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Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 469 records · Page 26Linked to original sources

Improvement in the histopathology of hearts from cardiomyopathic BIO TO-2 hamsters following long-term administration of amlodipine and cilnidipine.

The effect of long-term administration of amlodipine and cilnidipine was examined on the histopathology and 1,4-dihydropyridine (DHP) calcium channel antagonist receptors in the left ventricle of BIO TO-2 hamsters, a model of dilated cardiomyopathy (DCM). Oral administration of amlodipine (3 and 10 mg/kg/d, 19 weeks) in 7 week-old BIO TO-2 hamsters produced a significant reduction in calcium deposition and necrosis with little change in the cavity area and fibrosis. A reduction of calcium deposition and necrosis in the myocardium of BIO TO-2 hamsters was also seen following similar administration of cilnidipine (10 mg/kg/d). The long-term administration of amlodipine (3 and 10 mg/kg/d) caused a significant increase (36.6 and 21.7%, respectively) in the Bmax for specific (+)-[3H]PN 200-110 binding in the myocardium from BIO TO-2 hamsters, compared with that in control hamsters. In conclusion, the present study has shown that long-term administration of amlodipine and cilnidipine improves calcium deposition and necrosis in the myocardium from BIO TO-2 hamsters. Thus, these data suggest that both agents may be effective pharmacological treatments of DCM.

Amlodipine↗

Peak systolic blood pressure in exercise testing is associated with scintigraphic severity of myocardial ischemia in patients with exercise-induced ST-segment depression.

Some electrocardiographic variables, including the degree of maximal ST-segment depression (STD), may not necessarily indicate the severity of exercise-induced myocardial ischemia. The present study examined whether maximal STD correlates with the severity and extent of exercise-induced myocardial ischemia, as assessed by thallium-201 (201Tl) imaging, and which parameter of exercise testing reflects scintigraphic severity and extent in 270 patients who had a 1 mm or greater horizontal or down-sloping STD on exercise 201Tl imaging. The scintigraphic severity and extent of exercise-induced ischemia was assessed and correlated with maximal STD, number of positive leads, workload, peak heart rate, peak systolic blood pressure (SBP), rate-pressure product, chest pain and the Duke treadmill score. Most of the scintigraphic markers of the severity and extent of ischemia had significant but weak correlation with all of those parameters. Multivariate analysis demonstrated that peak SBP and the Duke treadmill score (chest pain in only simple variables model) correlated independently with scintigraphic severity and extent of ischemia. Furthermore, most of the patients with a peak SBP of 200 mmHg or more had milder and less extensive ischemia. In patients with exercise-induced STD, the scintigraphic severity and extent of ischemia may be estimated by peak SBP and the Duke treadmill score.

Aged↗

Effects of physical training on the recovery of the autonomic nervous activity during exercise after coronary artery bypass grafting: effects of physical training after CABG.

Analysis of heart rate variability (HRV) can identify patients at risk of sudden cardiac death after myocardial infarction. The present study examined the effect of 2 weeks of supervised aerobic exercise training on the recovery of the autonomic nervous activity, exercise capacity, and cardiac output (CO) after coronary artery bypass grafting (CABG). Twenty-eight patients were randomly divided into the training group or the control group and performed exercise tests at 1 week, 3 weeks, 3 months, 6 months and 1 year after CABG. The HRV was measured, and the high-frequency component of HRV was used as an index of parasympathetic nerve activity (PNA); the plasma norepinephrine concentration (NE) was used as an index of sympathetic nervous activity. Cardiac output was also measured. In the training group, peak VO2, peak CO and PNA during exercise had improved at 3 weeks, but there was no improvement in these indices in the control group. NE decreased 1 week after CABG in both groups. These results indicate that physical training soon after CABG improves not only the exercise capacity, but also PNA.

Aged↗

Impaired heart rate response during incremental exercise in patients with acute myocardial infarction and after coronary artery bypass grafting: evaluation of coefficients with Karvonen's formula.

Heart rate (HR) response during exercise in patients with ischemic heart disease was evaluated, and the appropriateness of Karvonen's method for determining rehabilitation exercise target HR was investigated. The study group comprised 24 patients with acute myocardial infarction (AMI) and 37 patients who had undergone coronary artery bypass grafting (CABG). Cardiopulmonary exercise testing (CPX) was performed with a cycle ergometer and changes in HR (deltaHR)/changes in work rate (deltaWR) and interval changes of the coefficient of Karvonen's formula were evaluated. In the AMI group and the CABG group, deltaHR/deltaWR were significantly lower than those of age-matched control subjects (p<0.01). Karvonen's coefficients ranged from 0.37 to 0.54 when calculated from actual peak HR and 0.21 to 0.32 calculated from the predicted peak HR. An impaired HR response was found in patients with AMI and those who had had CABG up to 6 months previously. Because the Karvonen's coefficient values, which ranged from 0.6 to 0.8, were elevated for these patients, and considering the data from the CPX, increased exercise is recommended for such cases.

Adrenergic beta-Antagonists↗

Paeoniflorin, a major constituent of peony root, reverses muscarinic M1-receptor antagonist-induced suppression of long-term potentiation in the rat hippocampal slice.

We previously reported that paeoniflorin but not albiflorin, components of peony root, produced ameliorative effects on scopolamine-induced spatial cognitive impairment in rats. In this study, we examined the effects of paeoniflorin and muscarinic receptor antagonists on long-term potentiation (LTP) of population spike recorded from the CA1 region of rat hippocampal slices. Bath applications of an M1- and M2-receptor antagonist scopolamine and a selective M1-receptor antagonist pirenzepine, at a concentration of 10 microM, significantly suppressed LTP, whereas AF-DX116, a selective M2-receptor antagonist, failed to affect it. Paeoniflorin (0.1-1 microM), which alone was ineffective on LTP induction, significantly reversed the suppressive effects of scopolamine and pirenzepine (10 microM). In contrast, albiflorin (0.1- 1 microM) had no effect on the scopolamine-induced LTP suppression. These results suggest that paeoniflorin reversal of the muscarinic M1-receptor-mediated inhibition of LTP may be implicated in the ameliorative effect of paeoniflorin on spatial cognitive impairment caused by cholinergic dysfunction.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Effect of hydrogen peroxide on guinea pig nasal mucosa vasculature.

The effect of hydrogen peroxide (H2O2) on guinea pig nasal mucosa vasculature was studied by in vitro assay. H2O2 elicited relaxation of guinea pig nasal mucosa strips precontracted with phenylephrine in a concentration-dependent manner. The relaxant response to H2O2 was abolished in the presence of catalase. Preincubation of the strips with N(G)-nitro-L-arginine methyl ester or methylene blue significantly attenuated the relaxant responses elicited by H2O2. Fluorescence caused by DAF-2 DA, a fluorescence indicator for nitric oxide, was observed along the nasal mucosa vasculature in response to H2O2. These results suggest that H2O2 induced relaxation of the guinea pig nasal mucosa vasculature and that this relaxation is mediated by the NO/cGMP pathway.

Animals↗

Morphological study of the femur in osteopetrotic (op/op) mice using microcomputed tomography.

Osteopetrosis is an inherited metabolic disorder in which normal bone remodelling is inhibited. Its primary cause is considered to be disruption of the functional balance between osteoblasts and osteoclasts as well as a reduction in the quantity of osteoclasts. The purpose of this study was to observe morphological characteristics of the femur in osteopetrotic (op/op) mice, in which the pathogenic mechanism of osteopetrosis has been shown to operate, using microcomputed tomography (micro-CT), in addition to macro-anatomical observations. Previously, micro-CT has been used mainly for morphometry of a small portion of cancellous bone. However, with recent improvements it has become possible for three-dimensional (3D) observations of bone using slightly larger samples to be made. In this study, the accuracy of reconstructed 3D images of the femur produced by micro-CT was confirmed by comparison with the original femur. In addition, an arbitrary cross-section could be displayed on the screen for detailed examination of its internal structure, and the volume percentage of trabecular bone in a particular region of interest could be measured in three dimensions. The results of this study revealed that the femur was smaller and malformed in the op/op mouse compared with the controls, and the differences were greater at the age of 18 weeks than at 5 weeks. In the control mice, bone marrow occupied a large space in the centre of the body of the femur, whereas this area was occupied by calcified bone tissue in the mutant mice. Moreover, when 3D bone density was measured in the region of interest, the value was greater in the mutants than in the controls at both 5 weeks and 18 weeks of age. This study also showed that micro-CT can be applied to 3D morphometric analyses.

Animals↗

Ovomucoid rendered insoluble by heating with wheat gluten but not with milk casein.

The effect of wheat gluten, soybean protein and milk casein on the heat-induced in solubilization of egg white ovomucoid was investigated by using ELISA inhibition and immunoblotting analysis. Heat treatment at 180 degree C for 10 min of egg white mixed with wheat gluten specifically accelerated the heat-induced change in ovomucoid. Such an effect was weakly brought about by soybean protein, but not by casein.

Animals↗

Regulation of sex pheromone biosynthesis in three plusiinae moths: Macdunnoughia confusa, Anadevidia peponis, and Chrysodeixis eriosoma.

Virgin females of M. confusa, A. peponis, and C. eriosoma secrete (Z)-7-dodecenyl acetate as a common main pheromone component. Their pheromone titers decreased after decapitation, and increased in the decapitated females after injection of a synthetic hormone, pheromone biosynthetic activating neuropeptide (PBAN) of Bombyx mori. In addition, an extract of brain-subesophageal ganglion complexes of each Plusiinae species activated pheromone biosynthesis in decapitated females of not only the corresponding species, but also that of Mamestra brassicae. These results indicate that pheromone biosynthesis of the three Plusiinae species is also controlled by a PBAN-like substance. However, the Plusiinae females exceptionally contained remarkable amounts of the pheromone even 1 day after decapitation. Since it has been reported that pheromones completely disappear at least 1 day after decapitation in females of many other lepdidoptran species including B. mori and M. brassicae, a different mechanism is likely regarding the regulation of the studied Plusiinae pheromone biosynthesis. Furthermore, an incorporation experiment with a labeled pheromone precursor, D9-(Z)-7-dodecenoic acid, showed that moderate biosynthesis still proceeded in the pheromone glands of M. confusa females 1 day after decapitation, providing an evidence why complete disappearance of the pheromone was not observed in the females which otherwise lacked a source of the pheromonotropic neuropeptide.

Animals↗

Glucose metabolic analysis of musculoskeletal tumours using 18fluorine-FDG PET as an aid to preoperative planning.

We performed positron emission tomography (PET) with 18 fluorine-fluoro-2-deoxy-D-glucose (FDG) on 55 patients with tumours involving the musculoskeletal system in order to evaluate its role in operative planning. The standardised uptake value (SUV) of FDG was calculated and, to distinguish malignancies from benign lesions, the cases were divided into high (> or =1.9) and low (< 1.9) SUV groups. The sensitivity of PET for correctly diagnosing malignancy was 100% with a specificity of 76.9% and an overall accuracy of 83.0%. The mean SUV for metastatic lesions was twice that for primary sarcomas (p < 0.0015). Our results suggest that the SUV may be useful in differentiating malignant tumours from benign lesions. However, some of the latter, such as schwannomas, had high SUVs so that biopsy or wide resection was selected as the first operation. Thus, some other quantitative analysis may be required for preoperative planning in cases of high-SUV neurogenic benign tumours. The reverse transcription-polymerase chain reaction revealed that the RNA message of a key enzyme in glucose metabolism, phosphohexose isomerase (PHI)/autocrine motility factor, was augmented in only high FDG-uptake lesions, suggesting that a high expression of the PHI message may be associated with accumulation of FDG in musculoskeletal tumours.

Adolescent↗

Correlation between loss of E-cadherin expression and overexpression of autocrine motility factor receptor in association with progression of human gastric cancers.

Loss of intercellular adhesion and increased cell motility synergistically facilitate tumor cell invasion. We studied these factors in 90 patients with gastric cancers by using an immunohistochemical technique to detect strong or weak expression of E-cadherin (ECD) and autocrine motility factor receptor (AMFR). Normal gastric mucosa (control) reacted strongly for ECD and weakly for AMFR. In study cases, ECD was weak in 47 cases, and AMFR was strong in 39 cases. Weak ECD and strong AMFR expression were associated with tumor dedifferentiation. AMFR expression correlated positively with depth of invasion but not with lymph node metastasis. ECD expression correlated negatively with lymph node metastasis but not with depth of invasion. A strong inverse correlation was found between ECD and AMFR expression. Tumors with weak ECD and strong AMFR expression displayed a more aggressive phenotype than tumors with strong ECD and weak AMFR expression. The postoperative survival of patients with tumors with weak ECD and strong AMFR expression was significantly shorter than that of other groups. Since they are involved in the pathway to development of tumors with a more aggressive phenotype, ECD and AMFR should be examined to evaluate the biologic potential of gastric cancers.

Adenocarcinoma↗

Lamivudine as an alternative therapy for interferon-resistant chronic hepatitis B and the characteristics of hepatitis B virus: a case report.

A 27-year-old man who had been diagnosed as having chronic hepatitis B suffered disease exacerbation with marked reactivation of hepatitis B virus (HBV). Treatment with interferon (IFN) did not improve his condition, and his serum HBV DNA level increased to over 10 000 pg/ml during IFN administration. Following replacement with lamivudine, there was a substantial reduction in HBV DNA to an undetectable level, and liver function parameters subsequently improved to within the normal range. Quantitative analysis of the precore mutant HBV DNA, which is a variant that cannot express hepatitis B e antigen due to a G-to-A point mutation in the precore region of the viral genome, revealed that the amount present was greater than for the precore wild-type HBV DNA in the serum taken before IFN treatment. This case suggests that lamivudine would be an appropriate alternative to IFN, particularly in patients infected with HBV containing an excess of precore mutants resistant to IFN therapy.

Adult↗

Biological response to ionizing radiation in mouse embryo fibroblasts with a targeted disruption of the DNA polymerase beta gene.

Base excision repair (BER) is carried out by two distinct pathways in mammalian cells, one dependent on DNA polymerase beta (Polb) and the other on proliferating cell nuclear antigen (Pcna). We studied whether the Polb-dependent pathway plays an important role in BER in vivo after exposure to ionizing radiation. For this purpose, we used mouse embryo fibroblasts derived from wild-type and Polb gene knockout littermates. Both cell lines had essentially the same clonogenic cell survival and low levels of apoptosis as determined by a colony formation assay and by a change in mitochondrial membrane potential, respectively. No significant cleavage of protein kinase C delta (Pkcd) in vivo, which is a substrate for caspase 3, was detected, and intact Pkcd was retained in both cell lines for at least 72 h after irradiation. Similar significant increases in caspase 3-like activities as measured by Asp-Glu-Val-Asp (DEVD) cleaving activity in vitro were observed in both cell lines after irradiation. Radiation induced cell cycle arrest in the form of a G(2)-phase block, and G(2)/M-phase fractions reached a peak approximately 10 h after irradiation and decreased thereafter with a similar time course in both cell lines. Similar levels of chromatin-bound Pcna were observed immediately after irradiation in non-S-phase cells of both cell lines and disappeared by 4 h after irradiation. We conclude that the deficiency in Polb does not have a significant influence on the radiation responses of these cells. Together with evidence accumulated in vitro, these results strongly support the idea that the Pcna-dependent pathway predominantly acts in BER of radiation-induced DNA damage in vivo.

Animals↗

Magnetic resonance imaging findings in primary amyloidosis-associated arthropathy.

The MRI findings of amyloid arthropathy associated with primary amyloidosis are presented here possibly for the first time in the literature. Two types of lesions are noted: (1) capsular and tendon lesions; these regions are thickened, hypointense and enhanced by gadolinium (Gd) on T1 weighted imaging (T1WI), and hyperintense on T2 weighted imaging (T2WI), and (2) periarticular and osseous lesions; these regions appear to be tumor-forming and hypointense on both T1WI and T2WI and are not enhanced by Gd. It is necessary to differentiate these findings from other diseases such as chondrosarcoma, rhabdomyosarcoma and chronic inflammatory lesions such as tuberculosis.

Amyloidosis↗

Histological study of masseter muscle in a mouse muscular dystrophy model (mdx mouse).

Histological changes in the masseter muscle were observed over time in mdx mice, a muscular dystrophy model. It was found that marked necrosis occurs about the time of weaning at around 4 weeks of age; then the tissue actively regenerates at 8 weeks and stabilizes as regenerated muscle with centronuclei at 15 weeks old. This study examined the centronucleus in regenerated muscle. The process from necrosis to regeneration in muscle fibers occurs a little later in the masseter muscle than in other limbic muscles. Regenerated muscles observed around 15 weeks after birth showed a moth-eaten appearance. Transmission Electron Microscope (TEM) observation of transverse sections of muscle fibers revealed that myofibrils surrounded lost regions in the area showing a moth-eaten appearance. Thus, some defensive mechanism may affect the ability of muscle fibers to maintain a function close to normal in mdx mice even though the muscle fibers develop muscular dystrophy. The function of the masseter muscle drastically changes from sucking to mastication behavior at around 4 weeks, and this was considered to influence the morphological changes in the muscle tissue. The moth-eaten appearance seen at 15 weeks may represent an appropriate myofibril reconstruction preventing invasion of the lost regions.

Aging↗

Evolution of peripheral lung adenocarcinomas: CT findings correlated with histology and tumor doubling time.

OBJECTIVE: This study was performed to evaluate the evolution of peripheral lung adenocarcinomas using CT findings and histologic classification related to tumor doubling time. MATERIALS AND METHODS: The subjects were 34 patients, each with an adenocarcinoma smaller than 3 cm. All patients underwent chest radiography and 10 of them had previously undergone CT more than 6 months before surgery. Tumor doubling time was estimated by examining sequential radiographs using the method originally described by Schwartz. Tumor growth was also observed by studying the changes on CT in the 10 patients who had previously undergone CT. The histologic classification (types A-F) was evaluated according to the criteria of Noguchi et al. RESULTS: Five (83%) of the six adenocarcinomas with tumor types A or B showed localized ground-glass opacity on high-resolution CT. All six tumors had a tumor doubling time of more than 1 year. Fifteen (71%) of the 21 tumors with type C showed partial ground-glass opacity mixed with localized solid attenuation on high-resolution CT. Ten (48%) of these 21 type C tumors had a tumor doubling time of more than 1 year. In types B and C, the solid component or the development of pleural indentation and vascular convergence increased during observation before surgery. All seven tumors with types D, E, and F showed mostly solid attenuation, and the tumor doubling time was less than 1 year in six (87%) of the seven tumors. CONCLUSION: Two main types of peripheral lung adenocarcinoma exist. The first type appears on CT as a localized ground-glass opacity with slow growth, and the other appears as a solid attenuation with rapid growth.

Adenocarcinoma↗

A modification of Mayer's tannic acid-ferric chloride staining method for demonstrating cellular membranous systems for light microscopy.

To observe cellular membranous systems under a light microscope, we modified Mayer's tannic acid-ferric chloride stain method by adding a treatment with hematoxylin after the original procedure. We used the modified tannic acid-ferric chloride (MTA-Fe) stain method to examine kidneys, liver, heart, trachea, epididymides and other organs of rats and dogs. The MTA-Fe stain clearly demonstrated the basement membrane, brush border, basolateral invaginations and cell processes in the kidneys which enabled easy differentiation of the S1 and S3 segments of proximal convoluted tubules. Our technique also demonstrated hepatic cell membranes and bile canaliculi in the liver, cross striations and longitudinal traveling of myofibrils in the heart, cilia of the epithelial cells in the trachea, and stereocilia and terminal bars in the epididymis. The MTA-Fe stain is a convenient method to visualize cellular membranous systems even for light microscopy. The stain has the advantages of using no toxic materials, simple and easy technique, little variation of staining results, and little fading for several months after staining.

Animals↗