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Biomedical subjects

T Yamazaki

Publications and source records attributed to T Yamazaki.

At least 289 records · Page 16Linked to original sources

Proteolytic processing of Alzheimer's disease associated proteins.

Amyloid beta-peptide (A beta), the major component of senile plaques, is generated by proteolytic processing from the beta-amyloid precursor protein (beta APP). Mutations within the beta APP gene cause early onset familial AD (FAD) by affecting A beta generation. Interestingly, the much more abundant mutations within the presenilin (PS) genes also result in the abnormal generation of a 42 residue A beta (A beta 42), thus clearly supporting a pivotal role of A beta for the pathology of AD. PS proteins are proteolytically processed into stable 30 kDa N-terminal fragments (NTF) and 20 kDa C-terminal fragments (CTF). Beside the conventional proteolytic pathway. PS proteins can also be cleaved further C-terminal by proteases of the caspase superfamily. PS proteins were localized within the endoplasmic reticulum (ER) and early Golgi, compartments which we have demonstrated to be involved in A beta 42 generation and intracellular accumulation. Using Caenorhabditis elegans as a simple animal model, we demonstrate that PS proteins are involved in NOTCH signaling FAD causing mutations interfere with the biological function of PS proteins in NOTCH signaling.

Alzheimer Disease↗

Molecular breeding of the basidiomycete Coprinus cinereus strains with high lignin-decolorization and -degradation activities using novel heterologous protein expression vectors.

Two chromosome-integrating vectors, pLC1 and pLC2, were used. The former is the pUC19-based vector carrying the Lentinus edodes ras gene promoter and priA gene terminator, and the latter is the pBR322-based vector carrying the promoter and terminator of the priA gene. The manganese (II) peroxidase (MnP) cDNA (mnpc) derived from Pleurotus ostreatus was fused between the promoter and terminator of pLC1 and pLC2, yielding the recombinant plasmids pLC1-mnp and pLC2-mnp. These plasmids were introduced into protoplasts of the Coprinus cinereus trp1 strain with the C. cinereus TRP1-containing plasmid pCc1001 by co-transformation. Two Trp+ transformants for each plasmid, showing clearly higher lignin-decolorization activities, were obtained through introduction of pLC1-mnp and pLC2-mnp. Southern-blot analysis revealed that the four transformants all possess the mnpc sequence on their chromosomes. One Trp+ MnP+ transformant (named TF2-7), which was derived from the introduction of pLC2-mnp and carried the highest number of copies (approx. 10) of mnpc, showed remarkably high lignin-decolorization and -degradation activities; at the time of cultivation when only 35%-40% of the lignin was decolored and degraded by the control Trp+ transformant obtained by the introduction of pCc1001 alone, almost all of the lignin was decolored and degraded by TF2-7.

Blotting, Southern↗

Preservation of the knee joint in limb salvage of osteosarcoma in the proximal tibia. A case report.

A 12-year-old boy with osteosarcoma in the proximal tibia underwent a successful limb-saving operation with preservation of the epiphyseal and articular cartilage of the proximal tibia as a result of his remarkable response to chemotherapy. There was no evidence of tumour invasion to the adjacent physis, as demonstrated by image findings. The bone defect was reconstructed using autoclaved autogeneous bone with a vascularized fibula. The patient exhibits excellent function of the affected limb, and the knee joint remains disease-free 55 months postoperatively.

Bone Neoplasms↗

Stress coping and social support in glucose tolerance abnormality.

We examined coping with stress, including social support, dealing with illness, and mood states, in a sample of 600 persons who underwent primary health-care screening. Subjects were not yet diagnosed as having glucose tolerance abnormality and considered themselves healthy before the examination. Although no significant differences on the existence and perception of social support were found, the utilization of social support was significantly and negatively correlated with the level of glucose tolerance abnormality. The results suggest that poor utilization of social support is associated with the onset of glucose tolerance abnormality.

Adaptation, Psychological↗

Perception and utilization of social support in diabetic control.

This study examined the influence of social support (perception and utilization) on diabetic control. Subjects were 178 patients with diabetes mellitus [insulin dependent diabetes mellitus (IDDM) = 26, non-insulin dependent diabetes mellitus (NIDDM)= 152]. HbA1c values was used as an indicator of diabetic control. Assessment of social support was performed using the Stress and Coping Inventory. HbA1c values were significantly related to the presence or absence of participation in a diabetic education program as well as scores on perception and utilization of social supports. The participation in the diabetic education program was not significantly associated with the two social supports, however, the two social support factors interacted significantly with one another. As for type of DM, these findings were stronger in IDDM patients. These results suggest that, in particular patients with NIDDM, although diabetes education is effective for decreasing HbA1c, a combination of the two social supports also decrease the HbA1c value, independent of diabetic education.

Adolescent↗

Drop episodes in Coffin-Lowry syndrome: exaggerated startle responses treated with clonazepam.

A 16-year-old girl had fully manifested Coffin-Lowry syndrome and drop episodes. Her drop episodes were precipitated by sudden unexpected tactile or auditory stimuli associated with the electrostatic circumstances in her leg muscles immediately after the stimuli. Studies revealed that her drop episode symptom was an unusual type of startle response and that it may be associated with Coffin-Lowry syndrome.

Abnormalities, Multiple↗

Signalling pathways for cardiac hypertrophy.

Mechanical stretch is an initial factor for cardiac hypertrophy in response to haemodynamic overload (high blood pressure). Stretch of cardiomyocytes activates second messengers such as phosphatidylinositol, protein kinase C, Raf-1 kinase and extracellular signal-regulated protein kinases (ERKs), which are involved in increased protein synthesis. The cardiac renin-angiotensin system is linked to the formation of pressure-overload hypertrophy. Angiotensin II increases the growth of cardiomyocytes by an autocrine mechanism. Angiotensin II-evoked signal transduction pathways differ among cell types. In cardiac fibroblasts, angiotensin II activates ERKs through a pathway including the Gbetagamma subunit of Gi protein, Src family tyrosine kinases, Shc, Grb2 and Ras, whereas Gq and protein kinase C are important in cardiac myocytes. In addition, mechanical stretch enhances the endothelin-1 release from the cardiomyocytes. Further, the Na+ -H+ exchanger mediates mechanical stretch-induced Raf-1 kinase and ERK activation followed by increased protein synthesis in cardiomyocytes. Not only mechanical stress, but also neurohumoral factors induce cardiac hypertrophy. The activation of protein kinase cascades by norepinephrine is induced by protein kinase A through beta-adrenoceptors as well as by protein kinase C through alpha-adrenoceptors.

Angiotensin II↗

Infective endocarditis complicated by mycotic cerebral aneurysm: two case reports of women in the peripartum period.

Mycotic cerebral aneurysm is a relatively rare but very serious complication of infective endocarditis. Infective endocarditis is a rare but a potentially fatal complication of pregnancy. We report here two very rare cases of infective endocarditis associated with mycotic cerebral aneurysm in peripartum women. In one case, cardiac surgery was performed prior to cerebral surgery and after delivery. In the other case, emergency cerebral surgery was performed due to rupture on the day cardiac surgery had been scheduled, 45 days after delivery. The surgical management of a patient with infective endocarditis and mycotic cerebral aneurysm is reviewed. The surgical strategy for a pregnant patient is also reviewed.

Adult↗

Developmental changes in the NGF content in the brain of young, growing, low-birth-weight rats.

The NGF content in each region of the brain of four-week-old rats was ranked in the decreasing order of cerebral cortex, hippocampus, cerebellum, midbrain/diencephalon, and pons/medulla oblongata, and the NGF concentration, in the decreasing order of hippocampus, cerebral cortex, cerebellum, midbrain/diencephalon, and pons/medulla oblongata in both AFD and SFD groups. The NGF content and concentration in the cerebral cortex were about the same value at each age between those in the AFD and SFD groups. Those in the hippocampus were a little higher in the SFD group than in the AFD group at the ages of three and four weeks, unlike those in the other regions, where the values for the cerebellum, midbrain/diencephalon and pons/medulla oblongata tended to be somewhat higher in the AFD group than in the SFD group. The NGF concentrations in the hippocampus and cerebral cortex increased with growth: the concentration in the hippocampus at four weeks of age was about 4-fold of that at one week in the AFD group and about 5.7-fold of that at one week in the SFD group; and likewise the concentration in the cerebral cortex at four weeks of age was about 5.3-fold in the AFD group and about 7-fold in the SFD group. The NGF concentrations in the cerebellum decreased, and those in midbrain/diencephalon and pons/medulla oblongata hardly changed with growth in either AFD or SFD group. From these results NGF may have stronger implications for the neuronal growth in the hippocampus compared with those in the lower brain regions of the SFD rats.

Animals↗

Myocardial interstitial noradrenaline monitoring during occlusion of inferior vena cava in cats.

To investigate myocardial interstitial noradrenaline (NA) kinetics during activation of systemic sympathetic nerves, we applied a dialysis technique to the left ventricle of anaesthetised cats and monitored myocardial interstitial NA levels during 6-min occlusion of the inferior vena cava (IVC). Dialysis probes were implanted in the left ventricular wall, and dialysate NA levels as an index of myocardial interstitial NA levels, were measured with high-performance liquid chromatographic-electrochemical detection. During IVC occlusion, dialysate NA levels progressively increased from 110 +/- 17 pmol L-1 in the control and reached 620 +/- 160 pmol L-1 at 4-6 min of IVC occlusion. Local administration of omega-conotoxin GVIA at 10 microM decreased the control dialysate NA level to 35 +/- 0.2 pmol L-1. The IVC occlusion induced increase in dialysate NA was suppressed only at 0-2 min of IVC occlusion. Intravenous injection of omega-conotoxin GVIA (10 micrograms kg-1) did not increase the dialysate NA levels during IVC occlusion. Local administration of desipramine at 100 microM increased the control dialysate NA level to 900 +/- 73 pmol L-1. The IVC occlusion induced progressive increase in dialysate NA was augmented at 2-6 min of IVC occlusion. These results suggest that the early increase in myocardial interstitial NA levels is mainly caused by neuronal release of NA from cardiac sympathetic nerve terminals, and that extraction from the circulation and neuronal NA uptake contribute to changes in myocardial interstitial NA levels after a delay of several minutes.

Adrenergic Uptake Inhibitors↗

Arg260-Cys mutation in severe factor XIII deficiency: conformational change of the A subunit is predicted by molecular modelling and mechanics.

To explore the implications of the structure/ function relationships in factor XIII. a patient with severe A subunit deficiency was examined at the DNA and RNA levels. Nucleotide sequence analysis of the patient's DNA amplified by PCR revealed that the patient had a replacement of C by T in the codon for Arg260. RT-PCR analysis demonstrated that only one kind of mRNA coding for the Arg260-Cys mutation was expressed in the patient at a normal level. Another possible defective allele of the A subunit gene with a G-A polymorphism was not expressed (null allele). The substitution of Arg260 by Cys located on the interface of two A subunits would preclude the reciprocal ionic interaction (salt bridge) between Arg260 and Asp404. Molecular modelling and, for the first time, molecular mechanics calculated that Cys260 changed the local conformation of the A subunit and reduced the electrostatic interaction between two monomers, suggesting destabilization of the molecule's dimer.

Amino Acid Substitution↗

Cathepsin G enhances human natural killer cytotoxicity.

Cathepsin G is a serine protease located in the azurophil granules of neutrophils. In this study, we investigated the effect of cathepsin G on the functions of human natural killer (NK) cells in vitro. Cathepsin G enhanced NK cytotoxicity rapidly in a dose-dependent fashion. The ability to augment NK cytotoxicity was markedly reduced in the presence of the inhibitor, phenylmethanesulphonyl fluoride (PMSF) or chymostatin, demonstrating that the proteolytic activity of cathepsin G is essential for the induction of NK cytotoxicity. Granulocyte exocytosis is required for NK cell-dependent target killing. Cathepsin G induced the release of the granule enzyme, N-acetyl-beta-D-glucosaminidase, from human NK cells. Moreover, an increase in the cytosolic-free Ca2+ concentration was observed in NK cells after stimulation with cathepsin G. When human granulocytes were stimulated with cytochalasin B and N-formyl-methionyl-leucyl-phenylalanine (fMLP), cathepsin G was released. The cathepsin G released from granulocytes also caused enhancement of NK cytotoxicity. In the presence of serine protease inhibitor the supernatant including cathepsin G obtained from stimulated granulocytes did not enhance NK cytotoxicity, but the stimulated granulocytes did. Highly purified human NK cells treated with cathepsin G enhanced NK cytotoxicity, but NK-depleted lymphocytes did not, demonstrating that cathepsin G regulates NK cytotoxicity independently of other factors. We have shown recently that human cathepsin G binds to human NK cells. These combined data indicate that cathepsin G released from granulocytes binds to NK cells and augments NK cytotoxicity through its protease activity.

Calcium↗

Elevated B-type natriuretic peptide levels after anthracycline administration.

BACKGROUND: Cardiotoxicity leading to congestive heart failure is a complication of the anthracyclines. Biochemical methods to diagnose and monitor cardiac function after anthracycline administration would be most useful. We examined the diagnostic role of B-type natriuretic peptide (BNP), a potent biochemical marker of left ventricular dysfunction, in patients administered anthracyclines. METHODS: Twenty-seven consecutive patients receiving anthracyclines were investigated by serial measurements of BNP levels and other cardiac neurohormones (A-type natriuretic peptide, renin, aldosterone, angiotensin II, norepinephrine, and epinephrine) and myocardial markers (creatine kinase-MB and myosin light chain). Echocardiography was done to assess systolic (ejection fraction) and diastolic (mitral inflow A/E ratio) functions. RESULTS: Of the examined cardiac biochemical markers, BNP levels alone showed marked elevations to abnormal levels after anthracycline administration. Most patients showed transient increases (peak at 3 to 7 days). Patients with persistent elevations showed a poor prognosis. A/E ratio also correlated with increases in BNP levels in selected patients, which may suggest that raised BNP levels are reflective of induced diastolic dysfunction. CONCLUSIONS: Our studies suggest the possible use of BNP levels to assess the cardiac state after anthracycline administration. BNP levels most likely reflect cardiac tolerance to the cardiotoxic agent. Serial BNP profiles also suggest persistent elevations to be associated with potentially decompensatory states in contrast to tolerable transient increases. Diagnosis of degree of cardiac tolerance by response to drug administration may be analogous to use of stress testing (exercise) to help define underlying left ventricular dysfunction.

Adult↗

Serological and immunohistochemical diagnosis of amniotic fluid embolism.

The purpose of this study was to evaluate whether serological assays and immunohistochemical staining, employing antibody TKH-2, are sensitive methods for the serological and histologic diagnosis of amniotic fluid embolism (AFE). TKH-2 is a sensitive antibody directed to sialyl Tn (STN), NeuAcalpha2-6GalNAc. Nineteen samples of maternal sera with clinical AFE and 120 control sera and 15 specimen of formalin-fixed, paraffin-embedded lung tissue sections were examined in this study. Tissue sections were stained using the streptavidin-biotin-immunoperoxidase method. The concentration of STN in serum was measured by an immunoradiometric competitive inhibition assay using the monoclonal antibody TKH-2 in a one-step procedure. Remarkable positive TKH-2 stainings were easily seen within the pulmonary vasculature in 14 of the 15 (93%) patients with AFE. The serum STN levels (mean+/-SD) in patients with AFE (110.8+/-48.1 U/ml) showed significantly higher concentrations compared with those of patients with non-AFE (17.3+/-2.6 U/ml) (p <0.01). Seventeen of 19 sera (89%) were diagnosed as AFE by serum TRH-2 level. We conclude that both TKH-2 immunostaining and serum STN assay are sensitive methods to diagnose patients with AFE.

Antigens, Tumor-Associated, Carbohydrate↗

Physiological and psychological evaluation for visual display colour readability: a visual evoked potential study and a subjective evaluation study.

This study was conducted, by subjective and objective evaluation, to clarify the complex relationships among VDT (visual display terminal) display colour readability and the related physical and physiological factors. Readability was defined as participants being able to read sentences easily on a VDT screen irrespective of their meanings. In the subjective evaluation, paired comparison tests and a colour impression test using the semantic differential (SD) method with factor analysis were carried out for 30 colour stimuli with different dominant wavelengths and stimulus purity values. The former test yielded identification of the most readable stimulus purity, which was in the range of 0.2 to 0.55 for any dominant wavelength. From the latter test, a 'conspicuousness factor' and a 'comfort factor' were extracted for evaluating readability. In the objective evaluation, three kinds of dominant wavelengths and three levels of stimulus purity were used. This evaluation showed that P100 peak latencies of colour-VEPs (visual evoked potentials) evoked by the subjectively optimal stimulus purity colours fully displayed on the screen were significantly shorter than those evoked by any other stimulus purity colours. Moreover, VEP P100 peak latencies evoked by the text colours that had the most readable stimulus purities were also shorter than those evoked by any other stimulus purity colours. Consequently, it was concluded that the optimum VDT display colour was that which had the most readable stimulus purity for each dominant wavelength, and that colour-VEP peak latency could serve as an indicator for quantification of VDT display colour readability.

Adult↗

Amyloid beta-protein (A beta) accumulation in the putamen and mammillary body during aging and in Alzheimer disease.

Immunocytochemical studies clearly showed that amyloid beta-protein (A beta) deposits are widely distributed in the subcortical regions as well as the cortices of normal aged and Alzheimer disease (AD) brains. To investigate the temporal profile of A beta accumulation in the subcortical region, we quantitated A beta40 and A beta42 levels, using sensitive enzyme immunoassays, in the putamen and mammillary bodies of normal individuals aged 24 to 87 years and of AD patients. In these two regions, A beta42 was the predominant species; in particular, A beta42 was the only A beta species detected in the putamen. In several cases the mammillary body contained only A beta40, but not A beta42. Although the extent of A beta accumulation in the 2 subcortical regions was much less than that in the cortex of the same subject, A beta42 appears to accumulate in both subcortical regions at the same time as in the cortex and leptomeninges. In addition, the A beta42 levels in the putamen or in the mammillary body correlated with those in the occipitotemporal cortex. This strongly suggests that the extent of A beta42 accumulation in the brain is determined not only by the duration of A beta accumulation but also by other unknown regional factors. Western blotting showed that the initial A beta species to accumulate in the putamen or mammillary body varied among individuals. In some cases, an A beta42 stable dimer was the most predominant species, while in other cases a 3 or 4 kD A beta42 monomer was more abundant, suggesting that the clearance rates of the A beta42 stable dimer and monomer are different in vivo.

Adult↗

The accuracy of localizing equivalent dipoles and the spatio-temporal correlations of background EEG.

For the inverse problem of equivalent dipole localization, a new residual function was proposed which is based on spatio-temporal correlation of background electroencephalogram (EEG). This residual has the advantage that it allows the calculation of a confidence region for estimated dipole parameters. This method was applied to two sets of visual evoked potential (VEP) data. The localization was compared by using the volume of the confidence region. The outcome of the equivalent dipole localization was compared for three different residual functions: 1) least square; 2) based on spatial correlations in the background EEG; and 3) the proposed new function which is based on spatial and temporal correlations in the background EEG. It was found that the proposed residual function leads us to the highest accuracy and the fastest convergence in the equivalent dipole localization and that even for two-dipole localization, the present method yields more accurate solutions with less iterations than the conventional methods.

Algorithms↗