Biomedical subjects

T Kinoshita

Publications and source records attributed to T Kinoshita.

At least 127 records · Page 7Linked to original sources

PubMed2000

HSNF5/INI1 gene mutations in lymphoid malignancy.

hSNF5/INI1 is one of the components of the SWI/SNF multiprotein complex that is necessary for the transcriptional activation of several genes and functions by altering chromatin structure. This gene has been thought to be one of the tumor suppressor genes (TSGs) because deletions or mutations were reported in malignant rhabdoid tumors and atypical teratoid and rhabdoid tumors. To evaluate the hSNF5/INI1 gene as a TSG in lymphoid malignancies, we performed a mutational analysis in 23 patients with non-Hodgkin lymphoma (NHL), 24 with acute lymphoblastic leukemia (ALL), 24 with multiple myeloma (MM), 24 with adult T-cell lymphoma/leukemia (ATLL), and 19 with lymphoid cell lines, by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis. Nonsense and missense mutations were found in 1 NHL case and 2 cell lines. Mutations from this NHL case proved to be somatic in origin. These data indicated that alterations in the hSNF5/INI1 gene might be involved in the pathogenesis of lymphoid malignancies.

Base Sequence↗

PubMed2000

Critical roles of glycosylphosphatidylinositol for Trypanosoma brucei.

Trypanosoma brucei, the protozoan parasite responsible for sleeping sickness, evades the immune response of mammalian hosts and digestion in the gut of the insect vector by means of its coat proteins tethered to the cell surface via glycosylphosphatidylinositol (GPI) anchors. To evaluate the importance of GPI for parasite survival, we cloned and disrupted a trypanosomal gene, TbGPI10, involved in biosynthesis of GPI. TbGPI10 encodes a protein of 558 amino acids having 25% and 23% sequence identity to human PIG-B and Saccharomyces cerevisiae Gpi10p, respectively. TbGPI10 restored biosynthesis of GPI in a mouse mutant cell line defective in mouse Pig-b gene. TbGPI10 also rescued the inviability of GPI10-disrupted S. cerevisiae, indicating that TbGPI10 is the orthologue of PIG-B/GPI10 that is involved in the transfer of the third mannose to GPI. The bloodstream form of T. brucei could not lose TbGPI10; therefore, GPI synthesis is essential for growth of mammalian stage parasites. Procyclic form cells (insect stage parasites) lacking the surface coat proteins because of disruption of TbGPI10 are viable and grow slower than normal, provided that they are cultured in nonadherent flasks. In regular flasks, they adhered to the plastic surface and died. Infectivity to tsetse flies is partially impaired, particularly in the early stage. Therefore, parasitespecific inhibition of GPI biosynthesis should be an effective chemotherapy target against African trypanosomiasis.

Animals↗

PubMed2000

Endoscopic surgery for lateral cervical cysts. A report of three cases.

Recently, endoscopic surgery has been applied to cervical exploration. We have developed new techniques for endoscopic neck surgery, and in this paper report our experience with three patients with lateral cervical cysts. A 5- or 10-mm midline trocar for the endoscope and two 5- or 10-mm lateral trocars were inserted from the anterior chest wall and/or both axillary fossae to avoid neck scars. There were no intraoperative complications. Slight subcutaneus emphysema was present postoperatively, but it was limited to the neck and disappeared in a few days. The incisions were completely covered by the patients' undergarments. This is the first report of endoscopic lateral cervical cystectomy.

Adolescent↗

PubMed2000

Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2.

Glycosylphosphatidylinositols (GPIs) are attached to the C-termini of many proteins, thereby acting as membrane anchors. Biosynthesis of GPI is initiated by GPI-N-acetylglucosaminyltransferase (GPI-GnT), which transfers N-acetylglucosamine from UDP- N-acetylglucosamine to phosphatidylinositol. GPI-GnT is a uniquely complex glycosyltransferase, consisting of at least four proteins, PIG-A, PIG-H, PIG-C and GPI1. Here, we report that GPI-GnT requires another component, termed PIG-P, and that DPM2, which regulates dolichol-phosphate-mannose synthase, also regulates GPI-GnT. PIG-P, a 134-amino acid protein having two hydrophobic domains, associates with PIG-A and GPI1. PIG-P is essential for GPI-GnT since a cell lacking PIG-P is GPI-anchor negative. DPM2, but not two other components of dolichol-phosphate-mannose synthase, associates with GPI-GnT through interactions with PIG-A, PIG-C and GPI1. Lec15 cell, a null mutant of DPM2, synthesizes early GPI intermediates, indicating that DPM2 is not essential for GPI-GnT; however, the enzyme activity is enhanced 3-fold in the presence of DPM2. These results reveal new essential and regulatory components of GPI-GnT and imply co-regulation of GPI-GnT and the dolichol-phosphate-mannose synthase that generates a mannosyl donor for GPI.

Amino Acid Sequence↗

PubMed2000

Stereoselective synthesis of CF(2)-substituted phosphothreonine mimetics and their incorporation into peptides using newly developed deprotection procedures.

Stereoselective syntheses of all four stereoisomers of CF(2)-substituted nonhydrolyzable phosphothreonine derivatives (33, 39, and their enantiomers) and their incorporation into peptides are described herein. Key to the synthesis of these amino acids was construction of secondary phosphate-mimicking difluoromethylphosphonate units along with generation of two stereocenters. The former was achieved using a Cu(I)-mediated cross-coupling reaction of BrZnCF(2)P(O)(OEt)(2) (8) and beta-iodo-alpha,beta-unsaturated ester 12, with stereochemistry of both alpha- and beta-stereocenters being established using bornane-10,2-sultam as a chiral auxiliary. Diastereoselective hydrogenation of a chiral alpha,beta-unsaturated acylsultam (for the beta-center) (e.g., 16a) and subsequent stereoselective bromination (for the alpha-center of the threo derivative) or amination (for the alpha-center of erythro (allo) derivative) were utilized. Transesterification of the bromide to the benzyl ester followed by azide displacement of the halogen, then reduction of the resulting azide, followed by Boc-protection and finally removal of the benzyl group, afforded protected both L- and D-phosphothreonine mimetics (39 and its enantiomer). On the other hand, protected both L- and D-allo-phosphothreonine mimetics (33 and its enantiomer) were synthesized via transesterification of the above-mentioned amination product, followed by hydrogenolytic removal of the benzyl group. Key to utilization of these amino acid analogues in peptide synthesis was removal of ethyl protection from the difluoromethylphosphonate moiety. A two-step deprotection methodology, consisting of a combination of a first-step reagent [0.3 M BSTFA-TBAI in CH(2)Cl(2), BF(3).Et(2)O] followed by a second-step reagent [1 M TMSOTf-thioanisole in TFA, m-cresol, EDT] was developed for use in solid-phase protocols. A 12-residue Cdc (cell division cycle) 2-peptide 41, possessing two nonhydrolyzable phosphoamino acid mimetics (F(2)Pmab 6 and F(2)Pmp 4), was subjected to this deprotection procedure and was obtained in 25% yield based on the protected resin. The present synthetic method affords nonhydrolyzable phosphoamino acid mimetics-containing peptides in high yield without accompanying side reactions.

Indicators and Reagents↗

PubMed2000

Cloning and expression of human B cell-specific transcription factor BACH2 mapped to chromosome 6q15.

The transcription factor Bach2, a member of the BTB-basic region leucine zipper (bZip) factor family, binds to a 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive element and the related Maf-recognition element (MARE) by forming homodimers or heterodimers with Maf-related transcription factors. Bach2 regulates transcription by binding to these elements. To understand the function in hematopoiesis, we isolated a cDNA clone for human Bach2 (BACH2) encoding a protein of 841 amino acid residues with a deduced amino acid sequence having 89.5% identity to mouse homolog. Among human hematopoietic cell lines, BACH2 is expressed abundantly only in some B-lymphocytic cell lines. RT-PCR analysis of hematopoietic cells revealed that BACH2 mRNA is expressed in primary B-cells. Enforced expression of BACH2 in a human Burkitt cell line, RAJI that does not express endogenous BACH2, resulted in marked reduction of clonogenic activity, indicating that BACH2 possesses an inhibitory effect on cell proliferation. By fluorescent in situ hybridization, the BACH2 gene was localized to chromosome 6q15. Because deletion of the long arm of chromosome 6 (6q) is one of the commonest chromosomal alterations in human B-cell lymphoma, we examined for the loss of heterozygosity (LOH) of the BACH2 gene in human B-cell non-Hodgkin's lymphomas (NHL). Among 25 informative cases, five (20%) showed LOH. These results indicate that BACH2 plays important roles in regulation of B cell development.

Adult↗

PubMed2000

Requirement of PIG-F and PIG-O for transferring phosphoethanolamine to the third mannose in glycosylphosphatidylinositol.

Many eukaryotic proteins are anchored by glycosylphosphatidylinositol (GPI) to the cell surface membrane. The GPI anchor is linked to proteins by an amide bond formed between the carboxyl terminus and phosphoethanolamine attached to the third mannose. Here, we report the roles of two mammalian genes involved in transfer of phosphoethanolamine to the third mannose in GPI. We cloned a mouse gene termed Pig-o that encodes a 1101-amino acid PIG-O protein bearing regions conserved in various phosphodiesterases. Pig-o knockout F9 embryonal carcinoma cells expressed very little GPI-anchored proteins and accumulated the same major GPI intermediate as the mouse class F mutant cell, which is defective in transferring phosphoethanolamine to the third mannose due to mutant Pig-f gene. PIG-O and PIG-F proteins associate with each other, and the stability of PIG-O was dependent upon PIG-F. However, the class F cell is completely deficient in the surface expression of GPI-anchored proteins. A minor GPI intermediate seen in Pig-o knockout but not class F cells had more than three mannoses with phosphoethanolamines on the first and third mannoses, suggesting that this GPI may account for the low expression of GPI-anchored proteins. Therefore, mammalian cells have redundant activities in transferring phosphoethanolamine to the third mannose, both of which require PIG-F.

Amino Acid Sequence↗

PubMed2000

Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3.

Dolichol-phosphate-mannose (DPM) synthase generates mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein O- and C-mannosylation. In Saccharomyces cerevisiae, this enzyme is encoded by DPM1. We reported previously that mammalian DPM synthase contains catalytic DPM1 and regulatory DPM2 subunits, and that DPM1 requires DPM2 for its stable expression in the endoplasmic reticulum. Here we report that human DPM synthase consists of three subunits. The third subunit, DPM3, comprises 92 amino acids associated with DPM1 via its C-terminal domain and with DPM2 via its N-terminal portion. The stability of DPM3 was dependent upon DPM2. However, overexpression of DPM3 in Lec15 cells, a null mutant of DPM2, restored the biosynthesis of DPM with an increase in DPM1, indicating that DPM3 directly stabilized DPM1. Therefore, DPM2 stabilizes DPM3 and DPM3 stabilizes DPM1. DPM synthase activity was 10 times higher in the presence of DPM2, indicating that DPM2 also plays a role in the enzymatic reaction. Schizosaccharomyces pombe has proteins that resemble three human subunits; S.pombe DPM3 restored biosynthesis of DPM in Lec15 cells, indicating its orthologous relationship to human DPM3.

Amino Acid Sequence↗

PubMed2000

Retinoic acid is a negative regulator for the differentiation of cord blood-derived human mast cell progenitors.

We examined the effects of retinoids on the human mast cell development using a serum-deprived culture system. When 10-week cultured mast cells derived from CD34(+) cord blood cells were used as target cells, both all-trans retinoic acid (ATRA) and 9-cis RA inhibited the progeny generation under stimulation with stem cell factor (SCF) in a dose-dependent manner (the number of progeny grown by SCF plus RA at 10(-7) mol/L was one tenth of the value obtained by SCF alone). The early steps in mast cell development appear to be less sensitive to RA according to the single CD34(+)c-kit(+) cord blood cell culture study. The optimal concentration of RAs also reduced the histamine concentration in the cultured mast cells (3.00 +/- 0.47 pg per cell in SCF alone, 1.44 +/- 0.18 pg per cell in SCF+ATRA, and 1.41 +/- 0.10 pg per cell in SCF+9-cis RA). RT-PCR analyses showed the expression of RARalpha, RARbeta, RXRalpha, and RXRbeta messenger ribonucleic acid (mRNA) in 10-week cultured mast cells. The addition of an RAR-selective agonist at 10(-10) mol/L to 10(-7) mol/L decreased the number of mast cells grown in SCF, whereas an RXR-selective agonist at up to 10(-8) mol/L was inactive. Among RAR subtype selective retinoids used at 10(-9) mol/L to 10(-7) mol/L, only the RARalpha agonist was equivalent to ATRA at 10(-7) mol/L in its ability to inhibit mast cell growth. Conversely, the addition of excess concentrations of a RARalpha antagonist profoundly counteracted the retinoid-mediated suppressive effects. These results suggest that RA inhibits SCF-dependent differentiation of human mast cell progenitors through a specific receptor. (Blood. 2000;95:2821-2828)

Alitretinoin↗

PubMed2000

Pseudogap formation in the intermetallic compounds (Fe1-xVx)3Al

Optical conductivity data of the intermetallic compounds (Fe1-xVx)3Al ( 0</=x</=0.33) reveal that their density of states around the Fermi energy ( E(F)) is strongly reduced as x is increased. In particular, Fe2VAl ( x = 0.33) has a deep, well-developed pseudogap of 0.1-0.2 eV at E(F) and a small density ( approximately 5x10(20) cm(-3)) of carriers, which is highly unusual for intermetallic compounds. It is shown that the pseudogap results from the band structure of Fe2VAl, rather than from temperature-dependent correlation effects. Based on the present results, we propose a simple model that consistently explains both the semiconductorlike transport and the metallic photoemission results previously observed for Fe2VAl.

Journal Article↗

PubMed2000

Structure of porcine pancreatic elastase complexed with FR901277, a novel macrocyclic inhibitor of elastases, at 1.6 A resolution.

Human leukocyte elastase (HLE) is a serine protease that contributes to tissue destruction in various disease states-for example, in emphysema. FR901277 is a natural product isolated from the culture filtrate of Streptomyces resistomicificus and is a potent inhibitor of both HLE and porcine pancreatic elastase (PPE). FR901277 consists of four normal amino acids and three unusual amino acids, and is a unique bicyclic peptide compound. The crystal structure of PPE complexed with FR901277 has been determined at 1.6 A resolution. The Ogamma atom of Ser-195 in PPE did not form a covalent bond with FR901277, but formed a hydrogen bond with the Nvarepsilon atom of His-57. On the other hand, the portion from L-Orn(1) through dehydroxyThr(3) in FR901277 formed an antiparallel beta-sheet structure with the backbone of the active site in PPE. The S4 through S2' binding subsites in PPE were all occupied by the hydrophobic side chains of the inhibitor molecule. Especially, the ethylidene moiety of FR901277 occupied the S1 specific pocket, indicating a CH/pi interaction. In addition, the isopropyl side chain of L-Val(7) was located at the enzyme surface between the S2 and S1' pockets with several van der Waals contacts. However, the amino acid (4) residue was not involved in a significant interaction with PPE. Comparison of inhibitor structures in different environments showed that FR901277 has a highly rigid bicyclic framework; however, it can slightly change its conformation according to the circumstances. The binding mode of FR901277 at the active site of PPE was directly applicable to that in HLE, after consideration of induced fit. The structure of the PPE-FR901277 complex provided much information regarding potential sites for modification of the physicochemical properties of FR901277.

Amides↗

PubMed2000

A new system for the anterior restoration and fixation of thoracic spinal deformities using an endoscopic approach.

STUDY DESIGN: A report on the results of animal experiments in which the authors' new system that enables the anterior correction and fixation of thoracic spinal deformity by use of a thoracic endoscope and small incisions was used. The results suggest that the new approach involving thoracoscopic anterior correction and fusion for thoracic spinal deformity could be adapted successfully for the clinic. OBJECTIVE: To develop a new system that enables the anterior correction and fixation of thoracic spinal deformity by use of a thoracic endoscope and small incisions. SUMMARY OF BACKGROUND DATA: Anterior correction and fusion through open thoracotomy have been applied mainly for thoracic scoliosis because this approach provides effective correction with short fusion. However, excellent visualization of the spine during thoracic surgical procedures led to the development of thoracoscopic spine surgery. Therefore, the authors postulated that a thoracoscopic approach could allow not only discectomy but also correction and fusion of the deformed thoracic spine in a single surgical event. METHODS: The vertebral columns and attached thoracic walls were dissected from fresh porcine cadavers and used in the experimental surgery to evaluate the new system. As a next step, thoracoscopic surgery using this new system was performed on four or five vertebrae of five live pigs with an average weight of 50 kg. Initially, the discs and rib heads were removed through the thoracic wall. For each vertebra, a screw connected to a shaft used as a screw holder was inserted through the thoracic wall in a posterior to anterior direction. Each shaft then was linked outside the body to an outrigger. This outrigger was used to both create and restore scoliosis. A rod then was introduced through the thoracic wall and fixed to the screw heads. RESULTS: The animal experiments clearly showed that it was possible to change the Cobb angles of the spine through the use of the outrigger apparatus. In cadaver experiments, it was possible to create scoliosis and re-store it by 25 degrees to 35 degrees. Also, surgery on live pigs resulted in scoliosis of approximately 30 degrees, which means approximately 5 degrees to 10 degrees for each disc space. The procedures used also demonstrated that it was possible to fix a rod, introduced into the pleural cavity through a port, with screw heads. CONCLUSIONS: The use of this system successfully changed the Cobb angle of the spine, which suggests that its use should make it possible to correct spinal deformities. This apparatus also succeeded in fixing the rods in the screw heads, which raises the possibility of its use in spinal fixation. The authors believe that this apparatus could be adapted successfully for clinical use. Studies currently are under way in clinics using the new system.

Animals↗

PubMed2000

[Laparoscopic radical nephrectomy for renal cell carcinomas; report on two initial cases].

We recently performed a laparoscopic radical nephrectomy (LRN) on two patients with a renal cell carcinoma. Case 1, a 72-year-old man, was diagnosed as having a renal cell carcinoma 2.5 cm in diameter in the right kidney, and also a submucosal tumor of the cecum. LRN and laparoscopically assisted ileocecal resection were performed using a transperitoneal approach on September 28, 1999. Total operation time and blood loss during the operation were 308 minutes and 320 ml, respectively. The operation time needed for LRN, which was calculated as the total operation time minus the time spent on ileocecal resection, was 199 minutes. There were no complications after surgery, and the patient was recommended for discharge on the 7th postoperative day, but was actually discharged on the 10th postoperative day. Case 2, an 81-year-old man, was diagnosed as having a renal cell carcinoma 3.0 cm in diameter in the right kidney. He had been undergone a total gastrectomy for a gastric carcinoma at age 77, and a sigmoidectomy for a sigmoid colon carcinoma at age 79. A transperitoneal approach was applied for LRN to detect any recurrence of previous carcinomas on September 30, 1999. During adhesiolytic procedures, the colon was injured due to an inappropriate maneuver of the grasping forceps. A small laparotomy (5 cm) was required for repair of the colon. The total operation time and blood loss during surgery were 370 minutes and 850 ml. The operation time calculated from the video of LRN was 274 minutes. Two additional surgical procedures were required in this case. The first was for a postoperative intraperitoneal hemorrhage due to the hemoclip dropping out of the small vein. The second was for hemorrhage in the abdominal wall. Fortunately, the clinical course after surgery was good and the patient was discharged on the 8th postoperative day. There were no complications in case 1. Omitting ileocecal resection was considered to speed up oral intake, leading to earlier discharge. However, major complications occurred in case 2. It is important to clarify the cause of postoperative hemorrhage by careful observation of the video recording, in order to suggest safer procedures in laparoscopic surgery. Although these are only two LRN experiences, we are convinced that LRN can improve postoperative QOL (Quality of life) and is an acceptable alternative for the treatment of renal cell carcinomas.

Aged↗

PubMed2000

[The C tube in biliary surgery--its development and clinical application].

BACKGROUND: The T tube procedure for bile drainage after biliary surgery has been used all over the world for more than 90 years. However, this method has serious drawbacks: a high complication ratio and a need for long-term hospitalization. Therefore other bile drainage methods including PTGBD, PTBD and ENBD have been developed, but none has so far been able to replace T tube. We have developed a new technique for bile drainage using the C tube (cystic duct tube), which is a slender tube (6Fr. polyvinyl) inserted via the cystic duct into the common bile duct (CBD). We have used C tube in more than 400 cases over the last 20 years: for open surgery during the first 10 years, and for laparoscopic surgery in the last 10 years. Here we describe the history of improvements in the C tube method and the techniques of C tube application in biliary surgery. Elastic surgical suture has been used to fix the C tube to the cystic duct, which successfully prevented bile leakage from the ductal stump after withdrawal of the tube. C tube is not only used for postoperative bile drainage but also for the management of remnant stones. The purpose of this study is to assess the safety and benefits of the C tube procedure. METHODS: I: From 1980 to 1998, 335 cholecystectomized cases which had undergone the C tube procedure were examined for complications resulting from C tube placement. II: We analyzed 134 patients with choledocholithiasis: 34 patients had been treated using C tube drainage, and 100 patients had been treated with the T tube procedure after undergoing CBD exploration. The main outcome criteria were: the frequency of post-operative complications, quantity of bile drainage, drainage period, and length of post-operative hospital stay. III: Between 1990 and 1999, 131 patients (15.2%) of a total of 860 laparoscopically cholecystectomized patients with gallstones underwent C tube treatment. We assessed the usefulness of the C tube procedure for the detection and management of remnant stones. RESULTS: I: There were no major complications (bile-leakage, CBD stenosis, etc.) in 335 cases which underwent the C tube procedure. Minor complications related to C tube were: spontaneous withdrawal of the tube in 5 cases, movement of the tube tip in 17 cases, and difficulties during tube removal in 32 cases which included slight resistance. Two cases had liver dysfunction (GOT 705 IU/l and 488 IU/l), although this was easily normalized after withdrawal of the tube tip from the duodenal papillae into the CBD. II: The frequency of complications in patients who underwent the C tube procedure was zero, whilst in the T tube group the major complication rate was 3% and the minor complication rate was 21%. The quantity of bile drainage was 283.6 +/- 22.9 ml/day in the C tube group compared with 302.7 +/- 10.3 ml/day in the T tube group, showing no significant difference. The drainage period (5.9 +/- 0.6 days) in the C tube group was significantly shorter than in the T tube group (27.7 +/- 0.9 days). Hospital stays (11.6 +/- 0.6 days) in the C tube group were significantly shorter than in the T tube group (45.0 +/- 1.5 days). III: Remnant CBD stones were detected by postoperative cholangiography via the C tube in 28 (21.4%) of the C tube replacement cases and in 3.3% of all the laparoscopically cholecystectomized patients. Seventeen patients with remnant stones were managed using glyceryl trinitrate CBD perfusion-induced relaxation of the sphincter of Oddi. The remaining patients were managed with endoscopic papillary balloon dilatation (EPBD) and/or endoscopic sphincterotomy (EST) without reoperation. We also have described other applications of the C tube procedure for the evaluation of sphincter of Oddi motility as an indication for EST, for bile drainage in liver resection, in the treatment of liver injuries, and for duodenal decompression after duodenal surgery. Finally we have mentioned the possibility of C tube application in the management of obstructive jaundice and bile drainage in liver transplantation surgery. CONCLUSION: The C tube method in biliary surgery is safe and useful in comparison with the T tube method. We are strongly convinced that the T tube will be completely replaced by the C tube.

Aged↗

PubMed2000

c-Myb acetylation at the carboxyl-terminal conserved domain by transcriptional co-activator p300.

Transcription factor c-Myb plays important roles in cell survival and differentiation in immature hematopoietic cells. Here we demonstrate that c-Myb is acetylated at the carboxyl-terminal conserved domain by histone acetyltransferase p300 both in vitro and in vivo. The acetylation sites in vivo have been located at the lysine residues of the conserved domain (K471, K480, K485) by the use of the mutant Myb (Myb-KAmut), in which all three lysine residues are substituted into alanine. Electrophoretic mobility shift assay reveals that Myb-KAmut shows higher DNA binding activity than wild type c-Myb and that acetylation of c-Myb in vitro by p300 causes dramatic increase in DNA binding activity. Accordingly, transactivation activity of both mim-1 and CD34 promoters by Myb-KAmut is higher than that driven by wild type c-Myb. Furthermore, the bromodomain of p300, in addition to the histone acetyltransferase (HAT) domain, is required for effective acetylation of c-Myb, and hGCN5 is revealed to be a factor acetyl-transferase for c-Myb in vitro. We present a new manner of post-translational modification of the c-Myb protein and the potential significance of the acetylation in c-Myb.

Acetylation↗

PubMed2000

Distal pancreatectomy with resection of the celiac axis and reconstruction of the hepatic artery for carcinoma of the body and tail of the pancreas.

Distal pancreatectomy with resection of the celiac axis can increase resectability of carcinoma of the body and tail of the pancreas. We performed reconstruction of the hepatic artery to avoid complications caused by a decrease in hepatic arterial flow. We carried out distal pancreatectomy with resection of the celiac axis for carcinoma of the body and tail of the pancreas in four patients. When pulsation in the proper hepatic artery was weak after occlusion of the celiac axis, we performed reconstruction of the hepatic artery, using the splenic artery, which had been taken beforehand from the resected specimen. In two patients, we performed reconstruction of the hepatic artery. These two patients underwent reconstruction of the portal vein combined with prolonged clamping of the portal vein. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated just after the operation, but recovered to normal levels within 10 days. No complications related to hepatic ischemia were observed. These results suggested that reconstruction of the hepatic artery allowed us to safely perform distal pancreatectomy with resection of the celiac axis for carcinoma of the body and tail of the pancreas.

Aged↗

PubMed2000

Extended right hepatic lobectomy with resection of inferior vena cava and portal vein for intrahepatic cholangiocarcinoma.

We report a case of intrahepatic cholangiocarcinoma treated by extended right lobectomy and resection of the inferior vena cava (IVC) and portal vein. A 53-year-old man was referred with elevated serum alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) levels on April 23, 1999. He was not jaundiced and did not have any symptoms. Endoscopic retrograde cholangiopancreatography (ERCP) revealed irregular strictures in both the anterior and posterior segmental ducts. Contrast-enhanced computed tomography (CT) scan demonstrated a low-density tumor with an unclear margin in the right lobe of the liver. The patient underwent extended right hepatic lobectomy and total caudate lobectomy. Partial resection of the IVC (6 cm) was performed under total hepatic vascular exclusion. The main portal trunk and left portal vein were resected and reconstructed with an end-to-end anastomosis. Macroscopically, a 5.0 x 5.0 x 4.5-cm periductal infiltrating-type tumor occupied the right hepatic parenchyma along the posterior and anterior segmental ducts. Histological examination revealed moderately differentiated tubular adenocarcinoma with marked perineural invasion. Lymph node metastasis was observed in the hepatoduodenal ligament and posterior surface of the pancreatic head. The resected margins of the common bile duct and left hepatic duct were free of tumor. The patient's postoperative course was uneventful, and he was discharged from hospital on the 28th postoperative day. Nine months after the operation, he suddenly developed obstructive jaundice, and died with recurrent disease. This is the first reported case of intrahepatic cholangiocarcinoma treated with major hepatectomy and resection of the IVC and portal vein except ex situ procedure. This aggressive surgical approach may offer hope for patients with intrahepatic cholangiocarcinoma involving the IVC.

Anastomosis, Surgical↗

PubMed2000

Epithelioid hemangioendothelioma of the liver.

Epithelioid hemangioendothelioma (EH) of the liver is a rare tumor and is difficult to differentiate from cholangiocellular carcinoma or metastatic liver tumor on image diagnosis. A case of curatively resected EH of the liver is reported. A 48-year-old woman was admitted because she had a mass in the liver. Cholangiocellular carcinoma was suspected preoperatively. Right trisegmentectomy of the liver, combined with bile duct resection and portal vein resection and reconstruction, was performed. Characteristic macro- and microscopic findings of the resected specimen revealed EH of the liver. The patient has survived for more than 6 years without recurrence. Because of the tendency of EH of the liver to appear in multiple or scattered forms, only 12 cases of resection for EH have been reported.

Female↗