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Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 469 records · Page 26Linked to original sources

Diheteropeptin, a new substance with TGF-beta-like activity, produced by a fungus, Diheterospora chlamydosporia. I. Production, isolation and biological activities.

A new metabolite, diheteropeptin, was found in the culture broth of Diheterospora chlamydosporia Q58044 by screening for TGF-beta-like active substances. Diheteropeptin was extracted from the culture supernatant and purified by a series of chromatographies such as silica gel, gel filtration and HPLC. Diheteropeptin exhibited cytostatic activity in Mv1Lu cells with an IC50 value of 20.3 microM and inhibited histone deacetylase.

Anti-Bacterial Agents↗

[Syndrome of inappropriate secretion of antidiuretic hormone in a patient with myeloid antigen positive acute lymphoblastic leukemia after systemic chemotherapy including vincristine].

We report a case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after the patient had received several anti-cancer drugs, including vincristine (VCR), in a patient with myeloid antigen positive acute lymphoblastic leukemia (My(+)-ALL). A 53-year-old woman presented at the hospital complaining of high-grade fever and general lassitude. Further examination revealed that she had My(+)-ALL. On admission, she was treated with anti-cancer drugs, including VCR. On day 24, after the first administration of VCR, a conscious disturbance suddenly occurred and she was diagnosed with SIADH. A plain head CT scan showed a low density lesion through the gray matter to the white matter in the bilateral occipital lobe, as well as diffuse swelling of the cerebrum. This was not seen on the follow up CT scan, and we concluded that it had been a transient abnormal finding due to SIADH. She achieved complete remission after induction chemotherapy and 3 added courses of consolidation chemotherapy. VCR was also administered 4 times in the second consolidation chemotherapy, but hyponatremia did not occur. This case suggests that a head CT scan is a useful procedure for the diagnosis and monitoring of SIADH, and that VCR may still be used in a patient who has suffered from VCR-induced SIADH.

Antigens, Differentiation, Myelomonocytic↗

[An autopsy case of bilateral carotid artery occlusion with repetitive epilepsy and brain atrophy in a senile patient].

A 67-year-old man was referred to us for tonic-clonic convulsions. A review of his history revealed that he had been hospitalized for loss of consciousness, hypotension, and suspected apoplexy at age 67. He had experienced prior tonic-clonic convulsions at age 72 and age 74. He had malaria and tuberculosis in his history but had been otherwise generally well. Physical examination was normal, and his blood pressure was 100/80 mmHg. Laboratory findings were normal except alcalinephosphatase (292 U/l) and gamma-glutamyl transpeptidase(60 U/l). Neurological examination showed alert consciousness, mild upper gaze palsy, slight right-side hemiparesis and left Babinski signs was present. Cranial magnetic resonance imaging showed no abnormality, but cerebral angiography revealed bilateral carotid artery occlusion. There were abundant leptomeningeal anastomoses, and the posterior communicating artery was supplied by the left vertebral artery. Electroencephalography showed a spike wave in the temporal lobe and rebuild-up phenomenon in the right hemisphere. Brain atrophy in the anterior and temporal lobes progressed, and the patient experienced gradual disorientation, delirium and hypobulia. He was eventually bedridden. He also demonstrated repetitive tonic-clonic convulsions. After one convulsion, he remained unconscious and died of pneumonia. Autopsy revealed thickening of the intima and internal elastic lamina in the occluded internal carotid artery. The anterior and middle cerebral arteries showed the same pathological changes. Multiple small infarctions restricted to grey matter were present in the cerebral cortex and may have caused the progressive brain atrophy. There was no myelin pallor in the white matter of the cerebrum. Atherosclerotic changes, senile plaque, and neurofibrillary tangles were seen but were within normal limits. These pathological findings were strongly suggestive of moyamoya disease.

Aged↗

[Comparison between repeated antigen and acetylcholine-induced bronchoconstriction in development of airway wall thickness in a chronic guinea pig model of asthma].

Asthma is associated with a chronic remodeling of the airways, but it remains to be elucidated whether repeated bronchoconstriction (BC) influences any structural attributes of the lungs. To investigate the role of repeated BC on the morphology of the airways, we chronically exposed guinea pigs to an aerosol of acetylcholine (ACH) over a period of 6 months. The guinea pigs were challenged with either ACH or saline daily for 10 days and thereafter were challenged once a week. To compare repeated BC with a chronic model of allergic inflammation, an additional group of animals were sensitized to aerosolized ovalbumin (OA) and subsequently exposed with OA. The airway wall area and basement membrane (BM) thickness were measured by standard morphometric techniques. Both airway wall area and BM thickness were significantly increased in OA exposed guinea pigs compared with both saline control and AHC-exposed guinea pigs. Our results suggest that persistent bronchoconstriction and/or allergic airway inflammation in asthmatics may contribute to the thickness of the airway wall observed in this disorder. However, repeated acute bronchoconstriction events may not contribute to the increase in the airway wall or BM thickness.

Acetylcholine↗

Participation of pigment epithelium of iris and ciliary body in ocular immune privilege. 1. Inhibition of T-cell activation in vitro by direct cell-to-cell contact.

PURPOSE: To determine by what mechanism(s) iris and ciliary body (I/CB) pigment epithelial (PE) cells inhibit T-cell activation in vitro. METHODS: Pure cultured I/CB PE cells were obtained from eyes of normal and CD95 ligand (CD95L)deficient mice and tested for their capacity to suppress T-cell activation in three different T-cell receptor (Tcr) ligand systems: mixed lymphocyte reactions, stimulation of Tcr transgenic T cells (D011.10) by specific antigen (ovalbumin), and ligation of the Tcr-associated CD3 molecule by anti-CD3 antibodies. Proliferation and secretion of cytokines (interferon [IFN]-gamma, interleukin [IL]-2, IL-4, and IL-10) were assessed as measures of T-cell activation. Suppressive influences of I/CB PE cells were determined on the basis of RT-PCR- detected cytokine genes expressed by I/CB PE cells, immunosuppression mediated by supernatants of cultured I/CB PE cells, direct contact between I/CB PE cells and T lymphocytes, and promotion of apoptosis among responding T cells. Attempts to reverse I/CB PE-dependent suppression of T-cell activation included the use of neutralizing antibodies to IL-10, tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta, and the addition of exogenous IL-2 and IL-12. RESULTS: Cultured mouse I/CB PE cells (including CD95L-deficient cells), which were more than 95% keratin positive, suppressed T-cell proliferation and secretion of IFN-gamma, IL-2, IL-4, and IL-10 in a dose-dependent fashion in all three Tcr ligand systems. Supernatants of cultured I/CB PE cells displayed little suppression activity, whereas cultures in which I/CB PE cells contacted responding T cells directly were profoundly immunosuppressive. Cultured I/CB PE cells expressed mRNA for TGF-beta1, TGF-beta2, IL-6, IL-10, and TNF-alpha, but not IL-4, IFN-gamma, proopiomelanocortin (POMC), and CD95L (Fas L). Antibodies to TGF-beta, IL-10, and TNF-alpha failed to reverse suppression mediated by I/CB PE cells. Moreover, neither exogenous IL-2 or IL-12 relieved the suppression. CONCLUSIONS: Cultured I/CB PE cells, through direct cell-to-cell contact, prevent T cells from proliferating and secreting cytokines when stimulated through the Tcr for antigen by a mechanism that does not involve CD95 or apoptosis.

Animals↗

[An autopsy of parkinsonism after solitary living in Guam Island for 28 years].

The autopsy findings of an 82-year-old man with history of solitary living in the jungle of Guam, the endemic area of parkinsonism-dementia complex(PDC), for 28 years was reported in this paper. When he was 75 years old, about 20 years later to have come back to Japan, he developed parkinsonism. He noticed bradykinesia and was pointed out masked face, rigidity and tremor in his right hand. After 2 years, he was diagnosed as Parkinson's disease under the third degree of Hoehn-Yahr criteria. He also showed mild cognitive dysfunction, but no pyramidal signs, muscle atrophy of fasciculation at all. Anti-parkinsonian drugs were effective for his motor symptoms. He admitted at age 82 because of anorexia, and died after 3 months. Neuropathological study disclosed neuronal loss and gliosis with Lewy bodies in the substantia nigra, locus coeruleus and dorsal vagal nucleus. There were cortical type Lewy bodies in the limbic system and scanty amount in the neocortex. A few neurofibrillary tangles(NFT) were found in the hippocampus and parahippocampal gyrus, but no dominancy in the second or third layers of the cerebral cortex as reported in PDC. Senile plaques were not observed at all. Although the exact cause of PDC has not been clarified, environmental factors such as water or food seem to influence on the outcome of PDC. However, the pathological findings of the present case were compatible to those of idiopathic Parkinson's disease. Thus it is a very important fact that the present case was not suffered from PDC in spite of his long residence in the endemic area of Guam.

Aged↗

[Proposal of a new lymph node mapping system for pancreatic head cancer].

The Japanese Pancreatic Society published the 4th edition of the general guidelines for the study of pancreatic cancer (JPS guidelines) in 1993. The current JPS guidelines differ from the UICC classification of lymph nodes. Thirty-five lymph node stations are divided into three groups in the JPS guidelines. Group 1 (n1) corresponds closely with the regional lymph nodes in the UICC classification. Group 2 (n2) and group 3 (n3) are distant metastases in the UICC classification. To clarify practical lymph node mapping, 2,449 resected tubular adenocarcinomas of the pancreas head registered with the JPS were analyzed. Lymph node involvement was observed most frequently in posterior pancreatoduodenal (PPD) and anterior pancreatoduodenal (APD) and then in paraaortic (n2) nodes. Fifty-six patients who achieved 5-year survival were registered, of whom 19 had lymph node involvement. The sites of lymph node involvement were limited to the PPD and/or APD nodes in 14 cases. PPD and APD nodes differ from the other n1 in terms of high incidence of metastasis and fair prognosis. In conclusion, we propose a new practical lymph node mapping system in which PPD and APD nodes are the first station and the other n1 are the second station.

Humans↗

[Two cases of acute myelogenous leukemia complicated with fatal gastrointestinal tract bleeding after treatment with idarubicin and cytarabine].

We describe herein two newly diagnosed patients with acute myelogenous leukemia (AML), who were treated twice with an idarubicin hydrochloride (IDR)-containing regimen as a response-orientated induction therapy. Both patients had severe gastrointestinal tract hemorrhage complications at their nadir. The two patients were as follows: a 35-year-old male, FAB-M4, and a 47-year-old female, FAB-M0. They received the same induction chemotherapy (IDR 12 mg/m2 for four days and cytarabine 100 mg/m2 for ten days). No response (NR) was obtained in either, so they underwent the same regimen again. During the period of myelosuppression, they developed severe gastrointestinal hemorrhage. One died of sepsis, and the other of acute respiratory distress syndrome without a recovery in bone marrow. The fetal gastrointestinal tract complications may have been due to severe myelosuppression and mucosal damage in these patients. Careful observation will be needed to prevent such severe complications after the treatment with IDR.

Adult↗

DNA-dependent protein kinase activity correlates with Ku70 expression and radiation sensitivity in esophageal cancer cell lines.

We investigated the relationship between DNA-dependent protein kinase (DNA-PK) activity and radiation sensitivity using 14 esophageal cancer cell lines, TE 1-14. DNA-PK activities differed significantly among the cell lines. The highest DNA-PK activity observed in TE-8 was more than two times higher than the lowest DNA-PK activity observed in TE-5. Significant correlation was observed between DNA-PK activity and D0 (r = 0.766; P = 0.0008). Western blots analysis revealed a significant correlation between DNA-PK activity and Ku70 expression, suggesting that the regulation in DNA-PK activity was associated with Ku70 expression. The data suggest that the measurement of DNA-PK activity and/or Ku70 expression may provide a useful way to predict radiation sensitivity.

Antigens, Nuclear↗

[Molecular epidemiology of human alpha-herpesvirus infection].

Herpes simplex virus type 1, 2 (HSV-1, 2) and varicella-zoster virus(VZV) are significant pathogens in humans. These three viruses belong to the alpha-herpesvirus subfamily. The molecular epidemiological analyses of the viruses are based on the heterogeneity of each viral genome found in isolates. HSV-1, 2 strains are classified into genotypes as intratypic variations by gains or losses of cleavage sites using restriction endonucleases recognizing 6-base pairs. On the other hand, VZV strains can rarely be distinguished with respect to the presence or absence of restriation sites, so that the numbers and/or patterns of repeating units in the reinteration structures(R1, R2, R5) are also available to differentiate VZV isolates. Recently, analysis of viral DNA fragments amplified by polymerase chain reaction has been applied as an alternative method. The epidemiological relation of strains has been determined in various clinical conditions such as the transmission of the viruses by these molecular epidemiological methods.

Alphaherpesvirinae↗

[A case of glioblastoma multiforme which indicated the early stage on brain MRI].

A 57-year-old male was urgently carried to our hospital because of sudden loss of consciousness, lasting about 10 minutes. He had resumed consciousness before he arrived at our hospital. Neurologically, he had mild muscle weakness of the right arm. Deep tendon reflexes in the right upper extremity were reduced. In high level functions, speech disturbance, dysgraphia (disturbed ability to write Hiragana), and constructive apraxia were noted. A brain MRI upon admission showed a poorly demarcated, high signal intensity area in the cortical and subcortical layers of the left temporal and parietal lobes. This was visible on T 2 weighted images(T 2 WI), although no abnormalities were visible on T 1 weighted images(T 1 WI). No contrast enhancement was effected by Gd-DTPA. The patient was therefore suspected of having a tumor or degenerative disease and was monitored closely. About 4 months later after onset, his symptoms became aggravated, and brain MRI disclosed a marked low signal intensity area on T 1 WI and a heterogeneous high signal intensity area on T 2 WI. The abnormal signal intensity area was surrounded by extensive edema and mass effect. Ring-shaped, irregular, contrast enhanced areas were also visible. Cerebral angiography revealed a poorly demarcated tumor stain in the area supplied by the middle cerebral artery. The tumor was removed surgically and was histopathologically rated as glioblastoma multiforme(GBM). Because this case represents a valuable example of early stage of GBM, it will be discussed in this paper, along with differential diagnoses.

Brain Neoplasms↗

Analysis of HLA-DRB1 polymorphism in the Gidra of Papua New Guinea.

The genetic structure of the Gidra-speaking population inhabiting 13 villages in Papua New Guinea was investigated, based on the analysis of HLA-DRB1 polymorphism. Nei's fixation indices (F(IS), F(IT), and F(ST)) showed that the Gidra villages were genetically differentiated. The genetic distances significantly correlated with the geographic distances among the 13 villages. Thus, it is likely that a low intervillage migration rate has been maintained since the Gidra community was established. Correspondence analysis revealed that the Gidra, who belong to non-Austronesian-speaking groups, are genetically located at the intermediate point between the Aboriginal Australian groups and the Austronesian-speaking groups. Moreover, the HLA-DRB1*0802 allele, which has been observed in only two Polynesian groups (Austronesian-speaking groups) of Oceanian populations, was also found in the Gidra. These results suggest that the admixture of Austronesian and indigenous non-Austronesian groups beyond the linguistic boundary occurred partly in Papua New Guinea before Austronesian groups spread to the Pacific.

Black People↗

Long-term ethanol consumption in ICR mice causes mammary tumor in females and liver fibrosis in males.

BACKGROUND: Although epidemiological studies indicate that ethanol consumption and the risk of breast cancer are positively associated in women, experimental animal models have not yet been developed that provide evidence to support this relationship. To clarify alcohol-related liver injury, it is important to reproduce, in laboratory small animals, the liver fibrosis observed in human alcoholics. However, in mice the induction of fibrosis has failed. The present study describes the first experimental models to produce mammary tumors in female ICR mice and liver fibrosis in male ICR mice treated long-term with ethanol. METHODS: The study consisted of two parts. To induce mammary tumors, female ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 25 months, with solid diet supplied ad libitum. To induce liver fibrosis, male ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 10 to 15 months. Control female and male mice were given tap water. RESULTS: In 9 (45%) of 20 ethanol-treated female mice, mammary tumors occurred at 8 to 24 months after ethanol intake began, whereas spontaneous mammary tumor was not found in the 20 control female mice. The tumors were composed histopathologically of either papillary adenocarcinoma or medullary adenocarcinoma of glandular epithelial origin. In the ethanol-treated male mice, early hepatic fibrosis at the centrilobular and pericellular areas and central-central bridging were observed at the 10th month, and marked fibrosis at the centrilobular, pericellular, and periportal areas and bridging between the neighboring vascular tissues were observed at the 15th month, which suggested that the initial fibrosis arose from the centrilobular area. No abnormalities other than mild fatty infiltration were found in livers of the control male mice. CONCLUSIONS: These murine models may be useful to study the role of ethanol in mammary tumorigenesis and the pathogenetic mechanisms of ethanol liver injury.

Animals↗

Autologous iris pigment epithelial cell transplantation in monkey subretinal region.

PURPOSE: To establish autologous iris pigment epithelial (IPE) cell transplantation in monkey eyes. METHODS: Autologous IPE cells from three monkeys were obtained by peripheral iridectomy, and cell culture was performed with autologous serum. The cultured cells were labeled with DiI, and transplantation was performed by transvitreal approach to the submacular region of each monkey. Fundus examination, photography, and fluorescein angiography were performed monthly. Histochemical analysis and electron microscopy were also performed six months after transplantation. RESULTS: Auto IPE cells grew well in auto serum. No fluorescein leakage or retinal thickening was observed after submacular transplantation. We demonstrated the presence of autologous IPE cells in the region 6 months after transplantation by histologic and electron microscopic examination. Electron microscopy also demonstrated that the transplanted cells appeared to be less pigmented and to have less mitochondria than did the host retinal pigment epithelial cells. However, some transplanted cells looked as if they embrace the photoreceptor outer segments. DISCUSSION: Autologous IPE cell culture of the monkey was established using auto serum. Six months after transplantation of the cultured IPE cells, we could still observe the cells in the region. This method may have potential use in human disease that requires autologous cell transplantation to prevent host-graft rejection, and to provide an alternative substance that functions like retinal pigment epithelium.

Animals↗

Platelet surface P-selectin molecules increased after exposing platelet to a high shear flow.

BACKGROUND: P-selectin is known to play a crucial role in leucocyte recruitment at sites of vascular injury. Although platelet surface expression of P-selectin molecules are well known to occur after platelet stimulation by chemical agonists such as alpha-thrombin, it is still uncertain whether P-selectin expression occurs in the process of the more physiological platelet activation pathway mediated by interaction between von Willebrand factor (vWF) and platelet receptor proteins, including glycoprotein (GP) Ibalpha and GP IIb/IIIa, occurring under high shear rates generated by blood flow. METHODS: We have developed a method to detect P-selectin molecules expressed on platelet surface with flow-cytometer and monoclonal antibody, which can bind exclusively to P-selectin (WGA1), directly conjugated with fluorescein isothiocynate. This method allowed us to measure platelet surface P-selectin molecules semiquantitatively. RESULTS: We demonstrated that a significant increase in platelet surface P-selectin molecules occur after exposing platelets to a relatively high shear rate of 10,800 s(-1). We have also demonstrated that shear-induced surface expression of P-selectin as well as microparticle release from platelets depended at least on the interaction between von Willebrand factor and glycoprotein Ibalpha, a platelet surface receptor for the former. CONCLUSIONS: Shear-induced von Willebrand-mediated surface expression of P-selectin may play a role in leucocyte recruitment in platelet thrombi at vascular injury sites.

Antibodies, Monoclonal↗