Biomedical subjects

T Yoshizumi

Publications and source records attributed to T Yoshizumi.

At least 19 recordsLinked to original sources

PubMed2006

Feasibility of left lobe living donor liver transplantation between adults: an 8-year, single-center experience of 107 cases.

Operative mortality for a right lobe (RL) donor in adult living donor liver transplantation (LDLT) is estimated to be as high as 0.5-1%. To minimize the risk to the donor, left lobe (LL)-LDLT might be an ideal option in adult LDLT. The aim of the study was to assess the feasibility of LL-LDLT between adults based on a single-center experience of 107 LL-LDLTs performed over 8 years. The mean graft weight of LL grafts was 452 g, which amounted to 40.5% of the estimated standard liver volume of the recipients. The overall 1-, 3- and 5-year patient survival rates in LL-LDLT were 81.4, 76.9 and 74.7%, respectively, which were comparable to those of RL-LDLT. Twenty-six grafts (24.3%) were lost for various reasons with three losses directly attributable to small-for-size graft syndrome. Post-operative liver function and hospital stay in LL donors were significantly better and shorter than that in RL donors, while the incidence of donor morbidity was comparable between LL and RL donors. In conclusion, LL-LDLT was found to be a feasible option in adult-to-adult LDLT. Further utilization of LL grafts should be undertaken to keep the chance of donor morbidity and mortality minimal.

Adult↗

PubMed2005

Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values. METHODS: Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels. RESULTS: The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis. CONCLUSIONS: A high DCP value, namely >300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules.

Adult↗

PubMed2004

Is graft size a major risk factor in living-donor adult liver transplantation?

Graft size is known to be a major risk factor in living donor adult liver transplantation (LDALT). The aim of this study is to reassess whether graft size is a critical factor in LDALT or not. A series of 75 LDALTs excluding auxiliary transplantation and ABO blood-type incompatible transplantation were analyzed. The patients were divided into two groups, according to graft volume (GV) and standard liver volume (SLV): group 1 (small-size group) (GV/SLV: <40%), and group 2 (non-small-size group) (> or =40%). Perioperative clinical data were compared between the two groups, including graft survival and postoperative complications. These parameters were also compared under the conditions of cirrhotic recipients. No difference in graft survival was found between the two groups. No difference was found in incidence of postoperative complications, such as intractable ascites and persistent hyperbilirubinemia. Even in cirrhotic patients with Child-Pugh's class C, there was no difference in graft survival between the two groups. Risk factors related to graft loss were a preoperative urgent status due to chronic liver disease, pre-operative hyperbilirubinemia of over 10 mg/dl, and ABO blood type of not identical but compatible combination between donor and recipient. Graft size is not always considered to be a major risk factor in LDALT, although the number of patients was small in this study. Therefore, a left-lobe graft, even a "small-for-size" graft for adult recipients, remains a feasible option in LDALT.

Adolescent↗

PubMed2004

Accurate method for clinical assessment of right lobe liver weight in adult living-related liver transplant.

INTRODUCTION: Prior to transplantation of segmental liver grafts to adult recipients, it is crucial to confirm that the graft size is safe for the donor, yet adequate for the recipient's metabolic needs. Computed tomography (CT) and magnetic resonance imaging (MRI) are the current best standards. We applied a new formula to estimate right liver lobe weight in living donors and compared our results with CT and MRI. METHODS: Between August 1998 and December 20, 91 adults received right lobes from living donors. Donor liver volumes were assessed by CT or MRI. Actual weights of right lobe grafts were determined after back table flushing. We estimated whole liver weights using the formula: 772 x body surface area (BSA). Right lobe liver weight was calculated as 57% of the estimated whole liver weight (R-57). RESULTS: Mean actual right lobe weight (n = 90) was 855.83 +/- 183.4 g. Estimated right lobe weight was 858.08 +/- 90.80 (R-57, P = NS); 1077.35 +/- 263.07 mL for CT (P = .0001), and 1185.07 +/- 350.10 mL for MRI (P = .0001). Mean graft-recipient weight ratio (GRWR) was 1.23%; there was no significant difference with R-57 GRWR but there was a difference from CT and MRI-GRWR (P = .001). The proportion of cases of estimated right lobe weight and GRWR within 20% of the corresponding actual value were 80% and 90%, respectively, for R-57 versus 36% and 43% for the imaging studies (P = .0001). CONCLUSION: With readily available software to calculate BSA, physicians can predict right lobe weight knowing only the donor's height and weight. CT and MRI will only be necessary for anatomic liver mapping.

Adult↗

PubMed2004

S100 beta protein: the preoperative new clinical indicator of brain damage in patients with fulminant hepatic failure.

The aim of this study was to clarify the role of serum S100 beta on the accurate assessment of reversibility of brain damage after fulminant hepatic failure (FHF). Among the 13 patients with FHF enrolled in this study, 12 underwent living donor liver transplantation; one patient could not the procedure because of volvulus of the sigmoid colon. Serum S100 beta was serially measured using a chemiluminescent immunoassay. Preoperative serum S100 beta in patients with diffuse brain edema was significantly higher than that in patients with localized brain edema (P < 0.05). Patients with preoperative brain death showed serum S100 beta levels over 7.0 microg/L. Serum S100 beta levels correlated with the degree of brain edema of FHF. It has the potential to be a new clinical, noninvasive indicator of brain damage due to FHF.

Adult↗

PubMed2003

A simple new formula to assess liver weight.

INTRODUCTION: In cadaveric or segmental liver transplantation, accurate assessment of graft volume is desirable but not always easy to achieve based on donor morphometric data. We sought to establish a simple, reliable formula for accurate prediction of liver volume. METHODS: Data from 1,413 cadaveric adult and pediatric liver donors were analyzed using simple and multiple regression analysis. Liver weight (LW) was plotted against age, height, body weight (BW), body surface area (BSA) or body mass index (BMI); a formula was developed using simple regression: LW (g) = 772 (g/m(2)) x BSA, r = 0.73, P <.01. For donors with BSA </=1.0, a pediatric factor (PF) of 1.0 was included, resulting in the formula: LW (g) = 772 (g/m(2)) x BSA - 38PF, r = 0.73, P <.01. We then applied our formula on 5 published formulae to estimate LW of our donors. RESULTS: Among donors with BSA >1.0, there was no significant difference between the actual and the estimated mean LW as calculated by the new formula. For pediatric donors, there was no significant difference between estimated and actual mean liver weight with any formula. When the new formula was applied, the difference between the actual and the estimated liver weight was acceptable (<20%) in 1040 (73.6%) cases. In all races, there was no significant difference between actual and estimated mean liver weight as calculated by this formula. CONCLUSIONS: A simple formula to calculate liver weight in donors with BSA >1.0 is: LW = 772 x BSA, and for donors with BSA </=1.0: Liver Weight = 772 x BSA - 38.

Adolescent↗

PubMed2001

A novel approach for the development of selective Cdk4 inhibitors: library design based on locations of Cdk4 specific amino acid residues.

Identification of a selective inhibitor for a particular protein kinase without inhibition of other kinases is critical for use as a biological tool or drug. However, this is very difficult because there are hundreds of homologous kinases and their kinase domains including the ATP binding pocket have a common folding pattern. To address this issue, we applied the following structure-based approach for designing selective Cdk4 inhibitors: (1) identification of specifically altered amino acid residues around the ATP binding pocket in Cdk4 by comparison of 390 representative kinases, (2) prediction of appropriate positions to introduce substituents in lead compounds based on the locations of the altered amino acid residues and the binding modes of lead compounds, and (3) library design to interact with the altered amino acid residues supported by de novo design programs. Accordingly, Asp99, Thr102, and Gln98 of Cdk4, which are located in the p16 binding region, were selected as first target residues for specific interactions with Cdk4. Subsequently, the 5-position of the pyrazole ring in the pyrazol-3-ylurea class of lead compound (2a) was predicted to be a suitable position to introduce substituents. We then designed a chemical library of pyrazol-3-ylurea substituted with alkylaminomethyl groups based on the output structures of de novo design programs. Thus we identified a highly selective and potent Cdk4 inhibitor, 15b, substituted with a 5-chloroindan-2-ylaminomethyl group. Compound 15b showed higher selectivity on Cdk4 over those on not only Cdk1/2 (780-fold/190-fold) but also many other kinases (>430-fold) that have been tested thus far. The structural basis for Cdk4 selective inhibition by 15b was analyzed by combining molecular modeling and the X-ray analysis of the Cdk4 mimic Cdk2-inhibitor complex. The results suggest that the hydrogen bond with the carboxyl group of Asp99 and hydrophobic van der Waals contact with the side chains of Thr102 and Gln98 are important. Compound 15b was found to cause cell cycle arrest of the Rb(+) cancer cell line in the G(1) phase, indicating that it is a good biological tool.

Adenosine Triphosphate↗

PubMed2001

Abdominal ultrasonography reveals the perforation site of duodenal ulcers.

Regardless of whether or not the laparoscopic approach is used, the simple closure using an omental patch is considered to be preferable to other surgical therapies for a duodenal ulcer perforation. We used abdominal ultrasonography (US) to identify the perforation site of the duodenal ulcer. To our knowledge, this is the first report describing how the perforation site of duodenal ulcers can be identified using US. Three patients diagnosed with perforated duodenal ulcers based on abdominal computed tomography and abdominal radiographic findings were scheduled for surgery. Under general anesthesia, US demonstrated free air on the liver and a "fish-eye sign" when the anterior or lateral wall was perforated. We performed a simple closure using an omental patch through a skin incision measuring only 3 cm in diameter above the area showing the fish-eye sign. The postoperative recovery was no different from that seen when a laparoscopic approach is used at our hospital. Even though the laparoscopic procedure is still the surgical modality of choice, the US technique allows for a successful diagnosis without invasive examinations. We believe that most surgeons and/or radiologists should try to detect the fish-eye sign using US as the diagnostic modality of first choice if they suspect a duodenal ulcer perforation. This technique allows us to mark the perforation site accurately before surgery.

Duodenal Ulcer↗

PubMed2001

Cyclophosphamide-induced tolerance in rat orthotopic liver transplantation.

BACKGROUND: We previously established a cyclophosphamide (CP)-induced tolerance system in rodent skin graft models. In this study, we applied this system to rat liver transplantation. METHODS: Lewis recipients were inoculated on day -2 with spleen and bone marrow cells (SC+BMC) from Dark Agouti (DA) donors, followed by 100 mg/kg CP on day 0. On day 25, DA livers were orthotopically grafted. We assessed the alloresponses to the donors of the long-term surviving recipients, using the second skin grafting and in vitro assay. RESULTS: The recipients that had been treated with SC+BMC and CP survived for more than 165 days. None of control group that received SC+BMC alone (mean survival times [MST]=13.8 days), CP alone (MST=40.0), SC+BMC from third-party PVG rats and CP (MST=45.0), or no treatment (MST=13.8) survived over 50 days. The donor-specific tolerance was confirmed by second skin grafts onto recipients with permanent DA liver grafts, which accepted DA skins (MST>75) but not PVG (MST=8.3). However, the lymphocytes from the tolerant recipients showed alloresponse to DA in vitro. To investigate whether the T helper type 2 deviation contributed to this "split tolerance," we assessed the production of cytokines in mixed lymphocyte reaction. Interleukin 2 and interferon-gamma were detected but interleukin 4 was not. CONCLUSIONS: These data showed that this protocol induced split tolerance in rat liver transplantation and, furthermore, the mechanism of split tolerance was not due to T helper 2 deviation.

Animals↗

PubMed2001

Phytochrome-mediated control of COP1 gene expression in rice plants.

We isolated a COP1 cDNA from rice and found that it could complement the Arabidopsis cop1-4 mutant. The putative rice COP1 protein has the Ring-finger, coiled-coil. and WD-40 repeat domains, which are also conserved in pea, tomato, and mammalian COP1 proteins. The degree of overall identity between rice COP1 and Arabidopsis COP1 is 73%, and the similarity value is 83%. Expression of rice COP1 was detected in almost all plant tissues, with the level being relatively higher in calli and very low in etiolated leaves. The expression level was positively controlled by light in etiolated and green leaves. At the end of the light period, expression of the gene in green leaves could be down-regulated by far-red light. This far-red light effect could be prevented by subsequent irradiation with red light. These results indicate that phytochrome regulates rice COP1 expression.

Amino Acid Sequence↗

PubMed2001

Arabidopsis transcriptional regulation by light stress via hydrogen peroxide-dependent and -independent pathways.

BACKGROUND: High (intense) light stress causes the formation of oxygen radicals in chloroplasts and has the potential to damage them. However, plants are able to respond to this stress and protect the chloroplasts by various means, including transcriptional regulation in the nucleus. Although the corresponding signalling pathway is largely unknown, the high light response in the expression of the Arabidopsis APX2 gene is reported to be mediated by hydrogen peroxide. RESULTS: We characterized light stress signalling by analysing expression profiles of another high light-inducible gene of Arabidopsis, ELIP2, with the aid of an ELIP2 promoter-luciferase gene fusion. The established ELIP2:LUC transgenic Arabidopsis showed activation by high light, but not by hydrogen peroxide. On the other hand, the native ELIP2 gene as well as the APX2 gene was activated by the hydrogen peroxide. The activation of ELIP2:LUC by intense light was not inhibited by K252a but by okadaic acid. CONCLUSION: The light stress signalling from the chloroplast to the nucleus is revealed to be mediated through at least two pathways: both hydrogen peroxide-dependent and -independent. The latter pathway is thought to be mediated by the protein phosphatase 2A/1 activity that is suppressed by okadaic acid.

Arabidopsis↗

PubMed2001

DFL1, an auxin-responsive GH3 gene homologue, negatively regulates shoot cell elongation and lateral root formation, and positively regulates the light response of hypocotyl length.

A novel dominant mutant designated 'dwarf in light 1' (dfl1-D) was isolated from screening around 1200 Arabidopsis activation-tagged lines. dfl1-D has a shorter hypocotyl under blue, red and far-red light, but not in darkness. Inhibition of cell elongation in shoots caused an exaggerated dwarf phenotype in the adult plant. The lateral root growth of dfl1-D was inhibited without any reduction of primary root length. The genomic DNA adjacent to the right border of T-DNA was cloned by plasmid rescue. The rescued genomic DNA contained a gene encoding a GH3 homologue. The transcript was highly accumulated in the dfl1-D. The dfl1-D phenotype was confirmed by over-expression of the gene in the wild-type plant. The dfl1-D showed resistance to exogenous auxin treatment. Moreover, over-expression of antisense DFL1 resulted in larger shoots and an increase in the number of lateral roots. These results indicate that the gene product of DFL1 is involved in auxin signal transduction, and inhibits shoot and hypocotyl cell elongation and lateral root cell differentiation in light.

Amino Acid Sequence↗

PubMed2001

Small graft for living donor liver transplantation.

OBJECTIVE: To evaluate the impact of graft size on recipients in living donor liver transplantation (LDLT) to establish a clinical guideline for the minimum requirement. SUMMARY BACKGROUND DATA: Although the minimum graft size required for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver volume (SLV), the safety limit of the graft size was unknown. METHODS: A total of 33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a minimum observation period of 4 months. The 33 patients were divided into three groups according to GV/SLV: medium-size graft group, small-size graft group, and extra-small graft group. The effect of GV/SLV on graft function, graft regeneration, and survival was evaluated. RESULTS: The overall patient survival rate was 94% at a mean follow-up of 15 months with a minimum observation period of 4 months. There were no statistically significant differences in postoperative bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of postoperative complications among the three groups. One week after transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra-small and small groups was significantly higher than that of the medium group. The graft and patient survival rates were both 100% in the extra-small group, 75% and 88% in the small group, and 90% and 95% in the medium group. CONCLUSIONS: Small-for-size grafts less than 30% of SLV can be used with careful intraoperative and postoperative management until the grafts regenerate.

Adult↗

PubMed2001

One hundred nine living donor liver transplants in adults and children: a single-center experience.

OBJECTIVE: To summarize the evolution of a living donor liver transplant program and the authors' experience with 109 cases. SUMMARY BACKGROUND DATA: The authors' institution began to offer living donor liver transplants to children in 1993 and to adults in 1998. METHODS: Donors were healthy, ages 18 to 60 years, related or unrelated, and ABO-compatible (except in one case). Donor evaluation was thorough. Liver biopsy was performed for abnormal lipid profiles or a history of significant alcohol use, a body mass index more than 28, or suspected steatosis. Imaging studies included angiography, computed tomography, endoscopic retrograde cholangiopancreatography, and magnetic resonance imaging. Recipient evaluation and management were the same as for cadaveric transplant. RESULTS: After ABO screening, 136 potential donors were evaluated for 113 recipients; 23 donors withdrew for medical or personal reasons. Four donor surgeries were aborted; 109 transplants were performed. Fifty children (18 years or younger) received 47 left lateral segments and 3 left lobes; 59 adults received 50 right lobes and 9 left lobes. The average donor hospital stay was 6 days. Two donors each required one unit of banked blood. Right lobe donors had three bile leaks from the cut surface of the liver; all resolved. Another right lobe donor had prolonged hyperbilirubinemia. Three donors had small bowel obstructions; two required operation. All donors are alive and well. The most common indications for transplant were biliary atresia in children (56%) and hepatitis C in adults (40%); 35.6% of adults had hepatocellular carcinoma. Biliary reconstructions in all children and 44 adults were with a Roux-en-Y hepaticojejunostomy; 15 adults had duct-to-duct anastomoses. The incidence of major vascular complications was 12% in children and 11.8% in adult recipients. Children had three bile leaks (6%) and six (12%) biliary strictures. Adult patients had 14 (23.7%) bile leaks and 4 (6.8%) biliary strictures. Patient and graft survival rates were 87.6% and 81%, respectively, at 1 year and 75.1% and 69.6% at 5 years. In children, patient and graft survival rates were 89.9% and 85.8%, respectively, at 1 year and 80.9% and 78% at 5 years. In adults, patient and graft survival rates were 85.6% and 77%, respectively, at 1 year. CONCLUSION: Living donor liver transplantation has become an important option for our patients and has dramatically changed our approach to patients with liver failure. The donor surgery is safe and can be done with minimal complications. We expect that living donor liver transplants will represent more than 50% of our transplants within 3 years.

ABO Blood-Group System↗

PubMed2001

[Chemotherapy (low-dose CDDP + UFT) to advanced pancreatic cancer in an ambulatory setting improved survival and quality of life].

The prognosis of pancreatic cancer is very poor. Past attempts to treat advanced pancreatic cancer with single agent or combination chemotherapy have yielded low response rates and little reproducible impact on patient survival or quality of life. We performed systemic chemotherapy in case of unresectable or recurrent pancreatic cancer with CDDP 25 mg/body intravenous weekly or biweekly and oral administration of UFT (300-400 mg/day) as an outpatient treatment. Tumor markers were well controlled for about over one year or more. This ambulatory combination is a well-tolerated regimen that results in improved survival and quality of life.

Ambulatory Care↗

PubMed2000

Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation.

BACKGROUND: Proinflammatory cytokines such as interleukin 1-beta (IL-1beta) and tumor necrosis factor-a (TNF-alpha) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been characterized as a potent suppressant of IL-1beta and TNF-alpha production. The aim of this study was to evaluate the effect of FR167653 on cold ischemia/ reperfusion injury in rat liver transplantation. METHODS: Donor livers were preserved with cold University of Wisconsin solution for 48 hr and transplanted orthotopically. Immediately after reperfusion, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulation of IL-1beta and TNF-alpha mRNA in the liver was analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Tissue factor expression was subjected to immunohistochemical analysis. RESULTS: In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P<0.05 and P<0.02, respectively), and histological liver injury was less prominent, than in the control group. Accumulation of IL-1beta and TNF-alpha mRNA was suppressed in the FR-treated liver. Tissue factor expression on Kupffer cells and sinusoidal endothelial cells, marked in the control group, was almost absent in the FR-treated group. Seven-day survival in the FR-treated group (75%) was significantly better than that in the control group (12.5%) (P<0.01). CONCLUSIONS: These results indicate that treatment with FR167653 ameliorates cold ischemia/reperfusion injury in liver transplantation.

Animals↗

PubMed2000

Domino liver transplantation from a living related donor.

BACKGROUND: Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. METHODS: The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). RESULTS: The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. CONCLUSION: A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.

Amyloid Neuropathies↗

PubMed2000

Clip migration causes choledocholithiasis after laparoscopic cholecystectomy.

The migration of surgical clips after laparoscopic procedures was first reported in 1992, but such instances are extremely rare. We herein demonstrate a case of a migrated metal clip, which had been applied originally to the cystic duct, but thereafter had moved to the common bile duct. This clip caused choledocholithiasis in a patient 1 year after a laparoscopic cholecystectomy. A 63-year-old man underwent a laparoscopic cholecystectomy. During the operation, the inflamed cystic duct was divided accidentally, and three clips were applied immediately. The patient complained of upper abdominal pain from postoperative day 8. Endoscopic retrograde cholangiography demonstrated bile leakage from the cystic duct, but showed no clips or choledochal stones. The patient complained of severe upper abdominal and back pain 1 year after the operation. Endoscopic retrograde cholangiography showed a metal clip in the common bile duct and choledochal stones above the clip. The clip and the cholesterol stones were removed using a basket catheter. Three clips applied to the cystic duct should have been removed because of the necrosis in the remaining cystic duct. Thereafter, the clip may have migrated through the stump of the cystic duct into the lower part of the common bile duct. This clip seems to have later caused choledocholithiasis resulting from stagnation of the bile flow. Bile leakage after an operation seems to increase the risk of clip migration. Regardless of the primary lesion, a careful follow-up evaluation is necessary for patients demonstrating complications.

Cholangiography↗