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Biomedical subjects

P Chang

Publications and source records attributed to P Chang.

At least 127 records · Page 7Linked to original sources
PubMed1998

Serendipity in diagnostic imaging: magnetic resonance imaging of the breast.

BACKGROUND: Magnetic resonance imaging (MRI) of the breast has been proposed as a noninvasive diagnostic test for evaluation of suspicious ("index") lesions noted on mammography and/or clinical breast examination (CBE). However, women may have incidental ("serendipitous") lesions detected by MRI that are not found on mammography or CBE. To understand better whether or not biopsy procedures should be performed to evaluate serendipitous lesions, we estimated the breast cancer risk for women with this type of lesion. METHODS: A decision analysis model was used to estimate the positive predictive value (i.e., the chance that a woman with a serendipitous lesion has cancer) of MRI for serendipitous lesions in women who had an abnormal mammogram and/or CBE suspicious for cancer (where a biopsy procedure is recommended). We restricted the analysis to data from women whose index lesions were noncancerous and used meta-analysis of published medical literature to determine the likelihood ratios (measures of how test results change the probability of having cancer) for MRI and the combination of CBE and mammography. The positive predictive value of MRI was calculated using the U.S. population prevalence of cancer (derived from registry data) and the likelihood ratios of the diagnostic tests. RESULTS: Under a wide variety of assumptions, the positive predictive value of MRI was extremely low for serendipitous lesions. For instance, assuming sensitivity and specificity values for MRI of 95.6% and 68.6%, respectively, approximately four of 1000 55- to 59-year-old women with serendipitous lesions would be expected to have cancer (positive predictive value = 0.44%, 95% confidence interval = 0.24%-0.67%). CONCLUSION: In women with a suspicious lesion discovered by mammography and/or CBE that is found to be benign, serendipitous breast lesions detected by MRI are extremely unlikely to represent invasive breast cancer. Immediate biopsy of such serendipitous lesions may, therefore, not be required.

Adult↗
PubMed1998

Epidermal growth factor receptor-mediated motility in fibroblasts.

Cell motility is induced by many growth factors acting through cognate receptors with intrinsic tyrosine kinase activity (RPTK). However, most of the links between receptor activation and the biophysical processes of cell motility remain undeciphered. We have focused on the mechanisms by which the EGF receptor (EGFR) actuates fibroblast cell motility in an attempt to define this integrated process in one system. Our working model is that divergent, but interconnected pathways lead to the biophysical processes necessary for cell motility: cytoskeleton reorganization, membrane extension, formation of new adhesions to substratum, cell contraction, and release of adhesions at the rear. We postulate that for any given growth factor some of the pathways/processes will be actively signaled and rate-limiting, while others will be permissive due to background low-level activation. Certain couplings have been defined, such as PLCgamma and actin modifying proteins being involved in cytoskeletal reorganization and lamellipod extension and MEK being implicated in detachment from substratum. Others are suggested by complementary investigations in integrin-mediated motility, including rac in membrane protrusion, rho in new adhesions, myosin II motors in contraction, and calpain in detachment, but have yet to be placed in growth factor-induced motility. Our model postulates that many biochemical pathways will be shared between chemokinetic and haptokinetic motility but that select pathways will be activated only during RPTK-enhanced motility.

Actins↗
PubMed1998

Expansion of Philadelphia chromosome-negative CD3(+)CD56(+) cytotoxic cells from chronic myeloid leukemia patients: in vitro and in vivo efficacy in severe combined immunodeficiency disease mice.

We have developed culture conditions for the efficient expansion of cytotoxic effector cells from peripheral blood mononuclear cells (PBMNCs) by the timed addition of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and the monoclonal antibody (MoAb) OKT3. These cells, termed cytokine-induced killer (CIK) cells, are composed primarily of T cells, and the population of cells with the greatest cytotoxic activity is an otherwise rare population of CD3(+)CD56(+) cells that expand dramatically under these culture conditions. CIK cells were expanded from PBMNCs from 13 patients with chronic myeloid leukemia (CML). These cultures contained a variable number of T cells at the start of the culture (median 44%, range 1% to 64%), yet after 21 to 28 days of culture, virtually all of the cells were CD3(+) T cells (median 97%, range 90% to 99%). The CD3(+)CD56(+) subset of cells expanded significantly (median 25-fold, range 2.2- to 525-fold). CIK cells from all patients showed cytotoxicity against the tumor cell lines OCI-LY8 and K562. In four patients the expanded CIK cells suppressed colony growth of autologous CML blast cells and myeloid progenitor cells. Allogeneic CIK cells from normal donors also suppressed CML colony growth but did not inhibit growth of normal hematopoietic colonies. Twelve of the 13 cultures were exclusively composed of Philadelphia (Ph)-negative cells and one culture had 1 out of 20 Ph-positive metaphases after 4 weeks in culture. Intracellular cytokine production was assayed by fluorescence-activated cell sorter (FACS), and the expanded T-cell cultures produced IL-2, IFN-gamma, and tumor necrosis factor-alpha (TNF-alpha), but not IL-4. Both the CD4(+) and CD8(+) subsets secreted this cytokine profile. To test the in vivo activity of the expanded CIK cells, CML was engrafted into severe combined immunodeficiency disease (SCID) mice using matrigel. After 4 weeks, 4 x 10(7) autologous CIK cells were injected intravenously by tail vein injection into groups of mice, and the animals were sacrificed after a total of 18 weeks. Bcr-abl was detected in the bone marrow or spleen of 5 out of 6 control mice and only 2 out of 13 mice who received the autologous CIK cells (P = .02). In an additional series of animals, the mice did not engraft with CML but instead developed large human Epstein-Barr virus-associated lymphomas by 12 weeks. The mice who received autologous CIK cells at 4 weeks had either no tumor (5) or small tumors (5), whereas all 10 mice that received CIK cells at week 8 developed lymphomas; however, these were not as large as in the 10 control mice who did not receive CIK cells (P = . 03). This study shows that CIK cells, which are Ph chromosome-negative, can be expanded from patients with CML and have potent in vitro and in vivo efficacy against autologous tumor cells.

Animals↗
PubMed1998

Hormone-dependent regulation of GABAA receptor gamma subunit mRNAs in sexually dimorphic regions of the rat brain.

Transmission mediated by gamma-aminobutyric acid type A (GABAA) receptors expressed within the medial preoptic area (mPOA) and the ventromedial nucleus (VMN) of the hypothalamus is known to play critical, but contrasting, roles in regulating steroid-dependent sexual behaviours in rats. Previous studies have demonstrated a striking dichotomy in receptor composition between the two regions with regard to gamma, but not alpha or beta, subunit expression. To test if gonadal steroids regulate the expression of the gamma subunit genes within the mPOA and the VMN, in situ hybridization analysis for messenger RNAs encoding the gamma 1, gamma 2Short (gamma 2S) and gamma 2Long (gamma 2L) subunits was done in gonadectomized male and female rats and in gonadally intact females over the oestrous cycle. No significant differences in the expression of the gamma subunit mRNAs were observed in gonadectomized male versus female rats. Significant effects of gonadal state in female rats were observed for gamma 1 mRNA levels in the mPOA and gamma 2L levels in the VMN. These data demonstrate that gonadal hormones exert activational control of expression of GABAA receptor gamma subunit mRNAs and suggest that differences in receptor structure may contribute to the functional modulation of female sexual behaviours mediated by GABAergic transmission in these regions.

Animals↗
PubMed1998

Comparison of plasma prothrombin and factor VII and urine prothrombin F1 concentrations in patients on long-term warfarin therapy and those in the initial phase.

Control of warfarin anticoagulation during the initial phase of therapy is difficult and empirically based. Plasma and urine samples were obtained from normal controls, patients under stable anticoagulation, and patients in the initial phase of anticoagulation. Total plasma prothrombin, des-carboxy (non-adsorbable with barium chloride) prothrombin, and native (total minus non-adsorbable) prothrombin were quantitated using Echis carinatus venom activation. Functional plasma factor VII (VII) was measured using a one-stage clotting assay. Total and des-carboxy urine prothrombin F1 (F1) were measured by ELISA. All urine F1 in normals and both anticoagulated groups was adsorbed by barium chloride. Plasma des-carboxy prothrombin concentration was similar for the two anticoagulated groups and did not correlate with 1/INR. Native prothrombin correlated with 1/INR in both the stable (r = 0.76) and initial phase (r = 0.74) groups. For any given INR, the subjects on stable anticoagulation had lower native prothrombin concentrations than the initial phase patients. Functional factor VII concentration also correlated significantly with 1/INR in both the stable (r = 0.64) and initial phase (r = 0.76) patients. Unlike native prothrombin, VII concentrations did not vary between the two cohorts for any given INR. Previous studies indicate that native prothrombin is a superior predictor of both hemorrhagic and thromboembolic complications during warfarin therapy. Our findings indicate that VII, and not prothrombin, may be the predominant factor monitored by the INR. This further supports the need to reevaluate the usefulness of the INR in the monitoring of warfarin therapy during the initial phase.

Anticoagulants↗
PubMed1998

Deletion of P15 (MTS2) in head and neck squamous cell carcinomas.

INTRODUCTION: The purpose of this study was to determine whether the multiple tumor suppressor 2 (MTS2) gene, encoding an inhibitor (p15) of cyclin D-dependent kinases 4 and 6 (cdk4, cdk6), is deleted in head and neck squamous cell carcinomas (HNSCC). There is a high frequency of LOH for the 9p21-p22 region in HNSCCs, as well as in gliomas, leukemias, and cell lines from multiple tumor types; thus, this region is suspected to contain a tumor suppressor gene or genes. P16 (MTS1), an inhibitor of cdk4 and cdk6, resides within the deleted 9p21 region in these tumors. A neighboring gene, p15 (MTS2), has biochemical properties similar to those of p16, but has not been characterized in HNSCC. METHODS: Twenty-one head and neck squamous cell carcinomas and their proximal margins were snap frozen at the time of surgical resection. DNA isolation was performed using standard phenol and chloroform extraction. Standard PCR methods were used with primers P15-1F and P15-1R, specific for exon 1 of the p15 gene, as described previously. All samples were amplified for beta-Globin as a positive control. PCR products were stained with ethidium bromide and run on 6% polyacrylamide gels. Expected sizes for the PCR products were p15, 532 bp, and beta-globin, 238 bp. Results. Of 21 proximal margins, all demonstrated normal amplification of p15 DNA, all having a visible 532bp PCR product. Of 21 HNSCC tumors, 9 showed no amplification of the p15 gene; none of these 9 neoplasms had visible PCR products. All proximal margins and head and neck squamous cell carcinomas demonstrated amplification of the beta-globin gene, indicating that the DNA used was of good quality. CONCLUSIONS: Although PCR is not a quantitative technique, densitometric analysis of PCR products showed it was unlikely that the p15 gene was present in more than a small fraction of the tumor cells. The amount of the p15 PCR product in these cells was less than 3% of that observed in reactions containing an equal amount of DNA from normal cells. We are the first to show an absence of normal p15 exon 1 gene amplification in nearly 50% of HNSCCs studied. Loss of the MTS2 gene product, p15, may contribute to the loss of cell cycle and growth regulation seen in HNSCC.

Carcinoma, Squamous Cell↗
PubMed1998

Epidemiology of eating disordered symptoms in the Korean general population using a Korean version of the Eating Attitudes Test.

OBJECTIVE: The purposes of the present study were to estimate the proportion of subjects with a high score on the Korean version of Eating Attitudes Test--26 (KEAT-26), which may provide preliminary data regarding the prevalence rate of eating disorders in the Korean general population, and to further examine the sociocultural hypothesis of eating disorders. METHOD: Using a multi-stage questionnaire sampling method, we surveyed 3062 subjects (1249 males, 1813 females) from 3896 Korean adults in a nationwide area. RESULTS: 8.5% (260/3062) of subjects scored above the cut-off on the KEAT-26. Their demographic correlates, eating traits, and other characteristics relating to general psychopathology were similar to those of patients with eating disorders and female Caucasian controls in Western countries. DISCUSSION: These results suggest that changes in various sociocultural aspects have increased the risk of developing eating disorders in Korea, and support the sociocultural hypothesis of eating disorders.

Adult↗
PubMed1998

Neonatal neurological assessment of offspring in maternal phenylketonuria.

This study assesses the impact of prenatal and postnatal factors in maternal phenylketonuria (PKU). The Dubowitz Neurological Assessment of the Preterm and Full-term Newborn Infant was administered within the first 8 days of life to 56 offspring of women with PKU and 45 controls. Follow-up testing of the maternal PKU offspring at age 1 year consisted of the Bayley Scales of Infant Development and the Receptive-Expressive Emergent Language Scale (REEL). In addition, the Home Observation for Measurement of the Environment (HOME Scale) was given. Birth weight was lower (z = 2.0, p = 0.045), birth length was lower (z = 2.1, p = 0.03) and birth head circumference was smaller (z = 3.5, p = 0.0005) in the maternal PKU offspring than in the control infants. Examiners rated 29% of the maternal PKU offspring and 9% of the control infants abnormal (Fisher's exact test, p = 0.01). At 1 year of age, 19% of the maternal PKU offspring attained a Bayley Developmental Quotient (DQ) and a score on the Bayley Motor Scale below 85; 19% had receptive language delay; and 26% had expressive language delay. The gestational age at which the mother attained metabolic control was an important factor associated with birth measurements, the Dubowitz Rating and subsequent developmental scores. The Dubowitz Neurological Assessment score did not predict developmental outcome (chi-square = 1.3, p = 0.53), while the HOME score correlated with the DQ (r = 0.36, p = 0.02). In logistic regression analyses, the home environment was a greater determinant of risk for a low DQ than whether or not the mother attained metabolic control prior to pregnancy (OR = 0.85, p = 0.02). These results suggest that treatment strategies addressing both prenatal and postnatal factors will most effectively reduce risks in maternal PKU.

Developmental Disabilities↗
PubMed1998

Imaging destructive lesions of the petrous apex.

Cholesterol granuloma and cholesteatoma are the two most common destructive lesions of the petrous apex. Arachnoid cyst is less common. These three expansile lesions are often indistinguishable on clinical grounds. Cholesterol granulomas can be treated effectively through internal drainage into the mastoid cavity or middle ear. Cholesteatomas, however, are managed by more aggressive and complicated removal, which often mandates the sacrifice of hearing. Symptomatic arachnoid cysts are amenable to simple surgical drainage. Therefore, accurate preoperative recognition on computed tomography (CT) and magnetic resonance imaging (MRI) is important in planning proper treatment. Thirteen cases of destructive lesions of the petrous apex are analyzed. The authors' experience illustrates that the "typical" CT and MRI radiographic features are diagnostic in some cases, but not in all. In this study the pathologic findings have been correlated with the radiologic features on both MRI and CT.

Adolescent↗
PubMed1998

The cerebellopontine angle: does the translabyrinthine approach give adequate access?

A long-standing but unfounded criticism of the translabyrinthine approach is the misperception that this approach does not give adequate access to the cerebellopontine angle. Because of what is perceived as limited visualization and operating space within the cerebellopontine angle, some surgeons still believe that the translabyrinthine approach is inappropriate for large acoustic tumors. In this study, the surgical access to the cerebellopontine angle by virtue of the translabyrinthine approach is measured and analyzed. The parameters are compared with those measured for the retrosigmoid approach. This series objectively confirms that the translabyrinthine approach offers the neurotologic surgeon a shorter operative depth to the tumor, via a similar-sized craniotomy. This permits superior visualization by virtue of a wider angle of surgical access. Such access is achieved with the merit of minimal cerebellar retraction.

Cerebellopontine Angle↗
PubMed1998

Lipo layering of autologous fat: an improved technique with promising results.

When using free fat autologous grafts as a filling material was first proposed in 1893 by Neuber, the idea rapidly gained enthusiasm and endorsements. Our early experience with autologous fat transplantation was disappointing, but even then it was clear that fat could be transferred with partial success. Since then, further clinical works by Guerrerosantos, Coleman, and others have shown that it is possible, by careful handling of transplanted fat, to improve the survival of this tissue. We have reviewed our recent experiences and have found several patients with whom autologous fat transplant has been successful with up to an 8-year postoperative follow-up.

Adipocytes↗
PubMed1998

A propagated wave of MPF activation accompanies surface contraction waves at first mitosis in Xenopus.

During the period of mitosis, two surface contraction waves (SCWs) progress from the animal to vegetal poles of the Xenopus egg. It has been shown that these SCWs occur in parallel with the activation of MPF and with its subsequent inactivation in the animal and vegetal hemispheres, suggesting that they are responses to propagated waves of MPF activity across the egg. We have analysed the mechanism of MPF regulation in different regions of the egg in detail in relation to SCW progression. The distributions of histone HI kinase activity and of Cdc2 and cyclin B (the catalytic and regulatory subunits of MPF) were followed by dissection of intact eggs following freezing and in cultured fragments separated by ligation. Cdc2 was found to be distributed evenly throughout the egg cytoplasm. Loss of phosphorylated (inactive) forms of Cdc2 coincided spatially with the wave of MPF activation, while cyclin B2 accumulation occurred in parallel in animal and vegetal regions. In ligated vegetal pole fragments no MPF activation or Cdc2 dephosphorylation were detectable. A wave of cyclin B destruction that occurred in concert with the second SCW was also blocked. Taken together these results indicate that the triggering mechanism for MPF activation requires components specific to the animal cytoplasm, acting via Cdc2 dephosphorylation, and that MPF activation subsequently propagates autocatalytically across the egg. SCW progression in the vegetal hemisphere was followed directly by time-lapse videomicroscopy of subcortical mitochondrial islands. The first SCW traversed the vegetal pole at the time of MPF activation in this region. Like MPF activation and inactivation, SCWs were blocked in the vegetal region by ligation. These observations reinforce the hypothesis that the first SCW is a direct consequence of the MPF activation wave. It may reflect depolymerisation of the subcortical microtubule network since it coincided exactly with the arrest of the microtubule-dependent movement of 'cortical rotation' and was related in direction in most eggs. The cyclin B destruction wave and associated cortical contraction of the second SCW may be localised downstream consequences of the MPF activation wave, or they may propagate independently from the animal cytoplasm.

Animals↗
PubMed1998

EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCgamma signaling pathway.

A current model of growth factor-induced cell motility invokes integration of diverse biophysical processes required for cell motility, including dynamic formation and disruption of cell/substratum attachments along with extension of membrane protrusions. To define how these biophysical events are actuated by biochemical signaling pathways, we investigate here whether epidermal growth factor (EGF) induces disruption of focal adhesions in fibroblasts. We find that EGF treatment of NR6 fibroblasts presenting full-length WT EGF receptors (EGFR) reduces the fraction of cells presenting focal adhesions from approximately 60% to approximately 30% within 10 minutes. The dose dependency of focal adhesion disassembly mirrors that for EGF-enhanced cell motility, being noted at 0.1 nM EGF. EGFR kinase activity is required as cells expressing two kinase-defective EGFR constructs retain their focal adhesions in the presence of EGF. The short-term (30 minutes) disassembly of focal adhesions is reflected in decreased adhesiveness of EGF-treated cells to substratum. We further examine here known motility-associated pathways to determine whether these contribute to EGF-induced effects. We have previously demonstrated that phospholipase C(gamma) (PLCgamma) activation and mobilization of gelsolin from a plasma membrane-bound state are required for EGFR-mediated cell motility. In contrast, we find here that short-term focal adhesion disassembly is induced by a signaling-restricted truncated EGFR (c'973) which fails to activate PLCgamma or mobilize gelsolin. The PLC inhibitor U73122 has no effect on this process, nor is the actin severing capacity of gelsolin required as EGF treatment reduces focal adhesions in gelsolin-devoid fibroblasts, further supporting the contention that focal adhesion disassembly is signaled by a pathway distinct from that involving PLCgamma. Because both WT and c'973 EGFR activate the erk MAP kinase pathway, we additionally explore here this signaling pathway, not previously associated with growth factor-induced cell motility. Levels of the MEK inhibitor PD98059 that block EGF-induced mitogenesis and MAP kinase phosphorylation also abrogate EGF-induced focal adhesion disassembly and cell motility. In summary, we characterize for the first time the ability of EGFR kinase activity to directly stimulate focal adhesion disassembly and cell/substratum detachment, in relation to its ability to stimulate migration. Furthermore, we propose a model of EGF-induced motogenic cell responses in which the PLCgamma pathway stimulating cell motility is distinct from the MAP kinase-dependent signaling pathway leading to disassembly and reorganization of cell-substratum adhesion.

Animals↗
PubMed1998

Comparison of demands of sustained attentional events between public and private children's television programs.

The durations and variability of changing events were analyzed for 20 min. each of 13 children's television programs. These programs included selections from both publically and privately produced shows. Significantly different patterns of attentional demands were found between the programs. Public television programming is characterized by longer and more variable durations of sustained attentional events, while private television programming is best described as having fast-paced shorter events. The implications of this finding for difficulties in learning by school-age children to attend for longer periods are discussed.

Attention↗
PubMed1998

Patterns of sustained attentional demands in elementary classrooms: an observational study.

This study investigates the patterns of sustained attentional demands of events in Kindergarten through Grade 5. The durations and variability of sustained attention for events occurring in 12 elementary classrooms were observed. The data show a progression of sustained attentional demands across the grades; however, a substantial increase in students' sustained attention is required between Kindergarten and Grade 1. The implications of these findings on curriculum development are discussed.

Attention↗
PubMed1998

Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model.

BACKGROUND: Hypothermia is critical for proper lung preservation. Ideally, the lungs should be maintained at the optimal preservation temperature during the entire ischemic interval. Lung rewarming during implantation is commonly observed. This study was undertaken to investigate the severity of rewarming ischemia on preservation injury and the possibility of minimizing this by use of leukocyte depletion during initial reperfusion. METHODS: Four experimental groups were tested as follows: neonatal piglet heart-lung blocks were either (1) placed on an isolated, blood-perfused, working heart-lung circuit without intervening ischemia (control, n = 6), (2) reperfused on the circuit with whole blood (WB, n = 6) after 13 hours of preservation, (3) reperfused with WB after 12 hours of preservation and 1 hour of rewarming (RWB, n = 5), or (4) reperfused with leukocyte-depleted blood for an initial 10 minutes followed by WB, after 12 hours of preservation and 1 hour of rewarming (n = 6). All groups were studied for 4 hours. RESULTS: The partial pressure of arterial oxygen and lung compliance were significantly lower in the RWB group than in controls (113.8+/-33.1 vs 417.3+/-6.2 mm Hg, p < 0.01; and 0.8+/-0.2 vs 2.9+/-0.4 ml/cm H2O, p < 0.05, respectively). Pulmonary vascular resistance and lung wet/dry weight ratios were significantly higher in the RWB group than in controls (15884.1+/-11354.8 vs 6108.3+/-1309.9 dyne x sec x cm[-5], p < 0.05; and 7.13+/-0.24 vs 5.82+/-0.35, p < 0.05, respectively). The WB and leukocyte-depleted groups did not differ significantly from controls for any measured parameter. CONCLUSIONS: This model confirms that rewarming ischemia during lung implantation exacerbates reperfusion injury. Leukocyte-depleted reperfusion as tested for a short period of time (10 minutes) ameliorates this injury and therefore should be considered for clinical lung transplantation.

Animals↗