxicity. The induction of apoptosis is rapid, as evidenced by the fact that immediately after treatment, cells exposed to calphostin C with light activation exhibit both morphological and biochemical changes consistent with apoptosis (cellular and nuclear shrinkage and chromatin condensation). For example, 78% of cells treated with 100 nM calphostin C in combination with 2 h of light activation underwent apoptosis within 24 h of treatment. DNA ladder formation could be detected within 12 h of treatment. In the absence of light activation, treatment with calphostin C at all concentrations tested had no acute or durable cytotoxic effects in any of the cell lines. Our findings demonstrate that calphostin C cytotoxicity is strictly light dependent. Furthermore, its efficacy is independent of the genetic background, p53 status, or in vivo malignant potential of a cell, making it a suitable candidate for the treatment of heterogeneous tumor cell populations.

Animals↗
PubMed1997

Ethanolamine, but not phosphoethanolamine, potentiates the effects of insulin, phosphocholine, and ATP on DNA synthesis in NIH 3T3 cells--role of mitogen-activated protein-kinase-dependent and protein-kinase-independent mechanisms.

NIH 3T3 fibroblasts express a phospholipase D activity hydrolyzing phosphatidylethanolamine (PtdEtn) which produces ethanolamine (Etn) in response to a variety of growth regulating agents. The main objective of this work was to evaluate the effects of Etn on mitogenesis and to determine whether these effects require its metabolism to phosphoethanolamine (PEtn) or PtdEtn. To increase conversion of Etn to PEtn, an Etn-specific kinase derived from Drosophila was highly expressed in NIH 3T3 cells. Overexpression of this Etn kinase resulted in large (10-12.5-fold) increases in PEtn formation, but only in modest (1.2-1.7-fold) increases in PtdEtn synthesis. In both vector control and Etn kinase overexpressor cells, Etn had biphasic effects on insulin-induced DNA synthesis with maximal (approximately 2-fold) potentiating effects being observed at 0.5-1 mM concentrations, followed by an inhibitory phase at higher Etn concentrations. In the Etn kinase overexpressor lines, the inhibitory phase was elicited by lower Etn concentrations and it was partially blocked by 5 mM choline due to decreased formation of PEtn. In both vector control and Etn kinase overexpressor cells, phosphocholine (PCho) and insulin synergistically stimulated DNA synthesis; their effects were further enhanced by physiologically relevant (5-60 microM) concentrations of Etn by a mechanism independent of mitogen-activated protein (MAP) kinase. Concentrations of Etn >50 microM also enhanced the effects of both PCho and the synergistic effects of PCho plus ATP; however, in the latter case 20 microM Etn was inhibitory. The magnitude of both the potentiating and inhibitory effects of Etn on PCho-induced as well as PCho + ATP-induced DNA synthesis were similar in the vector control and Etn kinase overexpressor cells; they were associated with stimulation and inhibition, respectively, of p42 MAP kinase activity. The results indicate that in NIH 3T3 cells Etn exerts significant effects on DNA synthesis which, except inhibition of insulin-induced DNA synthesis by higher concentrations of Etn, do not correlate with the metabolism of Etn to PEtn or PtdEtn.

3T3 Cells↗
PubMed1997

A familial predisposition toward lumbar disc injury.

STUDY DESIGN: A retrospective case-control study was performed. OBJECTIVES: To test the hypothesis that there is a familial predisposition to lumbar disc pain and injury. SUMMARY OF BACKGROUND DATA: The few studies that have addressed this question have suggested that a familial predisposition is present, but the techniques used for identifying discogenic pain and accounting for potentially confounding extrinsic factors make it difficult to formulate a clear conclusion. METHODS: Immediate relatives of index patients who had surgically proven lumbar disc herniations (disc/case subjects) or repetitive upper extremity overuse syndromes (upper extremity/control subjects) were given a questionnaire that had been tested previously and found to reliably identify discogenic lower back pain. The prevalence of lumbar disc pain and injury was determined in the two groups of patients; logistic regression was used to control for demographic factors and activities known to increase risk for lumbar disc injury. RESULTS: The questionnaire was returned by 60 (59%) of 102 disc subjects and 41 (50%) of 81 upper extremity subjects. Sixteen (28%) disc subjects and one (2%) of the upper extremity subjects met questionnaire criteria for discogenic lumbar pain; seven (12%) disc subjects and no upper extremity subjects had received surgical therapy for lumbar disc pain. Logistic regression analysis identified familial grouping and a history of lifting as the only variables associated with a positive response on the questionnaire. Information obtained from index patients about their nonresponding relatives' history of significant back pain suggested similar findings. CONCLUSIONS: There is a familial predisposition toward lumbar disc pain and injury. This information may be helpful in occupational counseling or for targeting specific populations with preventative, interventional strategies.

Adult↗