Search PubMed⌕ Search

Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 613 records · Page 34Linked to original sources

Pathological changes of the spinal cord in centenarians.

In order to study the changes that occur in the spinal cords of the aged, 19 centenarian spinal cords from two men and 17 women (age range, 100-116 years at death; mean, 103 years) were pathologically examined. Cross-sections at each segmental level of the 19 autopsied spinal cords were examined for histopathological changes. The cross-sectional area and flattening ratio at the level of the C7 segment were measured. The size of the cords had some negative correlation with age, but the individual variation was considerably large. Among the 19 centenarians, macroscopic anteroposterior flattening appeared in the lower cervical cords in six individuals. In these cases, various degrees of neuron loss were observed in the anterior horn. White matter degeneration appeared frequently, especially in the posterior column. In 12 cases, myelin loss in the fasciculus of Goll at the cervical level was observed. The degeneration of the fasciculus of Goll was considered to be upward wallerian degeneration secondary to posterior root damage at the lumbosacral level. These changes seemed to be produced by disorders in the spinal canal or surrounding tissue, such as cervical spondylosis, degeneration of the intervertebral disk and spinal canal stenosis. Argyrophilic structures such as neurofibrillary tangles and neuropil threads were observed in 16 cases; however, this incidence was less than in the brain. Medial thickening of the anterior spinal artery was found in four cords. Amyloidangiopathy was noted in only one cord. Necrosis and hemorrhage due to vascular disturbance were not found.

Aged↗

Radicicol potentiates neurotrophin-mediated neurite outgrowth and survival of cultured sensory neurons from chick embryo.

Radicicol, an antifungal antibiotic with markedly low toxicity, is a potent inhibitor of the Src family of protein tyrosine kinases and causes morphological reversion of v-src-transformed fibroblasts. Recently, this antibiotic was also found to inhibit Raf kinase. In the present study, we found that nanomolar concentrations of radicicol (10 ng/ml) enhanced the survival and neurite outgrowth of neurons from embryonic chick dorsal root ganglia (DRGs) and sympathetic ganglia. It potentiated the trophic effects of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 on the cultured DRG neurons. This concentration of radicicol did not alter the tyrosine phosphorylation of Trk receptors or the activity of mitogen-activated protein (MAP) kinases. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), did not inhibit radicicol, excluding the involvement of PI3-kinase in the radicicol-dependent trophic actions. These results suggest that radicicol mediates neuronal growth presumably via a mechanism not involving the activation of Trk receptors, MAP kinase, or PI3-kinase.

Animals↗

Estrogen receptor mRNA in uteri of normal estrous cycling and ovariectomized rats by in situ hybridization.

Biological effects of estrogen are mediated via its binding to the estrogen receptor (ER), the contents of its protein and mRNA varying during the estrous cycle. In the present study, the ERalpha mRNA expression in different cell components of the uterus was investigated in normal estrous cycling rats using nonisotopic in situ hybridization. Additionally, ovariectomized (OVX) rats treated with 17beta-estradiol (E2: 5 microg/kg, sc injection daily) were also investigated to clarify the effects of exogenous E2. At proestrus and diestrus, and especially the former, the luminal and glandular epithelial (LE and GE) cells were strongly positive, along with stromal cells beneath the luminal epithelium. At estrus, the expression was slightly diminished in LE cells, but almost completely lacking in GE cells. At metestrus, positive signals appeared again in GE cells. In the myometrium, ER mRNA was demonstrated to be constantly positive in all estrous cycle stages. OVX rat uteri underwent marked atrophy, but ER mRNA still remained in all cell types. After 2 consecutive days of E2 treatment, markedly increased intensity was observed, especially in LE and GE cells. The uteri of OVX rats treated with E2 for 14 days, however, showed slightly diminished expression, whereas the serum concentration of E2 was comparable to that in rats after 2 days. These results provide evidence that cell-type specific patterns of ER mRNA expression characterize the uteri of both normal estrous cycling rats and OVX rats after estrogen treatment.

Animals↗

Posterior interosseous nerve syndrome due to pseudogout.

Posterior interosseous nerve palsy associated with pseudogout of the elbow joint in a 71-year-old woman is described. Local steroid injection and administration of a nonsteroidal anti-inflammatory drug was effective in treatment.

Adrenal Cortex Hormones↗

Scores of coronary calcification determined by electron beam computed tomography are closely related to the extent of diabetes-specific complications.

This study was aimed at investigating the degree of calcification of coronary arteries in type II diabetes mellitus for the purpose of examining as risk factors for coronary disease as well as parameters of diabetic complications. One hundred and three patients with type II diabetes were studied by the newly developed noninvasive technology of electron beam computed tomography, in which the degree of calcification was expressed as coronary calcification scores. The mean +/- SE value of coronary calcification scores were 247.5 +/- 48.1, which were significantly greater than the control patients without diabetes (148.9 +/- 48.3, p<0.05). In the diabetics, the coronary calcification scores had a significant (p < 0.01) correlation with patient age and duration of diabetes. The scores also had a significant (p<0.05) difference between patients who did and did not smoke cigarettes, and between patients with and without hypertension. The scores were significantly (p < 0.01) different between patients with and without hypertension. The scores were significantly (p < 0.01) different between presence and absence of diabetes-specific complications including retinopathy, neuropathy, and nephropathy. In a subgroup of patients without any signs of coronary disease, the scores showed a significant (p<0.01) difference between presence and absence of diabetes-specific complications, but no significant difference with smoking or hypertension. These data suggest that the extent of coronary calcifications and the development of ischemic heart disease seem to be closely related to the association of diabetic complications. Use of electron beam computed tomography seems to be useful in obtaining the information to predict future development of diabetic-specific complications.

Age Factors↗

Quantitative analysis of leukocyte dynamics in retinal microcirculation of rats with short-term ischemia-reperfusion injury.

PURPOSE: To characterize the time course of complete recovery of leukocyte velocities in the retinal microcirculation of rats from short-term (5-minute) retinal ischemia. METHODS: After 5 minutes of retinal ischemia produced by clamping the optic nerve, resulting in the occlusion of both central retinal artery and the central retinal vein, we used acridine orange (AO) and a scanning laser ophthalmoscope (SLO) to observe the velocities of leukocytes in precapillary arteriole ( v(a)), capillary (v(c)) and postcapillary venule (v(v)). Measurements were taken at reperfusion time points of 5, 10, 15, 20, 30, 40, 50, 60 and 80 minutes for the ischemic eyes and at 12, 22, 42 and 62 minutes for the control eyes, respectively. RESULTS: Each control velocity was arteriole 25.1 +/- 4.3 mm/ s; venule 16.9 +/- 3.2 mm/s; and capillary 1.54 +/- 0.31 mm/s, respectively. The leukocyte velocities after 5 minutes of ischemia in arteriole and venule recovered completely within 80 minutes of reperfusion; however, the recovery patterns were different. The recovery pattern showed a biphasic increase in arterioles and a monophasic increase in venules. The velocity in capillaries half recovered rapidly, within 5 minutes of reperfusion, but the subsequent recovery was slower and was not complete even at 80 minutes of reperfusion. CONCLUSIONS: In this study, leukocyte velocities in arterioles, venules and capillaries exhibited different recovery patterns following retinal ischemia and subsequent reperfusion. Capillaries, at least within 80 minutes of reperfusion, may have difficulty recovering completely from even short-term (5-minute) ischemia.

Acridine Orange↗

Epileptic falling spells after epidural haematoma in adult Down's syndrome.

A 35-year-old man with Down's syndrome showed epileptic falling spells. He had suffered from a traumatic right-sided epidural haematoma 3 years before. It had been neurosurgically treated, but MRI taken 5 days later had revealed a small contracoup contusion at the left temporal lobe. His falling spell was a brief tonic seizure without disturbance of consciousness. Background activities of EEG consisted of slow alpha waves interspersed with sporadic theta waves and the amplitude at the left temporal area was lower than the opposite one. Interictal EEG showed sharp waves or sharp and slow wave complexes predominantly at the right temporo-centro-parietal area as well as diffuse, though predominantly at frontal areas, bursts of slow waves with high amplitude. The EEG suggested focal epileptic activities evolving into secondary generalization. SPECT of the brain showed the hypoperfusion at the left temporal area and at the right posterotemporo-parietal area, where the hypoperfusion was somewhat reduced after the improvement of seizures. Seizures were well controlled with phenytoin combined with phenobarbital. The incidence of epilepsy in the Down's syndrome has been reported to increase after the middle age in association with the development of Alzheimer's neuropathology. When those people would sustain head injuries, it was necessary to follow carefully using SPECT and EEG.

Adult↗

Prevalence of mutilans-like hand deformities in patients with seropositive rheumatoid arthritis. A prospective 20-year study.

This study examined radiographically the prevalence of arthritis mutilans hand deformities in an inception cohort of 68 rheumatoid arthritis (RA) patients. Hand deformities of 103 RF-positive RA patients were evaluated after 8 years, 83 patients after 15 years and 68 patients 20 years after entry. The grade of destruction in the hand joints was assessed by the Larsen method and Larsen scores of 0-50 were determined for both PIP (+IP) and MCP joints. At the end point, 3 patients had Larsen scores > or =40 for both PIP and MCP joints. These three patients had severe resorption in most of the finger joints, but did not demonstrate classical opera-glass hand. The prevalence of mutilans-like hand deformities with RA was 3/68 (4.4%) in a prospective 20-year study.

Adolescent↗

Effect of charcoal hemoperfusion on clearance of cibenzoline succinate (cifenline) poisoning.

BACKGROUND: Management of cibenzoline succinate (cifenline) poisoning by symptomatic treatment is recommended because it has been reported cibenzoline succinate is not effectively removed by hemodialysis. The use of charcoal hemoperfusion for patients with cibenzoline succinate poisoning has not been reported previously. CASE REPORT: An 80-year-old woman with permanent right ventricular pacing was admitted to our hospital with general fatigue and clouding of consciousness. She had been receiving cibenzoline succinate for 1 month. The patient was clearly in shock on admission. Electrocardiogram showed a prolonged QRS and QTc interval and pacing failure. Hemodynamic failure, electrocardiographic abnormalities including pacing failure, and liver and renal dysfunction were compatible with cibenzoline succinate poisoning. Symptomatic treatment was provided. On day 4, charcoal hemoperfusion was initiated because of the development of hypoglycemia accompanied by liver and renal dysfunction. After charcoal hemoperfusion, the hypoglycemia, liver and renal dysfunction, prolonged QRS and QTc interval, and pacing threshold resolved. She was discharged on digoxin. We present a case of cibenzoline succinate poisoning treated with charcoal hemoperfusion which resulted in a rapid reduction of cibenzoline plasma concentrations with a significant clinical improvement.

Aged↗

Swelling and ketoprofen release characteristics of thermo- and pH-responsive copolymer gels.

Swelling-controlled drug delivery copolymer gels were newly synthesized by introducing thermo- and pH-responsive methacryloyl-glycine (MA-Gly) or pH-responsive methacrylic acid (MA-Ac) for comparison with thermoresponsive acryloyl-L-proline ethyl ester (A-ProOEt). A homopolymer gel of A-ProOEt was kept at degrees of swelling that were less than 0.5 at a pH from 2.5 to 7.5 at 37 degrees C. The thresholds of swelling for copolymer gels consisting of A-ProOEt/MA-Gly and A-ProOEt/MA-Ac with a composition of 40/60 mol% were found to be pH 3.0 and pH 5.5, respectively, in buffer solutions at 37 degrees C. The diffusion characteristics of 2-(3-benzoylphenyl)propionic acid (ketoprofen) from such copolymer gels was evaluated in buffer solutions at pH's more than 5.5, and it was found that A-ProOEt/MA-Gly gel possesses a case II transport mechanism that is completely linear time dependent in both the amount diffused and the penetrating swelling front position. On the other hand, A-ProOEt/MA-Ac gel exhibited a non-Fickian (or anomalous) diffusion behavior under the same conditions.

Diffusion↗

Tissue-specific somatic mosaicism in spinal and bulbar muscular atrophy is dependent on CAG-repeat length and androgen receptor--gene expression level.

The factors influencing the tissue-specific pattern of somatic mosaicism in CAG-repeat diseases have not yet been fully resolved. We performed a detailed analysis of the degree of somatic mosaicism in various tissues from 20 patients with spinal and bulbar muscular atrophy (SBMA), including 4 who were deceased. The most outstanding feature was the prominent somatic mosaicism observed in the cardiac and skeletal muscles, composed predominantly of postmitotic cells, and in the skin, prostate, and testis. The CNS tissues, liver, and spleen showed the least mosaicism. The tissue distribution of somatic mosaicism in patients with SBMA was markedly different from that in patients with Huntington disease (HD) and from that in patients with dentatorubral-pallidoluysian atrophy (DRPLA). The degree of somatic mosaicism correlated with the CAG-repeat number but not with age at examination. Furthermore, tissues with a higher mosaicism level corresponded well to those with a higher expression level of androgen receptor protein. The tissue-specific pattern of somatic mosaicism related not only to cell composition with different cell turnover rates but to repeat size and gene expression levels, and postnatal cell division is unlikely to be a major cause of somatic mosaicism probably because of the relative stability of CAG repeat in SBMA.

Adult↗

Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations.

Fragile X syndrome is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP and its structural homologues FXR1P and FXR2P form a family of RNA-binding proteins (FXR proteins). The three proteins associate with polyribosomes as cytoplasmic mRNP particles. Here we show that small amounts of FMRP, FXR1P and FXR2P shuttle between cytoplasm and nucleus. Mutant FMRP of a severely affected fragile X patient (FMRPI304N) does not associate with polyribosomes and shuttles more frequently than normal FMRP, indicating that the association with polyribosomes regulates the shuttling process. Using leptomycin B we demonstrate that transport of the FXR proteins out of the nucleus is mediated by the export receptor exportin1. Finally, inactivation of the nuclear export signal in two FXR proteins shows that FMRP shuttles between cytoplasm and nucleoplasm, while FXR2P shuttles between cytoplasm and nucleolus. Therefore, molecular dissection of the shuttling routes used by the FXR proteins suggests that they transport different RNAs.

Adhesins, Bacterial↗

Loss of the sarcoglycan complex and sarcospan leads to muscular dystrophy in beta-sarcoglycan-deficient mice.

beta-Sarcoglycan, one of the subunits of the sarcoglycan complex, is a transmembranous glycoprotein which associates with dystrophin and is the molecule responsible for beta-sarcoglycanopathy, a Duchenne-like autosomal recessive muscular dystrophy. To develop an animal model of beta-sarcoglycanopathy and to clarify the role of beta-sarcoglycan in the pathogenesis of the muscle degeneration in vivo, we developed beta-sarcoglycan-deficient mice using a gene targeting technique. beta-Sarcoglycan-deficient mice (BSG(-)(/-)mice) exhibited progressive muscular dystrophy with extensive degeneration and regeneration. The BSG(-)(/-)mice also exhibited muscular hypertrophy characteristic of beta-sarcoglycanopathy. Immunohistochemical and immunoblot analyses of BSG(-)(/-)mice demonstrated that deficiency of beta-sarcoglycan also caused loss of all of the other sarcoglycans as well as of sarcospan in the sarcolemma. On the other hand, laminin-alpha2, alpha- and beta-dystroglycan and dystrophin were still present in the sarcolemma. However, the dystrophin-dystroglycan complex in BSG(-)(/-)mice was unstable compared with that in the wild-type mice. Our data suggest that loss of the sarcoglycan complex and sarcospan alone is sufficient to cause muscular dystrophy, that beta-sarcoglycan is an important protein for formation of the sarcoglycan complex associated with sarcospan and that the role of the sarcoglycan complex and sarcospan may be to strengthen the dystrophin axis connecting the basement membrane with the cytoskeleton.

Animals↗

Drug-induced apoptosis and p53, BCL-2 and BAX expression in breast cancer tissues in vivo and in fibroblast cells in vitro.

BACKGROUND: Chemotherapeutic management of breast cancers is a difficult task as they show significant differences in chemosensitivity. The present study was undertaken to determine the usefulness of the apoptosis-related factors as indicators of tumor sensitivity to 5'-deoxyfluorouridine (5'-DFUR) in breast cancers. METHODS: (1) Forty-six breast cancer patients were randomly assigned to a group in which oral 5'-DFUR (1200 mg/day) was administered for more than 5 days before operation (24 patients) and a control group who received no preoperative chemotherapy (22 patients). Surgical specimens were examined for the frequency of apoptotic cells [apoptotic index (AI)] by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method and for the expression of p53, BCL-2 and BAX by immunohistochemical staining. (2) Normal human diploid fetal lung fibroblast, IMR90 and SV40 transformed IMR90 were exposed to 5-FU. Apoptotic cells were detected by flow cytometry and BCL-2 and BAX mRNAs by real-time quantitative RT-PCR analysis. RESULTS: (1) No significant difference in the AIs or in BCL-2 and BAX scores was observed between the 5'-DFUR-treated and control groups. However, in the p53 negative subgroup (n = 36), AI and BAX scores were higher and BCL-2 scores lower in the 5'-DFUR group than in the control group (P = 0.006, 0.008 and 0.050, respectively). (2) The sensitivity of IMR90 was significantly decreased by SV40 transformation and the 5-FU-induced cytotoxicity was mainly due to induction of apoptosis. The BCL-2/BAX mRNA ratio was decreased in response to 5-FU in IMR90. These results correlated with our clinical data. CONCLUSIONS: Preoperative treatment with 5'-DFUR induced apoptosis and changes in BCL-2 and BAX expression in p53 negative breast cancers. p53 status, AI and the BCL-2/BAX ratio may be useful information for the choice of postoperative chemotherapy for breast cancer.

Antineoplastic Agents↗

Adrenomedullin and atrial natriuretic peptide concentrations in normal pregnancy and pre-eclampsia.

Adrenomedullin (AM) is a peptide that elicits a long-lasting vasorelaxant activity, while atrial natriuretic peptide (ANP) has also been shown to be a potent vasodilatory agent. To clarify the possible role of AM and ANP in the physiology of pregnancy and pathophysiology of pre-eclampsia, we measured plasma concentrations of these peptides in non-pregnant women, normal pregnant women and women with pre-eclampsia. A gradual increase in plasma AM was observed as pregnancy progressed. The plasma AM concentrations during the second trimester (12.7 +/- 1.4 fmol/ml) were significantly elevated, in comparison with the non-pregnant follicular phase (6.4 +/- 0.61 fmol/ml), luteal phase (6.0 +/- 0.49 fmol/ml), and the first trimester (6.5 +/- 0.8 fmol/ml). The plasma AM concentrations of the third trimester (21.5 +/- 1.4 fmol/ml) were significantly elevated when compared with those of the second trimester (P < 0.05). Northern blot analysis confirmed the expression of the AM mRNA transcript (1.6 kb) in third trimester placentas. In comparison with those observed at term (25.3 +/- 4.5 fmol/ml), the plasma concentrations were significantly reduced post-partum (6.4 +/- 0.6 fmol/ml). In the third trimester, plasma AM concentrations did not differ significantly between women with pre-eclampsia (17.2 +/- 2.3 fmol/ml) and normal pregnant women. In contrast, the plasma ANP concentrations in pre-eclampsia (39.5 +/- 7. 1 pg/ml) were significantly elevated when compared with those of the normal third trimester (14.4 +/- 1.4 pg/ml) (P < 0.05). ANP concentrations were reasonably constant throughout the pregnancy.

Adrenomedullin↗

The stabilized structural array of two HMG1/2-boxes endowed by a linker sequence between them is requisite for the effective binding of HMG1 with DNA.

High mobility group (HMG) protein 1 contains two DNA binding motifs, called HMG1/2-boxes, linked with a linker region. The functional relationships between the two boxes and the mechanism of involvement of the linker region for effective binding of HMG1 were examined. The binding analyses of truncated HMG1 peptides with DNA indicated that the structural array of two boxes stabilizes the interaction of HMG1 with DNA. The mutation analyses of the linker region suggested that the region is equipped with tolerance for the deletion of a few amino acid residues to allow appropriate binding of the two boxes with DNA, and that the basic cluster in the linker sequence is in a position to interact with DNA. The existence of tolerance for the linker sequence was found to be conserved during the evolution of HMG1 protein homologues. A structural model for array of two boxes associating with DNA minor groove was constructed on the basis of the experimental results and energy minimization. The model proposes that the DNA binding region in HMG1 covers an 18 bp DNA region and induces its bending by about 140 degrees. The linker region may function to maintain the structural array of two HMG1/2-boxes by direct interaction with DNA.

Amino Acid Sequence↗