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Biomedical subjects

T Takagi

Publications and source records attributed to T Takagi.

At least 1,081 records · Page 60Linked to original sources
PubMedDate not supplied

Dynamics of cell wall formation in fission yeast, Schizosaccharomyces pombe.

Studies on the dynamics of surface and intracellular structures during cell wall formation from the reverting protoplast of Schizosaccharomyces pombe were reviewed, and the correlation between cell wall formation and actin cytoskeleton, which is the most important conductor of the mechanism, is described in this paper. A close spatial and temporal relationship between actin cytoskeleton and cell wall formation was found by using wild type and actin point-mutant cps8 of S. pombe. Concomitant with the cell wall formation, dynamic behavior of the intracellular secretion machinery, especially the Golgi apparatus and secretory vesicles, was analyzed by three-dimensional reconstruction of 40 to 80 serial sections at five reverting stages. Total reverting protoplast volume increased by 3.8 and 4.3 times at 3 and 5 h, respectively, and the volume of the Golgi apparatus in the corresponding stages increased 2.3- and 2. 5-fold over the same periods. The number of secretory vesicles also markedly increased by 3.4 and 5.8 times over that of the corresponding reverting protoplasts. Actin point-mutant cps8 cells have abnormal structure in the cell wall and septum, and the distribution pattern of the actin cytoskeleton during the reversion process was different from wild-type protoplasts. The profiles of actin showed one or two thick cables and patches in the cytoplasm which remained throughout reversion. The development of crosslinkage of the glucan fibrils which are beta-1,3-glucan in nature on the reverting protoplast surface was defective; the glucan networks consisted of thin, rope-shaped fibrils up to 30 nm in width which formed a ribbon-shape 200 nm wide in wild-type reverting protoplasts. The intrafibrillar space is not filled with amorphous particles of alpha-galactomannan in nature. The secretion machinery was seen to have a similar profile as the wild type. The above results suggest that actin cytoskeleton may control secretion of beta-1,6-glucan and other cell wall substances such as alpha-glucan and alpha-galactomannan rather than beta-1,3-glucan. Study of the role of actin cytoskeleton in the cell wall formation is contributing to the development of antifungal agents together with basic cell biology.

Actins↗
PubMedDate not supplied

Molecular characterization of the "26S" proteasome complex from rat liver.

The molecular properties of an ATP/ubiquitin-dependent "26S" proteasome complex purified from rat liver were examined by physicochemical, biochemical, and morphological analyses. On ultracentrifugation, the proteasome complex sedimented as almost a single component with a sedimentation coefficient of 30.3S. Dynamic light-scattering measurements indicated that it has a diffusion coefficient of 1.38 x 10(-7) cm2/sec and a Stokes radius of 15.5 nm. From these two coefficients, the protein complex was estimated to have the high molecular weight of 2.02 x 10(6). Static light-scattering analysis indicated a molecular weight of 1.91 x 10(6) and a radius of gyration of 16.8 nm. The proteasome complex was found to be composed of multiple subunits of the 20S proteasome with molecular weights of 2.1-3.1 x 10(4) and 15-20 protein species with molecular weights of 3.5-11.0 x 10(4), which were directly associated with the 20S proteasome. The electron micrographic finding that the 26S proteasome complex had a caterpillar shape, direct electronmicroscopic observations on the subunit arrangement of the 20S proteasome, and classification of the subunits of the latter into two groups with respect to sequence homology suggested that the 26S complex is a symmetrical assembly of two domains, each containing a large terminal subset and half the central 20S subset of components. For clarification of the molecular structure of the 26S proteasome complex in solution, its physicochemical parameters were calculated theoretically using a model based on this caterpillar-shaped complex. The values obtained for the Stokes radius and radius of gyration of 12.2 and 14.9 nm were consistent with the experimental values. These results provide evidence that the 26S proteasome complex is a cylindrical caterpillar-like structure of "30S" in solution, consisting of a 20S proteasome component with proteolytic function and multiple other components, which possibly have regulatory roles.

Adenosine Triphosphate↗
PubMedDate not supplied

Transcatheter arterial infusion therapy in the treatment of advanced pancreatic cancer: a feasibility study.

PURPOSE: To evaluate the effects of transcatheter arterial infusion (TAI) therapy in 18 patients with advanced pancreatic cancer. METHODS: The drugs infused were epirubicin 60 mg, mitomycin C 20 mg, and 5-fluorouracil 500 mg. The efficacy of TAI was evaluated by a tumor marker (CA19-9), computed tomography (CT) findings, and postoperative histopathological specimens. RESULTS: In 10 of 15 cases, the tumor marker level was decreased after TAI therapy. In 6 of 14 cases, CT showed a decrease in the tumor size, and in 1 case, the tumor disappeared completely. In 6 cases the tumor could be resected. Necrosis, fibrosis, and degeneration of cancer cells were seen in 3 of 4 cases for whom a histopathological evaluation was done. The median survival was 11 months. In 17 patients back pain was the chief complaint, and was reduced to a self-controlled level in 10 patients following TAI therapy. No major complications were encountered. CONCLUSION: TAI appears to be an effective palliative treatment for advanced pancreatic cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Breakage of shunt devices (Sophy programmable pressure valve) following implantation in the hypochondriac region.

We report on three cases in which shunt devices (Sophy programmable pressure valve) broke while implanted in the hypochondriac region. None of these patients had an apparent history of trauma related to the shunt valve. The outlet connector was broken at the same site in each case. The dissociation between the movement of the thorax and that of the abdomen may have caused the formation of a crack in the outlet connector.

Child, Preschool↗
PubMedDate not supplied

Posterior fossa cystic lesions--magnetic resonance imaging manifestations.

Cystic lesions of the posterior fossa remain a controversial subject as to clinical classification and diagnosis, especially for those in combination with other intracranial abnormalities. During the period of November 1985 to June 1991, 16 patients with cystic lesions of the posterior fossa were retrospectively reviewed on neuroradiological evaluation with MR images. The patients were 9 males and 7 females aged from 5 days to 15 years old (medium 1 year old). They were classified into three groups as Dandy-Walker cyst (group A, 5 patients), mega cisterna magna (group B, 4) and retrocerebellar pouch or cyst (group C, 7). Nine patients had associated intracranial anomalies, holoprosencephaly in 3 (group A, 3), dysgenesis of the corpus callosum in 4 (group A, 2; group C, 2), and occipital meningoceles in 2 (group C, 2). Hydrocephalus or ventricular enlargement was found in 10 patients (group A, 5; group B, 2; group C, 3). Surgical treatment (cyst-peritoneal shunt or cystectomy) was performed for 10 patients with clinical symptoms due to cyst. Postoperatively, clinical symptoms due to increased intracranial pressure or hydrocephalus improved in 7 patients. For long-term results, the cyst was reduced in 1 of 5 patients of group A and 2 of 5 of group C. Most of our patients have a poor prognosis because of the associated intracranial anomalies or atrophy of the cerebellum. Multiplanar MR images may provide sufficient evidence for the diagnosis of posterior fossa cysts, especially in the case of rotation or upward displacement of the cerebellar vermis. However, the cyst membrane, and the communication of fluid between the cyst and the cistern, cannot be demonstrated on MR images. Further investigation on these subjects and indications for surgical intervention is highly necessary.

Adolescent↗
PubMedDate not supplied

In vivo roles of alcohol dehydrogenase (ADH), catalase and the microsomal ethanol oxidizing system (MEOS) in deermice.

The relative importance of ADH and MEOS for ethanol oxidation in the liver has yet to be elucidated. The discovery of a strain of deermice genetically lacking ADH (ADH-) which can consume ethanol at greater than 50% of the rates seen in deermice having ADH (ADH+) suggested a significant role for non-ADH pathways in vivo. To quantitate contributions of the various pathways, we examined first the ethanol oxidation rates with or without 4-methylpyrazole in isolated deermice hepatocytes. 4-Methylpyrazole significantly reduced the ethanol oxidation in both ADH+ and ADH- hepatocytes. The reduction seen in ADH- cells can be applied to correct for the effect of 4-methylpyrazole on non-ADH pathways of ADH+ deermouse hepatocytes. After correction, non-ADH pathways were found to contribute 28% of ethanol metabolism at 10 mM and 52% at 50 mM. When using a different approach namely measurement of the isotope effect, MEOS was calculated to account for 35% at low and about 70% at high blood ethanol concentrations. Thus, we found that two different complementary approaches yielded similar results, namely that non-ADH pathways play a significant role in ethanol oxidation even in the presence of ADH.

Alcohol Dehydrogenase↗
PubMedDate not supplied

Increase in mitochondrial GOT (m-GOT) activity after chronic alcohol consumption: clinical and experimental observations.

In order to clarify the origin and the mechanism of increased serum activity of glutamic oxalacetic transaminase (GOT) in chronic alcoholics, clinical and experimental investigations were carried out. Mitochondrial (m-GOT) and cytosolic GOT (c-GOT) isoenzymes were separated chromatographically by using a mini-column packed with Sephadex A50. Sixty percent of 63 alcoholics had elevated serum GOT. The m-GOT activity in alcoholics with total serum GOT activity of over 50 Karmen Units was 17.2 +/- 1.6 K.U. and the m-GOT/GOT ratio was the highest when compared to those in non-alcoholic liver diseases. In in vitro study, six hours of incubation of isolated hepatocytes from rats fed ethanol chronically resulted in an increased leakage of m-GOT into the incubation medium and also showed a tendency of a higher m-GOT/GOT ratio than that from control rats. The m-GOT activity thus released into the medium showed a highly significant inverse correlation with the viability of hepatocytes. These data suggest that m-GOT substantially contributes to an increased serum GOT often observed in chronic alcoholics.

Alcoholism↗
PubMedDate not supplied

Gastrectomy enhances vulnerability to the development of alcoholism.

A history of gastrectomy was more frequently encountered in Japanese male alcoholics (9.7%, 47/486) than in male employee populations of two large companies (0.8%, 36/4,381, p < 0.001, and 0.6%, 6/950, p < 0.001). Gastrectomized men are known to achieve a higher blood ethanol level after the ingestion of the equal amount of ethanol than nongastrectomized men. To examine whether or not gastrectomy was responsible for the subsequent development of alcohol dependence, 47 gastrectomized alcoholics were compared with 47 age-matched nongastrectomized alcoholics. The mean lifetime duration of heavy drinking (> 120 g ethanol/day) was shorter in the former than in the latter (11 +/- 10 years vs. 16 +/- 9, p < 0.05), and the mean lifetime cumulative ethanol consumption level also smaller (834 +/- 497 kg vs. 1047 +/- 508, p < 0.05). The majority of gastrectomized patients (30/47) had no history of problem drinking before gastrectomy. The daily consumption was rapidly increased within 5 years after gastrectomy in 18 of 38 habitual drinkers (47%). Seven of the remaining nine nonhabitual drinkers (78%) became habitual drinkers and alcoholics within a short period of time (7 +/- 4 years), though with low lifetime cumulative consumption (< 400 kg). The incidence of disorders of the central and peripheral nervous systems observed did not differ between the two groups, except for frequent alcoholic blackouts reported in the gastrectomized patients. In conclusion, the majority of the gastrectomized patients changed their drinking habits after gastrectomy and developed alcohol dependence. They did not require as much lifetime cumulative ethanol as nongastrectomized patients to become ethanol dependent.

Adult↗
PubMedDate not supplied

Action of cyclic AMP on intracellular calcium concentration and bursting activity.

In order to clarify its role in the provocation of seizure activity, the effects of cyclic AMP were examined on the intracellular calcium concentration of pentylenetetrazol (PTZ)-sensitive neurons as well as of PTZ-non-sensitive neurons of the Japanese land snail, Euhadra peliomphala. Extracellular application of isobutylmethylxanthine (IBMX) and dibutyryl cyclic AMP showed bursting activity-like firing in the PTZ-sensitive neurons. When 5'-guanylylimidodiphosphate (GNP-PNP) was injected into PTZ-sensitive neurons in the extracellular presence of IBMX and dibutyryl cyclic AMP, bursting activity followed by long-lasting hyperpolarization occurred. Intracellular injection of cyclic AMP into PTZ-sensitive neurons caused hyperpolarization coincident with an increase in intracellular calcium concentration. This increase in intracellular calcium concentration was the same under conditions in which the calcium influx was inhibited by the substitution of extracellular calcium chloride by cobalt chloride. In PTZ-non-sensitive neurons, cyclic AMP-induced bursting activity was not observed. These results suggest that an increase in cyclic AMP provoked bursting activity via an increase in intracellular calcium concentration.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Two cases of malignant lymphoma complicated by hemophagocytosis resembling orbital cellulitis.

Two patients with malignant lymphoma complicated by hemophagocytic syndrome (HPS) are reported. Their clinical signs at onset were similar to those of orbital cellulitis. Lymphoma complicated by hemophagocytosis is called lymphoma-associated hemophagocytic syndrome (LAHS) and its prognosis is reported to be very poor. As far as we know, this is the first report in the ophthalmological field. In our patients, we suspected that the lesions occurred from the orbit or skin of this area. The first patient was a 22-year-old man and the second patient a 16-year-old girl. The diagnosis was very difficult at the onset of disease. They died within 6 months after the first ophthalmological examination. When orbital cellulitis is suspected and antibiotic therapy is ineffective, we should suspect HPS and should examine serum ferritin, which is a good marker of HPS. Early biopsy and consultation with a hematologist are very important.

Adolescent↗
PubMedDate not supplied

Noninvasive measurement of left internal mammary artery bypass graft flow by duplex Doppler echocardiography from the supraclavicular fossa.

To test the ability of duplex Doppler echocardiography from the supraclavicular fossa in detecting the left internal mammary artery (LIMA) graft flow and to verify the flow velocity measurement with this method, we studied 12 consecutive patients who underwent coronary artery bypass graft surgery with the LIMA graft. Duplex Doppler echocardiography detected the LIMA graft flow in 11 (92%) of the 12 patients. In these patients, simultaneous supraclavicular duplex Doppler and Doppler catheter measurements of the LIMA graft flow were performed. There were significant correlations in systolic peak velocity (r = 0.84, p < 0.01) and diastolic peak velocity (r = 0.79, p < 0.01) between the supraclavicular and Doppler catheter methods. There were also significant correlations in the diastolic to systolic peak flow velocity ratio (r = 0.86, p < 0.01) and diastolic fraction (r = 0.90, p < 0.01) between the supraclavicular and Doppler catheter methods. Thus, duplex Doppler echocardiography from the supraclavicular fossa is useful in the detection of the LIMA graft flow and permits accurate noninvasive measurement of the LIMA graft flow.

Blood Flow Velocity↗
PubMedDate not supplied

Phasic coronary flow characteristics in patients with hypertrophic cardiomyopathy: a study by coronary Doppler catheter.

Abnormal patterns of coronary flow velocity have been observed in patients with symmetric left ventricular hypertrophy in conditions such as aortic stenosis and systemic hypertension. However, phasic coronary flow characteristics have not been investigated in patients with asymmetric left ventricular hypertrophy in hypertrophic cardiomyopathy. The purpose of this study was to assess phasic coronary flow characteristics and their relation to echocardiographic and hemodynamic parameters in patients with hypertrophic cardiomyopathy. Coronary flow velocity was recorded in the left anterior descending artery with a 20 MHz Doppler catheter in eight patients with hypertrophic nonobstructive cardiomyopathy and eight control subjects with normal coronary arteries. Flow reversals observed in systole in all patients with hypertrophic cardiomyopathy, and the time velocity integrals of systolic flow were significantly smaller in patients with hypertrophic cardiomyopathy than in control subjects (-1.5 +/- 1.7 versus 4.3 +/- 1.2 cm; p < 0.01). The time from the beginning of diastole to peak diastolic velocity corrected by the square root of R-R interval (square root of RR) was prolonged significantly, and the velocity half-time from peak diastolic velocity corrected by square root of RR was shorter in the patients with hypertrophic cardiomyopathy compared with those in the control subjects (6.8 +/- 2.0 msec versus 4.0 +/- 0.6 msec [p < 0.01] and 9.2 +/- 4.9 msec versus 13.9 +/- 2.0 msec [p < 0.05], respectively). Peak velocity and time velocity integral of flow reversal showed significant correlations with anterior ventricular septal thickness (y = -0.5x + 13.5, r = 0.8, and p < 0.01; y = -1.3 +/- 16.8, r = 0.8, and p = 0.024, respectively), the septal/free wall thickness ratio (y = -0.1x + 1.1, r = 0.8, and p < 0.01; y = -0.2x + 1.4, r = 0.9, and p < 0.01, respectively), and the degree of narrowing of the first septal perforator arteries (y = 1.9x + 91.6, r = 0.8, and p = 0.012; y = 6.1x + 80.6, r = 0.9, and p < 0.01, respectively). In conclusion, flow reversal in systole and slow acceleration and rapid deceleration in diastole were characteristics in patients with hypertrophic cardiomyopathy. Flow reversal might be related to the degree of left ventricular asymmetry and compression of the septal perforator arteries.

Blood Flow Velocity↗
PubMedDate not supplied

Systolic coronary flow reversal and abnormal diastolic flow patterns in patients with aortic stenosis: assessment with an intracoronary Doppler catheter.

Decreased left ventricular coronary flow reserve has been reported in patients with normal coronary arteries and left ventricular hypertrophy in association with aortic stenosis. However, phasic coronary flow characteristics have not been analyzed in detail in similar patients. The purpose of this study is to assess phasic coronary flow characteristics and their relation to hemodynamic parameters in patients with aortic stenosis. Coronary flow velocities were recorded in the left anterior descending artery with a 20 MHz Doppler catheter in nine patients with aortic stenosis and nine control subjects with normal coronary arteries. Patient aortic valve area ranged from 0.34 to 0.51 cm2. Flow reversal was observed in systole in all patients with aortic stenosis, and time velocity integrals of systolic flow were significantly smaller in patients with aortic stenosis than in controls (-0.3 +/- 2.3 vs 4.0 +/- 1.1 cm, p < 0.01). The time to peak diastolic velocity corrected by square root R-R interval was prolonged and the velocity half-time from peak diastolic velocity corrected by square root R-R interval was shorter in patients with aortic stenosis than in controls (5.3 +/- 1.1 vs 4.0 +/- 0.5, p < 0.01, 8.0 +/- 2.6 vs 13.0 +/- 3.3, p < 0.01, respectively). Peak velocity and time velocity integral of flow reversal showed significant correlations with mean pressure gradient across the aortic valve (y = 1.3x + 37.3, r = 0.72, p = 0.03, y = 11.3x + 41.2, r = 0.81, p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

Improved transvalvular continuous-wave Doppler signal intensity after intravenous Albunex injection in patients with prosthetic aortic valves.

UNLABELLED: A lung-crossing contrast agent, sonicated albumin (Albunex), has been reported to enhance left-sided Doppler signals in patients with native valvular diseases. The purpose of this study was to clarify the ability of Albunex to enhance transvalvular Doppler signals in patients with prosthetic aortic valves. Forty-five consecutive patients were studied after they underwent aortic valve replacement. Transvalvular flow signals were recorded from the apical long-axis view with the use of continuous-wave Doppler echocardiography before and after intravenous injection of Albunex (0.04 to 0.08 ml/kg). Continuous-wave Doppler signal quality was graded as follows: 1, none; 2, poor; 3, suboptimal; and 4, optimal. RESULTS: Grade 4 continuous-wave Doppler signal could be detected in 64% of the cases (29 of 45). After contrast injection, continuous-wave Doppler signal quality improved in all, and grade 4 continuous-wave Doppler signal could be detected in 93% (0.04 ml/kg) and 100% (0.08 ml/kg), respectively. The transvalvular maximal velocities derived from contrast-enhanced, continuous-wave Doppler signals were well correlated with the highest available unenhanced. Doppler maximal velocities (y = 0.90x + 0.27, r = 0.93, p < 0.01, standard error of estimate = 0.08 m/sec). CONCLUSION: Intravenous Albunex injection improves transvalvular continuous-wave Doppler signal intensity in patients with prosthetic aortic valves.

Albumins↗
PubMedDate not supplied

Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.

1. Whole-genome scans have identified Dmo1 as a major quantitative trait locus for dyslipidaemia and obesity in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. 2. We have produced congenic rats for the Dmo1 locus through successive back-cross breeding with diabetic OLETF rats. Marker-assisted speed congenic protocols were applied to efficiently transfer chromosomal segments from non-diabetic Brown Norway (BN) rats into the OLETF background. 3. In the fourth generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. 4. We have concluded that Dmo1 primarily affects lipid homeostasis, obesity control and/or glucose homeostasis at fasting and is secondarily involved in glucose homeostasis after loading. 5. The results of the present study show that single-allele correction of a genetic defect of the Dmo1 locus can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

Alleles↗
PubMedDate not supplied

Estimating transcription factor bindability on DNA.

MOTIVATION: Precise analysis of the genetic network, gene function and transcription regulation requires accurate prediction of transcription factor (TF) bindability on DNA. For calculating the matching score between an input sequence and a set of known TF binding sites, we use positional weight matrices (PWMs) and Bucher's calculating method (Bucher, J. Mol. Biol., 212, 563-578, 1990). Since estimating TF binding sites requires cut-off values, we propose a robust cut-off value determining algorithm. RESULTS: We generalize the concept of local overrepresentation with statistics, and propose a new algorithm for determining the cut-off value using the background rate estimated on non-promoters. The algorithm iteratively determines parameters separating instances into phenomena-dependent and phenomena-independent subsets. Our system includes the method of re-estimating cut-off values of TFs that mis-recognize other TF preferred regions. Our data source comprised 433 non-redundant vertebrate promoters including viral promoters, from Eukaryotic Promoter Database (EPD) R.50. The method is applied to 205 vertebrate TFs that have frequency matrices in TRANSFAC Ver.3. 4 and the cut-off values of all of them can be determined. AVAILABILITY: The cut-off values and TF binding site predicting tool are available at http://www.hgc.ims.u-tokyo.ac. jp/service/tooldoc/TFBIND. We also provide the cut-off value estimating programs.

Algorithms↗