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S Ko

Publications and source records attributed to S Ko.

At least 37 records · Page 2Linked to original sources
PubMed2000

Efficacy and safety of preoperative lobar or segmental ablation via transarterial administration of ethiodol and ethanol mixture for treatment of hepatocellular carcinoma: clinical study.

Transarterial embolization (TAE) using various thrombotic substances for unresectable hepatocellular carcinoma (HCC) performed on many patients has resulted in a better survival rate. We evaluated the efficacy and clinical safety of using an Ethiodol-ethanol mixture as the embolizer for treatment of HCC and the possibility of a surgical approach for inoperable tumors after TAE. Twenty patients with HCC who underwent TAE and tumor resection were included in the study. Initially, eight had increased retention rate of indocyanine green dye via intravenous injection (0.5 mg/kg) at 15 minutes (ICGR15), and six had an insufficient residual volume that precluded them from undergoing tumor resection. TAE was performed by slowly infusing the mixture of Ethiodol and ethanol into the artery supplying the tumor until dual hepatic artery and portal vein embolization was achieved. Serum levels of alanine aminotransferase increased after embolization, but all biochemistry studies reverted to normal within 2 weeks. A decreased tumor size (n = 15), improved ICG (n = 8), and increased volume of the nonembolized lobe (n = 10) were noted. The operations performed were right lobectomy (n = 11), extended right lobectomy (n = 3), left lobectomy (n = 2), extended left lobectomy (n = 2), and wedge resection (n = 2), which included patients who did not want to undergo major hepatectomy. Complete tumor necrosis was found in seven cases. All patients survived with no associated complications. The 1-year survival rate was 95%. Transarterial Ethiodol and ethanol administration creating dual hepatic artery and portal vein embolization was a safe and efficacious method for treating HCC. It effectively decreases tumor size, causes compensatory hepatic hypertrophy, and improves the ICGR15, which allows a wider range of patients to undergo liver surgery and achieve better survival.

Adult↗
PubMed2000

Humoral human xenoreactivity against isolated pig pancreatic islets.

It is widely believed that the hyperacute rejection of vascularized xenografts in the pig-to-human combination is triggered by the binding of human preformed natural antibodies (PNAbs) to the Galalpha.(1,3)Gal epitope in pig endothelium and the subsequent activation of complement. However, it remains poorly defined whether xenogeneic pig pancreatic islets are damaged by antibody and complement-mediated mechanisms. We examined the expression of Galalpha(1,3)Gal on isolated adult pig islets and the presence of PNAbs in normal human sera directed against islets, using immunofluorescence staining and confocal laser scanning microscopy. The pig islets were not stained with Galalpha(1,3)Gal-specific lectin GSIB4, however, the exocrine cells reacted strongly with GSIB4, indicating that the Galalpha(1,3)Gal epitope was highly expressed on exocrine cells, but not on islets. Human sera showed weak reactivity of IgM and IgG class PNAbs to the islets, but strong reactivity to the exocrine cells. Furthermore, we investigated the cytotoxic effect of human serum on pig islets using an in vitro model of pig-to-human islet transplantation. The incubation of pig islets with normal human sera for 45 min resulted in less than 10% specific lysis despite the binding of PNAbs, whereas exposure of porcine aortic endothelial cells to the same human sera caused 56% complement-mediated lysis, determined using a MTT cytotoxic assay. These results support the view that pig islets might not undergo early antibody and complement-mediated rejection in humans.

Animals↗
PubMed2000

The impact of interferon gamma receptor expression on the mechanism of escape from host immune surveillance in hepatocellular carcinoma.

Interferon gamma (IFN-gamma) plays an important role in host defense mechanism and participates in the progression of chronic liver disease. IFN-gamma exerts its pleiotrophic effects by transcriptional regulation of expression of numerous genes, such as major histocompatibility complex (MHC) class I and Fas, through interaction with IFN-gamma receptor (IFN-gamma-R). Although hepatocytes in normal liver express weak or no IFN-gamma-R, those in acute and chronic liver disease up-regulate its expression. A study using IFN-gamma-R alpha-chain knock-out mice revealed the actions of IFN-gamma on tumor cells as an extrinsic tumor-suppressor mechanism. However, it is unclear whether or how hepatocellular carcinoma (HCC) blocks the signal transduction of IFN-gamma to evade host immune surveillance. We examined the expression of IFN-gamma-R and IFN-gamma-inducible genes in 44 cases with HCC using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In noncancerous liver tissues (n = 38), IFN-gamma-R expression on the cell surface was up-regulated in 27 cases. In IFN-gamma-R-negative cases (n = 15), tumor size was larger (P =.032), serum alpha-fetoprotein (AFP) level was higher (P =.001), intrahepatic and extrahepatic metastasis was more common (P =.044 and.013, respectively), and Ki-67 labeling index (LI) was higher (P =.041), compared with IFN-gamma-R-positive cases. Accordingly, the evasion mechanism may play an important role in progression, especially metastasis, in HCC. The significant correlation between the status of IFN-gamma-R and the expression of Fas and MHC implies that the loss of IFN-gamma-R might contribute to the mechanism of escape from host immune rejection in HCC.

Aged↗
PubMed2000

Slow rise of Ca2+ and slow release of reactive oxygen species are two cross-talked events important in tumour necrosis factor-alpha-mediated apoptosis.

Tumour necrosis factor-alpha (TNF-alpha) was found to be a cell cycle-independent apoptogenic cytokine in cultured fibroblast L929 cells. This assertion is based on the observations (1) TNF-alpha increased the number of cells with hypo-diploid DNA in a time dependent manner as revealed by flow cytometry, and (2) TNF-alpha induced DNA fragmentation as resolved by agarose gel electrophoresis. When cells were exposed to TNF-alpha (50 ng/ml), a slow rise in intracellular free Ca2+ level and a delayed increase in the production of reactive oxygen species (ROS) (both observed 3 h after the addition of TNF-alpha) were observed in fluo-3 and fura-red or dichlorofluorescein loaded cells, respectively. Interestingly, challenge of cells with TNF-alpha in the presence of BAPTA/AM, an intracellular Ca2+ chelator, decreased the release of ROS. Removal of ROS by 4-hydroxy 2,2,6,6-tetra-methyl-piperidinooxy (4OH-TEMPO) blocked the TNF-alpha-mediated Ca2+ rise. Moreover, when cells were exposed to TNF-alpha with both 4OH-TEMPO and BAPTA/AM, more viable cells were found than from treatment with either BAPTA/AM or 4OH-TEMPO. These results suggest that ROS and cellular Ca2+ are two cross-talk messengers important in TNF-alpha-mediated apoptosis.

Animals↗
PubMed2000

Sonic wave separation of invertase from a dilute solution to generated droplets.

It has previously been shown that a droplet fractionation process, simulated by shaking a separatory funnel containing a dilute protein solution, can generate droplets richer in protein than present in the original dilute solution. In this article, we describe an alternative method that can increase the amount of protein transferred to the droplets. The new method uses ultrasonic waves, enhanced by a bubble gas stream to create the droplets. The amount of protein in these droplets increases by about 50%. In this method, the top layer of the dilute protein solution (of the solution-air interface) becomes enriched in protein when air is bubbled into the solution. This concentrating procedure is called bubble fractionation. Once the protein has passed through the initial buildup, this enriched protein layer is transferred into droplets with the aid of a vacuum above the solution at the same time that ultrasonic waves are introduced. The droplets are then carried over to a condenser and coalesced. We found that this new method provides an easier way to remove the protein-enriched top layer of the dilute solution and generates more droplets within a shorter period than the separatory funnel droplet generation method. The added air creates the bubbles and carries the droplets, and the vacuum helps remove the effluent airstream from the condenser. The maximum partition coefficient, the ratio of the protein concentration in the droplets to that in the residual solution (approx 8.5), occurred at pH 5.0.

Glycoside Hydrolases↗
PubMed2000

Effect of shear on human insulin in zinc suspension.

Human insulin in zinc suspension was used as a model protein to test the effect of shear on the settling rate of proteins, a possible inference for protein denaturation. The rate of settling was determined directly in a spectrophotometer. Shear effects are important in retaining the activity of proteins and are present in bubble, foam, and droplet protein fractionation processes. A simple test, such as that conducted here, may even be useful for monitoring changes in protein structure caused by commercial shipping of the protein. The settling rate for insulin was continuously monitored in the original bottle by spectrophotometric absorbance changes as a function of time. A settling curve was determined following each shear experiment, which included shaking the "worked" insulin solution in a vortex mixer for different lengths of time. It was determined, when comparing long shaking times with short ones, that the initial settling rate was less for the long-term shaking of the insulin samples and greater for the short-term shaking. The secondary effects of light and heat, along with shaking, apparently did not produce differences from shaking alone.

Drug Stability↗
PubMed2000

Effect of protein denaturation on void fraction in foam separation column.

Foam fractionation is a cost-effective process that uses air to extract protein from a liquid (in this case "crude" dilute egg-albumin solution). This article deals with how the void fraction (fraction of air in the aerated solution) of foam is affected by heat denaturation of the protein. A 2-mm glass tube was used to sample the foam-liquid interface fluid in a 35-mm-diameter column in order to detect small changes in void fraction and foam production, which are not easily detected directly from the bulk foam. The main control variable in this study was the protein solution preheating time. As the preheating time increased, the initial void fraction in the column decreased. The initial void fraction of the undenatured solution ranged from about 0.73 to 0.80, and the void fraction for significant preheating times of 5 min ranged from approx 0.68 to 0.72. Furthermore, the period of foam production increased from 5 to 7 min for undenatured proteins in solution to as long 15 min for 5-min preheated solutions. Side-port sampling through a small capillary tube has the potential to be used as a rapid and inexpensive way to determine the level of protein denaturation by directly determining the void fraction and then estimating the effect of denaturation from a protein denaturation calibration curve of the void fraction.

Biotechnology↗
PubMed1999

The alteration of Fas receptor and ligand system in hepatocellular carcinomas: how do hepatoma cells escape from the host immune surveillance in vivo?

Escape from the immune surveillance may play an important role in tumor outgrowth and metastasis. Alteration of the Fas receptor (Fas)/ligand (FasL) system including soluble forms is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells. However, less attention has been paid to the role of Fas/FasL interaction in vivo. Therefore, we investigated the expression of Fas and FasL by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) and measured the serum levels of soluble Fas (sFas) and FasL (sFasL) in 44 patients with hepatocellular carcinoma (HCC). In the noncancerous liver tissues, Fas expression was up-regulated in most cases, and FasL expression was detected in 6 cases. In Fas-positive HCC cases (n = 15), the intrahepatic metastatic foci was less (P =.037), apoptosis of tumor cells was more (P =.004), the disease-free survival rate was higher (P =.004), and p53-positive cases were less (P =.003), compared with Fas-negative cases. The sFas and sFasL levels in HCC patients were significantly higher and lower than those in controls, respectively. RT-PCR and immunohistochemistry revealed generation of sFas in the hepatocytes and tumor-infiltrating mononuclear cells rather than in hepatoma cells. Accordingly, hepatoma cells may eliminate Fas expression on themselves and let the hepatocytes and infiltrating mononuclear cells generate sFas to escape from the immune system and to produce metastasis. FasL might contribute to malignant transformation in some circumstances, because hepatocytes in the pericancerous pseudolobules expressed FasL.

Adult↗
PubMed1999

The functional relevance of passenger leukocytes and microchimerism for heart allograft acceptance in the rat.

With an organ transplant, hematopoietic donor cells are transferred to the recipient. To study the relevance of the resulting microchimerism for allograft acceptance, we analyzed a rat model of cyclosporine-induced tolerance for strongly incompatible heart allografts. Using a monoclonal antibody that detects a donor-specific CD45 allotype (RT7a), we selectively depleted donor leukocytes at different times after transplantation (days 0 or 18). Depletion was similarly effective at both times. However, only depletion on day 0 prevented tolerance induction and was associated with severe acute or chronic graft rejection. This indicates that passenger leukocytes have an essential immunomodulatory effect on the induction phase of allograft acceptance.

Animals↗
PubMed1999

Partitioning invertase between a dilute water solution and generated droplets.

Water droplets or mist occur naturally in the air at seashores. These water droplets carry inorganic and organic substances from the sea to the land via the air, creating fertile land in sandy coastal areas (1). The same phenomenon occurs in an air-fluidized bed bioreactor (2). In an air-fluidized bed reactor, proteins can be transferred from the bioreactor semisolid bulk phase to an enriched droplet phase. This protein transfer process (droplet fractionation) can be experimentally simulated by shaking a separatory funnel containing a dilute solution of a given protein, which can be an enzyme like invertase. The created droplets become richer in invertase (protein) than that of the original dilute solution. The droplets can then be coalesced by trapping them and recovering the concentrated protein in the new liquid phase. Typically, in such a droplet fractionation process a collected enzyme can be degraded in its ability to catalyze a chemical reaction. In this article, we explore whether the initial solution pH control variable can be adjusted to minimize the decrease of enzyme activity in this process. The protein droplet recovery problem is one in which the recovered amount of desired protein (enzyme) in the droplet is maximized, subject to the minimization of the enzyme activity loss. The partition coefficient, which is the ratio between the protein concentration in the droplets and the residual solution, is maximized at approx 4.8 and occurs at pH 3.0. Here, the partition coefficient for invertase decreases as the initial solution pH increases, between pH 3.0 and 8.0. Interestingly, the initial solution surface tension seems to be inversely proportional to the partition coefficient. The partition coefficient reaches a maximum value at a surface tension value of approx 63 mN/m at pH 3.0. The enzymatic activity of the initial, the residual, and the droplet solutions all decrease as the bulk solution pH increases. A decrease of enzymatic activity was observed in the residual bulk solution when compared with that in the initial bulk solution at all pH levels. Also, up to 90% of the invertase activity was lost in the droplets when compared to the initial bulk solution.

Journal Article↗
PubMed1999

Enhanced production of mineralized nodules and collagenous proteins in vitro by calcium ascorbate supplemented with vitamin C metabolites.

BACKGROUND: Vitamin C or ascorbate is important in wound healing due to its essential role in collagen synthesis. To study wound healing in the periodontium, cells adherent to expanded polytetrafluoroethylene (ePTFE) augmentation membranes, recovered from edentulous ridge augmentation procedures, have been established in culture in our laboratories. The objective of this study was to determine whether treatment of these cells with a calcium ascorbate, which contains vitamin C metabolites (metabolite-supplemented ascorbate), would increase the production of collagenous protein and mineralized tissue in vitro, as compared to unsupplemented calcium ascorbate (ascorbate). METHODS: Cells derived from ePTFE membranes were cultured with beta-glycerophosphate and the test agents for 2 to 5 weeks, and the surface areas of the cell cultures occupied by mineralized nodules were measured using computerized image analysis. One experiment tested the effects of calcium threonate, one of the vitamin C metabolites in metabolite-supplemented ascorbate. Incorporation of radioactive proline and glycine was used as a measure of total protein (radioactivity precipitated by trichloracetic acid) and collagenase-digestible protein (radioactivity released by collagenase digestion.) Co-localization of collagen and fibronectin was examined by immunofluorescence. RESULTS: In vitro treatment of these cells with metabolite-supplemented ascorbate increased the area of the cell cultures occupied by mineralized nodules after 5 weeks. Cell cultures treated with metabolite-supplemented ascorbate also exhibited significant increases in total protein. The increase in collagenous proteins in these cultures accounted for 85% of the increase in total protein. The greatest difference between treatment groups was observed in the cell-associated fraction containing the extracellular matrix. The additional collagen exhibited normal co-distribution with fibronectin. In cultures treated with ascorbate spiked with calcium threonate, the area of mineralized tissue was significantly greater than in ascorbate-treated cultures, but was less than that observed in cultures treated with metabolite-supplemented ascorbate. CONCLUSIONS: In vitro treatment with ascorbate containing vitamin C metabolites enhanced the formation of mineralized nodules and collagenous proteins. Calcium threonate may be one of the metabolites influencing the mineralization process. Identifying factors which facilitate the formation of mineralized tissue has significant clinical ramifications in terms of wound healing and bone regeneration.

Alveolar Ridge Augmentation↗
PubMed1999

The serum interleukin 8 level reflects hepatic mitochondrial redox state in hyperthermochemohypoxic isolated liver perfusion with use of a venovenous bypass.

BACKGROUND: We have recently developed a simple method of hyperthermochemohypoxic isolated liver perfusion (HILP) as a regional therapy for unrecognized liver micrometastases. However, little is known about the influence of HILP on cytokine production and liver function. We investigated the influence of HILP on interleukin 8 (IL-8) production and the hepatic mitochondrial function and assessed the relationship between these 2 parameters. We also measured the serum tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels to examine the involvement of HILP-induced cytokines in the tumor response. METHODS: Sixteen patients with metastatic liver tumors were randomly assigned to undergo hepatectomy with HILP (group A, n = 9) or hepatectomy alone (group B, n = 7). The isolated liver was perfused for 30 minutes with Ringer's lactate solution containing chemotherapeutic agents warmed to 42 degrees C to 43 degrees C without oxygenation. RESULTS: The serum IL-8 levels in group A were markedly increased, with peaks at 3 hours after reperfusion, which was significantly higher than levels in group B (P < .01). In group A the arterial ketone body ratio, which reflects the hepatic mitochondrial redox state, decreased during perfusion and was gradually restored to the preperfusion level 1 hour after reperfusion. However, in group B it decreased during hepatectomy but rapidly recovered 5 minutes after hepatectomy. There was a significant negative correlation between the peak serum IL-8 level and the initial velocity of arterial ketone body ratio recovery for the first 5 minutes after reperfusion r = -0.83, P < .001). The serum TNF-alpha and IL-1 beta were temporarily detected only in 3 of 9 patients in group A. CONCLUSIONS: We have shown that HILP resulted in augmented IL-8 release but not TNF-alpha and IL-1 beta and that the serum IL-8 level reflects the hepatic mitochondrial redox state. These findings suggest that IL-8 production may be associated with hepatic mitochondrial impairment during ischemia. This work may contribute to new therapeutic strategies not only for hepatic ischemia reperfusion injury but also for metastatic liver tumors.

Aged↗
PubMed1998

The effect of VIP/PACAP family of peptides on pancreatic blood flow and secretion in conscious dogs.

The effects of PACAP-38, PACAP-27, VIP and secretin on pancreatic blood flow were compared with those of meals in five conscious dogs using an ultrasound transit-time blood flow meter. All peptides (1-100 pmol/kg) induced dose-related increases of pancreatic blood flow, and fluid and bicarbonate secretion. Only PACAPs stimulated protein secretion. Both PACAPs at doses which did not stimulate pancreatic secretion, induced significant pancreatic vasodilatation. VIP was less potent than PACAP-38 and PACAP-27 at lower doses (1-25 pmol/kg), but was similar to PACAPs at higher doses. The maximal effects of PACAPs and VIP were comparable to those observed after meals. Secretin was a significant but weak vasodilator. When pancreatic secretion was maximally stimulated by secretin, a reduction of vascular resistance was 75% of postprandial peak levels. PACAP(6-38), a competitive antagonist of PACAP, inhibited pancreatic vascular responses to PACAPs, but not those to VIP and secretin. Its inhibitory effects on protein response to PACAPs were not significant. Atropine inhibited pancreatic protein but not the vascular effect of PACAP-27. Pancreatic vasodilatation by PACAPs appears to be mediated by both PACAP-specific and VIP/PACAP common receptors in dogs. PACAP, like VIP, is a good candidate for a mediator of atropine-resistant vasodilatation of the pancreas.

Animals↗
PubMed1998

Hyperthermo-chemo-hypoxic isolated liver perfusion for hepatic metastases: a possible adjuvant approach.

As a possible intraoperative adjuvant approach to treating hepatic metastases we developed a method of hyperthermo-chemo-hypoxic isolated liver perfusion in combination with hepatic resection. This method was applied to 11 patients with colorectal hepatic metastases between 1992 and 1995. One patient died on postoperative day 14 of hepatic failure (9% mortality), the cause of which was live temperature that reached 42.9 degree C, which seems to be the maximum limit for thermal toxic effect on the human liver. The other 10 patients tolerated the perfusion well, with mild hepatic and non systemic toxicity after minor or even major hepatic resection; the serum aminotransferase and total bilirubin levels returned to normal levels by postoperative day 14. Only one of eight patients (13%) for whom cytotoxic drugs were added to the perfusate (mitomycin C 10 micrograms/ml or cisplatin 2 micrograms/ml) had hepatic recurrence by 19 months after the perfusion (mean follow-up 25.8 months; median 23 months; range 8-57 months). Two patients were alive with no evidence of disease at 13 and 57 months, respectively after the perfusion; the other five patients had postperfusion extrahepatic recurrences (median: 19 months; range 7-20 months). In contrast, hepatic metastases recurred 7 and 20 months after the perfusion, respectively, in the two patients not given a cytotoxic drug.

Aged↗