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Biomedical subjects

R H Hu

Publications and source records attributed to R H Hu.

At least 19 recordsLinked to original sources
PubMed2004

Do patients with acute liver failure have a better chance to receive liver grafting?

OBJECTIVE: Patients with acute hepatic failure (AHF) were always given first priority on the transplant waiting list. We investigated whether AHF patients will deprive other patients on the waiting list of the chance of liver transplantation (LTx). METHODS AND RESULTS: From January 1999 to March 2003, a total of 423 patients were on the transplant waiting list at the National Taiwan University Hospital. Sixty-five of the patients had AHF caused by hepatitis-B-related disease (HBV, n = 52, 80%), Wilson disease (n = 3, 4.6%), drug-induced AHF (n = 3, 4.6%), and other causes (n = 7, 10.8%).Thirty-three patients died and 16 survived by medical treatment. Two received LTx abroad and 14 underwent LTx at our hospital (7 living-related; 7 cadaver). A total of 140 patients died while waiting for a transplant during the period studied. Of them, 107 were among 358 non-AHF patients (30%), and time-to-death interval was 133 +/- 175 days (median: 62); 33 were among 65 AHF patients (51%); time to death was 19 +/- 28 days (median: 8). There were 35 cadaver donor livers available during the period; 28 of 358 non-AHF patients (7.8%), and 7 of 65 AHF patients (10.7%) received cadaveric LTx. Their waiting time totaled 342 +/- 316 and 12 +/- 9 days, respectively (P < .0001). CONCLUSION: Most AHF patients died unless they received liver grafts. Even with a higher priority assigned to them, AHF patients still have little chance to get a cadaver donor liver in Taiwan, and non-AHF patients have an even slimmer chance. Therefore, we need to encourage liver donation from living-related donors.

Cadaver↗
PubMed2000

Suppression of tumor necrosis factor secretion from white blood cells by synthetic antisense phosphorothioate oligodeoxynucleotides.

In this ex vivo, rather than in vitro, experiment, a synthetic antisense oligodeoxynucleotide was tested to suppress tumor necrosis factor - alpha(TNF) secretion from lipopolysaccharide-stimulated white blood cells. Antisense oligomer showed significant and specific suppressive effect to the secretion of TNF at concentrations of 1.0 and 10 microM. At the concentration of 1 microM, there were 68.4 and 63.9% suppression of TNF secretion at 2 and 24 h after resuspension of blood cells. At the concentration of 10 microM, the suppressions were slightly higher than those at 1 microM, which were 71.8 and 76.2%, respectively. A 50%-matched scrambler showed suppressive effect only at 10 microM concentration, and the suppression only occurred at 2 and 24 h after incubation. Sense oligomer showed no suppressive effects at any of the concentrations. The specificity of this oligomer was documented by dose-effect phenomenon, sequence-dependent suppression and absence of effect on the synthesis of another cytokine (interleukin-6). A series of parallel studies was performed and showed that all three oligomers at any concentration tested had no effect on the interleukin-6 secretion after LPS stimulation.In conclusion, properly designed antisense oligodeoxynucleotide can significantly and specifically suppress the secretion of TNF by blood cells in an ex vivo system and it may be a good "information" drug to treat diseases that are caused by over production of TNF.

Cycloheximide↗
PubMed1999

Secretion of acute-phase proteins before and after hepatocellular carcinoma resection.

Hepatocyte growth factor (HGF), interleukin-6 (IL-6), and C-reactive protein (CRP) are acute-phase reactants that are usually present at high concentrations in the serum of patients with liver disease. However, the origin of these high serum concentrations is not completely understood, and whether hepatocellular carcinoma (HCC) tissue is a contributing factor is a controversial issue. The purpose of this study was to investigate the profiles of these three proteins in patients with HCC before and after tumor resection, and to study factors that might affect the serum concentrations of these proteins. A retrospective cohort study was performed in 34 consecutive patients who underwent HCC resection at the National Taiwan University Hospital. Blood samples were collected before surgery and on days 1, 3, 5, 7, and 14 postoperatively for serum concentration determinations of these three proteins. Twenty-three patients admitted for health examinations were enrolled as normal controls. Multiple regression analysis was conducted to evaluate the correlations between the pre- and postoperative cytokine concentrations and various clinical parameters. Compared with normal controls, the HCC patients had a significantly higher preoperative concentration of HGF (1,472 +/- 73 vs 948 +/- 54 ng/mL, p < 0.001) and IL-6 (44.1 +/- 6.9 vs 8.1 +/- 3.2 pg/mL, p = 0.012). These concentrations peaked on the first postoperative day and then declined to preoperative values on the fifth postoperative day. The CRP concentration was also higher in HCC patients (0.88 +/- 0.22 vs 0.21 +/- 0.06 mg/dL, p = 0.222), but the difference was not statistically significant. However, the CRP concentration did not return to the preoperative value within 2 weeks postoperatively. Preoperatively, HGF and CRP concentrations were positively affected by larger tumor size, and IL-6 concentration was negatively affected by hepatitis B surface antigen positivity and a higher indocyanine green (ICG) retention rate. In summary, the serum concentrations of HGF and IL-6 were significantly higher in HCC patients than in normal controls. The serum concentrations of HGF, IL-6, and CRP rose dramatically after HCC resection. The concentrations of these proteins were affected by different clinical parameters. We proved indirectly that high serum concentrations of HGF, IL-6, and CRP in patients with HCC do not result primarily from synthesis by the tumor cells. Whether the preoperative concentrations of these proteins correlate with the clinical outcome needs further follow-up.

Acute-Phase Proteins↗
PubMed1998

A rabbit model for metabolic studies after burn injury.

BACKGROUND: A rabbit burn model was developed and characterized, which will allow conduct of repeated, noninvasive and more sophisticated in vivo metabolic studies to explore the pathophysiology of burn injury, owing to its larger blood volume and tissue mass than the rat. MATERIALS AND METHODS: A 20% body surface, full thickness burn was applied to the backs of six anesthetized rabbits by immersion into a boiling-water bath for 10 s, followed by resuscitation with saline. Resting energy expenditure (REE) was measured daily in pre- and postburn periods. Whole body protein kinetics were evaluated using L-[1(-13)C]leucine tracer, on the preburn and the third postburn day. Fasting plasma glucose was also measured. RESULTS: A significant elevation of REE began on the second postburn day and reached 34 +/- 8% above the preburn level (P < 0.05, paired t test) on the third postburn day. The fasting plasma leucine flux and oxidation were significantly elevated from their preburn levels (both P < 0.05), indicating an accelerated proteolysis and a more negative body protein balance (P < 0.05); however, the rate of whole body protein synthesis did not differ significantly pre- and postburn injury. Fasting plasma glucose also increased (P < 0.001). on the third postburn day. The burn scar remained intact during the study, without any sign of infection. CONCLUSIONS: The metabolic changes observed in this animal model can be attributed to burn injury per se and they mimic those for flow phase in burn patients. This rabbit burn model should be suitable for exploring mechanistic aspects of the burn-induced changes in metabolism and nutrient balance.

Animals↗
PubMed1997

Rapid induction of apoptosis by deregulated uptake of polyamine analogues.

Treatment of Chinese hamster ovary cells with alpha-difluoromethylornithine for 3 days, followed by exposure to cycloheximide, led to an unregulated, rapid and massive accumulation of polyamine analogues. This accumulation led to cell death by apoptosis within a few hours. Clear evidence of DNA fragmentation was seen in response to both N-terminally ethylated polyamines and to polyamines containing methyl groups on the terminal carbon atoms. Programmed cell death was induced within 2-4 h of exposure to 1 microM or higher concentrations of N1,N11-bis(ethyl)norspermine. The presence of cycloheximide increased the uptake of the polyamine analogues and therefore led to cell death at lower analogue concentrations, but it was not essential for the induction of apoptosis, since similar effects were seen when the protein synthesis inhibitor was omitted and the concentration of N1, N11-bis(ethyl)norspermine was increased to 5 microM or more. The induction of apoptosis was blocked both by the addition of the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, or by the addition of the polyamine oxidase inhibitor N1-methyl-N2-(2,3-butadienyl)butane-1,4-diamine (MDL 72,527). These experiments provide evidence to support the concepts that: (1) polyamines or their oxidation products may be initiators of programmed cell death; (2) regulation of polyamine biosynthesis and uptake prevents the accumulation of toxic levels of polyamines; and (3) the anti-neoplastic effects of bis(ethyl) polyamine analogues may be due to the induction of apoptosis in sensitive tumour cells.

Alkylation↗
PubMed1996

Regulation of ornithine decarboxylase in a transformed cell line that overexpresses translation initiation factor eIF-4E.

pMV7-4E cells (4E-P2), derived from NIH-3T3 cells, overexpress eIF-4E and exhibit characteristics of transformation, possibly due to translational relief of mRNAs encoding proteins that regulate cell growth. Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, is induced in 4E-P2 cells, and this induction appears to be related to the transformed phenotype of these cells. ODC mRNA contains extensive secondary structure in its 5' untranslated region (5'UTR) and may be regulated by eIF-4E, which melts mRNA secondary structure. To better understand this regulation, cDNA constructs containing the wild-type 5'UTR of ODC or deletion mutants inserted ahead of the luciferase gene were transfected into 4E-P2 and 3T3 cells. Expression of luciferase was higher in 4E-P2 cells in all cases, suggesting that the secondary structure of the ODC 5'UTR inhibits expression in 3T3 cells, and this inhibition is overcome by the high eIF-4E levels in 4E-P2 cells. When a small open reading frame present in the 5'UTR of ODC was destroyed by a point mutation, this luciferase construct was expressed about 6-fold over that containing the wild-type 5'UTR in both cell lines, although both of these 5'UTRs contain the same predicted secondary structure. Thus, factors in addition to eIF-4E may be involved in the regulation of ODC. To examine the differences in ODC regulation by polyamines in normal and transformed cells, the effect of N1,N12-bis(ethyl)spermine (BE-3-4-3) on the synthesis and degradation of ODC was examined. ODC activity in 4E-P2 cells was 10 times less sensitive to reduction by BE-3-4-3 compared to 3T3 cells, suggesting that high ODC levels in eIF-4E-overexpressing cells are the result of decreased regulation by polyamines as well as relief of translational regulation by eIF-4E.

3T3 Cells↗
PubMed1996

Surgical treatment of hepatocellular carcinoma originating from the caudate lobe.

Hepatocellular carcinoma (HCC) originating from the caudate lobe is rare, and its surgical management is difficult because of its unique anatomic location. We have seen six such cases at our hospital. For patients with fair to excellent liver reserve, we advocated caudate lobectomy combining other types of hepatic resection. For patients with marked liver cirrhosis and poor liver reserve or a small HCC, we advocated simple partial caudate lobectomy (limited hepatic resection). There was no operative mortality or major operative morbidity. We conclude that such approaches are safer, less time-consuming, and less technique-demanding, and they produce a fair survival result compared with the approaches of other procedures. With such approaches, it is our experience that patients with HCC from the caudate lobe have a prognosis comparable to that of patients with HCC in other parts of the liver.

Adult↗