Biomedical subjects

Richard Kim

Publications and source records attributed to Richard Kim.

9 recordsLinked to original sources

PubMed2006

Transcriptional profiling of C2C12 myotubes in response to SHIP2 depletion and insulin stimulation.

Phosphoinositide lipids generated at the cell membrane are a key component of a variety of signaling pathways. Among several inositol phosphatases that regulate the availability of signaling phosphoinositide lipids, the type II SH2-domain-containing inositol 5-phosphatase (SHIP2; approved gene symbol Inppl1) is believed to have multiple functions, including the regulation of insulin signaling and cytoskeletal functions. To understand the function of SHIP2 in C2C12 muscle cells, we depleted SHIP2 through the use of RNA interference and analyzed the global effect of SHIP2 depletion on gene expression using Affymetrix microarrays containing approximately 45,000 mouse probe sets. Expression of SHIP2-targeting small-hairpin RNA in differentiated C2C12 muscle cells led to >80% decrease in SHIP2 mRNA and 60-80% decrease in SHIP2 protein, which resulted in significant gene expression changes linked to cytoskeletal functions, including altered expression of adducin-alpha, pallidin, stathmin-like-2, and synaptojanin-2 binding protein. Insulin treatment of C2C12 muscle cells caused transcriptional changes associated with known signaling pathways. However, SHIP2 depletion had no discernible effect on insulin-regulated gene expression. Taken together, our results suggest that SHIP2 is involved in the regulation of cytoskeletal functions, but a large reduction of SHIP2 in C2C12 muscle cells is not sufficient to affect insulin-mediated gene expression.

Animals↗

PubMed2006

Prolonged penile strangulation with metal clamps.

Various different objects have been reported to strangulate the penis. We reported on a patient who used metal radiator clamps for an extended period of time. Workup included history, physical examination and urinalysis. The patient was taken to the operating room for further evaluation with cystourethroscopy and orthopedic wire cutters were used to break the metal bands.

Constriction, Pathologic↗

PubMed2006

Clinical inquiries. Should patients receive 23-valent pneumococcal vaccination more than once?

No patient-oriented evidence supports pneumococcal revaccination of any patient (high-risk or otherwise). Antibody levels may be augmented by revaccination; however, the clinical efficacy of revaccination, even among high-risk patients, is unknown. Revaccination is recommended by the Advisory Committee on Immunization Practices (ACIP) in certain circumstances (strength of recommendation [SOR]: C, expert opinion based on physiology/bench research). Revaccination once appears to be safe, especially if provided 5 years or more after primary vaccination (SOR: B, based upon consistent results of cohort studies and nonrandomized prospective trials).

Clinical Trials as Topic↗

PubMed2003

Repeat retroperitoneal lymph node dissection for metastatic testis cancer.

PURPOSE: We report pathological results, perioperative complications and patient outcome in 21 men after repeat retroperitoneal lymph node dissection for metastatic testis cancer. MATERIALS AND METHODS: We reviewed an institutional tumor registry at our cancer center and identified 417 patients who underwent retroperitoneal lymph node dissection for testis cancer during a 21-year period. Of these 417 patients 21 underwent repeat retroperitoneal lymph node dissection. We reviewed preoperative patient characteristics, operative data and pathological findings from repeat lymphadenectomy, and determined patient disease status, morbidity and mortality after surgery. RESULTS: We identified viable germ cell tumor in 5 patients (24%), teratoma in 14 (67%) and fibrosis or necrosis only in 5 (24%). Intraoperatively subadventitial dissection of the aorta occurred in 2 cases, which was severe enough in 1 to require an aortic graft. The most common postoperative complications were prolonged ileus or partial bowel obstruction and chylous ascites in 6 and 3 patients, respectively. Six patients died, including 5 of disease progression and 1 of postoperative pulmonary embolus. At a mean followup of 4.7 years (range 0.1 to 14) 15 patients (71%) were alive and 14 (67%) were disease-free. CONCLUSIONS: Repeat retroperitoneal lymph node dissection is safe and effective in the majority of patients with recurrent or residual retroperitoneal masses after initial multimodality treatments for metastatic testis cancer. Overall perioperative morbidity and mortality are low and yet the potential for significant vascular complications warrants careful preoperative planning and intraoperative judgment.

Adolescent↗

PubMed2002

Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein.

BACKGROUND: The efflux transporter P-glycoprotein, a member of the adenosine triphosphate-binding cassette superfamily, is a major determinant of the pharmacokinetics and pharmacodynamics of the opioid loperamide, a well-recognized antidiarrheal agent. Animal studies indicate that P-glycoprotein limits morphine entry into the brain. In this study, the authors examined whether other opioids of importance to anesthesiologists such as fentanyl, sufentanil, and alfentanil, and also morphine-6-glucuronide and morphine-3-glucuronide, are P-glycoprotein substrates and whether, in turn, these opioids act also as P-glycoprotein inhibitors. METHODS: The transcellular movement of the various opioids, including loperamide and morphine, was assessed in L-MDR1 (expressing P-glycoprotein) and LLC-PK1 cell monolayers (P-glycoprotein expression absent). A preferential basal-to-apical versus apical-to-basal transport in the L-MDR cells but not the LLC-PK1 cells is seen for P-glycoprotein substrates. In addition, the effect of the various opioids on the transcellular movement of the prototypical P-glycoprotein substrate digoxin was examined in Caco-2 cell monolayers. IC50 values were calculated according to the Hill equation. RESULTS: Loperamide was a substrate showing high dependence on P-glycoprotein in that basal-apical transport was nearly 10-fold greater than in the apical-basal direction in L-MDRI cells. Morphine also showed a basal-to-apical gradient in the L-MDR1 cell monolayer, indicating that it too is a P-glycoprotein substrate, but with less dependence than loperamide in that only 1.5-fold greater basal-apical directional transport was observed. Fentanyl, sufentanil, and alfentanil did not behave as P-glycoprotein substrates, whereas the morphine glucuronides did not cross the cell monolayers at all, whether P-glycoprotein was present or not. Loperamide, sufentanil, fentanyl, and alfentanil inhibited P-glycoprotein-mediated digoxin transport in Caco-2 cells with IC50 values of 2.5, 4.5, 6.5, and 112 microm, respectively. Morphine and its glucuronides (20 microm) did not inhibit digoxin (5 microm) transport in Caco-2 cells, and therefore IC50 values were not determined. CONCLUSIONS: Opioids have a wide spectrum of P-glycoprotein activity, acting as both substrates and inhibitors, which might contribute to their varying central nervous system-related effects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Genomic and physiological analysis of oxygen sensitivity and hypoxia tolerance in PC12 cells.

The mechanisms by which cells adapt and respond to changes in oxygen tension remain largely unknown. Our laboratory has used the PC12 cell line to study both biophysical and molecular responses to hypoxia. This chapter summarizes our findings. We found that membrane depolarization that occurred when PC12 cells were exposed to reduced O(2) was mediated by a specific potassium channel, the Kv1.2 channel. The membrane depolarization leads to increased Ca(2+) conductance through a voltage-sensitive channel, which in turn mediates the release of the neurotransmitters dopamine, adenosine, glutamate, and GABA. In addition, increased intracellular Ca(2+) and other signaling systems regulate hypoxia-induced gene expression, which contributes to the adaptive response to reduced O(2+). We identified several critical signaling pathways that regulate a complex gene expression profile in PC12 cells during hypoxia. These include the cAMP-protein kinase A, Ca(2+)-calmodulin, p42/44 mitogen-activated protein kinase (MAPK), stress-activated protein kinase (SAPK; p38 kinase), and the phosphatidylinositol 3-kinase-AKT as regulators of gene expression. Several of these pathways regulate hypoxia-specific transcription factors that are members of the hypoxia-inducible factor (HIF) family. Recently, we have successfully used subtractive cDNA libraries and microarray analysis to identify the genomic profile that mediates the cellular response to hypoxia.

Animals↗

PubMed2002

Development of a real-time in vivo transcription assay: application reveals pregnane X receptor-mediated induction of CYP3A4 by cancer chemotherapeutic agents.

We report the development of a rapid real-time assay that measures the transcription of luciferase reporter genes in transduced mouse hepatic cells in vivo. Luciferase activity is noninvasively measured by whole-body optical imaging within hours of the hydrodynamic injection of as little as 1 microg of naked DNA. Transcription of genes introduced as linearized DNA can be serially assayed for weeks in each animal. Transcription was quantified by extracorporal monitoring of bioluminescence as well as or better than by traditional in vitro bioluminescence assay. Our assay allows the measurement of transcription as it occurs, under the most informative biological conditions (i.e., in a living, intact organ). Furthermore, it substantially reduces the cost, time, and number of animals required for analysis of gene expression. The utility of the method is demonstrated in the discovery that topotecan and etoposide are ligands of pregnane X receptor that induce CYP3A4 transcription.

Animals↗

PubMed2002

Clinical importance of a unilateral striated pattern seen on sonography of the testicle.

OBJECTIVE: The purpose of this study was to determine the clinical importance of a unilateral striated pattern seen on high-resolution sonography of a testicle on the basis of follow-up imaging. CONCLUSION: In the absence of relevant clinical findings or an abnormal signal on color-flow or power Doppler sonography, a striated pattern of a testicle appears to have no clinical importance. It is presumed to represent fibrosis, and the patient most likely can be followed up clinically and sonographically rather than having to undergo surgical exploration.

Adult↗

PubMed2002

Using pullback pressure measurements to identify venous stenoses persisting after successful angioplasty in failing hemodialysis grafts.

OBJECTIVE: We used pullback pressure measurements to identify venous stenoses persisting after angioplasty of failing hemodialysis grafts. MATERIALS AND METHODS: Fifty angioplasty procedures were performed in 32 patients with elevated venous pressures at dialysis. Grafts were initially evaluated on digital subtraction angiography, and all stenoses measuring greater than 50% on angiography underwent angioplasty. In successful cases (residual stenosis < 30%), pullback pressure measurements were obtained from the superior vena cava to the graft to identify hemodynamically significant (> 10 mm Hg) stenoses. These lesions were then treated with repeated angioplasty. RESULTS: Hemodynamically significant stenoses with a gradient range of 10-27 mm Hg (mean, 16 mm Hg) were found in nine (18%) of 50 procedures. All gradients occurred at sites of previous angioplasty. Repeated angioplasty of these stenoses performed with larger angioplasty balloons reduced gradients to less than 3 mm Hg in six stenoses and to 5 mm Hg in three stenoses. In this subgroup, primary patency was eight (89%) of nine stenoses at 1 month and 2 months and five (56%) of nine stenoses at 6 months. Using life table analysis, we found that primary patency of the entire population was 84% at 1 month, 66% at 2 months, and 47% at 6 months. The mean time between interventions was 6 months, and the thrombosis rate was 0.32 per year. CONCLUSION: Pullback pressure measurements are a useful adjunct to angiography to evaluate the hemodynamic results of angioplasty in patients with failing hemodialysis grafts.

Adult↗