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Biomedical subjects

T Oda

Publications and source records attributed to T Oda.

At least 91 records · Page 5Linked to original sources

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↗

Purification and characterization of a dipeptidyl carboxypeptidase from the polychaete Neanthes virens resembling angiotensin I converting enzyme.

Dipeptidyl carboxypeptidase (DCP) is well known as a mammalian angiotensin I converting enzyme (ACE) which plays an important role in blood pressure homeostasis. DCP was purified from the whole body of a polychaete, Neanthes virens. The purified enzyme was homogeneous by SDS-PAGE, with a molecular mass of 71 kDa by SDS-PAGE and 69 kDa by gel filtration, indicating that it is monomeric. The isoelectric point was 4.5 and optimum pH for the activity was 8.0. It showed a specific activity of 466.8 U/mg, which is the highest of known DCPs. The enzyme hydrolyzed angiotensin I to angiotensin II and sequentially released Phe-Arg and Ser-Pro from the C-terminus bradykinin, but does not cleave imido-bonds. Activity was completely inhibited by 1 mM EDTA and 5 mM o-phenanthroline, but it was not affected by serine and aspartic protease inhibitors. The original activity of EDTA-inactivated DCP was restored by addition of cobalt, manganese or low concentrations of zinc. The Km and Vmax values of the enzyme for Bz-Gly-His-Leu were 0.56 mM and 600 mumol/min per mg, respectively. The Ki values for specific mammalian ACE inhibitors, such as captopril and lisinopril, were 1.38 and 2.07 nM, respectively. In conclusion, we have shown the existence of a DCP from the polychaete, N. virens, with similar properties to those of mammalian ACE.

Animals↗

Tricuspid valve replacement with the St. Jude Medical valve: 19 years of experience.

OBJECTIVE: The choice of the valve substitute in the tricuspid position remains controversial. A St. Jude Medical valve is a choice of valve substitute and its lower thrombogenicity and excellent hemodynamic performance have been reported even in the tricuspid position. However, little is known of the long-term durability of the St. Jude Medical valve in the tricuspid position. Our long-term experience of tricuspid valve replacement showed the higher thrombogenicity than we had expected, therefore, this study was done to reconsider our strategy for valve choice. METHODS: This study reviewed 23 patient who underwent 25 tricuspid valve replacements with the St. Jude Medical valves from 1980 to 1997. The mean age was 40 years. Eleven patients (48%) were men. There were four in-hospital deaths (17%). The remaining 19 patients were all alive and followed from 2.2 to 19.0 years (mean 11.8 years). RESULTS: The overall survival, including hospital mortality, was 83%, 10 and 15 years after surgery. Valve thrombosis occurred in six patients. Freedom from valve thrombosis was 78 and 70%, 10 and 15 years after surgery, respectively. The linearized rate of the valve thrombosis was 2.9%/patient-years. Six patients required reoperation. The mean interval to reoperation was 9.5 years. Freedom from reoperation was 83% and 75%, 10 and 15 years after surgery, respectively. The linearized rate of the reoperation was 2.8%/patient-years. No structural valve deterioration was found. Echocardiographic study showed that the function of the St. Jude Medical valve without valve-related complications was well maintained. CONCLUSIONS: The higher thrombogenicity of the St. Jude Medical valve in the tricuspid position altered our choice of valve substitutes from the St. Jude Medical valve to a bioprosthesis which is lack of need for anticoagulant therapy except for juvenile patients who are able to maintain potent anticoagulant therapy.

Adolescent↗

Cloning and sequence analysis of a gene (aly PG) encoding poly(alpha-L-guluronate)lyase from Corynebacterium sp. strain ALY-1.

The aly PG gene, coding for a poly alpha-l-guluronate lyase (PG lyase) of Corynebacterium strain ALY-1, was cloned and sequenced. The gene consists of 768 bp encoding a signal peptide of 32 amino acids and a mature protein of 224 amino acids. Two disulfide bond cross-linkages were found to be formed between Cys-4 and Cys-51 and between Cys-200 and Cys-206 in the native PG lyase molecule. The deduced amino acid sequence of the Corynebacterium sp. aly PG gene exhibited 29% homology toward that of the Klebsiella pneumoniae, subsp. aerogenes aly A gene, with two conserved regions (the amino acid sequences from Y-102 to M-110 and from Y-221 to Q-229).

Journal Article↗

Interstitial fibrosis in mice with overload proteinuria: deficiency of TIMP-1 is not protective.

BACKGROUND: Progressive renal interstitial fibrosis is characterized by up-regulated expression of the gene that encodes the tissue inhibitor of metalloproteinases-1 (TIMP-1), a regulator of extracellular matrix remodeling, suggesting that impaired matrix turnover contributes to the fibrogenic process. The present study was designed to develop a murine model of renal interstitial fibrosis, and to determine the functional significance of up-regulated Timp-1 expression by comparing the severity of this renal disease in wild-type mice and mice genetically deficient in Timp-1. METHODS: Initial pilot studies developed and characterized a murine model of bovine serum albumin (BSA)-induced protein-overload proteinuria with respect to the degree of proteinuria, severity of interstitial fibrosis, and renal mRNA levels for genes encoding matrix proteins, transforming growth factor-beta1 (TGF-beta1), and TIMP-1, -2, -3, and -4. In the final study, the severity of interstitial fibrosis was compared in wild-type and Timp-1-deficient mice after six weeks of proteinuria. RESULTS: Mice injected with large daily intraperitoneal doses of BSA developed proteinuria, interstitial inflammation, and progressive interstitial fibrosis. A time course study based on measurements after one, two, and six weeks of BSA injections showed increased renal mRNA levels for the matrix genes procollagens alpha1(I), alpha1(III), and alpha2(IV) and TGF-beta1 and Timp-1. Timp-2 and Timp-3 genes were constitutively expressed at high levels in the normal kidneys and showed little change in the proteinuric kidneys. Timp-4 transcripts were not detected in any of the kidneys. After six weeks of BSA overload-proteinuria, the groups (N = 8 per group) of wild-type and Timp-1-deficient mice developed significant interstitial fibrosis compared with the control saline-injected groups. The severity of the interstitial fibrosis was similar in both proteinuric groups based on an assessment of the final kidney weight, total kidney collagen content, and the number of interstitial fields with increased fibronectin staining. CONCLUSIONS: Results of the present study indicate that TIMP-1 deficiency does not alter the degree of interstitial fibrosis in the murine overload proteinuria model. Potential explanations include Timp-1 genetic redundancy, as suggested by the observation that, despite significant intrarenal induction of the Timp-1 gene expression, net renal metalloproteinase-9 (MMP-9) activity was not significantly altered. TIMP-1 is a multifunctional protein that may play a metalloproteinase-independent role in response to renal injury.

Animals↗

Free vascularized bone graft for nonunion of the scaphoid.

We used a free vascularized small periosteal bone graft to treat scaphoid nonunion. The graft consisted of periosteum, full-thickness cortex, and the underlying cancellous bone and was harvested from the supracondylar region of the femur. The graft was nourished by the articular branch of the descending geniculate artery and vein. Unlike the currently used vascularized bone grafts, this graft can be easily harvested and shaped to accommodate the bone defect of the scaphoid without disturbing its vascularity and can then be transferred with microvascular anastomosis of the nutrient vessels to the radial artery and its venae commitantes. Ten patients with longstanding nonunion of the scaphoid secondary to avascular necrosis, confirmed by radiologic and intraoperative findings, were treated with this vascularized bone graft. Union was achieved in all 10 patients at an average of 12 weeks after surgery. The average follow-up period for all fractures was 3.5 years. The scores for overall outcome, according to the Mayo wrist scoring system, were excellent in 4 patients, good in 4, and fair in 2. Two unsatisfied patients had preoperative signs of early periscaphoid osteoarthrosis. This free vascularized small bone graft from the supracondylar region of the femur is an attractive alternative to the conventional vascularized bone grafting procedures.

Adolescent↗

Simultaneous development of a pineal tumor and an intradural spinal mass during remission of acute lymphocytic leukemia.

A small percentage of children with acute lymphocytic leukemia experience relapse in the central nervous system in spite of prophylaxis. Diffuse leptomeningeal infiltration is common but an intracranial leukemic mass or spinal cord involvement is a rare manifestation. We report a child with acute lymphocytic leukemia who simultaneously developed a pineal tumor and an intradural spinal cord mass as her first relapse. She was successfully managed by comprehensive combined treatment including peripheral blood stem cell transplantation. She remains in continuous complete remission for more than 5 years without further evidence of neurological sequelae.

Child, Preschool↗

Mitochondrial targeting signal-induced conformational change and repression of the peroxisomal targeting signal of the precursor for rat liver serine:pyruvate/alanine:glyoxylate aminotransferase.

In the rat liver, two mRNAs for serine:pyruvate (or alanine:glyoxylate) aminotransferase are generated from a single gene by alternative transcription initiation. The longer mRNA encodes a precursor of a mitochondrial enzyme that has a mitochondrial targeting signal at the N-terminus and is translocated into mitochondria. The shorter mRNA encodes a peroxisomal enzyme of mature size that is imported into peroxisomes. We have been interested in the mechanism of selective targeting to mitochondria of the precursor protein that also contains a peroxisomal targeting signal in the molecule. In this study, we examined the effect of the mitochondrial targeting signal on the conformation of the protein and on the function of the peroxisomal targeting signal in the precursor molecule. The results suggest that the mitochondrial targeting signal causes the conformation of the protein to become unfolded and that this conformational change in turn causes repression of the putative peroxisomal targeting signal contained in the precursor protein.

Alternative Splicing↗

The effect of single residue substitutions of serine-283 on the strength of head-to-tail interaction and actin binding properties of rabbit skeletal muscle alpha-tropomyosin.

Vertebrate skeletal muscle alpha-tropomyosin polymerizes in a head-to-tail manner and binds cooperatively to actin. It has been postulated that the cooperative actin binding is governed by the strength of the head-to-tail interaction. In order to know the relationship between the head-to-tail affinity and actin binding, we studied the properties of tropomyosin variants with single residue substitutions at serine-283, the penultimate residue at the carboxyl terminus that is involved in the head-to-tail interaction. It has been shown that the phosphorylation of serine-283 strengthens the head-to-tail interaction. Viscometry was employed to compare the head-to-tail affinity of tropomyosin variants. Variant S283E showed higher viscosity whereas variant S283K showed lower viscosity compared with the wild type non-phosphorylated alpha-tropomyosin. The results confirm the idea that the interaction is sensitive to the ionic properties of residue 283. The strength of the head-to-tail interaction was assessed directly by sedimentation equilibrium using two pairs of tropomyosin variants designed so that only dimeric interactions were allowed within each pair. From one pair of variants with serine-283, the association constant was determined to be 2.6 x 10(4) M(-1) (SD =1.0 x 10(4)), whereas for the second pair with glutamate-283, the affinity was 3.9 x 10(4) M(-1) (SD =1.6 x 10(4)), slightly stronger than the former, consistent with the results of viscometry. The results indicate that the head-to-tail association is weak as previously implicated from light scattering measurements. Cosedimentation was employed to measure the cooperative actin binding of tropomyosin variants. Although previous results indicated the phosphorylation has no significant influence on the actin affinity, variant S283E shows a lower affinity compared with the control. Variants S283K and S283A show even lower affinities to actin, although these species bind to actin more cooperatively than does variant S283E. The results indicate that the affinity of the head-to-tail interaction between adjacent tropomyosin molecules is weak, and is substantially influenced by an extra charge at residue 283. On the other hand, the interaction with actin, the affinity and the cooperativity in actin binding, is dependent on amino acid residues at 283 and is not simply correlated with the strength of the head-to-tail interaction between Tm molecules in solution.

Actins↗

Store depletion by caffeine/ryanodine activates capacitative Ca(2+) entry in nonexcitable A549 cells.

Capacitative Ca(2+) entry is essential for refilling intracellular Ca(2+) stores and is thought to be regulated primarily by inositol 1, 4,5-trisphosphate (IP(3))-sensitive stores in nonexcitable cells. In nonexcitable A549 cells, the application of caffeine or ryanodine induces Ca(2+) release in the absence of extracellular Ca(2+) similar to that induced by thapsigargin (Tg), and Ca(2+) entry occurs upon the readdition of extracellular Ca(2+). The channels thus activated are also permeable to Mn(2+). The channels responsible for this effect appear to be activated by the depletion of caffeine/ryanodine-sensitive stores per se, as evidenced by the activation even in the absence of increased intracellular Ca(2+) concentration. Tg pretreatment abrogates the response to caffeine/ryanodine, whereas Tg application subsequent to caffeine/ryanodine treatment induces further Ca(2+) release. The response to caffeine/ryanodine is also abolished by initial ATP application, whereas ATP added subsequent to caffeine/ryanodine induces additional Ca(2+) release. RT-PCR analyses showed the expression of a type 1 ryanodine receptor, two human homologues of transient receptor potential protein (hTrp1 and hTrp6), as well as all three types of the IP(3) receptor. These results suggest that in A549 cells, (i) capacitative Ca(2+) entry can also be regulated by caffeine/ryanodine-sensitive stores, and (ii) the RyR-gated stores interact functionally with those sensitive to IP(3), probably via Ca(2+)-induced Ca(2+) release.

Caffeine↗

Depletion of intracellular NAD(+) and ATP levels during ricin-induced apoptosis through the specific ribosomal inactivation results in the cytolysis of U937 cells.

Our previous studies demonstrated that ricin induces the apoptotic death of U937 cells as evidenced by DNA fragmentation, nuclear morphological changes, and increases in caspase-like activities. In this study, we have found that intracellular NAD(+) and ATP levels decrease in ricin-treated U937 cells and that this decrease is followed by the ricin-mediated protein synthesis inhibition. The PARP inhibitor, 3-aminobenzamide (3-ABA), prevents the depletion in NAD(+) and ATP levels and concomitantly protects U937 cells from the lysis that follows ricin treatment. Hence, the protective action of 3-ABA is due to the inhibition of PARP and does not result from its other pharmacological side effects. Moreover, the enzymatic activity of PARP gradually increases and reaches a maximum level after ricin exposure for 3 h, whereas no significant change in activity was observed in untreated cells. However, 3-ABA has no effect on ricin-mediated DNA fragmentation. In addition, immunoblot analysis revealed that significant PARP cleavage occurred more than 12 h after ricin addition, while DNA fragmentation reached a maximum level within 6 h of incubation. Thus, in the case of ricin-induced apoptosis, it appears that PARP cleavage is not an early apoptotic event associated with the onset of apoptosis. Our results suggest that multiple apoptotic signaling pathways may be triggered by ricin-treatment. Probably, the pathway leading to cell lysis via PARP activation and NAD(+) depletion is independent of the pathway leading to DNA fragmentation in which caspases may be profoundly involved. Other protein synthesis inhibitors, including diphtheria toxin and cycloheximide, were less effective in terms of inducing DNA fragmentation and cytolysis, even at concentrations that cause significant inhibition of protein synthesis. Thus, a specific ricin action mechanism through which ribosomes are inactivated may be responsible for the apoptotic events induced by ricin.

Adenosine Triphosphate↗

Deep venous thrombosis after total hip or total knee arthroplasty in patients in Japan.

A single center, prospective, epidemiologic study was conducted to estimate the incidence of deep venous thrombosis detected by venography in patients in Japan undergoing total hip arthroplasty or total knee arthroplasty without prophylactic anticoagulant therapy. Venograms of 164 patients who had total hip arthroplasty and 138 patients who had total knee arthroplasty were evaluated. The incidences of deep venous thrombosis were 22.6% in patients who had total hip arthroplasty and 48.6% in those who had total knee arthroplasty. The incidences of proximal deep venous thrombosis were 9.8% in patients who had total hip arthroplasty and 14.5% in those who had total knee arthroplasty. Statistical analysis revealed that the type of operation influenced the development of deep venous thrombosis. Patients who had total knee arthroplasty were 3.2 times more likely to have deep venous thrombosis develop than were patients who had total hip arthroplasty. Body mass index and age were identified as statistically significant risk factors.

Adult↗

A novel TATA-binding protein-binding protein, ABT1, activates basal transcription and has a yeast homolog that is essential for growth.

Identification of a novel mouse nuclear protein termed activator of basal transcription 1 (mABT1) that associates with the TATA-binding protein (TBP) and enhances basal transcription activity of class II promoters is described. We also identify mABT1 homologous counterparts in Caenorhabditis elegans and Saccharomyces cerevisiae and show the homologous yeast gene to be essential for growth. The mABT1 associated with TBP in HeLa nuclear extracts and with purified mouse TBP in vitro. In addition, ectopically expressed mABT1 was coimmunoprecipitated with endogenous TBP in transfected cells. More importantly, mABT1 significantly enhanced transcription from an adenovirus major late promoter in a reconstituted cell-free system. We furthermore demonstrate that mABT1 consistently enhanced transcription from a reporter gene with a minimal core promoter as well as from reporter genes with various enhancer elements in a cotransfection assay. Taken together, these results suggest that mABT1 is a novel TBP-binding protein which can function as a basal transcription activator.

Amino Acid Sequence↗

Effects of the ethyl and benzyl ethers of indenestrols A and B on cytotoxicity in Chinese hamster V79 cells.

We recently investigated the relationship between the structures of various indenestrols and their cytotoxicity, and reported that indenestrol A (IA), a metabolite of the synthetic nonsteroidal estrogen diethylstilbestrol, and indenestrol B (IB), an analog of IA, disrupt the microtubule architecture of Chinese hamster V79 cells in vitro. We then synthesized 16 optically active indenestrol derivatives by substituting monoethyl, monobenzyl and diethyl ether groups at the 6- and/or 4'-hydroxyl positions, and examined their cytotoxic activities in Chinese hamster V79 cells. The results indicated that the monoethyl ethers had cytotoxic activities similar to monomethyl ethers. However, the (+)- and (-)-monobenzyl ethers were less cytotoxic than the corresponding monomethyl and monoethyl derivatives.

Animals↗

Plasma and urinary levels of heart fatty acid-binding protein in patients undergoing cardiac surgery.

To evaluate the clinical significance of the plasma and urinary levels of heart fatty acid-binding protein (H-FABP) in patients undergoing cardiac surgery, a prospective study was conducted. Ten patients undergoing coronary artery bypass grafting were enrolled. Blood samples for determination of plasma H-FABP (pH-FABP), the MB isoenzyme of creatine kinase (CK-MB) and troponin-T (TnT), and urine samples for determination of urinary H-FABP (uH-FABP) were collected serially. None of the patients had perioperative myocardial infarction. The time to reach the peak level after aortic declamping was significantly (p<0.05) shorter for pH-FABP (1.4+/-0.5 h) than for CK-MB (2.5+/-0.5 h), TnT (6.6+/-1.3 h) or uH-FABP (3.0+/-0.6 h). Peak levels of pH-FABP correlated with those of CK-MB (r = 0.51, p = 0.04), TnT (r = 0.60, p = 0.03) and uH-FABP (r = 0.61, p = 0.03), and peak levels of uH-FABP correlated with CK-MB (r = 0.57, p = 0.04). Postoperative uH-FABP levels correlated inversely with the left ventricular stroke work index (r = -0.63, p = 0.04). This study demonstrated that H-FABP appears rapidly in plasma after reperfusion and reaches its peak earlier than other available biochemical markers; it appears also in urine and the levels correlated with cardiac function. Plasma and urinary H-FABP may be an early and sensitive biochemical marker for the diagnosis of myocardial injury in patients undergoing cardiac surgery.

Blood Pressure↗