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Biomedical subjects

C D Lee

Publications and source records attributed to C D Lee.

31 records · Page 2Linked to original sources

Predictive factors for beneficial response to interferon-alfa therapy in chronic hepatitis C.

OBJECTIVES: Interferon is the only established treatment for chronic hepatitis C but the host-dependent or virus-related factors affecting the response rate to interferon therapy are not yet clear. The purpose of this study was to investigate the factors predictive of response to interferon-alfa therapy in chronic hepatitis C. METHODS: Twenty-five consecutive patients with chronic hepatitis C were randomized to three regimens of interferon-alfa: group A (n = 7, 3 MU every day for 3 months), group B (n = 8, 3 MU every other day for 3 months) and group C (n = 10, 3 MU every other day for 6 months). We quantified serum HC RNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR) and performed HCV genotyping using type-specific primers deduced form the NS5 region of the HCV genome. We also attempted to identify which demographic, biochemical and histologic factors in addition to virus-related factors would significantly predict beneficial response to interferon by multivariate analysis. RESULTS: Sustained responders were 8 (36.4%), nonsustained responders were 2 (9.1%) and nonresponders were 12 (54.5%) of 22 patients who had received complete therapy. The initial HCV RNA level (logarithmic transformed copy numbers per ml of serum) in sustained responders (5.75 +/- 0.39) was significantly lower than that of nonsustained responders (6.80 +/- 0.71) and nonresponders (6.70 +/- 0.52) (p < 0.05). In multivariate multiple logistic regression analysis, the serum HCV RNA level before therapy was only the independent predictor of a sustained response to interferon-alfa therapy (p = 0.001). CONCLUSIONS: Serum HCV RNA level before therapy was the most useful predictor of a sustained response to interferon-alfa therapy for chronic hepatitis C.

Adult↗

111Indium labeling of hepatocytes for analysis of short-term biodistribution of transplanted cells.

Hepatocyte transplantation is useful for ex vivo gene therapy and liver repopulation. Methods for hepatic reconstitution have recently been developed but optimization of hepatocyte transplantation systems is necessary. To develop systems for noninvasive assessment of the biodistribution of transplanted cells, we labeled hepatocytes with 111indium-oxine. Our initial studies showed that hepatocytes incorporated 111indium-oxine with an efficiency of approximately 20%. After labeling, cell viability was unchanged and 111indium was present in hepatocytes after overnight culture, as well as after intrasplenic transplantation. Transplanted cells were successfully localized by means of scintigraphic imaging. The scintigraphic patterns of cell distribution were different when hepatocytes were transplanted by means of either spleen or internal jugular vein, which deposit cells into separate vascular beds. Quantitative analysis of the biodistribution of 111indium-labeled hepatocytes indicated that within 2 hr of intrasplenic transplantation, cells were predominantly localized in liver and spleen, and occasionally in lungs. To determine whether the rate of intrasplenic cell injection influenced translocation of hepatocytes, we transplanted cells in normal rats. Despite intrasplenic cell injection at a variety of rates, organ-specific distribution of 111indium-labeled hepatocytes remained unchanged. Labeling with 111indium did not affect long-term survival of transplanted hepatocytes. These results indicate that 111indium-labeling of hepatocytes should greatly assist noninvasive analysis in the short-term of the biodistribution of transplanted hepatocytes.

Animals↗

Hepatocytes exhibit superior transgene expression after transplantation into liver and spleen compared with peritoneal cavity or dorsal fat pad: implications for hepatic gene therapy.

For hepatic gene therapy or applications of hepatocyte transplantation in liver failure, survival and function of transplanted cells is critical. Insights into site-specific gene regulation will significantly facilitate development of appropriate strategies for transplanting hepatocytes. To assess the function of transplanted cells, we used a transgenic hepatitis B virus (HBV) hepatocyte system, which allowed analysis of cellular gene expression with HBV surface antigen (HBsAg) mRNA expression, as well as secretion of HBsAg into peripheral circulation. When congeneic HBV hepatocytes were transplanted into the liver (via spleen), serum HBsAg promptly appeared in circulation and persisted for the entire duration of the studies. In contrast, transplantation of hepatocytes into the peritoneal cavity or dorsal fat pad resulted in serum HBsAg levels that were either significantly lower or gradually rose after a lag period. HBsAg mRNA expression was several-fold greater in transplanted hepatocytes in liver or spleen versus in peritoneal cavity or dorsal fat pad. Despite persistence of transplanted hepatocytes in peritoneal cavity or dorsal fat pad, serum HBsAg was cleared by antibody to HBsAg (anti-HBs) but this was not observed after hepatocyte transplantation into spleen. As the function of transplanted hepatocytes is optimally regulated in the liver, hepatic reconstitution with cell transplantation will be most appropriate for gene therapy.

Adipocytes↗

Studies on the safety of intrasplenic hepatocyte transplantation: relevance to ex vivo gene therapy and liver repopulation in acute hepatic failure.

Hepatocytes transplanted into the host liver engraft promptly, retain normal function, and survive indefinitely. Although intrasplenic transplantation is effective in delivering hepatocytes to the liver, to define potentially limiting complications, we studied its safety in normal, cirrhotic, and partial portal vein-ligated rats. In normal rats, portal pressures increased severalfold after hepatocyte transplantation but returned to normal within 3 weeks. In contrast, in portal hypertensive rats with partial portal vein ligation or cirrhosis, portal pressures were either unchanged or increased less after hepatocyte transplantation. However, more transplanted cells migrated to the lungs along with a rise in right atrial pressures in portal hypertensive rats. Further quantitative studies using 111Indium-labeled hepatocytes showed that intrasplenic retention of transplanted hepatocytes was similar in all animal groups. Intrahepatic cell translocation was comparable in normal and cirrhotic rats, whereas fewer cells migrated to the liver in partial portal vein-ligated rats. The most remarkable difference, however, was significantly greater intrapulmonary translocation of hepatocytes in portal hypertensive rats, which was presumably related to portosystemic shunting. These results indicate that because intrasplenic hepatocyte transplantation induces only temporary portal hypertension in normal subjects, potential strategies to augment liver repopulation could include repeated cell transplantation. This should be useful for optimizing the results of ex vivo gene therapy, or other hepatocyte-based therapies. However, the hepatic and portal hemodynamic status requires careful evaluation in portal hypertensive or cirrhotic subjects if serious complications are to be avoided.

Animals↗

Seroprevalence of antibody against hepatitis C virus (anti-HCV) in various groups of individuals in Korea.

We studied the prevalence of anti-HCV in 585 sera from various individuals, using enzyme immunoassay (EIA, Abbott Lab.). Anti-HCV was detected in 16 (10.7%) out of the 150 patients with HBsAg positive liver diseases diagnosed by liver biopsy and they consisted of none out of 10 acute viral hepatitis, 3 out of 15 chronic persistent hepatitis, 4 out of 50 chronic active hepatitis, 2 out of 32 liver cirrhosis, and 7 out of 43 hepatocellular carcinoma. Anti-HCV was detected in 43 (45.3%) out of 95 patients with HBsAg negative liver diseases diagnosed by liver biopsy and they consisted of 5 out of 8 acute viral hepatitis, 2 out of 10 chronic persistent hepatitis, 17 out of 30 chronic active hepatitis, 4 out of 15 liver cirrhosis, and 15 out of 32 hepatocellular carcinoma. Anti-HCV was detected in 22 (38.6%) out of 57 hemodialysis patients, in 3 (6.7%) out of 45 kidney transplants, in 2 (11.1%) out of 18 fatty liver diagnosed by liver biopsy, in 2 (1.3%) out of 150 healthy blood donors, in none out of 40 healthy volunteers, in 6 (31.6%) out of 19 rheumatoid arthritis and in 6 (54.5%) out of 11 systemic lupus erythematosis cases. There were familial clusters of chronic liver diseases in 4.7% of patients with HBsAg negative/anti-HCV positive chronic liver diseases, while in 19.4% of patients with HBsAg positive/anti-HCV negative liver diseases. Incidence of anti-HCV within patients with HBsAg positive liver diseases was higher in HBsAg negative patients than in HBsAg positive patients (17.6% and 10.3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Chi-Square Distribution↗

A case of subcutaneous seeding of hepatocellular carcinoma after fine needle aspiration biopsy.

Cancer spread along the needle track following fine needle aspiration biopsy is said to be a rare complication. The authors report a case of subcutaneous implantation of hepatocellular carcinoma following ultrasono-guided fine needle aspiration biopsy. The patient, a 67-year-old Korean male was found to have a large hepatocellular carcinoma diagnosed by fine needle aspiration biopsy. Four months later, the patient felt two subcutaneous growing lumps at the previous aspiration site. The authors confirmed them histologically 11 months after aspiration.

Aged↗

Activation/inactivation of human factor V by plasmin.

The effect of human plasmin on human coagulation factor V was studied using isolated proteins. Incubation of factor V with plasmin resulted in a rapid increase in procoagulant activity, followed by a subsequent decline in the ability of factor V to serve as a cofactor in the prothrombinase complex. Identical results were obtained when these reactions were conducted in the presence of dansylarginine-N-(3-ethyl-1,5-pentanediyl) amide (DAPA), indicating that the changes observed could not have occurred as a consequence of cleavage by alpha-thrombin. Analysis of the products of the reaction by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a temporal correlation between the rise and fall in factor V activity and the presence of several transient intermediates. These fragments are distinct from the subunits of alpha-thrombin-activated factor V (factor Va). The activation phase of the reaction was not significantly affected by the presence of phospholipid. In contrast, the rate of degradation of active fragments of factor V and the accompanying loss of activity were markedly enhanced in the presence of phospholipid vesicles. These data suggest that the action of plasmin upon factor V results in the transient formation of proteolytic fragments which express significant procoagulant activity.

Arginine↗

Cryopreservation and short-term storage of human lymphocytes for surface marker analysis. Comparison of three methods.

Three methods were compared for the cryopreservation and short-term storage of human lymphocytes for cell surface marker analysis with monoclonal antibodies and flow cytometry. These methods were controlled-rate freezing followed by storage in liquid nitrogen (CR), direct placement into liquid nitrogen (LN), and direct placement at -70 degrees C (-70). Our findings show that the LN and -70 methods of cryopreserving lymphocytes are as effective as the CR method for the purpose of determining T cell and large granular lymphocyte subsets within 1 month after freezing.

Antibodies, Monoclonal↗

Late development of umbilical metastasis after laparoscopic cholecystectomy for a gallbladder carcinoma.

A periumbilical mass developed 47 months after laparoscopic cholecystectomy. Pathologic examination of this mass showed features of moderately differentiated papillary adenocarcinoma, similar to that identified within the previously removed early stage (pT1b) gallbladder carcinoma. The cause of this at the laparoscope port is unclear. after laparoscopic cholecystectomy for gallbladder carcinoma has not been reported previously. We reported a case with late periumbilical tumor seeding at the navel trocar insertion site in a 65-year-old female. A review of the preventative information of tumor recurrence and management is discussed. The use of gasless laparoscopy, slow desufflation, trocar site washout, wound protector and specimen bags are recommended.

Abdominal Neoplasms↗

Evaluation of a media-based mammography program.

Reports indicate that only 15%-20% of women 50 years of age and older have had a mammogram. To promote screening mammography, the San Diego County Unit of the American Cancer Society sponsored a community-wide program that featured (1) discounted mammograms through participating clinics, (2) program promotion through television news, and (3) availability of a phone bank for obtaining referrals for mammography. Pre- and postintervention random sample phone surveys indicated that women's intentions to obtain a mammogram increased significantly after the media campaign, particularly in those aware of the program. Women's intentions after the media campaign predicted mammography compliance in the following year. A total of 3,102 women received mammograms directly through the program, with a "suspicious finding" rate of 4%. Participant satisfaction with the program was high.

Adult↗