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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
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↗
PubMed1996

Surgical resection for recurrent hepatocellular carcinoma: prognosis and analysis of risk factors.

BACKGROUND: Hepatocellular carcinoma (HCC) is common in Asian countries, and tumor recurrence is the most common cause of treatment failure after curative resection. Repeated hepatectomy is performed only for selected patients because most patients with HCC also have liver cirrhosis and poor liver function reserve. The purposes of this study were to clarify the outcome of the patients after second hepatectomy for recurrent HCC and to evaluate the prognostic factors after second hepatectomy. METHODS: We used retrospective cohort study to examine the disease-free survival, cumulative survival, and possible prognostic factors for recurrence and death in 59 patients who underwent surgical resection for recurrent HCC at the National Taiwan University Hospital from August 1986 to December 1993. Another 64 patients with unresectable recurrent HCC were used as a historical control group. The survival curves between those patients with resectable HCC and those with unresectable HCC were compared. RESULTS: After resection for recurrent HCC, gender and multiplicity (n > 3) of tumor affect recurrence rate (p = 0.046 and 0.021, respectively), whereas gender, age, and tumor invasiveness affect survival rate significantly (p = 0.024, 0.021, and 0.046, respectively). The survival rate of patients with resectable HCC was significantly better than that of those with unresectable HCC. CONCLUSIONS: For recurrent HCC surgical resection is an effective mode of treatment in selected patients. Whether surgery is better than other modes of treatment in the treatment of resectable recurrent HCC demands further investigation.

Adult↗
PubMed1995

Effect of polyamine analogues and inhibition of polyamine oxidase on spermidine/spermine N1-acetyltransferase activity and cell proliferation.

Several bis(ethyl)polyamine analogues are currently undergoing trials as antitumor agents. The ability of some of these analogues to induce spermidine/spermine N1-acetyltransferase and to inhibit cell proliferation was examined in a number of different cell lines. Although N1,N11 bis(ethyl)norspermine was a potent inducer of the acetylase in all cell lines tested, there was a striking difference in the acetylase induction in response to N,N'-bis(ethylamino)propyl]-1,7-heptanediamine. This was a very strong inducer in CHO cells but had no effect in HT29 cells and very little effect in COS-7 or L1210 cells. There was no correlation between the induction of the acetylase and the ability of these analogues to inhibit cell proliferation since N1,N11-bis(ethylamino)-propyl]-1,7-heptanediamine was as at least as strongly antiproliferative as N1,N11-bis(ethyl)-norspermine or N1,N12-bis(ethyl)spermine. Acetylase induction and the intracellular level of the analogues were increased in CHO cells by treatment with a polyamine oxidase inhibitor suggesting that they are degraded by polyamine oxidase. The absence of polyamine oxidase in some tumors may therefore contribute to their sensitivity to these analogues.

Acetyltransferases↗
PubMed1995

Changes of white blood cells, immunosuppressive acidic protein, and interleukin-2 receptor after open heart surgery.

There are a lot of immunological changes after major surgery, especially in open heart surgery when blood flows through a cardiopulmonary bypass system. We monitored leukocyte count, lymphocyte subpopulation count, soluble IL- 2 receptor (sIL-2r) and serum IL-2 levels, and an immunosuppressive acidic protein (IAP) level before and on the 1st, 7th, and 14th day after open heart surgery. It was noted that there were significant increases of total leukocyte and granulocyte counts for more than two weeks. But total lymphocyte, T-lymphocyte, b-lymphocyte, natural killer cell, suppressor T-cell, and helper T-cell all showed significant decreases in absolute numbers for more than one week as compared to the preoperative values. Serum IAP level was elevated for more than two weeks after operation. Serum IL-2 decreased but serum sIL-2R increased in the postoperative period. It is concluded that there is a period of immunosuppression after open heart surgery which lasts for at least one week and perhaps more than two weeks.

Adolescent↗
PubMed1995

Clinical management of recurrent hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to evaluate the long-term benefits of the aggressive treatments with resection or transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Primary HCC is one of the most fatal malignancies in Taiwan. The result of resection for HCC remains unsatisfactory, primarily due to the high recurrence rate. To improve surgical results, recurrent HCC must be treated with aggressive resection or TACE. METHODS: The authors evaluated the results of repeated hepatic resection among 25 patients with recurrent HCC and of TACE among 12 patients with resectable recurrent HCC. The outcomes of an additional 64 patients with unresectable recurrent HCC were also evaluated. RESULTS: During the follow-up period from 2-112 months, 52% (13/25) of patients receiving repeat resection (group 1) were alive, whereas 42% (5/12) of patients receiving TACE (group 2) were alive. No perioperative deaths within 30 days after surgery occurred in the repeated resection group. The cumulative survival rates at 1, 2, 3, and 5 years after the first operation were 92%, 84%, 71.6%, and 65.1% in group 1 and 83.3%, 75%, 75%, and 22.5% in group 2. The survival rates at 6 months and at 1, 2, and 3 years after recurrence were 92%, 72%, 64%, and 44.8% in group 1 and 83.3%, 75%, 66.7%, and 48% in group 2. The survival of patients with unresectable recurrent HCC was much worse: 1-, 2-, 3-, and 5-year survival after surgery was 57.8%, 29.8%, 15.5%, and 0%; and 6-month and 1-, 2-, and 3-year survival after recurrence was 46.5%, 29.2%, 12.5% and 7.8%. CONCLUSIONS: More aggressive treatment with repeated hepatic resection can prolong survival time after recurrence of HCC in selected patients. However, TACE can also achieve good results although it is not thought of as curative.

Aged↗
PubMed1995

Hepatic portal vein gas following blunt colon injury: report of a case.

Blunt colon injuries sometimes result in signs of peritoneal irritation requiring exploratory laparotomy. More frequently there are no specific symptoms, and this leads to a delay in diagnosis and management. Some imaging studies point to blunt colon injury, but gas in both the hepatic portal and mesenteric veins has rarely been reported. Hepatic portal venous gas (HPVG) is a rare roentgenographic picture, and its presence usually represents a serious intra-abdominal catastrophe. Computed tomography and plain abdominal X ray in a 52-year-old man with blunt abdominal injury showed significant gas in the portal venous system and pneumatosis intestinales of the ascending colon. Exploratory laparotomy revealed segmental necrosis of the transverse colon in front of the vertebrae. The presence of HPVG may have been due to mucosal disruption, vascular compromise or prolonged increased intra-abdominal pressure. Its presence in patients with blunt abdominal trauma suggests the possibility of bowel injury. Surgical exploration should be considered when HPVG is noted on roentgenographic studies.

Colectomy↗
PubMed1994

Effects of the S-adenosylmethionine decarboxylase inhibitor, 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine, on cell growth and polyamine metabolism and transport in Chinese hamster ovary cell cultures.

The regulation of polyamine transport and the roles of polyamine transport and synthesis in cell growth were investigated using cultured Chinese hamster ovary (CHO) cells and CHOMG cells which are mutants lacking polyamine-transport activity. Metabolically stable methylated polyamine analogues were used to measure polyamine accumulation, and the irreversible S-adenosyl-L-methionine decarboxylase inhibitor, 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine (AbeAdo), was used to inhibit synthesis. Exposure to AbeAdo lead to a dose-dependent decrease in growth for both cell lines, although CHOMG cells were more sensitive. Intracellular putrescine levels were greatly increased in AbeAdo-treated CHO cells and to a lesser extent in CHOMG cells, whereas intracellular spermidine and spermine levels were substantially reduced in both. Treatment with AbeAdo increased putrescine content in the culture medium to a much greater extent in CHOMG cultures indicating that a portion of the excess putrescine synthesized in response to AbeAdo treatment is excreted, but that CHO cells salvage this putrescine whereas it is lost to CHOMG cells which cannot take up polyamines. AbeAdo treatment increased polyamine transport into CHO cells despite high intracellular putrescine, suggesting that spermidine and/or spermine, and not putrescine, are the major factors regulating transport activity. The accumulation of either 1-methylspermidine or 1,12-dimethylspermine was significantly increased by AbeAdo treatment. Accumulation was increased even further when protein synthesis was blocked by cycloheximide, indicating that a short-lived protein is involved in the regulation of polyamine uptake. In the presence of cycloheximide and AbeAdo or alpha-difluoromethylornithine, methylated polyamine derivatives accumulated to very high levels leading to cell death. These results show that the polyamine-transport system plays an important role in retaining intracellular polyamines and that down-regulation of the transport system in response to increased intracellular polyamine content is necessary to prevent accumulation of toxic levels of polyamines.

Adenosylmethionine Decarboxylase↗