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Biomedical subjects

K C Chung

Publications and source records attributed to K C Chung.

At least 73 records · Page 4Linked to original sources

Mutation of Di-leucine residues in the juxtamembrane region alters EGF receptor expression.

Di-leucine motifs have been implicated in the internalization or degradation of many membrane proteins. The epidermal growth factor receptor (EGFR) contains two di-leucine residues at 658 (TLRRLLQER) and 679 (NQALLRIL). To determine the role of these di-leucine motifs in regulating EGF receptor expression, activity, or ligand-induced degradation, the di-leucine residues at positions 658 or 679 were mutated to di-alanine residues, and the mutant receptors were stably expressed in CHO cells. The results indicate that mutation of either di-leucine motif generates and promotes cell surface expression of carboxy-truncated EGF receptors (M(r) 120, 140 kDa) that do not undergo EGF-induced autophosphorylation or degradation. In contrast, full-length EGF receptors (170 kDa) containing di-alanine substitutions resemble wild type receptors in that they respond to EGF by autophosphorylation, their tyrosine kinase activity is inhibited by protein kinase C, and they are degraded. The level of autophosphorylation of the 170 kDa mutant receptors and EGF-induced tyrosine phosphorylation of other cellular proteins is lower than that of the wild type receptor, consistent with formation of kinase-inactive heterodimers between the truncated and full-length mutant receptors. These results demonstrate that removal of either of the di-leucines leads to generation of inactivating carboxy-truncated receptors, suggesting that the two di-leucine motifs within the juxtamembrane region of the EGFR are important for ensuring normal receptor expression.

Alanine↗

Augmentation of tumor metastasis by platelet-activating factor.

The effect of platelet-activating factor (PAF) on experimental pulmonary metastasis by the B16F10 murine melanoma and the possible involvement of PAF in the activities of tumor necrosis factor alpha (TNF-alpha) and interleukin 1alpha (IL-1alpha) in tumor metastasis were investigated. i.p. injection of PAF enhanced the lung colonization in a dose- and time-dependent manner. PAF enhanced lung colonization when it was administered after, but not before, B16F10 inoculation. Multiple injections of PAF were more effective than a single injection. Neutralization of endogenous PAF with PAF antagonist BN50739 decreased lung colonization, suggesting that endogenous PAF plays an important role in pulmonary metastases. A single i.p. injection of TNF-alpha or IL-1alpha caused a marked enhancement in lung colonization. TNF-alpha- and IL-1alpha-mediated enhancement in lung colonies was significantly inhibited by BN50739. These results demonstrate that PAF has a metastasis-enhancing effect and is a mediator of the metastatic activities of TNF-alpha and IL-1alpha.

Animals↗

Wrist arthrography versus arthroscopy: a comparative study of 150 cases.

One hundred fifty patients with suspected wrist ligamentous injuries were studied with both triple injection wrist arthrography and arthroscopy. The diagnoses obtained by these two techniques were compared to determine the differences between these two modalities. All the patients in this study had both the clinical diagnosis of ligamentous injuries of the wrist and normal findings on x-ray films. Intercarpal abnormalities were found in 106 patients (71%) at wrist arthrography and in 136 patients (91%) at arthroscopy. There was only 42% agreement (63 patients) between the arthrographic and arthroscopic diagnoses. Eighty-seven patients (58%) had alterations of their arthrographic diagnoses following arthroscopy. For patients with normal arthrographic findings (44 patients), 88% underwent arthroscopy because there was insufficient correlation between the physical examination findings and the arthroscopic findings. Out of the 44 patients with normal arthrographic findings, 35 patients (80% of the subgroup) had injuries found at arthroscopy. Over half of the patients had alterations in their arthrographic diagnoses following arthroscopy. In a patient with suspected ligamentous injury of the wrist, wrist arthroscopy may be the most efficient method in arriving at a definitive diagnosis.

Adolescent↗

Use of modern craniofacial techniques for comprehensive reconstruction of the acromegalic face.

The severe acromegalic patient poses a difficult reconstructive dilemma to the craniofacial surgeon. Significant facial deformities can include frontal bossing, prominent supraorbital ridges, malar flatness, maxillary hypoplasia, mandibular prognathism with class III malocclusion, and macrogenia. Reports on the correction of these deformities are rare. Prior publications describe long hospital stays, weeks of intermaxillary fixation, requirement for a tracheostomy, as well as the need for multiple, staged procedures and interdisciplinary teams. In an effort to extend the advances of modern craniofacial techniques to this group of patients, we performed an extensive reconstruction on a 28-year-old acromegalic patient using a one-stage procedure without the use of intermaxillary fixation and without the added morbidity of a tracheostomy. The procedure addressed the skeletal deformities of the upper face, the midface, and the lower face. The operation was performed by a single plastic surgery team and the patient was extubated in 36 hours and discharged in 6 days. We believe that the use of rigid fixation and the judicious application of modern craniofacial principles can allow a complex yet safe one-stage procedure to reconstruct the acromegalic face. Such an approach showed decreased perioperative morbidity and provided an excellent functional and aesthetic result.

Acromegaly↗

Diagnosis of silicone gel breast implant rupture by ultrasonography.

To prospectively evaluate the efficacy of ultrasonography in the diagnosis of ruptured silicone gel breast implants, 98 patients (192 implants) underwent preoperative breast ultrasonography prior to silicone gel breast implant removal. The prevalence of implant rupture confirmed at surgery in this group of patients was 62 of the 192 implants (32 percent). Of the 60 implants diagnosed as ruptured by ultrasonography, 46 were confirmed as having visible defects at surgery (true positive) for a positive predictive value of 77 percent. Of the 132 implants diagnosed as intact by ultrasonography, 116 were confirmed as intact at surgery (true negative) for a negative predictive value of 88 percent. Overall, the sensitivity of ultrasonography for implant rupture was 74 percent, and the specificity was 89 percent. These findings demonstrate that ultrasonography is an effective imaging modality for the diagnosis of silicone gel breast implant rupture. Compared with mammography, ultrasonography appears to offer superior sensitivity and specificity without radiation exposure or discomfort. Although magnetic resonance imaging has shown considerable promise in the diagnosis of implant rupture, ultrasonography provides comparable sensitivity at a fraction of MRI's cost.

Breast↗

A system for the analysis of seat support surfaces using surface shape control and simultaneous measurement of applied pressures.

A system for the design and analysis of seat support and buttock tissue interfaces has been developed. It has the ability to control the seating surface shape while measuring the pressure applied to the buttocks by the surface. Pressures are measured over an 11 x 12 rectangular array of support elements using silicon pressure sensors mounted in a swiveling head atop each support element. Control of surface shape is mediated by selective linear translation of the support elements along their respective vertical axes. Closed-loop control of the system allows for the dynamic formulation of a support surface on the basis of programmable criteria. The system is intended to function as a research tool to facilitate the study of the relationships between support surface shape and interface pressure, and support surface shape and soft tissue distortion. The purpose of this paper is to present the system instrumentation and the rationale behind its design and development. The paper also presents the results of several tests to evaluate the accuracy and performance of the system. This evaluation included a pilot study on 10 able-bodied subjects. The results of these system evaluations indicate that the system is capable of making repeatable and precise measurements of pressure and surface element position and can formulate support surface shapes that satisfy specified optimization criteria.

Back↗

Pericardiectomy for pericardial constriction.

Constrictive pericarditis is a pathologic condition that may lead to significant morbidity. Definitive management of constrictive pericarditis requires pericardiectomy. A retrospective review of pericardiectomy for constrictive pericarditis at the Ochsner Clinic was undertaken. Twenty-one patients (17 male, four female) underwent pericardiectomy for constrictive pericarditis between January 1969 and June 1994. Ages ranged from 15 to 66 years (mean 41.5 years). Pedal edema, dyspnea, fatigue, and chest pain were the most common symptoms. Fifteen patients had important comorbidities. Preoperative New York Heart Association (NYHA) class was I (2), II (8), III (6), IV (5). Mean preoperative catheterization data, available in 17 patients (81%), demonstrated elevated intracardiac pressures (right atrial 17.4 mm Hg, right ventricular end-diastolic 22.4 mm Hg, pulmonary artery 26.2 mm Hg, pulmonary capillary wedge 20.2 mm Hg, left ventricular end-diastolic 20.1 mm Hg). A total pericardiectomy was performed in nine patients (sternotomy 8, thoracotomy 1). Pericardiectomy limited anteriorly to the phrenic nerves was performed in 11 patients (sternotomy 9, thoracotomy 2). One partial pericardiectomy was performed through a sternotomy. Cardiopulmonary bypass was used in six patients (29%). Mean hospital stay was 12 days (preoperative 4.2, postoperative 7.67). All patients achieved NYHA Class I postoperatively. Sixteen patients were discharged in sinus rhythm. No early mortality (<30 days), or major postoperative complications were observed. Pericardiectomy for pericardial constriction can be performed safely low morbidity and mortality and can favorably impact the natural history of this debilitating condition.

Adolescent↗

Repletion of high energy phosphates in the postischemic neonatal heart.

Milrinone improves function in failing adult hearts, but it has not been examined in the immature myocardium. The purpose of this study was to characterize the effects of milrinone, a phosphodiesterase inhibitor, on immature hearts, and compare these to dobutamine, a commonly used catecholamine inotrope. One hundred isolated working neonatal rabbit hearts were used. Hearts were made ischemic (37 degrees C) for 1 hour and reperfused for 0, 10, 40, or 70 minutes. In separate groups, infusion of milrinone (1.0 microg/mL) or dobutamine (0.1 microg/mL) was begun after reperfusion for 10 or 40 minutes. High energy phosphates, total nondiffusable nucleotides, cyclic adenosine monophosphate (cAMP), and the percent recovery of cardiac output were determined. Cardiac output returned to normal, and adenosine triphosphate (ATP) and total nondiffusable nucleotide levels did not decline when dobutamine or milrinone were begun after 10 minutes of reperfusion. In hearts receiving inotropes after 40 minutes of reperfusion, when high energy phosphates were low, ATP increased, and total nondiffusable nucleotide repletion was observed. Cardiac output did not improve when inotropes were begun after 40 minutes. cAMP was higher in milrinone hearts compared to dobutamine, but there was no simple relation between cAMP and ventricular function. Inotropes may increase purine salvage pathway activity. Deriving maximum benefit from inotropes may depend on beginning infusions early, before the appearance of irreversible changes.

Adenosine Triphosphate↗

Stability of granisetron hydrochloride in a disposable elastomeric infusion device.

The stability and sterility of granisetron hydrochloride in 5% dextrose injection or 0.9% sodium chloride injection when stored in a disposable elastomeric infusion device were studied. Granisetron was diluted to 0.02 mg/mL (as the hydrochloride salt) in 5% dextrose chloride injection. The solution was placed in the drug reservoir of a disposable elastomeric infusion device and refrigerated at 4 degrees C for 14 days. A total of eight pumps were prepared, four containing granisetron 0.02 mg/mL in 5% dextrose injection and four containing granisetron 0.02 mg/mL in 0.9% sodium chloride injection. The solutions were assayed for granisetron concentration by stability-indicating high-performance liquid chromatography at 0 hours, 24 hours, 48 hours, 7 days, and 14 days. Each solution was inspected for clarity, color, and precipitation, and sterility testing was performed. Throughout the study, the mean concentration of granisetron remaining was more than 92% of the initial concentration both in 5% dextrose injection and in 0.9% sodium chloride injection. Individual solutions in 0.9% sodium chloride injection consistently maintained more than 90% of the initial drug concentration for only seven days. No microbial growth was detected. No precipitation, color change, or haziness was seen. Granisetron 0.02 mg/mL (as the hydrochloride salt) was stable and free of microbial growth in 0.9% sodium chloride injection for up to 7 days and stable and free of microbial growth in 5% dextrose injection for up to 14 days when stored at 4 degrees C in a disposable elastomeric infusion device.

Antiemetics↗

Multifocal congenital hemangiopericytomas associated with Kasabach-Merritt syndrome.

A newborn male with multifocal congenital hemangiopericytomas complicated by Kasabach-Merritt syndrome was treated by excision of a large hemangiopericytoma in the right mandibular area. After excision of this lesion, the associated consumptive coagulopathy abated. Spontaneous regression of other subcutaneous tumours over the thighs and left flank was noted by age 6 months; this illustrates the benign course of most congenital hemangiopericytomas. Surgical excision of congenital hemangiopericytoma is indicated when there is a coexisting consumptive coagulopathy or for the definitive control of large lesions. For smaller lesions and in the absence of Kasabach-Merritt syndrome, the benign nature and predilection for spontaneous regression of congenital hemangiopericytomas render observation as the preferred strategy.

Disseminated Intravascular Coagulation↗

Adriamycin-inducible proteins associated with drug sensitivity in resistant immunoblastic B lymphoma cells.

We have previously established an immunoblastic B lymphoma cell line, designated HOB1. This cell line is hypersensitive to a wide spectrum of chemotherapeutic agents. Two co-regulated polypeptides around 64 kDa (termed p64) were induced 10-30-fold in response to adriamycin and some other drugs at the IC50 (the concentration inhibiting cell growth by 50%). These inducible proteins are localized as monomeric forms in the cytosolic fraction, with isoelectric points of pH = 6.2 (major protein) and pH = 7.0 (minor protein). An adriamycin-resistant cell line was established from HOB1 cells. The p64 inducibility was dramatically reduced in resistant HOB1 cells or unrelated cell lines which show phenotypic resistance to adriamycin toxicity. The loss of p64 inducibility in resistant cells is not due to a failure of cells to take up adriamycin since drug accumulation kinetics remained the same as in the parental cells.

Antibodies, Neoplasm↗