Biomedical subjects

C Watanabe

Publications and source records attributed to C Watanabe.

At least 55 records · Page 3Linked to original sources

PubMed2000

Efficacy of yeast phytase in improving phosphorus bioavailability in a corn-soybean meal-based diet for growing pigs.

Crossbred barrows (n = 66; 6 wk old) were used in a 6-wk experiment to evaluate the efficacy of phytase from yeast or Aspergillus niger on performance, tibial characteristics, and serum inorganic P concentration. We also investigated the stability of these phytases in acidic solutions with pepsin, which simulated gastric conditions. Pigs were fed a P-adequate diet containing .34% nonphytate-P or a low-P diet containing .20% nonphytate-P. The low-P diet was supplemented with 0, 1,000, 2,000, or 4,000 phytase units (PU; the activity at optimal pH, i.e., pH 4.2 for yeast phytase and pH 5.5 for phytase from Aspergillus niger)/kg of yeast phytase, or 1,000 PU/kg phytase from Aspergillus niger. The graded level of yeast phytase linearly increased ADG (P = .047), tibial weight (P = .091), tibial density (P < .001), and P concentration in tibial cortex (P = .018). Aspergillus niger phytase also increased ADG (P = .022), serum inorganic P concentration (P < .001), tibial density (P = .007), and tibial P concentration (P = .025). The pigs given 1,000 PU/kg Aspergillus niger phytase showed greater ADG (P = .091), tibial density (P= .001), and tibial P concentration (P = .062) than those given 1,000 PU/kg yeast phytase. No measurements differed (P > .31) between the pigs given 1,000 PU/kg Aspergillus niger phytase and those given 4,000 PU/kg yeast phytase. These results suggested that yeast phytase improves bioavailability of P in the diet for growing pigs but the efficacy of yeast phytase is less than that of Aspergillus niger phytase. During incubation in acidic solutions with pepsin, yeast phytase (P < .001) lost more of its activity than Aspergillus niger phytase. This lesser stability of yeast phytase may be responsible for the poorer efficacy of yeast phytase than that of Aspergillus niger. In summary, supplementation of swine diets with yeast phytase is beneficial, but its efficacy is less than that of Aspergillus niger phytase.

6-Phytase↗

PubMed2000

[Clinicopathologic study of calcified aortic valve stenosis in the aged, and evaluation of the indications for percutaneous aortic balloon valvuloplasty].

OBJECTIVES: We performed clinicopathologic study of 56 aged patients with calcified aortic valve stenosis and investigated the indications for percutaneous aortic balloon valvuloplasty. METHODS: The patients were 24 men and 32 women with a mean age of 81.9 years, who were classified into the following 3 types by etiology: 33 patients (58.9%) had senile aortic stenosis, 10 patients (17.9%) had bicuspid aortic stenosis, and 13 patients (23.2%) had rheumatic aortic stenosis. The sites of calcification were divided into the following 3 categories: cusp bases (base type), free edges (edge type), and both bases and edges (mixed type). RESULTS: Among the 33 patients with senile aortic stenosis, 10 (30.3%) had calcification of base type, 2 (6.1%) of edge type and 21 (63.6%) of mixed type. Among the 10 patients with bicuspid aortic stenosis, one (10%) had calcification of base type and 9 (90%) of mixed type. Among the 13 patients with rheumatic aortic stenosis, 3 (23.1%) had calcification of edge type and 10 (76.9%) of mixed type. In addition, 2 or 3 commissures were fused in patients with rheumatic aortic stenosis. The cusps of the aortic valves in the bicuspid type were the most severely thickened among the 3 groups. Soft X-ray imaging showed the aortic valves of rheumatic aortic stenosis were the most severely calcified (calcification score: 2.4), followed by those of bicuspid aortic stenosis (1.9) and senile aortic stenosis (1.6). CONCLUSIONS: Percutaneous aortic balloon valvuloplasty is most suitable in patients with calcified senile aortic stenosis because of the milder calcification, compared with those of the other 2 types.

Aged↗

PubMed1999

Numerous conglomerate inclusions in slowly progressive familial amyotrophic lateral sclerosis with posterior column involvement.

A 59-year-old woman with slow progression of the loss of motor function and predominant lower motor manifestation during a 14-year period showed familial amyotrophic lateral sclerosis (fALS) with posterior column involvement, neuropathologically. Conglomerate inclusions (CIs) were observed in the remaining neurons in various areas, including the spinal anterior horn, posterior horn, Clark's column, accessory cuneate nucleus, tegmental reticular formation, motor nucleus of the trigeminal nerve, nucleus of the facial nerve, hypoglossal nucleus, medial nucleus of the thalamus, dentate nucleus, and motor cortex (Betz cells). Immunohistochemically, it was newly identified that the CIs showed marked immunoreactions with antibodies to phosphorylated and non-phosphorylated neurofilaments and to 64, 120, and 200 kD neurofilaments. The CIs were partially immunoreactive with the anti-ubiquitin antibody, although they reacted only weakly (or not at all) with anti-Cu/Zn superoxide dismutase (SOD1) antibody. Ultrastructurally, the CIs were comprised of neurofilaments. These data suggest that this case might have been different from an example of fALS with Ile 113 Thr mutation in the SOD1 gene.

Amyotrophic Lateral Sclerosis↗

PubMed1999

Separation of selenium-containing proteins in human and mouse plasma using tandem high-performance liquid chromatography columns coupled with inductively coupled plasma-mass spectrometry.

An analytical method that uses two different high-performance liquid chromatography (HPLC) columns in tandem has been developed that separates three major selenium-containing proteins (albumin, glutathione peroxidase, and selenoprotein P) found in human blood plasma. The first column was a heparin affinity column and the second was a gel filtration column whose outlet was directly connected to an inductively coupled plasma-mass spectrometer. The method successfully separated plasma selenium into the three selenium-containing proteins and revealed the preferential retention of selenium in the form of selenoprotein P in a selenium-deficient human and in selenium-deficient mice. Our results also confirm the results of previous studies that showed a preference for supplemented selenium to be taken up as selenoprotein P in rats. Advantages of the tandem column method are that it allows rapid and convenient analyses of the distribution of plasma selenium, and that it is suitable for stable isotope tracer studies and metal interaction studies.

Adult↗

PubMed1999

In utero methylmercury exposure differentially affects the activities of selenoenzymes in the fetal mouse brain.

Pregnant ICR mice were subcutaneously injected with 0,5, or 3x3 mg Hg/kg of methylmercury (MeHg) on days 12,13, and 14(G12-14) of gestation and were sacrificed on G17. Activity of selenoenzymes, including glutathione peroxidase (GPx) and 5'- or 5-iodothyronine deiodinases (5'-DI, 5-DI), was determined in fetal brain and placenta. MeHg did not affect the concentration of Se in these tissues, while it significantly inhibited the activity of GPx in the fetal brain and placenta, but not in the maternal brain. Although the levels of thyroid hormones in the maternal and fetal plasma were not affected by MeHg, 5-DI decreased and 5'-DI increased in the fetal brain, as if they had responded to hypothyroidism. Because the level of T4 in the fetal plasma was not affected by MeHg, these changes in enzymatic activities may result in a harmful excess of T3 in the fetal brain. In addition, 5-DI activity was increased in the placenta of MeHg-treated mice. These effects of prenatal MeHg exposure on fetal and placental DIs differed from those of dietary-induced Se deficiency, where the activities of DIs were decreased or not affected. Further evaluation of the effect of MeHg on selenoenzymes, especially 5-DIs, is warranted.

Animals↗

PubMed1999

Matrix interferences in the analysis of digested biological tissues with inductively coupled plasma-mass spectrometry.

To investigate the physiological roles or toxicity of trace or toxic elements, multielement analysis of limited quantities of samples in the biological tissues is required. Inductively coupled plasma mass spectrometry (ICP-MS) suits this requirement, but spectral and nonspectral interferences are inevitable. We examined correction methods for the nonspectral interferences by analyzing signals of 21 elements in various concentrations of HNO3 as well as five major elements (Na, K, P, Ca, and Cl). Using internal standards, the interferences caused by the major elements were corrected, but the interferences caused by HNO3 were impossible to correct for elements with high ionization potentials. The analytical results using the standard addition method on 14 elements in standard reference materials and fresh brain tissues confirmed the accuracy of this method. Thus, we concluded that the standard addition method is useful to correct for the nonspectral interferences.

Artifacts↗

PubMed1999

Adenosine triphosphate-sensitive potassium channels are involved in insulin-mediated glucose transport in humans.

We investigated the influence of treatment with nicorandil, a K-channel opener currently used for angina, on glucose homeostasis in patients with non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD). Adenosine triphosphate (ATP)-sensitive K (K-ATP) channels are present in various tissues, including pancreatic B cells and skeletal muscle, and are the putative targets of this agent. Nine NIDDM patients with CAD and five healthy subjects participated in the study. Fasting plasma levels (mean+/-SEM) of glucose (144+/-11 to 180+/-22 mg/dL, P<.05) and insulin (5.8+/-1.6 to 7.0+/-1.8 microU/mL, P<.05) and hemoglobin A1c (7.54+/-0.47 to 8.11+/-0.55%, P<.01) increased significantly in nine NIDDM patients after treatment with nicorandil at a dose of 5 mg three times daily for 2 to 8 months. Glucose tolerance as examined by an identical meal test deteriorated (P<.001), but the insulin response did not change significantly. A washout of nicorandil for 1 to 4 months restored glucose tolerance almost to pretreatment levels in four patients. A 5- to 7-day trial of nicorandil (5 mg three times daily) in five healthy subjects resulted in a marginal to twofold increase in fasting plasma insulin, reflecting the progression of insulin resistance. In addition, three healthy subjects showed a substantial reduction in the glucose infusion rate (GIR) required in the euglycemic-hyperinsulinemic clamp study. Since the therapeutic dose of nicorandil did not affect pancreatic B-cell function but caused insulin resistance in both healthy and NIDDM subjects, we conclude that K-ATP channels play a regulatory role in insulin-mediated glucose transport in humans.

ATP-Binding Cassette Transporters↗

PubMed1999

Spinal actions of GR73632, a novel tachykinin NK1 receptor agonist.

Behavioral characterization of GR73632, a newly synthesized tachykinin NK1 receptor agonist, was examined in mice. Intrathecal (IT) injection of GR73632 in the spinal subarachnoid space of mice elicited a dose-dependent behavioral syndrome, consisting of scratching, biting and licking. The time course of the response to GR73632 was almost similar to that of substance P. GR73632 evoked much more licking and biting than did substance P, that in turn caused less scratching. GR73632 was approximately 200-fold more potent than substance P in inducing the characteristic behavioral response. The GR73632-induced behavioral response was inhibited by IT co-administration of CP-96,345, a non-peptide NK1 receptor antagonist, but not its inactive enantiomer CP-96,344. CP-96,345, co-injected IT with substance P, also inhibited the behavioral response to substance P. These results demonstrate that the scratching, biting and licking response induced by IT GR73632 may be mediated by the NK1 receptor in the spinal cord. These findings suggest that GR73632 may be useful as a tachykinin NK1 receptor agonist and also for evaluating spinal pharmacological activities of NK1 receptor antagonists.

Animals↗

PubMed1999

Major metabolites of substance P degraded by spinal synaptic membranes antagonize the behavioral response to substance P in rats.

Substance P (SP) was degraded by synaptic membranes of rat spinal cord. Cleavage products were separated by reversed phase high performance liquid chromatography and identified by amino acid composition analyses. Major products of SP were phenylalanine, SP(1-4), SP(1-6), SP(1-7), SP(10-11), and SP(8-9). Both the degradation of SP and the accumulation of the major cleavage products were strongly inhibited by a metal chelator, o-phenanthroline, and also by specific inhibitors of endopeptidase-24.11, thiorphan, and phosphoramidon. Thus, endopeptidase-24.11 plays a major role in SP degradation in the rat spinal cord. N-Terminal fragments, SP(1-7) and SP(1-4), detected after incubation with spinal synaptic membranes were examined in vivo for antagonism against the scratching, biting, and licking response induced by intrathecal (IT) injection of SP (3.0 nmol) in rats. When IT coadministered with SP, SP(1-7) and SP(1-4) produced a significant inhibition of behavioral response to SP with ED50 of 135.0 pmol and 6.2 nmol, respectively. These results suggest that the degradation of SP in the spinal cord is not only responsible for inactivation of parent peptide, but may also lead to the formation of N-terminal SP-fragments which are shown to display a novel physiological function.

Animals↗

PubMed1999

Inhibitory mechanisms of glycoprotein fraction derived from Miscanthus sinensis for the immediate phase response of an IgE-mediated cutaneous reaction.

We investigated the inhibitory effect of the glycoprotein fraction (fraction 2) extracted from Miscanthus sinensi ANDERSSON (M. sinensis) on biphasic cutaneous reactions in mice passively sensitized with IgE. Biphasic skin reactions with peak responses at 1 (IPR, immediate phase reaction) and 24 h (LPR, late phase reaction) were caused by passive sensitization with an anti-dinitrophenol IgE monoclonal antibody (anti-DNP IgE mAb) followed by an epicutaneous challenge of 0.1% dinitrofluorobenzene (DNFB) in 100% ethanol. Intraperitoneal injection of fraction 2 before the DNFB challenge significantly inhibited the biphasic ear swelling response in passively sensitized mice in a dose-dependent manner (1-30 mg/kg). We also found that fraction 2 was effective at inhibiting the vascular permeability in mouse ear induced by an injection of compound 48/80, histamine or serotonin. In addition, fraction 2 inhibited scratching behavior as well as ear edema observed within 2 h after DNFB challenge. Marked inhibition was observed in both passively sensitized and non-sensitized mice. The locomotor activity of mice was also reduced by the administration of fraction 2 as well as by diphenhydramine. These results suggest that the inhibitory effect of glycoprotein fraction 2 of M. sinensis on an IgE-mediated allergic inflammatory reaction is due to the protection of mediator-induced vascular permeability and that in addition to the inhibition of an inflammatory reaction, a sedative action is responsible for the inhibition of allergy-induced scratching responses.

Acute-Phase Reaction↗

PubMed1999

Implications of marked fatty infiltration around and in the atrophic atrioventricular node in elderly patients with permanent pacemaker implantation for symptomatic sick sinus syndrome.

The present study undertook an extensive analysis of the histopathological findings of the atrioventricular conduction system in 14 elderly patients treated with permanent pacemakers for sick sinus syndrome (SSS). Special attention was given to the lowest Wenckebach block points of atrioventricular conduction during rapid atrial pacing, and ventricular rate or duration of ventricular pause during chronic atrial fibrillation. An electrophysiological study (EPS) was conducted under sinus rhythm in 13 patients and under junctional escape rhythm in 1 patient. Three of the 14 cases showed a lower Wenckebach block point of 130 beats/min or less. Two of these 3 cases showed excessive fatty infiltration around the atrionodal junction area and into the atrophic atrioventricular node (AVN) itself. Of the 6 patients who had chronic atrial fibrillation after pacemaker implantation, 2 cases showed a slow ventricular response of less than 60 beats/min and/or a long ventricular pause of 3.3 s. One of the 2 cases showed a lower Wenckebach block point of 130 beats/min at the time of EPS. The other, who later progressed to idiopathic atriomegaly, also showed marked fatty infiltration around the AVN. This fatty lesion was closely associated with diffuse disruption of the muscular fibers connecting the atrophic AVN with the atrium. In addition, most of the remaining cases also had an atrophic AVN. In conclusion, a sparse or absent atrionodal connection and an atrophic AVN due to excessive fatty infiltration in the atrionodal transitional area should be investigated in atrioventricular conduction disturbances in the elderly with SSS.

Aged↗

PubMed1999

Torsades de pointes in a case of hypertrophic cardiomyopathy with special reference to the pathologic findings of the heart including the conduction system.

A clinicopathologic study was performed in a 77-year-old female with hypertrophic cardiomyopathy who had experienced recurrent syncopal attacks due to Torsades de Pointes (TdP) following QT prolongation and atrioventricular block. She died suddenly two years later while eating dinner. Pathologic findings of the heart showed a dilated and hypertrophied left ventricle. The heart weighed 550 g. There were two foci of localized endocardial fibroelastosis (EFE) beneath the aortic valve, one with a size of 3.5 x 3.5 cm, and the other (2 x 1 cm) located on the upper ventricular septum. Histologic findings showed hypertrophy and disarray in the left ventricular myocardium. The conduction system using serial sectioning revealed remarkable bilateral bundle branch fibrosis and hypertrophied Purkinje fibers in the left bundle branch adjacent to the EFE on the ventricular septum. These findings were thought to be related to the occurrence of TdP.

Aged↗

PubMed1999

The effect of prenatal methylmercury exposure on the GSH level and lipid peroxidation in the fetal brain and placenta of mice.

Effect of prenatal exposure to methylmercury (MeHg) on the glutathione (GSH) levels and lipid peroxidation in the fetal brain was examined. Pregnant ICR mice were injected with 3 mgHg/kg of MeHg on gestational day 12, 13 and 14 (G12-14). On the G14 or G17, the fetal brains were removed and their GSH levels and thiobarbituric acid-reactive substances (TBARS) levels were determined. On the G17, GSH level of MeHg-treated fetal brain was significantly higher than that of the control brain; the TBARS level showed the similar trend but the difference was not significant. These results indicated that the prenatal MeHg treatment disturbed the normal GSH level in the fetal brain and warranted further investigation on the significance of this GSH perturbation.

Animals↗

PubMed1999

[Collecting duct carcinoma (Bellini duct carcinoma) of the kidney with tumor extension into the inferior vena cava].

We report a case of collecting duct carcinoma (Bellini duct carcinoma) of the left kidney accompanied with a tumor thrombus in the inferior vena cava and the lymph node metastasis. A 69-year-old male presented with gross hematuria and left flank dullness. Computed tomography revealed an isodensity tumor in the left kidney with tumor extension into the inferior vena cava and the regional lymph node swelling. The T1-weighted magnetic resonance image displayed a slightly heterogeneous low-intensity-mass. Renal angiography revealed a hypervascular tumor. We performed left radical nephrectomy with tumor thrombectomy and regional lymphadenectomy. Histopathological examination revealed a collecting duct carcinoma (pT3bN1M0V2a). Seven months after surgery, multiple metastates in bone and liver developed. Then we performed systemic chemotherapy consisting of methotrexate and cisplatin. However, the patient died from the carcinoma 10 months postoperatively.

Adenocarcinoma, Papillary↗

PubMed1999

Biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia.

The purpose of this study was to investigate the biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia (ALL). We carried out in vitro tests with a 4-day culture and a methyl-thiazol-tetrazolium assay on bone marrow samples from 209 children newly diagnosed with ALL. After testing the resistance of leukemic cells to 14 drugs, we classified the patients into two groups according to their sensitivity to three drugs (prednisolone, L-asparaginase, and vincristine) used in remission induction therapy. The three-drug resistant group (RR: sensitive to no drugs or to one drug) correlated with both short-term and long-term treatment failure. Three-year event-free survival (95% confidence interval) for the sensitive group (SS: sensitive to two or three drugs) was 0.813 (0.773-0.853) and that of the RR group was 0.616 (0.569-0.669) (P = 0.0001). Univariate analysis showed that Philadelphia-chromosome (Ph1) positivity and immunophenotype of mixed lineage were also prognostic factors in the 209 patients. The prognosis of the SS/RR drug resistance profile within 14 Ph1 patients was marginally significant (P = 0.062). Multivariate Cox regression analysis showed that Ph1 was an overwhelmingly adverse factor in event-free survival, with a relative hazard of 5.37 (2.57-11.21, P < 0.0001), followed by RR, with a relative hazard of 2.98 (1.69-5.25, P = 0.0001). Furthermore, we clarified the characteristics of the RR group by examination of the pattern of drug resistance to other drugs in comparison with the SS group. The leukemic cells of RR patients were more resistant than those of SS patients (P < 0.0001) to all the drugs tested, with resistance ratios of 1.6 to 13.1 (mean 3.4). In conclusion, in vitro three-drug resistance at the initial stage is an important independent predictor of treatment failure for both induction response and long-term outcome in childhood ALL.

Adolescent↗

PubMed1998

Slowly progressive L-DOPA nonresponsive pure akinesia due to nigropallidal degeneration: a clinicopathological case study.

We report an autopsy case of a 51-year old man who showed slowly progressive pure akinesia: freezing phenomenon and festination during 21 years of illness without tremor, rigidity, upward gaze palsy, bradykinesia and dementia, which were not responded to L-DOPA clinically. Neuropathological findings revealed the circumscribed regions in the substantia nigra and middle portion of the internal globus pallidus (GPi), without neurofibrillary tangles, neuropil threads, and glial fibrillary tangles. So this case was clearly distinguished with progressive nuclear palsy and pallidonigroluisian atrophy. It was first reported to describe that L-DOPA nonresponsive pure akinesia can arise from nigopallidal atrophy.

Disease Progression↗

PubMed1998

WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors.

Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we report the identification of two genes, WISP-1 and WISP-2, that are up-regulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1, but not by Wnt-4. Together with a third related gene, WISP-3, these proteins define a subfamily of the connective tissue growth factor family. Two distinct systems demonstrated WISP induction to be associated with the expression of Wnt-1. These included (i) C57MG cells infected with a Wnt-1 retroviral vector or expressing Wnt-1 under the control of a tetracyline repressible promoter, and (ii) Wnt-1 transgenic mice. The WISP-1 gene was localized to human chromosome 8q24.1-8q24.3. WISP-1 genomic DNA was amplified in colon cancer cell lines and in human colon tumors and its RNA overexpressed (2- to >30-fold) in 84% of the tumors examined compared with patient-matched normal mucosa. WISP-3 mapped to chromosome 6q22-6q23 and also was overexpressed (4- to >40-fold) in 63% of the colon tumors analyzed. In contrast, WISP-2 mapped to human chromosome 20q12-20q13 and its DNA was amplified, but RNA expression was reduced (2- to >30-fold) in 79% of the tumors. These results suggest that the WISP genes may be downstream of Wnt-1 signaling and that aberrant levels of WISP expression in colon cancer may play a role in colon tumorigenesis.

Amino Acid Sequence↗

PubMed1998

Functional analysis of peripheral blood B cells in patients with X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations of Bruton tyrosine kinase (Btk); Btk plays an essential role in the development of mature B cells. However, small numbers of B cells ("leaky B cells") are present in the peripheral blood of most XLA patients. In this study, we analyzed the function of these leaky B cells obtained from XLA patients. Enough numbers of B cells were available for analysis from five of nine XLA patients originally screened. Sequence analysis revealed missense mutations of Btk in four of the five XLA patients. No mutation was found in the coding region of Btk in one patient. Western blotting and/or flow cytometric analysis failed to detect Btk protein in all five patients. B cells isolated from peripheral blood of these XLA patients were CD5-, CD20+, CD19+, and CD21-. If stimulated with anti-CD40 and IL-4, XLA B cells proliferated normally and produced significant amounts of IgE. Anti-CD40 stimulation of XLA B cells resulted in normal expression of CD23. In addition, three of the five XLA patients studied were immunized with bacteriophage phiX174 and produced low but detectable levels of antiphage-specific Ab. Similarly, X-linked immunodeficiency mice, which carry a missense mutation in Btk, produced substantial amounts of antiphage Ab. These results indicate that CD40 signaling is intact in B cells lacking demonstrable Btk, and that leaky B cells in XLA patients can proliferate, undergo isotype switching, and differentiate into specific Ab-producing cells.

Adolescent↗