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Biomedical subjects

N Tajima

Publications and source records attributed to N Tajima.

At least 37 records · Page 2Linked to original sources

Lipoprotein analysis using agarose gel electrophoresis and differential staining of lipids.

We established a strategy to directly measure cholesterol and triglyceride levels of each lipoprotein fraction using a combination of agarose gel electrophoresis and differential staining. The cholesterol and triglyceride levels determined by electrophoresis correlated significantly with those of ultracentrifugation. The correlation coefficients between these methods were, for cholesterol levels 0.975(very low density lipoproteins, VLDL), 0.986(low density lipoproteins, LDL) and 0.965(high density lipoproteins, HDL) and for triglyceride levels 0.994(VLDL), 0.963(LDL) and 0.959(HDL) respectively. Both intra-and inter-assays showed low values of coefficients of variation (CV) (less than 3.57%). We observed a strong linearity between staining and triglyceride concentration. An increased VLDL-cholesterol was observed in type III subjects, a result which enabled distinction between type III and type IIb or type V lipoproteinemia. The method revealed lipoprotein patterns in some samples otherwise unexpected from their corresponding serum lipid parameters. Analyses of these electrophoretic patterns thus provide an effective technique to classify types of hyperlipidemia defined by the WHO. Furthermore, quantitative measurement of chylomicrons, usually difficult, proved to be achievable, providing an additional analysis of postprandial hyperlipidemia and the exact measurement of LDL-cholesterol after diet. Consequently, we recommend this simple and easy method for clinical evaluation of abnormalities in lipoprotein profiles.

Chylomicrons↗

Kinetic and theoretical studies on the mechanism of alkaline hydrolysis of DNA.

The reaction mechanism of alkaline hydrolysis of DNA has been investigated by kinetic analysis and density-functional-theory calculation. The rates of hydrolysis of thymidine 3'-monophosphate esters (including thymidylyl(3'-5')thymidine (Tp-OT)) monotonically decrease as the leaving groups get poorer. According to the theoretical calculation in which the solvent effects are incorporated, no intermediate is formed in the course of the reaction. In the alkaline hydrolysis of the activated Tp-OT analogues having good leaving groups, the 3',5'-cyclic monophosphate of thymidine is concurrently formed through the intramolecular attack by the 5'-alkoxide ion. In the hydrolysis of the native dinucleotide, however, this side reaction does not occur, since the transition state leading to the departure of its poor leaving group cannot be formed due to conformational restraint. These arguments are supported by the theoretical analysis on the hydrolysis of both dimethyl phosphate and its O(bridging)-->S substituted analogue.

DNA↗

The effect of verbal feedback on motor learning--a PET study. Positron emission tomography.

The purpose of this study was to investigate brain mechanisms underlying feedback effects on motor learning. We measured human brain activity using positron emission tomography (PET) during length-of-line drawing tasks in the presence or absence of verbal feedback, i.e., information on the precision of motor performance. The average error in responses was significantly lower and the percentage of correct responses was significantly higher in the case of tasks with feedback than those in the absence of feedback. The contralateral sensorimotor, premotor, supplementary motor, the right prefrontal, bilateral parietal and temporal, and anterior cingulate cortices, and the left basal ganglia were activated during all the line-drawing tasks. The right lateral prefrontal and occipital cortices and the left basal ganglia exhibited marked increase in activity after learning. The right inferior parietal and the anterior cingulate cortices were activated in the presence of feedback which provided information on how the subjects should correct their performances. The results indicate that these brain areas may play an important role in representing knowledge of results during motor learning and that appropriate feedback may facilitate motor learning.

Adult↗

Comparison of the fasting and the 2-h glucose criteria for diabetes in different Asian cohorts.

AIMS/HYPOTHESIS: The American Diabetes Association recommended that only a single fasting plasma glucose of greater than or equal to 7.0 mmol/l should be used for diagnosing diabetes in epidemiological studies and did not recommend using a 2-h oral glucose tolerance test. We evaluated the effect of diagnostic changes on the prevalence of diabetes and on the choice of subjects diagnosed with diabetes. METHODS: Existing epidemiological data collected from Asian people between 30 and 89 years of age, was re-analysed separately in 11 population-based studies (n = 17,666), 6 pre-selected hyperglycaemic cohorts (n = 12,221) and one suspected diabetic cohort (n = 8382). RESULTS: Among the 11 population-based studies, the new fasting glucose criteria resulted in an overall reduction of 1.8% in the prevalence of diabetes, which ranged from a reduction of 4.8% to an increase of 1.7% in the different studies. Of 1215 subjects diagnosed with diabetes by either criteria, only 449 met both criteria, a concordance of 37%. More than half of the diabetic subjects had isolated post-challenge hyperglycaemia and three quarters of the subjects with impaired glucose tolerance, according to the 2-h glucose criteria, were normal according to the fasting glucose criteria. Subjects diagnosed as diabetic based only on the 2-h glucose criteria were, on average, older than those with diabetes according to the fasting criteria. CONCLUSION/INTERPRETATION: The fasting and the 2-h glucose criteria diagnose different groups of subjects. It would therefore be inappropriate to use the fasting glucose criteria alone for screening diabetes in Asian populations.

Adult↗

Biomechanical analysis of effects of foot placement with varying chair height on the motion of standing up.

Individual experience reveals that posterior foot placement enables one to stand up easily from a chair. However, the way in which foot placement affects this motion has not been investigated in detail. This study was performed to examine the effects of foot placement in the initial stage of the dynamics of standing up from a chair. Subjects wearing light-emitting diode markers and surface electrodes stood up from a chair over force plates, and ground reaction force, joint angle, and muscle activity were measured. The motions required to stand up from chairs 30, 40, or 50 cm in height were analyzed with anterior, vertical, and posterior foot placement. With anterior foot placement, the forward-acceleration components of the ground reaction force were recorded with simultaneous and long-sustained activity of the muscles in order to shift the center of gravity of the body forward even more after lift-off. Our findings indicate that the distance between the center of gravity and the point of application of ground reaction force at lift-off are critical factors in the standing-up motion, and that chairs should be of adequate height as well as having sufficient space under the seat to permit the backward movement of the lower legs.

Activities of Daily Living↗

[A case of systemic lupus erythematosus associated with superior vena cava syndrome].

We report on a case of systemic lupus erythematosus associated with superior vena cava syndrome. A 46-year-old woman developed polyarthralgia in December 1994. She was treated with nonsteroidal anti-inflammatory drugs. In February 1995, she was admitted to our hospital with systemic convulsion and disturbance of consciousness (III-300/Japan coma scale). Severe facial edema was also present. Laboratory studies revealed the presence of anti-nuclear antibody, anti-DNA antibody, anti-Sm antibody, and proteinuria. An X-ray film of the chest showed pericardial effusion and bilateral pleural effusions. Computed tomography of the chest showed a severe swelling of mediastinal lymph nodes. A diagnosis of systemic lupus erythematosus was made according to the American Rheumatism Association criteria. Initial treatment with intravenous dexamethasone improved the level of consciousness and decreased the facial edema, mediastinal lymphadenopathy, and the effusions on computed tomography of the chest. We believe that the most likely explanation for the facial edema is superior vena cava syndrome due to severe mediastinal lymphadenopathy.

Humans↗

[The role of daunorubicin in induction therapy for adult acute myeloid leukemia].

The relationship between the total dose of daunorubicin (DNR) in induction therapy and the treatment outcome were evaluated based upon individualized doses of DNR during induction therapy for patients with acute myeloid leukemia(AML). Ninety-two previously untreated adult AML patients admitted to our hospital were analyzed for the dose of DNR required for complete remission (CR), the CR rate, disease-free survival (DFS) and overall survival (OS). The induction therapy consisted of DNR (40 mg/m2/d, i.v., from D 1 until the marrow was hypoplastic), Ara-C, prednisolone, and/or 6-thioguanine. Eighty-three out of 92 patients were assessable. Sixty-three patients entered CR (76%), of whom 52 attained CR with the first course of induction therapy. The 10-year DFS and OS rates were 31.2% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120-480 mg/m2), which was not influenced by initial WBC count, or FAB type. These results indicate that when the dose is linked to the observed tumor response, the optimal dose of DNR in the induction therapy is around 280 mg/m2 (40 mg/m2 x 7 times), which is higher than the conventional dose of 40-60 mg/m2 for 3 days. The higher dose of DNR in the induction therapy for adult AML should be selected when the feasibility of a new drug is evaluated in a randomized trial.

Adolescent↗

[A case of rheumatoid arthritis associated with autoimmune hemolytic anemia due to weekly low-dose methotrexate therapy].

A 57-year-old woman was found to have rheumatoid arthritis (RA) in 1996. Treatment with different immunoregulatory agents, including actarit and bucillamine, produced no improvement. Therefore, combined therapy with methotrexate (MTX) (5 mg/week oral) and low-dose prednisolone (PSL) (5 mg/day) was started in April 1997. Sulindac and famotidine were also administered. In August 1997, she was admitted to our hospital because of palpitations and shortness of breath due to severe anemia. Results of laboratory studies were hemoglobin, 2.9 g/dl; reticulocyte count, 225/1000; and haptoglobin, less than 10 mg/dl. The direct and indirect Coombs'tests were positive. A diagnosis of autoimmune hemolytic anemia (AIHA) was made on the basis of the laboratory findings. Treatment with high-dose PSL (50 mg/day) was started, and the anemia improved. The hemoglobin level increased to 6.0 g/dl within the 1st week and to 12.6 g/dl 6 weeks later. We believe that the most likely explanation for this anemia was the low-dose MTX because the anemia appeared soon after treatment was started.

Anemia, Hemolytic, Autoimmune↗

[Therapeutic efficacy of cyclosporin A in four cases of amyopathic dermatomyositis with rapidly progressive interstitial pneumonia].

OBJECTIVES: We investigated the clinical features of amyopathic dermatomyositis (ADM) with rapidly progressive interstitial pneumonia (IP), and the effectiveness of cyclosporin A (CsA) for IP. METHODS: In our four patients who were accorded with the notion of amyopathic dermatomyositis proposed by Euwer and treated with CsA for IP, and eight reported patients for whom we could obtain details of the clinical course, we investigated the relationship between the clinical features of them at the start of CsA administration and the clinical effectiveness of CsA. RESULTS: When we investigated the effectiveness of CsA in our four patients and eight reported patients, we could judge that effective cases were four and ineffective cases were eight. We compared the PaO2 at the start of CsA administration between effective and ineffective cases, the average PaO2 at the start of CsA administration was 65.7 mmHg in four effective cases, while it was 51.0 mmHg in eight ineffective cases. There was a statistically significant difference between the groups. CONCLUSIONS: Because our results suggested that many ineffective cases were treated with CsA after they had developed severe respiratory failure, we think that CsA should be given to ADM patients with rapidly progressive IP before the progression of respiratory failure.

Adult↗

Differentiation-induced insulin secretion from nonendocrine cells with engineered human proinsulin cDNA.

To investigate the effects of differentiation on insulin secretion from engineered nonendocrine cells, modified human proinsulin cDNA (INS/fur) was transfected to THP-1 monocyte and C2C12 myoblast cell lines. When THP-1 was differentiated into macrophages with phorbol ester, the insulin secretion rate was increased by 3.1-fold. This increase in insulin secretion is accompanied by a 17.6-fold increase in the processing efficiency of the modified human proinsulin and by a 3.5-fold increase in the abundance of furin mRNA. In addition, differentiation of C2C12 into myotubes, which can be induced by changing the serum, showed a 9.9-fold increase in insulin secretion and was accompanied by a 1.6-fold increase in the abundance of furin mRNA. The involvement of posttranslational processing and the exocytotic process in differentiation-induced insulin secretion could lead to the possibility of regulation of insulin secretion from genetically engineered cells.

3T3 Cells↗

Characterization of GFR, a novel guanine nucleotide exchange factor for Rap1.

Three groups of Rap1-specific guanine nucleotide exchange factors including C3G, CalDAG-GEFI, and Epac/cAMP-GEFI/II have been identified to date. In the present study, we report a new Rap1 guanine nucleotide exchange factor which we have named GFR (guanine nucleotide exchange factor for Rap1). GFR shows close sequence similarity to EPAC/cAMP-GEFI/II although GFR lacks a cAMP binding domain and contains a nuclear localization signal. We demonstrated that GFR can activate Rap1 but not H-Ras in 293T cells and that the cdc25 domain of GFR is required for the activation of Rap1. Northern blot analysis suggested that GFR mRNA is strongly expressed in the brain. In transfected HeLa cells, GFR has been found to be localized in the nuclei.

Amino Acid Sequence↗

A comparative study of chemonucleolysis with recombinant human cathepsin L and chymopapain. A radiologic, histologic, and immunohistochemical assessment.

STUDY DESIGN: Investigation of the effects of recombinant human cathepsin L on intervertebral discs and comparison with the effects of chymopapain. OBJECTIVE: To evaluate the effects of cathepsin L on intervertebral discs as an agent for chemonucleolysis. SUMMARY BACKGROUND DATA: Cathepsin L is a typical cysteine proteinase that belongs to the papain superfamily. It plays a major role in intracellular proteolysis and is not believed to induce anaphylactic reactions. METHODS: In vivo: Rabbit intervertebral discs were injected with recombinant human cathepsin L, its buffer solution, and chymopapain. After 1, 4, and 16 weeks the animals were killed, and radiologic and histologic examinations were performed. In vitro: The enzymatic actions of recombinant human cathepsin L and chymopapain on human intervertebral disc proteoglycans were examined immunohistochemically using antiproteoglycan antibodies. RESULTS: In rabbit models, roentgenography showed that disc spaces treated with cathepsin L and chymopapain had become narrower 1 week after injection. Histologically, loss of safranin-O staining was observed in the anulus fibrosus of discs treated with cathepsin L. After 16 weeks, nucleus pulposus had regenerated with chondrocyte-like cells, and the safranin-O staining characteristics of the matrix also had recovered. In an immunohistochemical study, all components of the proteoglycan stained weakly after chymopapain digestion. After cathepsin L digestion, unsulfated chondroitin and core protein staining was weaker, but the chondroitin 6-sulfate staining was unaffected. CONCLUSIONS: Cathepsin L seems to be an effective agent for chemonucleolysis. Its enzymatic action on proteoglycan appears to be different from that of chymopapain.

Adult↗

A biomechanical study of posterolateral lumbar fusion using a three-dimensional nonlinear finite element method.

Biomechanical analyses under compressive load, flexion, and extension torque were performed, using a nonlinear three-dimensional finite element method, to evaluate stability in posterolateral fusion. Effects of facet fusion and disc denucleation on posterolateral fusion were also examined. Using an initially prepared L4-5 motion segment model, we prepared a denucleation model, posterolateral fusion models classified by presence or absence of denucleation and facet fusion, and an interbody fusion model. In the denucleation model, rigidity was less than in the normal model, and maximum rigidity was analyzed for the interbody fusion model. The effect of denucleation on posterolateral fusion was also analyzed. Taking into account the instability of the anterior elements, including the intervertebral disc, appears to be clinically important. In the posterolateral fusion model under compressive load, the axis of rotation moved principally toward the fusion mass, and axial displacement and flexion rotation were induced. Sagittal rotation angles under flexion and extension torque were 1.5 degrees -2.3 degrees at a maximum moment of 15 N-m, demonstrating elasticity of posterolateral fusion. When combined with facet fusion, posterolateral fusion yielded increase of load transfer across the lamina and decrease of rotation angle of about 10% under flexion-extension torque. Adjunctive clinical use of facet fusion should permit more solid posterolateral fusion.

Biomechanical Phenomena↗

Preferential transmission of maternal allele with DQA1*0301-DQB1*0302 haplotype to affected offspring in families with type 1 diabetes.

To approach the possible involvement of an epigenetic mechanism in the pathogenesis of type 1 diabetes, we investigate here a parent-of-origin effect in transmission of the susceptible alleles at HLA-DQ loci by the transmission disequilibrium test. When we examined alleles of affected offspring of Japanese origin in 28 nuclear families, the maternal alleles were significantly different from the paternal alleles. Furthermore, the maternal alleles with the susceptible DQA1*0301-DQB1*0302 haplotype showed strong transmission disequilibrium with antiglutamic acid decarboxylase antibody-positive type 1 diabetes, while the paternal alleles with the same haplotype did not. This differential transmission disequilibrium of the susceptible allele was confirmed by the contingency table analysis for transmitted or nontransmitted alleles of both parental origin. The unique transmission of the susceptible allele observed supports the hypothesis that an epigenetic mechanism including genomic imprinting at the HLA-DQ region is involved in the pathogenesis and the genetic complexity of type 1 diabetes.

Asian People↗

Effect of highly purified eicosapentaenoic acid ethyl ester on insulin resistance and hypertension in Dahl salt-sensitive rats.

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to lard on the development of hypertension and insulin resistance in Dahl salt-sensitive (Dahl-S) rats fed a high-sucrose diet (HSD), a model of salt-sensitive hypertension. After 16 weeks of treatment, the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test significantly increased in the HSD-EPA-E group compared with the HSD-water or -lard control group. The GIR was approximately three times higher in the HSD-EPA-E group versus the HSD-water or -lard control group, and it was about 70% of the rate in the calorically deprived control group fed a low-fat-high-fiber diet (LF-HFD). In addition, EPA-E significantly suppressed the elevation of plasma glucose and insulin levels after oral glucose loading. These results indicate that EPA-E prevents the development of insulin resistance in Dahl-S rats fed a HSD. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase in C18:2, C20:5, and C22:5 components in the HSD-EPA-E group and, conversely, a significant decrease in C16:0, C20:4, and C22:6. The present results indicate that the beneficial effect of EPA-E on insulin resistance in Dahl-S rats fed a HSD is likely dependent on the modification of phospholipid components in the skeletal muscle membrane. These findings suggest that EPA-E might prevent the development of insulin resistance in dietary obesity. In addition, the HSD-EPA-E group showed a significant increase in the level of uncoupling protein (UCP) in brown adipose tissue as compared with the HSD-water or -lard control group. However, EPA-E had no effect on the development of hypertension and obesity in Dahl-S rats fed the HSD.

Animals↗

Solitary fibrous tumor of the spinal nerve rootlet: case report and literature survey.

Solitary fibrous tumor (SFT) is a rare tumor that arises most commonly in the pleura. Recent evidence indicated that it is a tumor that originates from mesenchymal, probably fibroblastic, cells and is not restricted to the pleura. This report presents a case of primary SFT occurring as a dumbbell-shaped tumor of the cervical spine (C4/5) in a 46-year-old Japanese female, probably originating from the spinal rootlet. The tumor was predominantly extradural, loosely attached to the dura mater, with a small intradural extramedullary part attached to the C5 anterior and posterior rootlets. Histologically, the tumor was predominantly composed of a haphazard proliferation of spindle cells separated by abundant collagen. Immunohistochemically, the cells were strongly positive for CD34, bcl-2 and vimentin, but were negative for S-100 protein, neuron specific enolase, cytokeratin and epithelial membrane antigen. The present case and review of the literature strongly suggest that SFT is an entity that should be considered in the differential diagnosis of tumors of the cerebrospinal region.

Antigens, Nuclear↗

Mechanism of preventive effect of HMG-CoA reductase inhibitor on diabetic nephropathy.

BACKGROUND: Previously, we have found that pravastatin prevents diabetic nephropathy in streptozotocin-induced diabetic rats independently of serum lipid levels. The aim of this study was to clarify the impact of pravastatin on the mesangial cells exposed to high glucose. METHODS: Rat mesangial cells were cultured in DMEM containing low glucose (5 mM glucose), high glucose (25 mM glucose) and 25 mM glucose with 500 microM pravastatin for 48 hours, respectively. After harvesting, we examined membrane-associated Ras with immunoblot analysis, activity of mitogen-activated protein kinase (MAPK) in the cytosol fraction with in-gel kinase assay and expressions of TGF-beta mRNA with Northern blot analysis. RESULTS: Membrane-associated Ras, activity of MAP kinase, and expression of transforming growth factor-beta (TGF-beta) mRNA were increased in the mesangial cells cultured exposed to high glucose compared to low glucose. Pravastatin suppressed all these changes in membrane-associated Ras, MAP kinase and TGF-beta mRNA in high glucose. CONCLUSIONS: This study suggests that pravastatin suppresses the activity of Ras-MAP kinase cascade and induction of TGF-beta in the mesangial cells that have been exposed to high glucose.

Animals↗

Insulin resistance and angiotensin converting enzyme polymorphism in Japanese hypertensive subjects.

Renin-angiotensin system activity has been shown to affect insulin sensitivity. However, the relationship between I/D polymorphism and insulin resistance is controversial. Therefore, we examined the relationship between the ACE genotype and insulin sensitivity in 51 Japanese hypertensive patients using the glucose clamp technique. The ACE genotype distribution in the hypertensive subjects was: 7 subjects with DD, 20 subjects with ID, and 24 subjects with II. Insulin sensitivity in terms of the glucose disposal rate was not significantly different among the three ACE genotypes, although there was a tendency for insulin sensitivity to decrease in the order of II, ID and DD, DD being the lowest. These findings are contrary to previous reports that insulin sensitivity was increased in normotensive subjects with the DD genotype who were Caucasian or African-American. There might be a difference due to race and whether the subjects are hypertensive or obese. We concluded that insulin sensitivity was not different among the ACE genotypes in the Japanese hypertensive subjects, supporting a previous report on the Chinese population. To date, insulin sensitivity has not been found to differ with ACE genotypes in the oriental population.

Adult↗