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Biomedical subjects

D C Han

Publications and source records attributed to D C Han.

At least 37 records · Page 2Linked to original sources
PubMed1999

The role of ultrasound in patients with possible penetrating cardiac wounds: a prospective multicenter study.

BACKGROUND: Ultrasound is quickly becoming part of the trauma surgeon's practice, but its role in the patient with a penetrating truncal injury is not well defined. The purpose of this study was to evaluate the accuracy of emergency ultrasound as it was introduced into five Level I trauma centers for the diagnosis of acute hemopericardium. METHODS: Surgeons or cardiologists (four centers) and technicians (one center) performed pericardial ultrasound examinations on patients with penetrating truncal wounds. By protocol, patients with positive examinations underwent immediate operation. Vital signs, base deficit, time from examination to operation, operative findings, treatment, and outcome were recorded. RESULTS: Pericardial ultrasound examinations were performed in 261 patients. There were 225 (86.2%) true-negative, 29 (11.1%) true-positive, 0 false-negative, and 7 (2.7%) false-positive examinations, resulting in sensitivity of 100%, specificity of 96.9%, and accuracy of 97.3%. The mean time from ultrasound to operation was 12.1+/-5 minutes. CONCLUSION: Ultrasound should be the initial modality for the evaluation of patients with penetrating precordial wounds because it is accurate and rapid.

Acute Disease↗
PubMed1999

Integrin-mediated signal transduction pathways.

Integrins serve as adhesion receptors for extracellular matrix proteins and also transduce biochemical signals into the cell. They regulate a variety of cellular functions, including spreading, migration, proliferation and apoptosis. Many signaling pathways downstream of integrins have been identified and characterized and are discussed here. In particular, integrins regulate many protein tyrosine kinases and phosphatases, such as FAK and Src, to coordinate many of the cell processes mentioned above. The regulation of MAP kinases by integrins is important for cell growth or other functions, and the putative roles of Ras and FAK in these pathways are discussed. Phosphatidylinositol lipids and their modifying enzymes, particularly PI 3-kinase, are strongly implicated as mediators of integrin-regulated cytoskeletal changes and cell migration. Similarly, actin cytoskeleton regulation by the Rho family of GTPases is coordinated with integrin signaling to regulate cell spreading and migration, although the exact relationship between these pathways is not clear. Finally, intracellular pH and calcium fluxes by integrins are suggested to affect a variety of cellular proteins and functions.

Animals↗
PubMed1999

High glucose stimulates proliferation and collagen type I synthesis in renal cortical fibroblasts: mediation by autocrine activation of TGF-beta.

Renal tubular epithelial cells and interstitial fibroblasts are active participants in tubulointerstitial fibrosis, the best correlate of decreased glomerular filtration in diabetic nephropathy. It was reported previously that high ambient glucose stimulates transforming growth factor-beta (TGF-beta) mRNA and bioactivity, promotes cellular hypertrophy, and increases collagen synthesis in proximal tubular cells. This study evaluates the effects of high glucose and TGF-beta on the behavior of murine renal cortical fibroblasts (TFB) in culture. High glucose (450 mg/dl) significantly increased [3H]-thymidine incorporation (by 60 to 80% after 24 to 72 h) and cell number, without significantly increasing cell death when compared with normal glucose (100 mg/dl). There also was a transient increase in the mRNA of the c-myc and egr-1 early-response genes. Exogenous TGF-beta1 was promitogenic rather than antiproliferative in contrast to other renal cell types. Northern blot analysis demonstrated constitutive expression of TGF-beta1, -beta2, and -beta3 transcripts. Exposure to high glucose increased all three TGF-beta isoforms in a time-dependent manner. High glucose as well as exogenous TGF-beta1 also increased [3H]-proline incorporation, alpha2(I) collagen mRNA, and type I collagen protein (measured by immunoassay). Treatment with a neutralizing pan-selective monoclonal anti-TGF-beta antibody markedly attenuated the stimulation by high ambient glucose of thymidine incorporation, TGF-beta1 mRNA, and type I collagen mRNA and protein levels. It is concluded that high ambient glucose and exogenous TGF-beta1 share similar actions on renal fibroblasts. Moreover, the stimulation of cell proliferation and collagen type I synthesis in these cells by high ambient glucose are mediated by activation of an autocrine TGF-beta system.

Animals↗
PubMed1998

Identification of p130Cas as a mediator of focal adhesion kinase-promoted cell migration.

Previously we have demonstrated that focal adhesion kinase (FAK)-promoted migration on fibronectin (FN) by its overexpression in CHO cells is dependent on FAK autophosphorylation at Y397 and subsequent binding of Src to this site. In this report, we have examined the role of FAK association with Grb2 and p130(Cas), two downstream events of the FAK/Src complex that could mediate integrin-stimulated activation of extracellular signal-regulated kinases (Erks). We show that a Y925F FAK mutant was able to promote cell migration as efficiently as FAK and that the transfected FAK demonstrated no detectable association with Grb2 in CHO cells. In contrast, cells expressing a FAK P712/715A mutant demonstrated a level of migration comparable to that of control cells. This mutation did not affect FAK kinase activity, autophosphorylation, or Src association but did significantly reduce p130(Cas) association with FAK. Furthermore, FAK expression in CHO cells increased tyrosine phosphorylation of p130(Cas) and its subsequent binding to several SH2 domains, which depended on both the p130(Cas) binding site and the Src binding site. However, we did not detect increased activation of Erks in cells expressing FAK, and the MEK inhibitor PD98059 did not decrease FAK-promoted cell migration. Finally, we show that coexpression of p130(Cas) further increased cell migration on FN and coexpression of the p130(Cas) SH3 domain alone functioned as a dominant negative mutant and decreased cell migration. Together, these results demonstrate that p130(Cas), but not Grb2, is a mediator of FAK-promoted cell migration and suggest that FAK/ p130(Cas) complex targets downstream pathways other than Erks in mediating FAK-promoted cell migration.

Animals↗
PubMed1998

Accelerated radiotherapy regimen for malignant gliomas using stereotactic concomitant boosts for dose escalation.

The purpose of this pilot study was to determine the feasibility and toxicities of an accelerated treatment program by using a concomitant stereotactic radiotherapy boost given weekly during a course of standard external-beam irradiation (EBXRT) in patients with malignant gliomas. Twelve patients underwent biopsy or subtotal resection of a malignant glioma and were enrolled on the protocol, which delivered 44 Gy-EBXRT and a 12-Gy stereotactic radiotherapy boost given on 3 consecutive weeks of treatment for a total dose of 80 Gy over 33 days. Three patients with anaplastic astrocytoma and nine patients with glioblastoma multiforme had median survival times of 33 months and 16 months, respectively. All of the tumor recurrences were within or were closely adjacent to the region of high-dose irradiation. None of the patients required a treatment break, and there were no acute complications. Two patients developed seizures in the follow-up period, and four patients were diagnosed with radionecrosis at the time of the second operation. The treatment program was found to be feasible and was well tolerated, and it resulted in a rate of late complications similar to those of radiosurgery or interstitial brachytherapy.

Adult↗
PubMed1998

Glycated albumin stimulates fibronectin gene expression in glomerular mesangial cells: involvement of the transforming growth factor-beta system.

Albumin modified by Amadori glucose adducts, formed in increased amounts in diabetes, stimulates collagen IV production and gene expression in renal glomerular mesangial cells, and induces mesangial matrix accumulation accompanied by increased mRNA encoding alpha 1 (IV) collagen and fibronectin in diabetic animals. These effects contribute to the pathogenesis of diabetic nephropathy, and resemble biologic activities of the cytokine TGF-beta 1, which also has been causally implicated in diabetic renal disease. We postulated that Amadori-modified glycated albumin modulates TGF-beta 1 expression in mesangial cells, and that TGF-beta 1 participates in mediating the glycated albumin-induced increases in mesangial cell matrix production. To test this hypothesis, we measured mRNA encoding TGF-beta 1, the TGF-beta Type II receptor and fibronectin, a key matrix component of the TGF-beta 1 tissue response, after incubation of mesangial cells with glycated albumin. Steady state levels of the mRNAs encoding for these proteins were stimulated when mesangial cells were cultured in the presence of albumin containing Amadori glucose adducts compared with levels in cells cultured with the nonglycated, glucose-free counterpart. The glycated protein-induced changes in mRNA expression were observed with concentrations of glycated albumin encompassing those found in clinical specimens and in media containing physiologic (5.5 mM) glucose concentrations, indicating that they were due to the glucose-modified protein and not to a hyperglycemic milieu. Further, they were accompanied by increased translated fibronectin protein, which was prevented with TGF-beta neutralizing antibody, as was the glycated albumin-induced increase in fibronectin mRNA. The findings indicate that Amadori-modified glycated albumin stimulates mesangial cell TGF-beta 1 gene expression by mechanisms that are operative under normoglycemic conditions. These data provide the first link between elevated glycated serum albumin concentrations and increased TGF-beta 1 bioactivity in the pathogenesis of mesangial matrix accumulation in diabetes.

Animals↗
PubMed1998

Effect of prolonged subcutaneous implantation of peritoneal catheter on peritonitis rate during CAPD: a prospective randomized study.

We conducted a prospective randomized controlled study to confirm our earlier observation that prolonged subcutaneous implantation of peritoneal catheter reduced peritonitis rate when compared to retrospective data from patients with catheters placed by conventional access technique. A total of 60 patients were randomized into two groups: 30 patients had catheters left implanted subcutaneously for 6 weeks (I) and the other 30 patients had catheters inserted by conventional technique and had 6 weeks of break-in period (C). Subgroups of 15 patients each with new and conventional techniques used Y-connector (IY, CY) and remaining patients used standard spikes (IS, CS). Mean age was 47.7 years (range 16-71); 61.0% were male and 44.1% diabetics. Peritonitis, exit site infection, simultaneous peritonitis and exit site infection, and complication related to Staphylococcus or Pseudomonas infections were observed for up to 2 years in each patient after initiation of bag exchange or until termination of CAPD by transfer to hemodialysis or by death. Total duration of observation was 493.2 patient-months for new access technique and 409.6 patient-months for conventional technique. Patients in IY group had the lowest incidence of peritonitis (1/14.9 patient-months) and exit site infection (1/16.8 patient-months) among four subgroups. Peritonitis rate in IY was significantly lower compared to CY or CS. The total peritonitis-free period in those patients who did not experience peritonitis during the observation period was also significantly longer in IY (120 patient-months) than in CY (26 patient-months), IS (10.6 patient-months), or CS (10.4 patient-months). Simultaneous peritonitis and exit site infection was observed in none of IY group but 3 episodes in CY, 4 episodes in IS, and 3 episodes in CS. The rates of complications related to Staphylococcus aureus and Pseudomonas infections were also significantly lower in IY than in CY, IS, or CS. Technique survival did not differ between the two groups. The present results confirm our previous observation that the new access technique reduces the incidence of peritonitis probably by reducing infection via periluminal route. The Y-connector system further reduces peritonitis rate by reducing infection via intraluminal route.

Adolescent↗
PubMed1998

The clinical complexity of splenic vein thrombosis.

Upper gastrointestinal hemorrhage secondary to splenic vein thrombosis is a curable form of localized portal hypertension when treated with splenectomy. A high index of suspicion is necessary in order to promptly diagnose and treat this underrecognized condition that is most commonly caused by inflammation or neoplasm of the pancreas. The triad of isolated gastric varices, splenomegaly, and normal hepatic function is classic; it is not uncommon, however, for patients to have only some or even none of these conditions. Mesenteric angiography with venous phase imaging is the gold standard of diagnosis. Ultrasound and CT may identify splenic vein thrombosis, but are most helpful in delineating concomitant upper abdominal pathology. Early recognition and intervention allow associated underlying conditions to be treated under the same anesthetic with minimal morbidity and mortality.

Adenocarcinoma↗
PubMed1996

In situ detection of hepatitis C virus RNA in liver tissue using a digoxigenin-labeled probe created during a polymerase chain reaction.

The cellular localization of hepatitis C virus (HCV) RNA in liver tissue was studied by nonisotopic in situ hybridization using a digoxigenin-labeled cDNA probe created during a polymerase chain reaction on samples from 16 patients with chronic HCV infection. Hybridization signals were recognized in the cytoplasm of the hepatocytes, and a few hepatocytes had hybridization signals in the nucleus as well. HCV RNA positive hepatocytes were found in 1 of 9 patients with chronic persistent hepatitis, 2 of 5 patients with chronic active hepatitis, and in each of 2 patients with chronic active hepatitis and cirrhosis. Positive signals were found in many hepatocytes within the lobule in liver sections of patients with advanced chronic active hepatitis. A number of HCV RNA positive hepatocytes were found in nodules, but not in the area of fibrosis. On the other hand, positive signals were found in a few hepatocytes scattered in the lobule in a patient with chronic persistent hepatitis. The mean ALT levels in the patients with positive signal (175.6 +/- 44.2 U/L) were significantly higher than in those without a signal (70.27 +/- 16.1 U/L) (P < 0.05). The findings suggest that a larger amount of HCV may be present during the advanced than during the early stages of type C hepatitis and nonisotopic in situ hybridization using a digoxigenin-labeled HCV cDNA probe created during a polymerase chain reaction deserves wider application for the detection of HCV replication in specimens.

Adult↗
PubMed1996

Ultrasound training during ATLS: an early start for surgical interns.

OBJECTIVES: Determine if: (1) surgical interns could learn essential ultrasound principles of the focused assessment for the sonographic examination of the trauma patient (FAST) during Advanced Trauma Life Support (ATLS), and (2) swine are adequate models for learning the FAST. DESIGN: Lecture, videotape, pre/posttests, and practical examination. METHODOLOGY: Day 1: Survey, pretest, lecture, and videotape. Day 2: Three swine, used in ATLS, had diagnostic peritoneal lavage catheters reinserted to infuse fluid and produce "positive" ultrasound examinations. Two fresh swine were "negatives"; however, all five swine were draped similarly to disguise interventions. Interns were tested individually by surgeon-sonographers to determine whether the ultrasound image was "positive" or "negative." Posttests were completed while surgeons performed postmortem examinations on two swine. STATISTICS: Paired Student's t test and Wilcoxon Rank Sum test. RESULTS: Survey (5 min): 48% had exposure to ultrasound. Relationship of test scores showed no significant difference (p = 0.46 to 0.91) between interns with and without ultrasound experience. Tests (30 min): Mean pre- and posttests scores = 65.6 and 90.8, respectively (p < 0.001). Practical examination (140 min): Mean score = 89.6. Postmortem examinations: Left hepatic lobe partially obscured the spleen. CONCLUSIONS: (1) Surgical interns can learn essential ultrasound principles of the FAST during ATLS (2) Swine are feasible models for learning the FAST.

Animals↗
PubMed1995

Surgical treatment of acute myocardial infarct: clinical considerations.

Most clinicians have become convinced of the fundamental role of an early reperfusion strategy in the improved outcome for patients suffering acute myocardial infarction. An increasing body of work suggests that the surgeon has the best opportunity for control of the conditions of acute reperfusion, attenuation of secondary injury, and provision of superior myocardial salvage compared with thrombolytic or angioplasty therapy. Before general acceptance or implementation of surgical treatment as an initial treatment for certain acute infarct patient subgroups, the policy must be compared with our current standards of care in a prospective, randomized fashion. The available data suggest that such inclusion of a primary surgical option in trials investigating treatment of acute myocardial infarct is long overdue.

Angioplasty, Balloon, Coronary↗
PubMed1994

A mutation in the receiver domain of the Agrobacterium tumefaciens transcriptional regulator VirG increases its affinity for operator DNA.

We fused the wild-type Agrobacterium tumefaciens virG gene and the constitutive virGN54D allele to the malE gene of Escherichia coli, and studied the binding of MBP-VirG fusions to the autoregulated virG promoter. MBP-VirGN54D protein bound this promoter with 10-fold higher affinity than MBP-VirG, and bound to vir box I with eightfold higher affinity than to vir box III. Disruption of vir box III did not alter the affinity for vir box I, suggesting a lack of cooperativity between these sites. We provide evidence that protein bound at a single vir box may have a higher oligomeric state than non-bound protein, and that a DNA distortion adjacent to vir box I may occur during activation.

Agrobacterium tumefaciens↗
PubMed1993

Effects of delayed treatment with enalapril and/or lovastatin on the progression of glomerulosclerosis in 5/6 nephrectomized rats.

To evaluate the effect of delayed treatment with enalapril or lovastatin on the progression of glomerulosclerosis and to examine if the combined treatment with enalapril and lovastatin show synergistic effect, a total of 31 Sprague-Dawley rats were studied for 16 weeks following 5/6 nephrectomy (NPX). Treatment was delayed until 8 weeks after NPX. In untreated control rats (n = 8), sustained systemic hypertension with increasing proteinuria, serum cholesterol, triglyceride, BUN and widespread glomerulosclerosis and mesangial expansion were observed. Treatment with enalapril alone (R, n = 8) reversed systemic hypertension, prevented a further increase in proteinuria, and significantly reduced glomerulosclerosis relative to the control group. Treatment with lovastatin alone (L, n = 7) also reduced glomerulosclerosis and serum cholesterol compared to the controls. The drug also prevented a further increase in proteinuria and systemic blood pressure although the difference from the control rats did not reach statistical significance. Treatment with both enalapril and lovastatin (RL, n = 8) almost completely prevented glomerulosclerosis and significantly reduced mesangial expansion, systemic blood pressure, serum cholesterol, and proteinuria compared to controls. Only the combined treatment stabilized BUN and reduced mesangial expansion compared to control R, or L groups. Conclusion. Delayed treatment with enalapril or lovastatin is effective in preventing the progression of glomerulosclerosis, and combined treatment appears to show synergistic effect in 5/6 nephrectomized rat model.

Animals↗
PubMed1992

Altered-function mutations of the transcriptional regulatory gene virG of Agrobacterium tumefaciens.

Three point mutations were isolated in the Agrobacterium tumefaciens virG gene by screening for vir gene expression in the absence of added phenolic inducing compounds. All three mutations were localized in the predicted amino-terminal phosphoryl receiver domain of the protein. One mutant (N54D) bypasses the requirement for VirA and phenolic inducers both for transcriptional activation of all tested vir promoters and for plant tumorigenesis. This mutant also activates vir gene expression efficiently at neutral pH, indicating that the step in induction that is normally stimulated by acid pH occurs before or during VirG phosphorylation. The other two mutants (M13T and H15R) require VirA for activity but are sensitized to low levels of inducing stimuli.

Acetophenones↗