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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 91 records · Page 5Linked to original sources
PubMed2000

Distribution of apoptotic cells and expression of apoptosis-related proteins along the intrahepatic biliary tree in normal and non-biliary diseased liver.

AIMS: The cell kinetics and homeostasis of biliary epithelial cells may be maintained differently along the biliary tree. In this study, the role of apoptosis in the maintenance and homeostasis of the intrahepatic biliary tree was evaluated. METHODS AND RESULTS: By counting apoptotic biliary cells and by immunostaining apoptosis-related proteins in normal liver, fatty liver, and those with acute viral hepatitis, chronic viral hepatitis, and hepatitis virus-related cirrhosis, it was found that the larger the intrahepatic bile ducts became, the more biliary epithelial cells underwent apoptosis. bcl-2, an inhibitor of apoptosis, was diffusely expressed in the interlobular bile ducts, but rarely detectable in the large and septal bile ducts. bcl-XL and mcl-1, inhibitors of apoptosis, and bax, a promoter of apoptosis, were diffusely expressed along the intrahepatic biliary tree. CD95, a direct inducer of apoptosis, was present in the large and septal bile ducts, but rarely in the interlobular bile ducts. CONCLUSION: The ratio of bax to bcl-2, as well as the expression of CD95 which differed at the interlobular versus large and septal bile ducts, may be responsible for the unique distribution of apoptotic biliary cells and involved in the homeostasis of the intrahepatic biliary tree.

Aged↗
PubMed2000

The calcium-independent protein kinase C participates in an early process of CD3/CD28-mediated induction of thymocyte apoptosis.

Thymocyte negative selection eliminates self-reactive clones and involves both a T-cell receptor (TCR)/CD3-mediated signal and a costimulatory signal, which can be delivered via CD28. Anti-CD3/anti-CD28-triggered apoptosis in isolated CD4+CD8+ thymocytes in vitro provides a basic model for negative selection. Effects of isoform-selective and non-isoform-selective inhibitors of protein kinase C (PKC) on this apoptotic process suggest that activation of Ca2+-independent PKC isoforms during the first 2-3 hr of culture is essential for inducing apoptosis, and that Ca2+-dependent PKC isoforms may be influential, but not essential, for apoptosis. To assess the CD3/CD28-mediated activation of PKC in the apoptotic process, we prepared CD4+CD8+ thymocytes (without contamination with cells that had received negative or positive selection signals in vivo) by establishing TCR-transgenic mice with RAG-2-deficient and non-selecting major histocompatibility complex (MHC) backgrounds, in addition to a CD4+CD8+ thymocyte-enriched population from normal mice. Translocation of Ca2+-independent PKC from the cytosolic fraction to the particulate fraction of CD4+CD8+ thymocytes was induced by CD3/CD28-mediated stimulation, but not by CD3- or CD28-mediated stimulation alone, and peaked 2 hr after the start of culture. The kinase activity of the translocated Ca2+-independent PKC was dependent on cofactors in vitro, indicating that novel (n)PKC, but not atypical (a)PKC or a proteolytic PKC fragment, was responsible for the activity. Immunoblotting analysis indicated that the nPKC-theta isoform was the major contributor among nPKC isoforms, and that the classical (c)PKC-alpha isoform was the major contributor among cPKC isoforms. These results suggest that activation of nPKC (especially the theta isoform) in CD4+CD8+ thymocytes is involved in a pathway for negative selection.

Animals↗
PubMed2000

Neutrophil activation in immunoadsorption.

Immunoadsorption therapy (IAT) is used in the treatment of autoimmune diseases. Although IAT has been reported to modify humoral immunity by inducing chemokines and activating complements, much remains unknown about the biological effects of IAT on cellular components in peripheral blood. To define the influence of IAT on leukocytes, we determined leukocyte L-selectin (CD62L) and Mac-1 (CD11b) as parameters for activation of leukocytes in peripheral blood during IAT. Peripheral leukocyte L-selectin and Mac-1 were determined continuously by flow cytometry in 6 patients with neuroimmunological disorders in whom IAT was conducted using a Plasma Flow OP-05 (Asahi Medical Corp., Tokyo, Japan) as a plasma separator and Immusorba TR-350 (Asahi Medical Corp., Tokyo, Japan) as an adsorption column. Expression of neutrophils (PMN) L-selectin was decreased 30 min after starting IAT, with the decreases particularly marked at the end of IAT, while expression of mononuclear cells (MNC) L-selectin slightly increased during IAT. Expression of PMN Mac-1 was markedly increased at the end of IAT, whereas expression of MNC Mac-1 did not change during IAT. Leukocyte counts decreased 30 min after starting IAT, and then increased to the initial level or higher in parallel with L-selectin downregulation and Mac-1 upregulation on PMN. L-selectin downregulation and Mac-1 upregulation on PMN suggested that activation of PMN associated with changes in peripheral leukocyte counts occurred during IAT and might play some role in modulating the human circulating blood and immune systems.

Adolescent↗
PubMed2000

Presynaptic modulation of the norepinephrine-induced beta-adrenergic receptor desensitization phenomenon in vivo.

BACKGROUND: In vivo administration of norepinephrine fails to cause beta-adrenergic receptor desensitization. However, short-term exposure of cultured cells to norepinephrine induces the phenomenon in vitro. We sought to identify the local regulatory mechanisms responsible for in vivo beta-adrenergic receptor desensitization in congestive heart failure. METHODS AND RESULTS: Control rabbits received norepinephrine (n = 7) or saline (n = 7) for 1 week, and rabbits with chemical denervation induced by 6-hydroxydopamine also received norepinephrine (n = 7) or saline (n = 7). Myocardial norepinephrine content decreased 80% in both groups of denervated rabbits. beta1-Adrenergic receptor density in denervated rabbits receiving norepinephrine was lower than in those receiving saline but not in control rabbits receiving norepinephrine. Isoproterenol-competition assay revealed that there was a lower number of high-affinity binding sites with loss of guanosine triphosphate shift in denervated rabbits receiving norepinephrine. Isoproterenol-stimulated adenylyl cyclase activity in control rabbits receiving norepinephrine was lower than in those receiving saline. In denervated rabbits receiving norepinephrine, forskolin-stimulated adenylyl cyclase activity was also reduced. Immunoreactive G-protein coupled receptor kinase-2 level was increased in denervated rabbits receiving norepinephrine. CONCLUSION: There are profound alterations in beta-adrenergic receptor signaling after exposure to norepinephrine in the denervated heart. Defects in neuronal uptake may play a pivotal role in beta-adrenergic receptor desensitization in vivo.

Animals↗
PubMed2000

Cerebroside elicitors found in diverse phytopathogens activate defense responses in rice plants.

Cerebrosides A and C, compounds categorized as glycosphingolipids, were isolated in our previous study from the rice blast fungus (Magnaporthe grisea) as novel elicitors which induce the synthesis of rice phytoalexins. In this paper, these cerebroside elicitors showed phytoalexin-inducing activity when applied to plants by spray treatment and also induced the expression of pathogenesis-related (PR) proteins in rice leaves. This elicitor activity of the cerebrosides showed the structural specificity as that for the induction of phytoalexins. Ceramides prepared from the cerebrosides by removal of glucose also showed the elicitor activity even in lower level compared to the cerebrosides. In field experiments, the cerebroside elicitors effectively protected rice plants against the rice blast fungus, an economically devastating agent of disease of rice in Japan. The cerebrosides elicitors protected rice plants from other disease as well and were found to occur in a wide range of different phytopathogens, indicating that cerebrosides function as general elicitors in a wide variety of rice-pathogen interactions.

Cerebrosides↗
PubMed2000

Evidence of relativistic laser beam filamentation in back-reflected images

The back-reflected image of a 100 TW laser incident on a long scale length plasma is measured. The plasma is deliberately preformed on a solid planar target in a controlled way. Multiple highly intense spots are observed inside the original focal spot. These spots could be the experimental evidence for the laser beam relativistic filamentation in the plasma. Three-dimensional particle-in-cell (PIC) simulations for parameters close to the experimental values are performed. The experimental observations and the filamentation dynamics obtained in the PIC simulations are in a good agreement.

Journal Article↗
PubMed2000

Topographic mapping of P300 and frontal cognitive function in Parkinson's disease.

The purpose of this study was to evaluate the relationship between P300 that is one of the event-related potentials and frontal cognitive functions in Parkinson's disease (PD) without clinically apparent dementia. Subjects were 20 PD cases 48 to 79 years of age, all of whom were within normal limits on the Mini-Mental State examination, and 55 age-matched healthy adults. P300 was elicited with an auditory oddball paradigm and recorded at 15 sites on the scalp. Cognitive functioning of the frontal lobe was evaluated using the New Modified Wisconsin Card Sorting Test (WCST) and the Letter Pick-Out Test (LPOT) which reflects selective attention and semantic categorization. P300 latency was delayed in 30.0% of P300 demonstrated abnormal distribution in 20.0%. the WCST and the LPOT were abnormal in 15.0%, P300 latency significantly correlated with number of subcategories achieved on the WCST. P300 amplitude correlated with scores on the LPOT. These results suggest that cognitive dysfunction which linked partly to the frontal lobe might begin in PD even without clinically apparent dementia.

Journal Article↗
PubMed2000

Hyperthyroid Graves' disease after hemithyroidectomy for papillary carcinoma: report of three cases.

Here we report three cases of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary carcinoma. In Case 1, the patient first developed hyperthyroidism 2 years after resection of left thyroid lobe, was treated for 2 years with antithyroid drug which was then discontinued, and relapsed with periodic paralysis after 8 years of remission. In Case 2, a hyperfunctioning remnant thyroid was noted 22 years after right hemithyroidectomy. In Case 3, where thyrotoxic symptoms became evident 7 weeks after right hemithyroidectomy, autoantibodies to thyroglobulin and thyroid microsome were positive in preoperative serum, in line with a report by others detecting these antibodies in 2 out of 3 such cases examined. Later bioassay revealed activity of thyroid stimulating antibodies in that serum, with further increase in titer in the sample taken at the clinical manifestation. Hence in Case 3, surgical stress may have altered immunological homeostasis, promoting a preclinical Graves' disease to full-blown hyperthyroidism.

Adult↗
PubMed2000

Fusion of the nucleoporin gene, NUP98, and the putative RNA helicase gene, DDX10, by inversion 11 (p15q22) chromosome translocation in a patient with etoposide-related myelodysplastic syndrome.

We report a 50-year-old man who developed therapy-related myelodysplastic syndrome after treatment with etoposide-including chemotherapy for extratesticular germ cell tumor. Chromosomal analysis showed inversion 11 (p15q22) translocation. Reverse transcriptase-polymerase chain reaction amplification of patient RNA showed a fusion transcript of nucleoporin gene NUP98, and putative DEAD-box RNA helicase gene DDX10. NUP98 is implicated in the transformation through aberrant nucleocytoplasmic transport. DDX10 is suggested to be involved in ribosome assembly. The NUP98-DDX10 fusion transcript may promote the development of secondary hematological malignancies caused by DNA-topoisomerase II inhibitors through aberrant nucleocytoplasmic transport and/or alteration in ribosome assembly.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Atypical Fabry's disease presenting with cholesterol crystal embolization.

We describe a 65-year-old man who presented with pulmonary hemorrhage and progressive renal insufficiency three months after resection surgery for an abdominal aortic aneurysm. Intensive treatment with corticosteroids and hemodialysis were not effective, and the patient died. Postmortem examination of the kidneys revealed widespread cholesterol clefts within the renal arterioles and a number of lamellar inclusion bodies were observed by electron microscopy. The diagnosis of Fabry's disease was made by the absence of plasma alpha-galactosidase A activity. This was a very rare case of subclinical Fabry's disease coexistent with cholesterol crystal embolization, mimicking pulmonary-renal syndrome.

Aged↗
PubMed2000

[Clinical evaluation of pioglitazone].

Pioglitazone is the second thiazolidinedione derivative to be clinically used for type 2 diabetes in Japan. It is ten times more potent than troglitazone in glucose-lowering effect. Favourable effects against abnormal lipid levels including decreasing blood triglyceride levels, free fatty acid levels and increasing HDL-cholesterol is advantage to treat obese diabetic patient who may develop atherosclerosis. Up to now, there has been no report of severe hepatic dysfunction due to pioglitazone treatment. Pioglitazone should be carefully monitored in its clinical treatment regarding possible its side effect of hepatic dysfunction.

Animals↗
PubMed2000

[In vitro activities of carbapenem antibiotics against the various clinical isolates].

The annual changes of antibacterial activities of beta-lactam antibiotics, mainly carbapenem antibiotics, were investigated against 5 bacterial species, S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa, which had been isolated from the clinical materials at Toho University Omori Hospital during the period of 1995 to 1997. In addition, antibacterial activities against other main bacterial strains isolated from the clinical materials during 1997 were also determined. The five bacterial species on which annual changes of the sensitivity were investigated did not show any remarkable trend to increase in resistance to the carbapenem antibiotics tested. The antibacterial activities of the carbapenem antibiotics against MRSA were weak, and MIC90 values were between 25 and 50 micrograms/ml. In S. marcescens and P. aeruginosa on which high resistance by the production of metallo-beta-lactamase has become a problem in recent years, there were no remarkable changes in annual changes of sensitivities. Especially, MIC90 valuses of the carbapenem antibiotics against P. aeruginosa were between 12.5 and 25 micrograms/ml, 4 to 8 times better than that of PIPC, like the case of CAZ. Furthermore, the carbapenem antibiotics showed strong antibacterial activities against clinically important 16 bacterial species, from Gram-positive to Gram-negative bacteria.

Carbapenems↗
PubMed2000

[Treatment with interferon-alpha 2a in a patient with chronic inflammatory demyelinating polyneuropathy].

We report an adult patient with refractory chronic inflammatory demyelinating polyneuropathy (CIDP) who resisted conventional immunological therapies but could be successfully treated with interferon (IFN)-alpha 2a. A 56-year-old man was admitted to our hospital with progressive distal dominant muscle weakness and sensory disturbance of all extremities. He was diagnosed as CIDP based on laboratory examinations which revealed conduction block on peripheral nerve conduction studies and demyelinating findings on sural nerve biopsy. He was given several immunological treatments, including immunoadsorption therapy (IAT), oral corticosteroid, immunosuppressive agents such as cyclophosphamide and mizoribine, but without satisfactory efficacy although transient improvement of muscle weakness was observed for two weeks after IAT. A session of IAT every four weeks was therefore continued to maintain his symptoms for nine months. He was then treated with IFN-alpha 2a intramuscular injections every other day. Four weeks after starting of IFN-alpha 2a therapy, the worsening of his symptoms stopped and his muscle strength improved gradually to normal level without IAT, suggesting that IFN-alpha 2a may be effective in some patients with refractory CIDP. Further studies are needed to confirm the efficacy of IFN-alpha 2a for CIDP.

Humans↗
PubMed2000

[Activities of antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. Levofloxacin--Surveillance Group].

The surveillance study was conducted to determine the antimicrobial activity of fluoroquinolones (ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin) and other 20 antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. The resistance to fluoroquinolones was remarkable in Enterococci, methicillin-resistant staphylococci and Pseudomonas aeruginosa from UTI. However, many of the common pathogens such as Streptococcus pneumoniae including penicillin-resistant isolates, methicillin-susceptible Stahylococcus aureus, Moraxella catarrhalis, the family of Enterobacteriaceae, Haemophilus influenzae including ampicillin-resistant isolates have been kept to be susceptible to fluoroquinolones. About 90% of P. aeruginosa isolates from RTI were susceptible to fluoroquinolones. In conclusion, the results from this surveillance study suggest that fluoroquinolones are useful in the treatment of various bacterial infections including respiratory infections.

Anti-Infective Agents↗
PubMed2000

[A case of chorea gravidarum with moyamoya disease].

A 16-year-old girl developed acute left choreic movements during her fourth week of pregnancy. She had sometimes had transient ischemic attacks since she was 10 years old. During the eighth week of pregnancy, a brain MRI showed old ischemic lesions deep in the right frontal white matter. Her angiograph revealed a complete obstruction of the terminal portion of the right internal carotid artery with a developed moyamoya net work. After her abortion, all involuntary movements completely subsided. The choreic movements might have been caused not only by ischemia, but also by enhanced dopaminergic sensitivity mediated by elevations in female sex hormones due to pregnancy.

Abortion, Therapeutic↗
PubMed2000

[A comparative study of the prognosis for Japanese patients with idiopathic interstitial pneumonia or BOOP based on histopathologic subsets].

We explored the prognosis for 123 patients with either idiopathic interstitial pneumonia (IIP) or bronchiolitis obliterans organizing pneumonia (BOOP). All patients underwent either open lung biopsy or thoracoscopic lung biopsy procedures. The histopathologic diagnosis of IIP included patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and desquamative interstitial pneumonia with respiratory bronchiolitis-associated interstitial lung disease. The prognosis was poorest for patients with a histologic diagnosis of UIP, and excellent for those who received a diagnosis of BOOP. Although the prognosis is generally considered to be good for patients with NSIP, some NSIP patients in our study died. Histopathologic diagnosis based on surgical lung biopsy is useful in evaluating the prognosis for patients with IIP.

Aged↗