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Biomedical subjects

M Okuno

Publications and source records attributed to M Okuno.

At least 73 records · Page 4Linked to original sources
PubMed1998

Expression of the mismatch repair gene hMSH2 in sporadic colorectal cancer.

At least four genes involved in DNA mismatch repair (MMR), hMSH2, hMLH1, hPMS1 and hPMS2, have been cloned and characterized. These genes have been demonstrated to be altered in the germline of patients with hereditary non-polyposis colorectal cancer (HNPCC). HNPCC is an autosomal dominant disease characterized by a preponderance of proximal colon, young age of onset, increased multiplicity, and improved stage-specific survival. In this study, we examined the expression of hMSH2 protein in sporadic colorectal cancer (CRC). As a result, the frequency of right-sided CRC and multiple CRCs were significantly higher in the patients with hMSH2-negative CRC than in those with hMSH2-positive CRC. The rate of p53 positivity was significantly lower in the hMSH2-negative tumours than that in the hMSH2-positive tumours. The disease-free survival rate tended to be higher in the patients with hMSH2-negative CRC than in the patients with hMSH2-positive CRC. Our findings suggest that both the clinicopathological and biological features of hMSH2-negative sporadic CRC seemed to be similar to those of HNPCC. To clarify the mechanism of carcinogenesis in HNPCC and sporadic CRC, further investigations of genetic alterations caused by MMR genes will be needed.

Adult↗
PubMed1998

Clinical study on arthroplasties for osteoarthritic hip by quantitative gait analysis. Comparison between total hip arthroplasty and bipolar endoprosthetic arthroplasty.

The present study was undertaken to serially observe gait of patients after hip arthroplasty, using quantitative gait analysis, and to compare it between patients after total hip arthroplasty (THA) and those after bipolar endoprosthetic arthroplasty (BEA). The subjects were 53 women with unilateral osteoarthritis of the hip. Thirty-one of them underwent THA (mean age: 59.5 years) and 22 underwent BEA (mean age: 58.0 years). The stance time and characteristic parameters calculated from the vertical component of floor reaction force (FRF) were analyzed by use of FRF plate. The stance time, which indirectly represents the walking speed, tended to decrease for one year after THA and for 3 years after BEA. The decrease in this parameter was greater on the unaffected side than on the affected side. The deceleration effect and the weighing-off effect are indicators useful for observation of gait recovery. Significant differences in these indicators between the unaffected and affected sides were seen for one year after THA and 3 years after BEA. This indicates that cadence and balance of the gait recovers earlier after THA than after BEA.

Acceleration↗
PubMed1998

[A cooperative study on concomitant with low-dose divided administration of cisplatin (CDDP) and sustained drip infusion of 5-fluorouracil (5-FU) for unresectable advanced gastric cancer. Osaka Cisplatin Gastric Cancer Study Group].

For patients with unresectable gastric cancer registered between July 1994 and September 1995, the following dosage regimen was examined: a drip infusion of cisplatin (CDDP) at 7 mg/m2/day for 5 consecutive days and 2-day withdrawal a week for 3 weeks with concomitant sustained drip infusion of 5-FU at 300 mg/m2/day for 21 days. The whole cycle was repeated again after 2-week withdrawal. The antitumor effect was seen in 39.4% among 33 cases. With respect to histological classification, there was no difference in appearance of the effect between the moderately differentiated type at 62.5% and the low-differentiated type at 42.9%. The cases which became resectable after the administration included those in which the tumor disappeared completely in the resected specimens. As adverse reactions encountered in the cases above Grade 3, anorexia, nausea and vomiting and diarrhea were seen as clinical symptoms in 10, 5.3 and 11.8%, respectively. As laboratory test values, decrease in hemoglobin, leukocytopenia and thrombocytopenia were seen in 16.7, 15.8 and 5%, respectively, while renal or liver dysfunction did not occur. This dosage regimen was considered useful for unresectable advanced gastric cancer, although myelosuppression should be watched carefully.

Adult↗
PubMed1997

9,13-di-cis-Retinoic acid induces the production of tPA and activation of latent TGF-beta via RAR alpha in a human liver stellate cell line, LI90.

We studied the mechanism by which 9,13-di-cis-retinoic acid (9,13dcRA), a novel and endogenous stereoisomer of all-trans-RA, induces TGF-beta formation in a human liver stellate cell line, LI90. 9,13dcRA induced the expression of RAR alpha and RARbeta, enhanced the production of tissue-type plasminogen activator (tPA), thereby, surface plasmin levels, and induced the activation of latent TGF-beta. Similar effects were obtained with RAR alpha-selective retinoid, but not with RARbeta- or RARgamma-selective retinoid, and the induction was inhibited by RAR alpha-selective antagonist. These results suggest that 9,13dcRA up-regulates tPA expression, resulting in the formation of TGF-beta by LI90 cells, at least in part, via induction and activation of RAR alpha.

Animals↗
PubMed1997

Overexpression of cyclin D1 and p53 associated with disease recurrence in colorectal adenocarcinoma.

Multiple genetic changes occur during the evolution of normal cells into cancer cells. It has been reported that both cyclin D1 and p53 genes play major roles in oncogenesis and/or cell cycle control in various cancers. In this study, we examined the overexpression of cyclin D1 and p53 by the immunohistochemical method and investigated the correlation between expression of these antigen and prognosis in patients with colorectal adenocarcinoma. Disease-free survival was significantly lower in the patients with cyclin D1-strongly positive tumors than in those with cyclin D1-negative tumors. Similarly, disease-free survival of the patients with p53-strongly positive tumors was significantly lower than that of those with p53-negative tumors. Moreover, multivariate analysis indicated that both cyclin D1 and p53 overexpression are independent prognostic factors in patients with colorectal adenocarcinoma. In conclusion, both cyclin D1 and p53 overexpression may be useful predictors of disease recurrence in patients with colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Propolypeptide of von Willebrand factor is a novel ligand for very late antigen-4 integrin.

We have previously reported that propolypeptide of von Willebrand factor (pp-vWF) promotes melanoma cell adhesion in a beta1 integrin-dependent manner. In this report, we identified the alpha subunit of the cell adhesion receptor for pp-vWF as alpha4. Human leukemia cell lines that express alpha4beta1 integrin (very late antigen-4, VLA-4), but not cell lines which lack VLA-4, attached well to pp-vWF substrate and these adhesions were completely inhibited by anti-alpha4 integrin monoclonal antibody HP2/1. Adhesion of mouse melanoma expressing alpha4 integrin was also inhibited by anti-mouse alpha4 mAb PS/2. Furthermore, transfection of human alpha4 cDNA into alpha4(-) Chinese hamster ovary cells resulted in an acquisition of adhesive activity to pp-vWF, indicating that pp-vWF is a ligand for VLA-4 integrin. Using a recombinant fragment of pp-vWF, the cell attachment site was shown to be located within amino acid residues 376-455 of pp-vWF. A series of synthetic peptides covering this region were tested for the ability to promote cell attachment and a 15-residue peptide designated T2-15 (DCQDHSFSIVIETVQ, residues numbered 395-409) promoted VLA-4 dependent cell adhesion. The peptide was also capable of inhibiting cell adhesion to pp-vWF, suggesting that this sequence represents the cell attachment site. By affinity chromatography using peptide T2-15-Sepharose, it was found that alpha4beta1 integrin complex from extracts of surface iodinated B16 cells specifically bound to the peptide. These results strongly suggest that pp-vWF is a novel physiological ligand for VLA-4.

Animals↗
PubMed1997

Frog experiment onboard space station Mir.

Japanese tree frogs (Hyla japonica) showed unique postures and behavior during an 8-day flight to the Russian space station Mir. When floating in the air, the animals arched their back and extended their four limbs. This posture resembles that observed during jumping or parachuting of the animals on the ground. Frog sitting on a surface bent their neck backward sharply, did not fold their hind limbs completely, and pressed their abdomen against the substrate. They walked backwards in this posture. The typical posture resembles that adopted during the emetic behavior process on the ground, although the posture in space lasts much longer. The possible mechanism of induction of this unique posture in orbit is discussed. Frogs in this posture might be in an emetic state, possibly due to motion sickness. Response behavior to some stimuli was observed in orbit. Body color change in response to the background color appeared to be delayed or slowed down. Response behavior to other stimuli showed little change as long as the animal maintained contact with a substrate. Once it left the surface, the floating frog could not control its movements so as to provide coordinated motility for locomotion and orientation. Adaptation to microgravity was observed in the landing behavior after jumping. Readaptation of the frogs to the Earth environment took place within a few hours after return. Postflight histological and biochemical analysis of organs and tissues showed some changes after the 8-day spaceflight. Weakening and density loss in vertebrae was noted. The beta-adrenoreceptor activity of the gastrocnemius was natriuretic decreased. Skin collagen and liver protein synthesis were lowered. The distribution of the atrial factor-like peptides in the brain was changed.

Adaptation, Physiological↗
PubMed1997

Retinoids exacerbate rat liver fibrosis by inducing the activation of latent TGF-beta in liver stellate cells.

Liver stellate cells (SCs) play central roles in both the storage of retinol and the development of liver fibrosis. The present study is aimed to understand the mechanism by which retinoic acid (RA, an active metabolite of retinol) enhances hepatic fibrosis in rats. We tested the effect of 9-cis-RA on several aspects in vitro rat SC cultures, including the activity of cellular plasminogen activator (PA), messenger RNA (mRNA), and protein levels of transforming growth factor-beta (TGF-beta) mRNA level of type-I procollagen, and the activity of type-I collagenase. Employing the rat liver fibrosis model produced by porcine serum, we also estimated the effect of oral administration of a stable RA analog on the progression of the fibrosis, as well as on hepatic TGF-beta contents. In vitro SC cultures, 9-cis-RA enhanced cellular PA and plasmin levels thereby induced plasmin-mediated activation of latent TGF-beta. Active TGF-beta generated self-stimulated its synthesis as well as that of collagen and suppressed the production of collagenase in an autocrine manner. In in vivo rat models, an RA analog accelerated the porcine serum-induced fibrosis by enhancing TGF-beta contents and, thus, collagen levels in the liver, although the RA analog alone was not fibrogenic. These results suggest that RA exacerbated liver fibrosis, at least in part, by inducing the activation and production of latent TGF-beta in liver SCs.

Adipocytes↗
PubMed1997

Trial of rural practice evaluation: mutual rotation by family physicians.

OBJECTIVES: We aimed to investigate the usefulness of mutual rotation by family physicians in providing an evaluation of rural medical practices. METHODS: Between June and October 1994, each of four family physicians rotated to the practices of the other three, where they worked as a transient locum for 4-5 days and evaluated each practice. They were field faculty physicians of the Department of Community and Family Medicine, Jichi Medical School, and based at general practices accredited for undergraduate and postgraduate training. Two school-based faculty physicians also participated in the study as spare members. RESULTS: The rotation was conducted four times to complete the mutual rotation programme. There was some difference in evaluation among the practices, which indicated the characteristics of the practices. The evaluation accorded relatively well among the participants. CONCLUSIONS: Mutual rotation by family physicians provides an objective and practicable evaluation of general practices and contribute to upholding their quality, which is crucial to medical education.

Faculty, Medical↗
PubMed1997

Perilla oil prevents the excessive growth of visceral adipose tissue in rats by down-regulating adipocyte differentiation.

We examined the effect of dietary oils with different fatty acid compositions on the growth of visceral adipose tissue in rats. Rats were fed for 4 mo starting at weaning a basal diet containing (12 g/100 g diet) perilla oil rich in (n-3) polyunsaturated fatty acids (PUFA), safflower oil rich in (n-6) PUFA, olive oil rich in monounsaturated fatty acid, or beef tallow rich in saturated fatty acids. The amount of food consumed and body weight gain did not differ among the four dietary groups. The weight of the epididymal fat pad and the serum triglyceride concentration in perilla oil-fed rats were significantly lower (P < 0.05) than those of olive oil- and beef tallow-fed groups. The product of [(volume of individual adipocytes) x (number of adipocytes in epididymal fat pad)], which presumably represents total adipocyte volume in the fat pad, was significantly lower (P < 0.05) in perilla oil-fed rats than in beef tallow- and olive oil-fed groups. Expression of the late genes of adipocyte differentiation, peroxisome proliferator-activated receptor alpha, adipocyte P2 and adipsin, was significantly (P < 0. 05) down-regulated in epididymal fat tissue of rats that had been fed perilla oil rather than beef tallow or olive oil, whereas expression of the early gene, lipoprotein lipase, was not significantly affected. Greater levels (P < 0.05) of (n-3) PUFA in the membrane phospholipid fraction of the fat tissue were observed in perilla oil-fed rats than in the other dietary groups. These results suggest that perilla oil or (n-3) PUFA prevents excessive growth of adipose tissue in rats at least in part by suppressing the late phase of adipocyte differentiation.

Adipocytes↗
PubMed1997

Association of atrial septal defect with Poland-Moebius syndrome: vascular disruption can be a common etiologic factor. A case report.

The authors describe an association of atrial septal defect with partial symptoms of the Poland-Moebius syndrome. Both are thought to be caused by developmental disorders of the mesenchyme and ectodermal derivatives. This anomalous association can be accepted as one concept of the subclavian artery blood supply disruption sequence during embryo-genesis.

Bundle-Branch Block↗
PubMed1997

Horseshoe lung: demonstration by electron-beam CT.

Horseshoe lung is a rare pulmonary anomaly characterized by fusion of the posterobasal portions of the right and left lungs behind the pericardial reflection, anterior to the aorta. The majority of reported cases occur in conjunction with scimitar syndrome, including hypoplasia of the right lung, anomalous right pulmonary venous return and systemic arterial supply to the lung. Horseshoe lung is usually diagnosed on pulmonary arteriography when the right inferior pulmonary artery crosses the midline and extends to the left lung base. Bronchography is also diagnostic when the branch of horseshoe portion arises from the right bronchus and passes within the lung parenchyma to midline of the lung tissue. The only described CT finding of horseshoe lung is the contiguity of the right and left lungs behind the heart. Most cases are infants under 12 months of age and CT images are severely hampered by respiration motion artefacts. Such artefacts are minimized by using electron-beam computed tomography, allowing a more detailed CT appearance of horseshoe lung in this case.

Child, Preschool↗
PubMed1997

The Frog in Space (FRIS) experiment onboard Space Station Mir: final report and follow-on studies.

The "Frog in Space" (FRIS) experiment marked a major step for Japanese space life science, on the occasion of the first space flight of a Japanese cosmonaut. At the core of FRIS were six Japanese tree frogs, Hyla japonica, flown on Space Station Mir for 8 days in 1990. The behavior of these frogs was observed and recorded under microgravity. The frogs took up a "parachuting" posture when drifting in a free volume on Mir. When perched on surfaces, they typically sat with their heads bent backward. Such a peculiar posture, after long exposure to microgravity, is discussed in light of motion sickness in amphibians. Histological examinations and other studies were made on the specimens upon recovery. Some organs, such as the liver and the vertebra, showed changes as a result of space flight; others were unaffected. Studies that followed FRIS have been conducted to prepare for a second FRIS on the International Space Station. Interspecific diversity in the behavioral reactions of anurans to changes in acceleration is the major focus of these investigations. The ultimate goal of this research is to better understand how organisms have adapted to gravity through their evolution on earth.

Acceleration↗
PubMed1997

Work and workload of nursing personnel in a nursery school and two institutions for handicapped children.

Work-related low back pain and cervicobrachial disorders have become increasingly common among nursing personnel with the increase in the number of social welfare institutions and workers. The aim of this study is to assess the burden on the low backs of personnel caring for children. We measured work content, working time, posture and muscular activity in 16 nursery workers in three different types of institutions for healthy and handicapped children. The working time and posture of 7 nursery teachers in a public nursery school for healthy children (A school), 7 nursing workers (4 nursery teachers and 3 nursery instructors) in a public daycare center for mentally and physically handicapped children (B center), and 2 nursery instructors in a private home for severely handicapped children (C home) were analyzed. The muscular activity of the erectores spinae muscle of three subjects was measured using a newly developed EMG monitor (portable EMG monitor, PEMM). The following results were obtained. The average length of a lesson or activity in A school was greater than that in B center and C home. The time required by care for meals was longest in C home. The arrangement and rearrangement times were longest in the classes of children aged 3-5 in A school. The time occupied for clerical work and other work was relatively longer, while recess including lunch time was approximately one hour. The most commonly observed posture was sitting on the floor in all kinds of classes, with this occurring most often in C home. Hazardous postures such as bending forward, squatting, and kneeling appeared in 11-18% (48-81 min) of a day's working time. The average muscular activity of the erectores spinae muscle of three subjects throughout a day was approximately 10% of the maximum isometric contraction (% maximum work load, %MWL), when muscular activities were measured by PEMM. The relatively high %MWL values (19-27%MWL) were obtained at a slightly bending posture and a kneeling posture, while lower (1-9%MWL) values were observed at a sitting posture. The %MWL values at a sitting posture varied according to such conditions as duration of sitting, back rest, weight on the arms, twisting of the trunk, and hip movement. The risky nature of the sitting posture are also discussed.

Adult↗
PubMed1997

[Malignancy of colorectal cancer analyzed by expression of cyclin D1].

We evaluated the clinical significance of cyclin D1 expression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal cancers were investigated by staining with a monoclonal antibody against cyclin D1. The possible correlations among cyclin D1 expression, clinicopathologic factors and prognosis were studied. There was no significant association between cyclin D1 expression and various clinicopathological factors. However, disease-free survival was significantly worse in the patients with cyclin D1 strongly positive tumors than in those with cyclin D1 negative tumors. Cyclin D1 overexpression may be useful as a predictor of disease recurrence in patients with colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Deletion of serum lectin-reactive alpha-fetoprotein by acyclic retinoid: a potent biomarker in the chemoprevention of second primary hepatoma.

A goal of cancer chemoprevention is the deletion of latent premalignant or malignant clones before they expand to a clinically detectable tumor. However, such clonal deletion has not been demonstrated in clinical studies. We have evaluated serum levels of lectin-reactive alpha-fetoprotein (AFP-L3), which suggests the presence of latent hepatoma cells, in a randomized controlled trial that used acyclic retinoid to prevent second primary hepatomas in patients who had received treatments that cured initial hepatomas. The trial involved 21 patients in each acyclic retinoid (600 mg daily) and placebo group and consisted of a 12-month period of drug administration and a subsequent follow-up period. Serum AFP-L3 was determined at entry and at the end of the 12-month treatment period using lectin-affinity electrophoresis and antibody-affinity blotting. Although neither treatment affected serum levels of total AFP, acyclic retinoid significantly reduced AFP-L3 levels after a 12-month administration (P < 0.01). Acyclic retinoid not only deleted AFP-L3 from patients who had been positive for AFP-L3 at entry but also prevented the appearance of AFP-L3 in patients who had been negative at entry (P < 0.01). In contrast, placebo significantly raised the incidence of AFP-L3-positive patients after a 12-month administration from that at entry (P < 0.05). Patients positive for AFP-L3 after a 12-month treatment had a significantly higher risk of second primary hepatomas in the subsequent follow-up period (P = 0.03). Acyclic retinoid may have deleted a clone of latent hepatoma cells producing AFP-L3 and thereby inhibited second primary hepatomas. Serum AFP-L3 may be a useful intermediate biomarker in the chemoprevention of second primary hepatomas by acyclic retinoid.

Antineoplastic Agents↗