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Biomedical subjects

N Shibata

Publications and source records attributed to N Shibata.

At least 127 records · Page 7Linked to original sources
PubMed1998

Inducible nitric oxide synthase (iNOS)-like immunoreactivity in argyrophilic, tau-positive astrocytes in progressive supranuclear palsy.

The immunoreactivity to the free radical-related enzymes, nitric oxide synthase (NOS) and superoxide dismutase (SOD), was examined in brain tissue in progressive supranuclear palsy (PSP). To determine the relationship between the immunoexpression of these enzymes and tau-positive, argyrophilic cytoplasmic inclusions, which are constantly present in PSP brains, double-label immunohistochemistry was applied. We demonstrated for the first time that strong inducible NOS-like immunoreactivity (iNOS-ir) was detected in tau-positive astrocytes that bore tufts of abnormal fibers (TAF), but not in oligodendrocytes containing argyrophilic/tau-positive coiled bodies nor in microglia. No brain NOS-ir was detected in neurons with neurofibrillary tangles. MnSOD-ir was also detected in tau-positive astrocytes and oligodendrocytes. Nitrotyrosine-ir of variable intensity was observed in astrocytes, oligodendrocytes and neurons. Our results indicate: (1) that TAF-bearing astrocytes may be a major source of excessive NO in PSP brains; (2) that after the induction of iNOS by unknown stimulating factors, TAF-bearing astrocytes produce an excessive amount of NO that exceeds the detoxification capability of SOD; and (3) that peroxynitrite and excessive NO, both cytotoxic, may be present in astrocytes, oligodendrocytes and neurons. Although the precise relationship between NO production and neuronal cell death in PSP remained uncertain, based on the specificity of TAF for PSP brains, our results indicated a possible mechanism of NO-mediated cytotoxicity that may contribute to the neuronal and glial cell damage followed by abnormal tau accumulation in this disease.

Aged↗
PubMed1998

Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy.

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are characterized by their unique clinical features and neuronal pathology. Although astrocytic plaques and tufts of abnormal fibers have been suggested to be specific histopathologic markers, recent studies have revealed significant clinicopathologic overlap between CBD and PSP. Based on the distinctive camera lucida profile of astrocytic inclusions on Gallyas-Braak silver staining, we found that astrocytic plaques and tufts of abnormal fibers did not coexist in the same patient among 30 cases of clinically diagnosed CBD, PSP and atypical Parkinson's disease. Using Tau immunohistochemistry it was difficult to verify the absence of tufts of abnormal fibers. A morphometric analysis revealed that the two groups classified by the presence or absence of astrocytic plaques and tufts of abnormal fibers exhibited significant differences in the density of ballooned neurons and neurofibrillary tangles and degeneration of the subcortical nuclei. Assessment using the NINDS neuropathologic criteria revealed that the cases with astrocytic plaques and tufts of abnormal fibers closely correspond to CBD and typical PSP, respectively. In addition, the cases lacking either of these two astrocytic inclusions had atypical PSP according to the NINDS criteria, and were associated with novel tau-positive astrocytes (spiny astrocytes). We thus conclude that astrocytic plaques and tufts of abnormal fibers are highly characteristic structures for CBD and typical PSP, respectively. We emphasize the importance of strict differentiation between different astrocytic inclusions not only for diagnosis, but also for further studies for elucidation of their role in the disease mechanisms of CBD and PSP.

Aged↗
PubMed1998

Immunocytochemical demonstration of the expression and induction of manganese-superoxide dismutase in the adenohypophysis.

Immunocytochemistry for manganese-superoxide dismutase (Mn-SOD) was studied in 12 normal adenohypophyses and 38 various pituitary lesions. The proportions of cells with granular immunoreactivity for Mn-SOD in normal adenohypophysis ranged from 9.8% to 29.6% (mean +/- SD; 18.4+/-6.2%). Some positive cells tended to accumulate in clusters, distribution of which corresponded well with those immunopositive for mitochondrial protein and cytochrome oxidase. The number of Mn-SOD-positive cells increased in adjacent residual adenohypophysis in eight of nine recent infarcts, in two of five old infarcts, in all four cases of lymphocytic hypophysitis, in two of four abscess cases and in one of three metastatic tumour cases, whereas the immunoreactivities of mitochondrial protein- and cytochrome oxidase-positive cells either did not vary or decreased. The intensity of the histological inflammatory reactions showed a positive correlation with reactivity for Mn-SOD in these lesions. Of eight adenomas, the surrounding area of compressed adenohypophysis showed increased numbers of Mn-SOD- and mitochondrial protein-/cytochrome oxidase-positive cells in four and six cases respectively. It is suggested that positivity for Mn-SOD may be related to some functional activity of mitochondria. It is further suggested that adenohypophysial cells have a high potential to induce Mn-SOD by inflammatory and ischaemic stress and, in addition, by enhanced mitochondrial activity.

Adenoma↗
PubMed1998

Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses.

BACKGROUND: Calponin is a calmodulin-and actin-binding protein expressed in smooth muscle. It promotes actin polymerization and inhibits actin-activated myosin ATPase activity. Despite the molecular and functional characterization of calponin in vitro, the physiological role of calponin in vivo has not been clarified. RESULTS: We investigated the in vivo function of smooth muscle calponin (also called basic calponin or calponin h1) by generating mice carrying a targeted mutation in both alleles of the calponin gene. Mice lacking basic calponin expression displayed enhanced ectopic bone formation in vivo, induced by recombinant human bone morphogenetic protein-2 (rhBMP-2), and an augmentation of the degree of osteoblastic differentiation of embryonic mesenchymal cells when they were stimulated by rhBMP-2. Basic calponin messenger RNA was shown to be expressed in developing and healing bone tissues, and in undifferentiated MC3T3-E1 osteoblasts. An examination of the skeletons of mutated mice showed an early onset of cartilage formation and ossification, and increased postnatal bone formation characterized by an increase in the number of activated periosteal osteoblasts. Bone fracture healing was accelerated in mutated mice. CONCLUSION: This is the first demonstration of animals with enhanced BMP responsiveness in host cells, suggesting that endogenous basic calponin may play a negative role in an osteogenic programme.

Animals↗
PubMed1998

A model analysis of aftereffects of high-intensity DC stimulation on action potential of ventricular muscle.

The mechanism for aftereffects of high-intensity dc stimulation on ventricular muscle was studied by using Beeler-Reuter's action potential model. A leak conductance (Gpore, maximal value from 40 to 80 microS for 1 cm2 of membrane), which mimics reversible dielectric breakdown of the cell membrane by the shock, was incorporated into the model. To simulate resealing process, Gpore was assumed to decrease after the shock exponentially at a time constant (tau pore) of 5-50 s. The simulation results are qualitatively consistent with our experimental observations in guinea pig papillary muscle [1]; they include prolonged depolarization, diastolic depolarization or oscillation of membrane potential leading to a single or multiple spontaneous excitation. The phase-independence and shock intensity-dependence can also be reproduced. Analysis of current components has revealed that: 1) a large inward leak current (Ileak) is responsible for the prolonged depolarization; 2) time-dependent decay of outward current (IX1) in combination with Ileak and slow inward current (I(s)) results in diastolic depolarization or oscillation of membrane potential; 3) spontaneous excitation depends on an activation of I(s). These findings support our hypothesis that strong shocks (> 15 V/cm) will produce abnormal arrhythmogenic responses in ventricular muscle through a transient rupture of sarcolemmal membrane.

Action Potentials↗
PubMed1998

Mapping epileptic foci by the dipole tracing method in a brain tumor patient with olfactory seizures: comparison with intraoperative electrocorticograms.

We estimated the position of the epileptic foci in a case of brain tumor with olfactory seizures using the Dipole Tracing Method (DTM) and compared the results with electrocorticograms (ECoGs) recorded during surgical resection. The case was a 24-year-old male. Electroencephalograms (EEG) showed frequent focal spikes in the right temporal area. Magnetic resonance imaging revealed a tumor in the right hippocampus region. We analyzed the spikes using DTM with a CDT-1000 EEG analyzer. The locations of two independent foci were analyzed; one was thought to be in the right hippocampus and the other in the right superior temporal gyrus. When the ECoG was taken, the results were in very close correlation with those of DTM, demonstrating the accuracy of DTM in the estimation of the location of epileptic foci in epileptic seizures with brain lesions.

Adult↗
PubMed1998

Familial amyotrophic lateral sclerosis with widespread vacuolation and hyaline inclusions.

This report presents a familial amyotrophic lateral sclerosis (FALS) patient with widespread vacuoles and hyaline inclusions strongly immunostained with the anti-superoxide dismutase (SOD1) antibody. The overall pathologic similarity between our non-SOD1-linked FALS patient and transgenic mice expressing a mutated human SOD1 gene suggests that common pathogenetic mechanisms other than an SOD1 mutation exist in the development of these diseases.

Aged↗
PubMed1998

[Percutaneous ethanol and acetic acid injection for liver metastasis from colon cancer--two case reports].

Two cases of liver metastasis from colon cancer were treated by percutaneous ethanol (PEI) and acetic acid (PAI) injection for the recurrent lesion after surgery. Case 1 was a 60-year-old female who received sigmoidectomy with partial hepatectomy, and intraarterial 5-FU infusion was done after surgery. One year later, recurrence of liver tumor was detected, and PEI and PAI were performed for the metastatic lesions of the liver. Tumor regression and histopathological examination revealed coagulative necrosis. The patient died of lung metastasis 2 years and 10 months after treatment. Case 2 was a 58-year-old-male with ascending colon cancer and liver metastasis, who received surgery, and chemotherapy with intraarterial 5-FU infusion was continued. Four months later, recurrence of liver metastasis with elevation of serum CEA was noted. The patient received PEI three times and CEA decreased. Re-operation of hepatectomy revealed complete necrosis at the site of PEI. The patient has been alive for 1 year and 6 months with a new recurrence in the liver and is receiving repeated PEI therapy. PEI and PAI seem to be useful for the treatment of unresectable liver metastasis.

Acetic Acid↗
PubMed1998

Relationship between area under the concentration versus time curve of cyclosporin A, creatinine clearance, hematocrit value, and other clinical factors in Japanese renal transplant patients.

We evaluated the relationship between the area under the concentration versus time curve (AUC) of cyclosporin A (CsA) and several other clinical factors, because the clinical utility of AUC monitoring has been ambiguous. Fifty-four clinical time courses from 14 Japanese renal transplant patients during hospitalization, in the period from April 1990 to March 1997, were examined. In a bivariate regression analysis there was no correlation between the AUC and the daily dose of CsA (mg/kg/day) when the individual data or total series data were analyzed. In a chi-square test, the donor type of kidney (chi(2) = 25.254, df = 1, p = 0.0000) and renal function-related episodes, i.e. acute tubular necrosis, hemodialysis, hypertension, nephrotoxicity, or rejection (chi(2) = 13.982, df = 1, p = 0.0002) directly affected posttransplant renal function assessed by creatinine clearance, while episodes of hepatic function as assessed by the glutamate-pyruvate transaminase (GPT) activity level had no correlation with the posttransplant renal function evaluated according to creatinine clearance. In contrast, the renal function-related episodes significantly affected the AUC after renal transplantation (chi(2) = 4.934, df = 1, p = 0.0263), while hepatic function assessed by GPT did not. In a multivariate analysis, the creatinine clearance and obesity had significant positive correlations with the AUC, whereas the hematocrit had a significant negative correlation with the AUC. From these observations, we concluded that the dosage adjustment of CsA cannot be performed using the linear relationship between the daily oral dose and the AUC, and that renal function, obesity, and the CsA blood distribution properties affect the CsA pharmacokinetics after renal transplantation. Posttransplant renal function as well as obesity and CsA blood distribution properties are important factors to be considered when therapeutic monitoring is performed.

Adult↗
PubMed1998

Activation of protein phosphatase 1alpha promoter in ascites hepatoma cells.

We have already reported the nucleotide sequence of 5'-flanking region of rat PP1alpha gene and identified the promoter region in NIH3T3 cells. Here we determined the promoter activity of PP1alpha gene in ascites hepatoma cells and compared with that of hepatocytes. Reporter analysis showed that the promoter activity was enhanced in an ascites hepatoma AH13 compared with normal hepatocytes at two regions, -37 to -198 bp and -492 to -848 bp upstream of the translation start site. At -37 to -198 bp region with high GC content, binding of Sp1 was markedly increased in all of five ascites hepatomas examined. At -492 to -848 bp region, two bands were clearly detected in two of the five ascites hepatomas, AH13 and AH7974F, by gel shift analysis. These results strongly suggest that the increase in PP1alpha mRNA expression in ascites hepatomas is at least in part due to the enhanced promoter activity of PP1alpha gene.

Animals↗
PubMed1998

[Perioperative management for nephrectomy in a long-term hemodialysis patient with anticoagulants for coronary stent].

A 53-year old man on long-term hemodialysis (HD) with anticoagulant therapy was scheduled for nephrectomy due to renal cell carcinoma. Two months before surgery, a coronary stent had been placed due to right coronary artery disease. One week before surgery, percutaneous transmural coronary angioplasty (PTCA) was performed for unstable angina. Aggressive oral antiplatelet therapy (aspirin and ticlopidine) was absolutely required to maintain patency. Following withdrawal of the antiplatelets, unfractionated heparin (UFH) was titrated to an activated partial thromboplastin time (APTT) of 1.5 times greater than the control value. Maintenance UFH (800 U.h-1) was continued until the time of arrival in the operation room (activated clotting time (ACT) was 166 seconds). One hour after arrival, reduced dose of UFH (200 U.h-1) was reinfused, and ACT was 121 140 seconds. Hemodynamic change was minimized using balanced general anesthesia (nitrous oxide-isoflurane, fentanyl, midazolam and vecuronium) accompanied by nitroglycerin and diltiazem. There was no ischemic change on ECG or transesophageal echocardiography. Following surgery, the UFH dose was augmented (400 U.h-1), and the maintenance dose was attained 11 hours after surgery. HD on the second postoperative day was performed uneventfully. This hemodynamic stability might be come from the no water removal. Fourteen days after surgery, the patient was discharged without hemorrhagic complications or clinical ischemic events. We conclude that perioperative UFH infusion is not contraindicated for dialysis patient if strict ACT control is maintained.

Anticoagulants↗
PubMed1998

[Clinical application of ischemic microwave coagulation therapy for malignant liver tumor].

By means of ischemic coagulation of the hepatic artery and portal vein in a microwave coagulation experiment of in vivo swine [correction of bovine] liver, we confirmed approximate doubling of the coagulation diameter compared to the usual coagulation. Based on this fact, for treatment of patients with metastatic liver tumor, we developed an ischemic percutaneous microwave tumor coagulation method using IVR method and applied it in one case, and performed laparotomy microwave tumor coagulation in three cases. We performed the ischemic percutaneous microwave tumor coagulation method on one of the cases. Coagulation was performed for one minute at a dose of 100 W for treatment of metastatic liver tumor of 2 cm in diameter via laparotomy. The postoperative CT showed an extensive coagulation larger than 3 cm. A 2 cm liver tumor was coagulated under balloon ischemia of the hepatic vein and hepatic artery for 13 minutes at a dose of 60 W. The maximum coagulation diameter was 5 cm. Extensive coagulation was possible with percutaneous microwave tumor coagulation through ischemia.

Animals↗
PubMed1998

[Good response in case of hepatocellular carcinoma; a case report of interdisciplinary local therapy].

A 47-year-old male patient with chronic hepatitis had a high AFP level during the follow-up period. Abdominal CT revealed at S5, which led to a diagnosis of hepatocellular carcinoma. In August 1992, partial resection of S5 was performed, and ethanol was injected into the tumor at S2. In July 1993, recurrent tumors were observed at S5 and S3. PEIT was performed for each lesion. In December 1994, multiple recurrence was observed and 4 mg SMANCS was injected through the proper hepatic artery. In July 1995, another 4 mg of SMANCS was injected into the tumors. In June 1996, only a 20 mm lesion at S5 remained while the other lesions disappeared. Under general anesthesia, the patient underwent percutaneous microwave tumor coagulation. In December 1997, the AFP level was normal, and imaging revealed disappearance of the recurrent tumor. Selection of local therapy for hepatocellular carcinoma achieved long survival in our case considering the QOL and frequent therapy administration.

Antineoplastic Agents↗
PubMed1997

Transcriptional activation of the intercellular adhesion molecule 1 (CD54) gene by human T lymphotropic virus types I and II Tax is mediated through a palindromic response element.

In vitro infection of T cells with human T lymphotropic virus types I and II (HTLV-I and HTLV-II) resulted in constitutive expression of ICAM-1. Higher levels of ICAM-1 mRNA were expressed in HTLV-transformed cell lines (MT-2, MoT, C8166) when compared with uninfected T cell lines (A301). We demonstrate that this activation is conferred through a site on the ICAM-1 promoter that is activated in trans by the Tax protein of HTLV-I and HTLV-II. Enhanced promoter activity was detected when the ICAM-1 construct (-1162/+1) was transfected into HTLV-I-infected (MT-2), HTLV-II-infected (MoT, AI 1050), or an HTLV-I Tax-only-expressing (C8166) cell line as compared to the uninfected T cell line (A3.01). Cotransfection of the uninfected T cell line A3.01 with the ICAM construct along with Tax-I and Tax-II expression plasmid also resulted in increased promoter activity. Furthermore, experiments with deletion constructs of the ICAM-1 promoter region indicated that a region between -88 and -53 bp relative to the transcription start site is sufficient for Tax-inducible CAT expression. This segment includes an 11-bp palindromic segment (TTTCCGGGAAA) that has homology with the IFN-gamma and IL-6 response element. An 11-bp segment containing this regulatory region proved to be sufficient to confer Tax-I and Tax-II inducibility on a heterologous promoter (TK-CAT). Taken together these findings indicate that constitutive expression of ICAM-1 by HTLV-infected cells is influenced by the viral trans-activator protein Tax. This increased expression of ICAM-1 in response to the Tax protein may play an important role in the lymphoproliferation associated with HTLV infection.

Cell Line↗
PubMed1997

Morphologic difference of neuropil threads in Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy: a morphometric study.

Using Gallyas-Braak's silver stain, neuropil threads (NTs) in Alzheimer's disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) were analyzed morphologically and morphometrically. The NT density was highest in the cerebral cortical layer V in AD and CBD, and in the subcortical white matter in PSP. An overlaid, two-dimensional, camera lucida drawing revealed differences in the fine profile of NTs among these three disease groups. The differences were confirmed by computerized feature analysis which revealed differences in maximum length, breadth, Feret's angle and orientation of the NTs. Unlike a previous assumption that all NTs have a similar appearance, our study revealed that NTs in AD, CBD and PSP were distinctively different with respect to their morphology.

Aged↗