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Biomedical subjects

K Oda

Publications and source records attributed to K Oda.

At least 163 records · Page 9Linked to original sources

Morphogenesis of vertebral deformities in involutional osteoporosis. Age-related, three-dimensional trabecular structure.

STUDY DESIGN: The relation between the semiquantitative data of alteration in three-dimensional trabecular structure and deformities of the vertebral body was analyzed to clarify the morphogenesis of vertebral deformities in involutional osteoporosis. OBJECTIVES: To evaluate semiquantitatively the age-related alterations of the three-dimensional structure of trabeculae of the vertebral body and to clarify their relation to vertebral deformities in involutional osteoporosis. SUMMARY OF BACKGROUND DATA: Recent studies have shown that bone fractures and deformities in osteoporosis do not depend only on a reduced amount of bone tissue. There is no previous study on the relation between bone deformity and the alterations of the three-dimensional structure of trabeculae. METHODS: The second lumbar vertebrae were removed at autopsy from 25 patients who had no disease predisposing them to secondary osteoporosis and no severe vertebral deformities. The sections of the vertebral body were immersed in sodium hypochlorite solution to corrode the bone marrow. Atrophy of trabeculae and increased spacing between trabeculae were evaluated semiquantitatively under stereoscopic microscopy. The authors examined the relation between the semiquantitative data found in the autopsy vertebrae and the patterns and frequencies of each deformity of the second lumbar vertebrae in 99 patients with involutional osteoporosis. RESULTS: The most frequent vertebral deformity was wedge-shaped vertebrae with compression of the anterosuperior portion, and the alterations of the trabecular structure of the anterosuperior portion were severe and closely related to aging. Severe trabecular alterations with no relation to aging did not necessarily cause vertebral deformity. CONCLUSIONS: Trabecular abnormality, which is significantly correlated with aging, may be the necessary and sufficient condition for vertebral deformities in involutional osteoporosis.

Aged↗

Activation of the rat cyclin A promoter by ATF2 and Jun family members and its suppression by ATF4.

Cyclin A plays an essential role in the G1 to S phase transition in the cell cycle. The expression of cyclin A is restrained during G0 and G1, but steeply induced at the G1/S boundary. Analysis of the rat cyclin A promoter elements with the 5' sequential deletion derivatives of the promoter fused to the luciferase cDNA indicated that the ATF/CRE motif primarily determines the inducibility at G1/S. Gel shift analysis of the complex formed at the ATF/CRE site indicated that the complex was not formed with the G0/G1 cell extract, but maximally formed with the late-G1 cell extract. The complex was supershifted by anti-JunD antibody, and Western blot analysis of the immune complexes prepared with anti-JunD antibody revealed the presence of ATF2, suggesting heterodimerization of JunD with ATF2. The cyclin A promoter in a reporter plasmid was activated by nearly 10-fold in quiescent rat 3Y1 cells by cotransfection with the expression of plasmids encoding ATF2 and Jun family members. In contrast, cotransfection with the ATF4 expression plasmid suppressed the promoter activation mediated by ATF2 and Jun family members. The expression of Jun family members during G1 to S progression was induced biphasically in early and late G1 and the level of JunD increased markedly at the G1/S, while that of ATF family members was gradually increased along with the G1 to S progression. These results indicate that the cyclin A promoter activity is regulated, at least in part, by relative amounts of the ATF and Jun family members.

Activating Transcription Factor 2↗

Expressions of p53 and PCNA do not correlate with the international index or early response to chemotherapy in non-Hodgkin's lymphoma.

The expression of p53 and PCNA on deparaffinized sections of tumor was assessed in relation to the International Index and response to chemotherapy. Thirty-five non-Hodgkin's lymphoma (NHL) patients were divided into three groups: aggressive NHL, mantle cell lymphoma (MCL), and low-grade NHL. None of the expressions correlated with the International Index or early response to chemotherapy in any group. In low-grade NHL, none of the patients expressed p53. Only one of three patients with overexpression of p53 showed conformational change and alteration of sequence in exon 7 by PCR-SSCP and DNA sequencing. The results showed that p53 and PCNA staining were not useful for predicting early response to chemotherapy, and that their expressions had no correlation with the International Index.

Adult↗

Influence of ANOVA design and anatomical standardization on statistical mapping for PET activation.

We have created images of z value, error, and variation components for a PET activation study using various ANOVA designs and anatomical standardization methods. Data were acquired in four PET centers. In each center, CBF was measured on six normal male subjects under resting and covert verb generation, three times for each. The images were anatomically standardized with LINEAR transformation, SPM (Ver. 95), HBA (Karolinska/Tohoku), or MICHIGAN (Minoshima). ANOVA was performed pixel by pixel to compute t (and z) for the task main effect (Verb vs Rest) in four different designs: (i) two way (subject and task) (2W), (ii) two-way with interaction (2WI), (iii) subject considered a random factor (2WI-MX), and (iv) three-way (subject, task, and replication) (3W). A large area extending from the Broca to the left premotor cortex was activated. The localization of the highest peak depended both on the anatomical standardization and on the ANOVA design, the variation ranging 3-4 cm. Smoothing reduced the variation while erasing possible subfoci. The z images of 2W, 2WI, and 3W looked alike, whereas 2WI-MX presented lower peak z values. SPM tended to present higher z values than the other methods. The error was high in the gray and low in the white matter. The root mean square for the subject effect was high on the border of gray matter especially in LINEAR and HBA, revealing intersubject mismatch in the gray matter distribution. The root mean square for the subject-by-task interaction effect revealed individual variation in activation.

Adult↗

Data base and management system for clinical positron emission tomography (PET) studies.

A data base and management system connected to an image analysis system has been developed and utilized for clinical positron emission tomography (PET). This data base system, 1) is based on "GBASE", a general purpose data base, which runs on a UNIX work station, 2) works on a network file system and is connected to PET cameras and other data acquisition devices as well as to an image analysis system "Dr.View", 3) centrally manages the data stored in a data storage unit, 4) is easily modifiable and expandable, and 5) has a human friendly interface which requires minimum operation for registration, retrieval and management. We have been using this system to handle clinical PET data for seven years and have optimized the data base schema. As a result, this system has become a truly practical tool for the daily operation and is well-received by technologists, nuclear physicians and attending physicians.

Brain↗

Metabolite analysis of [11C]flumazenil in human plasma: assessment as the standardized value for quantitative PET studies.

Analysis of carbon-11 labeled metabolites in plasma was carried out during positron emission tomography (PET) studies with a central benzodiazepine receptor ligand [11C]flumazenil ([11C]FMZ) in 24 human subjects (14-76 y.o.) including five normal volunteers and 19 patients with neurological disorders. Arterial plasma samples were obtained at 3, 5, 10, 15, 20, 30 and 60 min after i.v. injection of the tracer, and were analyzed by high-performance liquid chromatography. The rate of plasma [11C]FMZ degradation was associated with a large individual variation, but no significant difference was found in the degradation of [11C]FMZ either between male and female, young and old, or between normal subjects and patient groups. When the mean fraction of unchanged [11C]FMZ at each time point was used instead of individually measured metabolite data for the arterial input function, as much as a 30% error occurred in the distribution volume of the [11C]FMZ binding in the brain. These results indicate that the mean percentage of unchanged [11C]FMZ fraction in subjects cannot be used as the standardized value, and that the analysis of metabolites in plasma is necessary to determine the exact arterial input function for quantitative PET measurement.

Adolescent↗

Successful management of left main bronchial stenosis as a rare complication of pericardiectomy.

We present a rare complication of pericardiectomy and the effective management thereof. A 67-year-old female with dyspnea and upper abdominal pain was received at our department upon referral. Chest roentgenogram and cardiac catheterization preceded a diagnosis of constrictive pericarditis. Pericardiectomy was performed subordinate to median sternotomy and left anterolateral thoracotomy. Extubation was carried out on day 2 but reintubation was necessitated on the same day as a result of progressive dyspnea. Chest roentgenogram revealed an atelectasis of the left lung. Fiberoptic bronchoscopy showed left main bronchial stenosis resulting from a pulsating external structure. A postoperative computed tomogram substantiated the stenotic left main bronchus between the dilated left pulmonary artery and the thoracic descending aorta. An expandable metallic stent for the treatment of this complication was selected over other invasive procedures. Two years of follow-up reveal no complications. Accordingly, an expandable metallic stent has demonstrated its effectiveness not only on bronchial stenosis due to malignancy or tuberculosis but on benign cases such as this as well.

Aged↗

Surgery for local pelvic recurrence after resection of rectal cancer.

This retrospective study evaluated outcome with regard to procedure, local control, and survival after curative surgical resection with and without preoperative radiotherapy for local pelvic recurrence. A total of 58 consecutive patients with local pelvic recurrence of rectal cancer after previous curative resection for primary tumors were reviewed. Of these, 36 underwent both initial resection and follow-up in our department; the remaining 22 had initial surgery and follow-up elsewhere. Of the 58 patients 27 underwent curative re-resection, 9 had palliative resection, and 22 were treated by conservative therapy. Among the 27 patients with curative resection 17 received preoperative radiotherapy (40 Gy) plus surgery and 10 surgery only. No patients were lost to follow-up; median follow-up time was 36.3 months. The overall rate of curative resection was 46.6%: 55.6% in our own follow-up group and 31.8% in the others. With regard to surgical procedure, abdominoperineal resection (APR) with or without sacral resection was standard following previous low anterior resection, and total pelvic exenteration (TPE) with or without sacral resection was common following APR. There was a high incidence of morbidity (71.4%) after TPE. Re-recurrence was observed in 12 (44.4%) after curative re-resection. There was local re-recurrence in 6 (22.2%). The local re-recurrence rate was 11.8% (n = 2) with radiotherapy plus surgery, and 40.0% (n = 4) with surgery alone. The estimated 5-year survival following curative re-resection was 45.6% (61.2% with radiotherapy plus surgery, 29.6% with surgery alone). Both survival and local control with radiotherapy plus surgery tended to be better than with surgery alone. Thus, in selected patients pelvic local recurrence of rectal cancer can be re-resected curably by APR or TPE (with or without sacral resection) combined with preoperative radiotherapy.

Adult↗

A new quadruple therapy for the eradication of Helicobacter pylori. Effect of pretreatment with omeprazole on the cure rate.

To elucidate whether pretreatment with omeprazole decreases the cure rate of Helicobacter pylori infection with a new quadruple therapy, and thus, whether this pretreatment should not be used in clinical practice, we conducted a randomized trial. Ninety patients with chronic peptic ulcer disease and nonulcer dyspepsia, with biopsy-proven H. pylori infection were randomly assigned to the two following regimens: Group 1 (n = 45) received omeprazole 20 mg once daily for 2 weeks (days 1-14), and 500 mg amoxicillin granules and 250 mg metronidazole thrice daily, and roxithromycin 150 mg twice daily for 1 week (days 8-14), Group 2 (n = 45) received the same antibiotic treatment as group 1 for 1 week (days 1-7), in addition to omeprazole treatment for 2 weeks (days 1-14). Four weeks after the treatment ended, endoscopy was repeated, with two biopsy specimens each taken from the antrum and the corpus (total of four specimens) for a urease test, histological analysis, and culture to establish cure of infection. A patient was regarded as cured only if all three methods gave negative results for H. pylori. In the intention-to-treat analysis, 42 of 45 patients (93.3%; 95% confidence intervals [CI], 81.7%-98.6%) in group 1 were cured compared with 43 of 45 patients (95.6%; 95% CI, 84.9%-99.5%) in group 2. In the per-protocol analysis, the corresponding figures were 42/44 (95.5%; 95% CI 84.5%-99.4%) and 43/44 (97.7%; 95% CI, 88.0%-99.9%). There were no significant differences in the cure rate between the two groups on either analysis. All patients, except for one who had an allergic reaction, completed the treatment regimens. Fifty to sixty percent of the patients had no side effects while the rest had mild to moderate side effects. The new quadruple therapy consisting of omeprazole, amoxicillin, metronidazole, and roxithromycin appears suitable for use in clinical practice, as the cure rate was 95% and no severe side effects were observed. Pretreatment with omeprazole did not reduce the cure rate for this new quadruple therapy.

Adult↗

Assessment of internal thoracic artery graft with intraoperative color Doppler ultrasonography.

BACKGROUND: Intraoperative ultrasonography has the potential to provide anatomic and functional information about internal thoracic artery (ITA) graft, but this potential has been hindered by the relatively large standard probe. In this study, we used a color Doppler microprobe to evaluate ITA grafts. METHODS: The subjects were 15 consecutive patients who underwent elective coronary artery bypass grafting either with cardiopulmonary bypass (n = 14) or without (n = 1). All patients underwent anastomosis of the left ITA to the left anterior descending artery. The ITA graft was assessed before the chest was closed, with the microprobe placed directly on the graft. RESULTS: A good-quality color Doppler image of the ITA graft was easily obtained in all 15 patients within a few minutes. The ITA graft function was assessed by analyzing the shape of the pulsed Doppler wave. All ITA grafts were patent, and the mean graft diameter was 1.8 +/- 0.04 mm. The peak systolic velocity, peak diastolic velocity, and mean velocity were 52.0 +/- 14.9 cm/s, 58.3 +/- 22.4 cm/s, and 36.5 +/- 10.9 cm/s, respectively. The ratio of peak diastolic velocity to peak systolic velocity was 1.24 +/- 0.66. The ITA graft seemed to function well when the biphasic diastolic predominant flow appeared. The mean blood flow was 55.1 +/- 22.0 mL/min. CONCLUSIONS: Intraoperative ultrasonography using the microprobe provides adequate anatomic and hemodynamic information regarding ITA grafts. As the Doppler flow evaluation has high sensitivity and specificity, we suggest that intraoperative ultrasonography is useful for the assessment of these grafts.

Anastomosis, Surgical↗

Primary lymphoma of the liver with bile duct invasion and tumoral occlusion of the portal vein: report of a case.

A 55-year-old woman presented to hospital with epigastric pain and jaundice. Diagnostic imaging studies revealed a biliary stricture of the hepatic confluence and a hepatic tumour of the left and caudate lobes with a portal tumour thrombus, which occupied the main portal trunk, the umbilical portion of the left portal vein, and the right anterior and posterior portal branches. Left hepatic trisegmentectomy, caudate lobectomy, portal tumour thrombectomy, bile duct resection and bilioenteric anastomosis were performed. There were no other lesions, and so it was diagnosed as a primary lymphoma of the liver (B-cell, diffuse, large cell type). The patient underwent postoperative chemotherapy and has remained well for 4.5 years after surgery. Primary lymphoma of the liver is very rare, and this is the first case report with bile duct invasion and tumoral occlusion of the portal vein.

Bile Duct Neoplasms↗

14q11 abnormality and trisomy 8q are not common in Japanese T-cell prolymphocytic leukemia.

We studied ten cases of Japanese T-cell prolymphocytic leukemia (T-PLL) collected over the last 9 years. Median age was 61 years with a male predominance (M:F, 8:2). The main disease features were splenomegaly, lymphadenopathy, hepatomegaly, skin lesions and serous effusions. The clinical course was progressive with a median survival of 10 months. Immunophenotyping showed that the prolymphocytes had a post-thymic phenotype (TdT-, CD1a-, CD2+, CD3+, CD5+, CD7+) with a predominant CD4+ immunophenotype. Cytogenetic analysis showed no consistent abnormalities. 14q abnormality and trisomy 8q, which are frequently seen in T-PLL of Western countries, were found in only two and zero cases, respectively. We conclude that the clinical and biological characteristics of T-PLL in Japan are almost the same as those in Western countries. However, the cytogenetic findings of T-PLL in Japan might be different.

Adult↗

Ratio of CD44 epithelial variant to CD44 hematopoietic variant is a useful prognostic indicator in gastric and colorectal carcinoma.

BACKGROUND: The CD44 is a cell adhesion molecule that is present as numerous isoforms created by mRNA alternative splicing. Expression of variant isoforms of CD44 is associated with tumor growth and metastasis. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in gastric and colorectal cancer. METHODS: We performed a polymerase chain reaction analysis following reverse transcriptase treatment for CD44 expression in fresh surgical specimens obtained from 25 colon carcinomas and 30 gastric carcinomas and matched adjacent normal mucosa. We determined the epithelial variant/hematopoietic variant (E/H) ratio (the amount of the CD44 epithelial variant transcript relative to the CD44 hematopoietic variant transcript) in cancer tissues and examined it for correlations with clinicopathological parameters and survival rate. RESULTS: The E/H ratio in tumor tissue was significantly higher than that in adjacent non-cancerous mucosa. In gastric and colorectal cancer tissues, there was no significant relationship between E/H ratio and clinicopathological parameters. However, patients who died due to tumor recurrence had a higher E/H ratio than surviving patients with colorectal cancer. In gastric cancer, patients with high E/H tumors had a shorter survival time than those with low E/H tumors. CONCLUSIONS: Our results suggest that the E/H ratio is a useful indicator of prognosis in gastric and colorectal carcinoma.

Adult↗

Defective intracellular transport of tissue-nonspecific alkaline phosphatase with an Ala162-->Thr mutation associated with lethal hypophosphatasia.

We have studied the biosynthesis and intracellular transport of tissue-nonspecific alkaline phosphatase (TNSALP) transiently expressed in COS-1 cells. Mutations were introduced into TNSALP to examine the effects of a single amino acid substitution on the activity and biosynthesis of TNSALP. The cells expressing wild-type TNSALP exhibited more than 200-fold higher alkaline phosphatase activity than untransfected ones. Pulse-chase experiments showed that TNSALP was synthesized as a 66-kDa endoglucosaminidase H (Endo H)-sensitive form and converted to EndoH-resistant forms with heterogenous molecular masses ( approximately 80 kDa), which finally appeared on the cell surface as judged by digestion with phosphatidylinositol-specific phospholipase C (PI-PLC). In contrast, a TNSALP with a Glu218-->Gly mutation exhibited no phosphatase activity at all and the 66-kDa Endo H-sensitive form was the only molecular species throughout the chase in the transfected cells. In accordance with this finding, digestion with PI-PLC and immunofluorescence observation confirmed that this mutant was never expressed on the cell surface. Another mutant with a Ala162-->Thr substitution, which naturally occurs in association with a lethal hypophosphatasia, exhibited a low activity and only a small fraction of the 66-kDa form acquired Endo-H resistance and reached the cell surface. Since the wild-type and the mutant TNSALPs were labeled with [3H]ethanolamine, a component of glycosylphosphatidylinositol (GPI), it is unlikely that the impaired intracellular transport of the two mutants is due to a failure in their modification by GPI. Interestingly, the 66-kDa Endo H-sensitive form of the TNSALP mutants but not that of the wild-type, was found to form an interchain disulfide-bonded high-molecular-mass aggregate within the cells. These results suggest that impaired intracellular transport of the TNSALP (Ala162-->Thr) molecule caused by its aggregation is the molecular basis for the lethal hypophosphatasia carrying this mutation.

Alanine↗

Substrate specificities and kinetic properties of proteinase A from the yeast Saccharomyces cerevisiae and the development of a novel substrate.

The substrate specificities and kinetic properties of proteinase A, an intracellular aspartic proteinase from the yeast Saccharomyces cerevisiae, were determined using a series of synthetic chromogenic peptides with the general structure P5-P4-P3-P2-Phe-(NO2)Phe-P2'-P3' [P5, P4, P3, P2, P2', P3' are various amino acids; (NO2)Phe is p-nitro-L-phenylalanine]. The nature of the residues occupying the NH2-terminal region of the substrate had a strong influence on the kinetic constants. Among those tested, Ala-Pro-Ala-Lys-Phe-(NO2)-Phe-Arg-Leu had the best kinetic constants (Km = 0.012 mM, kcat = 14.4 s-1, kcat/Km = 1,200 M-1.s-1). Compared with such aspartic proteinases as pepsin, cathepsin D, and renin, the substrate specificity of proteinase A was unique. Based on these results, a novel fluorescent substrate, MOCAc-Ala-Pro-Ala-Lys-Phe-Phe-Arg-Leu-Lys(Dnp)-NH2, was developed for the sensitive measurement of proteinase A.

2,4-Dinitrophenol↗

Substrate specificity of pepstatin-insensitive carboxyl proteinase from Bacillus coagulans J-4.

Bacillus coagulans J-4 carboxyl proteinase, designated as J-4, is characterized as alcohol-resistant and insensitive to aspartic proteinase inhibitors such as pepstatin, diazoacetyl-DL-norleucinemetylester, and 1,2-epoxy-3-(p-nitrophenoxy)propane. Here, its substrate specificity was elucidated by using two series of chromogenic substrates, Lys-Pro-Ala-Lys-Phe*Nph (p-nitrophenylalanine:* is cleavage site)-Arg-Leu (XVI) and Lys-Pro-Ile-Glu-Phe*Nph-Arg-Leu (RS6), in which the amino acid residues at positions P5-P2, P2', and P3' were systematically substituted. Kinetic parameters were determined for both sets of peptides. J-4 was shown to hydrolyze Lys-Pro-Ala-Ala-Phe-Nph-Arg-Leu most effectively among the XVI series. The kinetic parameters of this peptide were Km = 20.0 +/- 3.24 microM, kcat = 15.4 +/- 0.71 s-1, and kcat/Km = 0.769 +/- 0.128 microM-1.s-1. Among the RS6 series, Lys-Pro-Ile-Pro-Phe-Nph-Arg-Leu was hydrolyzed most effectively. The kinetic parameters of this peptide were Km = 13.7 +/- 1.30 microM, kcat = 9.65 +/- 0.38 s-1, and kcat/Km = 0.704 +/- 0.072 microM-1.s-1. These systematic analyses revealed that J-4 had a unique preference for the P2 position: J-4 preferentially hydrolyzed peptides having an Ala or Pro residue in the P2 position. Other carboxyl proteinases preferred peptides having hydrophobic and bulky amino acid residue such as Leu in the P2 position. Thus, J-4 was found to differ considerably in substrate specificity from the other carboxyl proteinases reported so far.

Amino Acid Sequence↗