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Biomedical subjects

T Ishihara

Publications and source records attributed to T Ishihara.

At least 73 records · Page 4Linked to original sources

Two distinct populations of neurons expressing nitric oxide synthase mRNA in the female rat preoptic area: site specific changes induced by sex steroids.

Non-isotopic in situ hybridization histochemistry in the basal forebrain of gonadectomized juvenile female rats visualized neuronal nitric oxide synthase (nNOS) mRNA in two distinct cellular populations, one in the organum vasculosum of the lamina terminals (OVLT) and the other in the rostral preoptic area at the level of the anteroventral periventricular nucleus (rPOA). In the rPOA, digoxigenin-labeled nNOS mRNA positive cells were in close proximity to the cell body of gonadotropin-releasing hormone (GnRH) -immunoreactive neurons. In the OVLT, the labeled cells were in an area rich in GnRH fibers. In the frontal section of the rPOA, the labeled cells were distributed in an inverted V-shaped area over the third ventricle. Combined treatment with estradiol and progesterone caused a significant reduction in the number of nNOS mRNA positive cells in the inverted V-shaped area in the female rat rPOA. The treatment induced a luteinizing hormone surge at the time of sacrifice. In the OVLT, ovarian steroids had no effect on nNOS mRNA expression. The results indicate that nNOS mRNA expression in the rPOA is regulated by ovarian steroids in a site-specific manner.

Animals↗

Size and composition changes in diaphragmatic fibers in rats exposed to chronic hypercapnia.

OBJECTIVE: To test the hypothesis that chronic hypercapnia changes the composition of the respiratory muscle by continuous augmentation of ventilation. MATERIALS AND METHODS: Eighteen male Wistar rats were housed in 10% CO(2) in air for 19 weeks, and their minute ventilation V(E) was measured every 6 weeks. The diaphragm, excited at 19 weeks of exposure, was classified as fiber type I, IIa, or IIb. Cross-sectional areas of individual fibers were measured. Fibers with a target-like appearance on reduced nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR) stain also were counted. The data were compared with those of rats kept in room air. RESULTS: The mean (+/- SD) PaCO(2) after 19 weeks of sustained hypercapnia was 71.0 +/- 4.7 mm Hg. The V(E) remained at a high level until 12 weeks of exposure, and then it significantly decreased at week 18. In a comparison with the control rats, a larger number of type I fibers and a smaller number of type IIb fibers were found in the diaphragm of the chronically hypercapnic rats. In addition, the latter group's cross-sectional area revealed fibers of a significantly smaller diameter. Target-like fibers were observed in 5% of the NADH-TR-stained fibers in the chronically hypercapnic rats but were not seen in the control rats. CONCLUSION: By increasing the ratio of fatigue-resistant fibers, the diaphragm was able to adapt to a sustained load induced by hypercapnia. However, this adaptive process was accompanied by a degenerative change in the tissue.

Animals↗

Cerebral amyloid angiopathy associated with hemorrhage: immunohistochemical study of 41 biopsy cases.

The relationship between cerebral amyloid angiopathy and hemorrhage was investigated by an immunohistochemical study of biopsy cases to characterize the involvement of amyloid beta-protein, apolipoprotein E, and cystatin C in cerebral amyloid angiopathy associated with hemorrhage. The amyloid-laden vessels were examined in biopsy specimens from 41 surgical cases of sporadic cerebral amyloid angiopathy (36 cases with hemorrhage and 5 cases without hemorrhage), using immunohistochemical staining with antibodies against amyloid beta-protein, apolipoprotein E, cystatin C, and alpha-smooth muscle actin. The relationship between the occurrence, recurrence, and enlargement of the hemorrhage, and the semiquantitative estimation of the cerebrovascular amyloid-related protein deposition was analyzed using Fisher's exact test. Severe amyloid beta-protein (p < 0.013) and apolipoprotein E (p < 0.013) immunoreactivity were risk factors for the occurrence of the hemorrhage. Severe cystatin C immunoreactivity was a risk factor for the occurrence (p < 0.002) and enlargement (p < 0.014) of the hemorrhage, and tended to induce recurrent hemorrhage (p < 0.103). In addition, loss of the vascular smooth muscle was observed in the intensely amyloid-laden vascular walls that showed cystatin C-immunoreactivity. The present study indicates that intense amyloid beta-protein deposition with cystatin C deposition weakens the cerebrovascular walls, and that cystatin C deposition is a strong predictor of hemorrhage in cerebral amyloid angiopathy.

Aged↗

Homozygous serum amyloid P component-deficiency does not enhance regression of AA amyloid deposits.

Serum amyloid P component (SAP) is a common protein constituent of all types of amyloid deposits. Using SAP-deficient mice generated through gene targeting, we and others have shown that SAP significantly promotes amyloid deposition. It has been speculated that SAP protects amyloid fibrils from degradation by coating their exterior surface. To assess potential ways of treating individuals with amyloidosis, we examined the persistence of splenic AA amyloid fibrils in SAP-deficient and wild-type mice. No enhancement in the rate of regression of splenic AA amyloid was observed in the SAP-deficient mice relative to wild-type mice. These results present, for the first time, evidence that lack of SAP in AA amyloid deposits does not enhance regression of the deposits in vivo and suggest that dissociation of bound SAP from AA amyloid deposits would not significantly accelerate regression of the deposits in vivo.

Amyloidosis↗

[Pathophysiological diagnosis of facial paralysis using 3-D MRI].

Bilateral facial paralysis(facial diplesia) is often observed in Guillain-Barré syndrome(GBS) and Fisher's syndrome (FS). We tried to observe injured facial nerves using three-dimensional(3-D) MRI in facial diplesia due to GBS and its variants and examined function of blood nerve barrier and clinical use of 3-D MRI for detecting injured facial nerves. In the four patients with GBS and its variants(GBS three cases, FS one case), while routine brain MRI did not show any abnormal findings, contrast-enhanced 3-D MRI revealed Gd-enhancement of the facial nerves. On the other hand, only one case showed visualization using contrast-enhanced 3-D MRI in twelve cases of Bell's palsy. Therefore, it may be presumed that the reason why the significantly higher rate of visualization in facial paralysis in GBS and its variants than in Bell's palsy is attributable to a difference in the mechanism of injury or the extreme seriousness of the disease. In conclusion, the observation of facial nerve using 3-D MRI was very useful to know the condition of the facial diplesia in GBS and its variants.

Adult↗

[A case of intrasellar meningioma mimicking pituitary adenoma].

The authors report a patient with a rare intrasellar meningioma mimicking pituitary adenoma. A 60-year-old man was admitted to our hospital for evaluation of general fatigue. He had no neurological deficit including visual function. Endocrinological tests revealed panhypopituitarism. The craniogram showed slight enlargement of the sella turcica with thinning of the dorsum sellae. CT scan and MR imaging demonstrated a homogeneously enhanced intrasellar mass with slight suprasellar extension. Partial removal of the mass was performed via the transsphenoidal approach because it was extremely firm and hemorrhagic. Histological diagnosis was transitional meningioma. The patient has been well for two years after surgery without tumor progression on MR imaging. It is mandatory to distinguish intrasellar meningioma from pituitary adenoma preoperatively because of marked difference in their treatment strategies. Despite recent advances in neurodiagnostic imaging, it may still be difficult to differentiate pituitary adenoma from intrasellar meningioma. When we re-evaluated the MR imaging, we recognized that the tumor had demonstrated specific findings, ruling out pituitary adenoma, namely bright and homogeneous enhancement, dense enhancement in the early phase on the dynamic MR study, and flow void signal within the mass. The authors emphasize that careful evaluations of MR imaging will allow the correct preoperative diagnosis in patients with intrasellar meningioma mimicking pituitary macroadenoma.

Adenoma↗

[AA amyloidosis].

Explore the source record for details and available documents.

Amyloidosis↗

Tryptanthrin inhibits nitric oxide and prostaglandin E(2) synthesis by murine macrophages.

Nitric oxide (NO) and prostaglandins have been implicated in the pathogenesis of several inflammatory diseases. In this study, we investigated the effect of tryptanthrin (6,12-dihydro-6, 12-dioxoindolo-(2,1-b)-quinazoline), an antimicrobial and antitumoral plant compound isolated from Porigonum tinctorium, on NO and prostaglandin E(2) production by interferon-gamma and lipopolysaccharide-stimulated murine macrophage-like RAW 264.7 cells. Tryptanthrin markedly inhibited both NO and prostaglandin E(2) production in a dose-dependent manner. Tryptanthrin at 20 microM fully inhibited expression of inducible NO synthase, suggesting that the inhibitory effect on NO synthesis was mediated by inhibited expression of the enzyme. On the other hand, tryptanthrin had no effect on the levels of cyclooxygenase-2 protein, but inhibited cyclooxygenase enzyme activity with a ICM(50) value of 1.5 microM. Thus, tryptanthrin has the dual functions of inhibiting both NO and prostaglandin E(2) production by activated macrophages, suggesting that tryptanthrin exhibits anti-inflammatory properties.

Animals↗

Pressure-controlled ventilation via a mini-tracheostomy tube for patients with neuromuscular disease.

The authors managed 10 patients with Duchenne muscular dystrophy (DMD) and five with MG with pressure-controlled ventilation (PCV) via mini-tracheostomy tube (MTT). The arterial partial pressure of CO2 (PaCO2) of the patients with DMD decreased after conversion to PCV via MTT from biphasic positive airway pressure (BIPAP) or a body ventilator. The MG patients could be converted from conventional volume-controlled ventilation to PCV via MTT. PCV via MTT achieves more effective ventilation than either BIPAP or a body ventilator and is as effective as ventilation via a conventional tracheal tube.

Adolescent↗

Strand invasion by mixed base PNAs and a PNA-peptide chimera.

Peptide nucleic acid oligomers (PNAs) have a remarkable ability to invade duplex DNA at polypurine-polypyrimidine target sequences. Applications for PNAs in medicine and biotechnology would increase if the rules governing their hybridization to mixed base sequences were also clear. Here we describe hybridization of PNAs to mixed base sequences and demonstrate that simple chemical modifications can enhance recognition. Easily synthesized and readily soluble eight and 10 base PNAs bind to plasmid DNA at an inverted repeat that is likely to form a cruciform structure, providing convenient tags for creating PNA-plasmid complexes. PNAs also bind to mixed base sequences that cannot form cruciforms, suggesting that recognition is a general phenomenon. Rates of strand invasion are temperature dependent and can be enhanced by attaching PNAs to positively charged peptides. Our results support use of PNAs to access the information within duplex DNA and demonstrate that simple chemical modifications can make PNAs even more powerful agents for strand invasion. Simple strategies for enhancing strand invasion should facilitate the use of PNAs: (i) as biophysical probes of double-stranded DNA; (ii) to target promoters to control gene expression; and (iii) to direct sequence-specific mutagenesis.

Base Pair Mismatch↗

Purification of a novel serine proteinase inhibitor from the skeletal muscle of white croaker (Argyrosomus argentatus).

A novel serine proteinase inhibitor has been purified to homogeneity from the skeletal muscle of white croaker (Argyrosomus argentatus). The purification was carried out by ammonium sulfate fractionation, DEAE-Sephacel, heating treatment followed by column chromatographies on SP-Sepharose, Sephadex G-150 and gel-filtration high performance liquid chromatography. The molecular mass of the inhibitor was 55 kDa as estimated by SDS-PAGE and gel filtration. It specifically inhibited a myofibril-bound serine proteinase (MBSP) isolated from the skeletal muscle of lizard fish (Saurida wanieso). No inhibition, however, was detected toward other serine proteinases such as bovine trypsin, bovine chymotrypsin and a myofibril-bound serine proteinase from carp (Cyprinus carpio) muscle. Interestingly, the sequences of tryptic digested peptide fragments of MBSPI revealed high identity to that of porcine phosphoglucose isomerase (PGI) (76%) and other PGIs. Furthermore, purified MBSPI exhibits PGI activity, suggesting the inhibitor is a protein closely related to PGI. When rabbit muscle PGI was investigated, it also specifically suppressed the activity of MBSP. It thus strongly suggests that MBSPI is actually PGI and conversely, PGI is a specific inhibitor toward myofibril-bound serine proteinase(s).

Amino Acid Sequence↗

IL-18 prevents the development of chronic graft-versus-host disease in mice.

The development of chronic graft-versus-host disease (GVHD), which is induced by the transfer of DBA/2 spleen cells into (C57BL/6 x DBA/2)F1 (BDF1) mice, is closely related to diminished donor anti-host CTL activity and host B cell hyperactivation. Therefore, an approach which activates donor CD8+ T cells or suppresses donor CD4+ T cell-host B cell interaction may have clinical utility in the treatment of chronic GVHD. We have previously demonstrated that IL-18 induces the development of naive CD8+ T cells into type I effector cells in DBA/2 anti-BDF1 MLC. In this paper we examined the effect of IL-18 administration on the development of chronic GVHD in mice. The treatment was started before or after the onset of clinical evidence of the disease. Regardless of the treatment schedule, IL-18 significantly decreased immunological parameters indicative of chronic GVHD, such as elevated serum IgG antinuclear Abs, IgG1, and IgE levels, and host B cell numbers and their activation. Importantly, IL-18-treated mice did not show the same acute GVHD-like symptoms reported for IL-12 treatment, because there was no weight loss, death, or severe immunodeficiency as indicated by a decrease in IL-2 and IFN-gamma production by Con A-stimulated spleen cells. In contrast, IL-18 treatment partially but significantly restored the production of these cytokines. Data further suggested that these IL-18-mediated therapeutic effects may be due to the induction of donor CD8+ CTL, the decrease in donor CD4+ T cell numbers, and a down-regulation of host B cell MHC class II expression. Thus, our results suggest that IL-18 has beneficial effects in the prevention and treatment of chronic GVHD.

Acute Disease↗

Cenozoic motion between East and West Antarctica

The West Antarctic rift system is the result of late Mesozoic and Cenozoic extension between East and West Antarctica, and represents one of the largest active continental rift systems on Earth. But the timing and magnitude of the plate motions leading to the development of this rift system remain poorly known, because of a lack of magnetic anomaly and fracture zone constraints on seafloor spreading. Here we report on magnetic data, gravity data and swath bathymetry collected in several areas of the south Tasman Sea and northern Ross Sea. These results enable us to calculate mid-Cenozoic rotation parameters for East and West Antarctica. These rotations show that there was roughly 180 km of separation in the western Ross Sea embayment in Eocene and Oligocene time. This episode of extension provides a tectonic setting for several significant Cenozoic tectonic events in the Ross Sea embayment including the uplift of the Transantarctic Mountains and the deposition of large thicknesses of Oligocene sediments. Inclusion of this East-West Antarctic motion in the plate circuit linking the Australia, Antarctic and Pacific plates removes a puzzling gap between the Lord Howe rise and Campbell plateau found in previous early Tertiary reconstructions of the New Zealand region. Determination of this East-West Antarctic motion also resolves a long standing controversy regarding the contribution of deformation in this region to the global plate circuit linking the Pacific to the rest of the world.

Journal Article↗

Biliary excretion of TT virus (TTV).

A novel DNA virus (TT virus; TTV) was isolated from a patient with post-transfusion hepatitis of unknown etiology. If TTV replicates in the liver, TTV may appear in the bile. In the present study, to clarify whether fecal-oral infection occur via biliary excretion, the presence of TTV DNA was assessed in paired serum and bile samples collected from 28 patients with obstructive jaundice without parenchymal liver disease. TTV DNA was detected by polymerase chain reaction (PCR) using semi-nested primers, and quantified by Real Time Detection PCR (RTD-PCR). The nucleotide sequence of isolates TTV DNAs was also determined and the sequences were compared between serum and bile samples. Among 28 patients, 7 were positive for TTV DNA in both samples, and 3 and 2 were positive in serum and bile respectively. Of 7 patients positive for TTV DNA in both samples, the TTV DNA titer was higher in serum of 4 patients and in bile of 1 patient. Among 7 patients positive for TTV DNA in serum and bile, 6 had the same sequence in both samples. Multiple distinct types of TTV DNA clones were isolated from serum in 2 patients and from bile in 4 patients. In conclusion, TTV DNA is detected frequently in bile from patients with obstructive jaundice, suggesting a fecal-oral route of infection and high prevalence of asymptomatic TTV carriers. TTV DNA was detected only in serum from some patients, suggesting that replication of TTV may occur in other organs as well as in the liver.

Aged↗

Association between the expression of mast cell chymase and intraperitoneal adhesion formation in mice.

BACKGROUND: Adhesion formation is a major source of postoperative morbidity and mortality. Mast cells and their major protease, chymase, have been shown to participate in the healing process as well as in tissue remodeling. We aimed to identify the role of mast cells in intraperitoneal adhesion formation and to assess whether there is an association between the expression of mast cell chymase and adhesion formation. MATERIALS AND METHODS: Both mast cell-deficient W/W(V) mice and congenic +/+ mice received a standardized lesion produced by cecal scraping and the application of 95% ethanol. Adhesions were assessed blindly 1 week later using a standardized scale. In addition, histamine content, mast cell numbers, and chymase activity in cecum as well as at the healing sites were evaluated before and 7 days after surgical injury. RESULTS: A significant reduction in adhesion formation was seen in mast cell-deficient W/W(V) mice (P < 0.05). In the normal cecum, histamine content did not significantly differ between W/W(V) and +/+ mice. Chymase activity in cecum was detected in control +/+ mice, but not in W/W(V) mice. Mast cell numbers and chymase activity levels at the healing sites of +/+ mice were significantly increased 7 days after surgery. CONCLUSIONS: Our results indicate that mast cells contribute to intraperitoneal adhesion formation in mice, and suggest that chymase originating from mast cells is important in the development of adhesions.

Animals↗

Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein.

Coding region and intronic mutations in the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome 17. Some of these mutations lead to an overproduction of tau isoforms with four microtubule-binding repeats. Here we have expressed the longest four-repeat human brain tau isoform in transgenic mice under the control of the murine Thy1 promoter. Transgenic mice aged 3 weeks to 25 months overexpressed human tau protein in nerve cells of brain and spinal cord. Numerous abnormal, tau-immunoreactive nerve cell bodies and dendrites were seen. In addition, large numbers of pathologically enlarged axons containing neurofilament- and tau-immunoreactive spheroids were present, especially in spinal cord. Signs of Wallerian degeneration and neurogenic muscle atrophy were observed. When motor function was tested, transgenic mice showed signs of muscle weakness. Taken together, these findings demonstrate that overexpression of human four-repeat tau leads to a central and peripheral axonopathy that results in nerve cell dysfunction and amyotrophy.

Animals↗