Skeletal muscle metastatic and pelvic leiomyosarcomas following hysterectomy.
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Aged↗
Biomedical subjects
T Mizuno
Publications and source records attributed to T Mizuno.
Clinical significance of immunohistochemically detectable lymph node metastasis in adenocarcinoma of the ampulla of Vater.
BACKGROUND: The aim of this study was to assess the impact of immunohistochemically identified lymph node metastasis on survival in patients with carcinoma of the ampulla of Vater. METHODS: Three hundred and twenty-six regional lymph nodes dissected from pancreatoduodenectomy specimens from 25 patients with ampulla of Vater carcinoma were immunostained with anticytokeratin antibody (CAM 5.2). The clinicopathological significance of immunohistochemically detectable lymph node metastasis was evaluated and compared with that of other potential prognostic factors. RESULTS: The frequency of lymph node involvement in relation to the total number of dissected lymph nodes increased from 5.5 per cent (18 of 326) using haematoxylin and eosin staining to 9.5 per cent (31 of 326) using cytokeratin immunostaining (P < 0.001). Lymph node involvement was revealed by haematoxylin and eosin staining in eight of 25 patients and by cytokeratin immunostaining in 11 of 25 patients (P = 0.006). Absence of immunohistochemically detectable lymph node metastasis was identified as an independent predictor of improved postoperative survival. CONCLUSION: Immunostaining of dissected lymph nodes adds additional information to data obtained by conventional haematoxylin and eosin staining when determining the prognosis of patients with carcinoma of the ampulla of Vater.
Adenocarcinoma↗
Small interfering RNA expression vector targeting hypoxia-inducible factor 1 alpha inhibits tumor growth in hepatobiliary and pancreatic cancers.
Hepatobiliary and pancreatic carcinomas are hypovascular tumors that can proliferate under hypoxic conditions. Recent reports have demonstrated that hypoxia-inducible factor 1 alpha (HIF1alpha) plays an important role in the survival of these cancers. Given these findings, the inhibition of the HIF1alpha pathway might prove to be a powerful tool in the treatment of these cancers. To inhibit HIF1alpha expression, we used small interference RNA (siRNA) expression vectors in this study. The transient transfection of siRNA expression vectors significantly reduced both HIF1alpha mRNA levels (13% of control) and protein levels (41% of control) and significantly inhibited the growth of cancer cell lines (P<0.05). VEGF, Glut1, and aldorase A expressions were also significantly reduced by transfection with these vectors (P<0.05), and we found that these vectors induced apoptosis but not cell cycle arrest. In a subcutaneous tumor model using nude mice, transfected MIA PaCa-2 cells, stably expressing siRNAs, barely formed tumors compared to control (P<0.05). This study thus demonstrates the usefulness of siRNA expression vector in targeting HIF1alpha and points to a potential clinical role in the treatment of pancreatic and hepatobiliary carcinomas.
Animals↗
Incremental limb hypometria.
To find out if patients with right hemisphere strokes (RHD) demonstrate a form of progressive or incremental limb hypometria (ILH), 11 RHD patients and eight matched controls were tested by having them draw a series of horizontal lines while blindfolded. Unlike controls, six RHD patients displayed an incremental decrease in the length of lines they drew, a sign of ILH. ILH might be a common source of disability and hinder rehabilitation efforts.
Aged↗
Production of interferon-gamma by microglia.
Neural cells do not usually interact with immune cells because of the lack of major histocompatibility complex (MHC) antigen expression. Interferon-gamma (IFN-gamma) enables this interaction via induction of MHC antigen expression in neural cells. Thus, IFN-gamma is a critical cytokine for the development of central nervous system (CNS) pathologies. IFN-gamma, however, is considered to be produced exclusively by lymphoid cells. Here, we show for the first time that murine microglia produce IFN-gamma in response to IL-12 and/or IL-18, using RT-PCR detection of IFN-gamma mRNA and Western blotting and immunohistochemical analysis for cytoplasmic expression of IFN-gamma. Stimulation of microglia with IL-12 and IL-18 resulted in MHC class II mRNA expression in microglia. Since IL-12 and IL-18 are produced in the CNS by glial cells, these cytokines may play a critical role in the initiation of neural-immune cell interaction and the induction of autoimmune processes in the CNS via induction of IFN-gamma and MHC antigens.
Animals↗
Clinical evaluation of cellulose porous beads for the therapeutic embolization of meningiomas.
BACKGROUND AND PURPOSE: Cellulose porous beads (CPBs) are a new, exceptionally uniformly sized, nonabsorbable embolic agent. We evaluated their efficacy in the preoperative embolization of meningiomas. METHODS: In 141 consecutive patients, we used CPBs (200-microm diameter) for the preoperative embolization of meningiomas. We selected patients whose tumors were > or =4 cm with 50% of blood to the tumor supplied by the external carotid artery (ECA). All patients underwent a provocation test before embolization. The percentage of blood supplied to the tumor by the internal carotid artery and ECA was determined angiographically. Nonenhanced areas on postembolization MR imaging were calculated. Intraoperative blood loss, units of blood transfusion, and hemostasis at the time of surgery were recorded for each patient. The interval between embolization and surgery was intentionally longer than 7 days. RESULTS: Of the 141 patients, 128 underwent CBP embolization. Eleven patients had positive provocation test results, and 2 had vasospasm; they were not CBP embolized. In 72% of the patients CBP embolization achieved reduction in the flow of the feeding artery by more than 50%. The nonenhanced area on MR imaging was not significantly correlated with the degree of ECA supply or devascularization. The interval between embolization and surgery was 8-26 days (mean, 9.9 days). The longer this interval, the greater was the tumor-softening effect and the rate of tumor removal. CONCLUSIONS: CPBs may be useful for the preoperative embolization of meningiomas. To increase the efficacy of CPB embolization, the interval to surgery should be at least 7 days.
Adult↗
Quantitative evaluation of cerebrovascular reactivity in brain tissue by a refill kinetic method of transcranial ultrasonic perfusion imaging: a comparison with Doppler sonography.
UNLABELLED: To confirm the reliability of a refill kinetic method of ultrasonic harmonic perfusion imaging (HPI) capable of quantifying separate parameters of microvascular blood flow velocity and volume in brain tissue, we evaluated acetazolamide (ACZ) cerebrovascular reactivity by transcranial HPI in comparison with Doppler sonography (TCD). Methods. HPI during continuous Levovist infusion with changing pulsing intervals (t) and TCD time-averaged maximum velocity (TAMX) in the middle and posterior cerebral arteries were evaluated before and after ACZ administration in 12 patients, 8 without and 4 with a temporal skull defect. Plateau value (A) and rise rate (beta) of intensity (I) represented by HPI time-intensity curves of I(t) = A(1 - e(-beta*t)) were analyzed on the axial diencephalic plane. RESULTS: 1) A significantly decreased in proportion to the region of interest location depth only in the intact skull cases. 2) Despite inter- and intra-individual data scattering, in correspondence with TAMX increases after ACZ, significant beta increases were more frequently identified than increases of A. CONCLUSIONS: Cerebral vasoreactivity analysis utilizing refill kinetics of transcranial HPI can potentially provide separate quantification based on microvascular blood velocity and volume (capillary patency) with consideration of depth-dependant ultrasound attenuation. This should be suitable for bedside evaluation of neurointensive care patients.
Acetazolamide↗
Optimization of aromatic side chain size complementarity in the hydrophobic core of a designed coiled-coil.
The coiled-coil structure plays an important roles, especially in protein assembly. Previously we constructed AAB-type heterotrimeric coiled-coils by manipulating the packing in the hydrophobic core using Trp and Ala residues, where one Trp and two Ala residues were placed in the hydrophobic core instead of three Ile residues. To optimize the packing complementarity in the hydrophobic core, we investigated the effects of introducing various aromatic amino acids on the formation of an AAB-type heterotrimeric coiled-coil, by circular dichroism, thermal stability, and nuclear magnetic resonance (NMR) studies. We found that the Phe residue was more suitable for heterotrimeric coiled-coil formation than the Trp residue, when combined with two Ala residues, whereas the Tyr and His residues did not induce the coiled-coil structure efficiently.
Amino Acid Sequence↗
Treatment of radiation-induced hemorrhagic duodenitis with argon plasma coagulation.
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Aged↗
Alternatively spliced transcripts of Fas mRNAs in feline lymphoid cells.
Fas belongs to the tumour necrosis factor receptor family and transduces the death signal after binding to the Fas ligand. Five feline lymphoma cell lines were shown, by reverse transcription-polymerase chain reaction, to express six species of Fas transcripts. Based on sequence comparison of these Fas transcripts with the genomic Fas gene, five of the six transcripts were found to be generated through alternative splicing and to encode five different Fas proteins lacking the transmembrane domain. We also detected such alternatively spliced transcripts in primary tumour tissues from cats with naturally occurring lymphoma. These results suggest a possible association of the alternatively spliced Fas variants with the pathogenesis of feline lymphoma.
Alternative Splicing↗
Binding of Cu(II) or Zn(II) in a de novo designed triple-stranded alpha-helical coiled-coil toward a prototype for a metalloenzyme.
We previously reported the IZ-3adH peptide, which formed a triple-stranded coiled-coil after binding Ni(II), Cu(II), or Zn(II). In this paper, we report the peptide, IZ-3aH, having a new metal binding specificity. The IZ-3aH peptide was found to bind Cu(II) and Zn(II) and form a triple-stranded coiled-coil. However, it did not bind Ni(II). Metal ion titrations monitored by circular dichroism revealed that the dissociation constants, K(d) were 9 microm for Zn(II) and 10 microm for Cu(II). The bound Cu(II) ion has a planar tetragonal geometry, where the coordination positions are three nitrogens of the His residues and one H(2)O.
Circular Dichroism↗
Quantitative analysis of Fas and Fas ligand mRNAs in a feline T-lymphoid cell line after infection with feline immunodeficiency virus and primary peripheral blood mononuclear cells obtained from cats infected with the virus.
Apoptosis is frequently observed in feline lymphocytes in association with feline immunodeficiency virus (FIV) infection. In this study, to investigate the mechanism of FIV-induced apoptosis, levels of Fas and Fas ligand mRNAs were measured by real-time reverse transcription-PCR. In a feline T-lymphoid cell line the amounts of Fas ligand mRNA increased along with the induction of apoptosis after in vitro infection with FIV. In PBMC collected from 10 cats naturally infected with FIV, Fas ligand mRNA levels were significantly higher than those in PBMC from five uninfected cats. These results indicate that the increased expression of Fas ligand may be involved in the induction of apoptosis of lymphocytes in FIV infection.
Animals↗
Dysferlin mutations in Japanese Miyoshi myopathy: relationship to phenotype.
OBJECTIVE: To study dysferlin gene mutations and genotype-phenotype correlations in Japanese patients with Miyoshi myopathy (MM). BACKGROUND: MM is an autosomal recessive distal muscular dystrophy that arises from mutations in the dysferlin gene. This gene is also mutated in families with limb girdle muscular dystrophy 2B. METHODS: The authors examined 25 Japanese patients with MM. Genomic DNA was extracted from the peripheral lymphocytes of the patients. The PCR products of each of 55 exons were screened by single strand conformation polymorphism or direct sequencing from the PCR fragments. RESULTS: The authors identified 16 different mutations in 20 patients with MM; 10 were novel. Mutations in Japanese patients are distributed along the entire length of the gene. CONCLUSIONS: Four mutations (C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent in this population, accounting for 60% of the mutations in this study. This study revealed that the G3370T mutation was associated with milder forms of MM and the G3510A mutation was associated with a more severe form.
Adult↗
A defect in a fatty acyl-CoA synthetase gene, lcf1+, results in a decrease in viability after entry into the stationary phase in fission yeast.
An intriguing mutant was isolated in Schizosaccharomyces pombe, which is defective in the maintenance of viability after entry into the stationary phase. In the logarithmic growth phase, the mutant cells grow at the same rate as the parental cells. Upon the onset of the stationary phase, however, the mutant cells lose viability very rapidly. It was found that this phenotype was due to a mutational lesion in the lcf1+ gene, which encodes a long-chain fatty acyl-CoA synthetase. The lcf1Deltamutant shows pleiotropic phenotypes, in that they are also sensitive to high temperature (37 degrees C) and to high salt concentrations (0.9 M KCl) in the medium. Based on the fact that Lcf1 is highly homologous to Faa1 and Faa4 of Saccharomyces cerevisiae, both of which have previously been suggested to play roles in the maintenance of endogenous acyl-CoA pools, the possible function of Lcf1 in S. pombe is discussed.
Coenzyme A Ligases↗
Gal11 is a general activator of basal transcription, whose activity is regulated by the general repressor Sin4 in yeast.
Mutations in SIN4, which encodes a global transcriptional regulator in Saccharomyces cerevisiae, have been suggested to lead to an increase in basal transcription of various genes by causing an alteration in chromatin structure. We reported previously that this activation of basal transcription occurs via a mechanism that differs from activator-mediated transcriptional enhancement. This finding prompted us to seek general activators of basal transcription by screening for extragenic suppressors of a sin4 mutation using PHO5, which is activated by the transcriptional activator Pho4, as a reporter gene. One of the mutations found, the semi-dominant ABE1-1, is described here. The ABE1-1 mutation reduced the enhanced basal transcription of PHO5 caused by the sin4 mutation, but did not impair Pho4-mediated activation of PHO5. The ABE1-1 mutation also suppressed the aggregation phenotype and the rough colony morphology of the sin4 mutant cells, while it exacerbated temperature sensitive growth and telomere shortening, suggesting that Abe1p is involved in the basal transcription not only of PHO5 but also of other diversely regulated genes. SWI1, which encodes a component of the Swi-Snf complex that has chromatin remodeling activity, was identified as a gene-dosage suppressor of the ABE1-1 mutation. ABE1-1 was found to be allelic to GAL11. These observations suggest that Gal11 acts as a general activator for the basal transcription of various genes, possibly by relieving torsional stress in chromatin, and that its function is repressed by the Sin4 protein.
Cloning, Molecular↗
Acetazolamide vasoreactivity evaluated by transcranial harmonic perfusion imaging: relationship with transcranial Doppler sonography and dynamic CT.
UNLABELLED: To establish the reliability and clinical significance of transcranial ultrasonic harmonic perfusion imaging (HPI), we evaluated HPI's relationships with transcranial Doppler (TCD) and with dynamic CT (DCT), during acetazolamide (ACZ) vasoreactivity tests. METHODS: The subjects were 12 neurological patients. Time-averaged maximum velocity (TAVMX) in the middle (MCA) and posterior cerebral arteries was measured by TCD. Time-intensity (-density) curves of HPI (DCT) after bolus intravenous contrast injections were created in 3 regions of interest (ROI) on the axial plane involving the temporal lobe, basal ganglia, and thalamus on both sides. Assessments of vasoreactivity were based on comparisons conducted before and after ACZ administration in terms of: a) relative changes (%delta) of the TCD TAVMX, b) HPI contrast area enlargement, c) %delta of calculated cerebral blood volume and flow of the HPI and DCT. RESULTS: 1) TCD vasoreactivity decrease in the left MCA tended to correlate with lower frequency of HPI contrast area enlargement on the left side. 2) HPI and DCT vasoreactivity tended to be disturbed in the same side ROIs. CONCLUSIONS: Transcranial HPI achieves repeatable non-invasive bedside evaluation of cerebrovascular reserve capacity through qualitative and quantitative measurements of brain tissue perfusion, and will have clinical value in pathophysiological follow-up and therapeutic effectiveness determination of neurointensive care patients.
Acetazolamide↗
Acetazolamide vasoreactivity in persistent vegetative state and vascular dementia evaluated by transcranial harmonic perfusion imaging and Doppler sonography.
UNLABELLED: To clarify the pathophysiological differences of the cerebrovascular reserve capacity in relation to cerebral cognitive impairments between persistent vegetative state (PVS) and vascular dementia (VD), we evaluated acetazolamide (ACZ) vasoreactivity testing by transcranial harmonic perfusion imaging (HPI) and Doppler sonography (TCD). METHODS: The subjects were 11 adult patients with severe cognitive impairments (4 PVS, 7 VD). TCD mean velocity (Vm) in the middle and posterior cerebral artery (MCA, PCA) and peak intensity (PI), area under curve (AUC), and mean transit time (MTT) analyzed by HPI time-intensity curves in the bilateral temporal lobe (TL), basal ganglia (BG), and thalamus (Th) were evaluated before and after ACZ administration. Resting values and relative changes (%delta) of TCD and HPI parameters were compared between PVS and VD. RESULTS: a) Resting values: There were no significant differences between the two groups. b) Vasoreactivity: 1) PVS: %delta Vm decreased in the left PCA and MCA. %delta PI/AUC/MTT decreased in the left TL and bilateral BG. 2) VD: %delta PI/AUC decreased in the right TL. %delta MTT tended to decrease in the right side. CONCLUSION: ACZ vasoreactivity tests by transcranial HPI and TCD allowed bedside, non-invasive, quantitative evaluation of the pathophysiology of cognitive function impairment and treatments, in relation to cerebrovascular reserve capacity in PVS and VD.
Acetazolamide↗
Endovascular coil trapping for ruptured vertebral artery dissecting aneurysms by using double microcatheters technique in the acute stage.
BACKGROUND: In the treatment of vertebral artery (VA) dissecting aneurysms, only proximal occlusion of the VA does not necessarily prevent rerupture. We evaluated the efficacy of coil trapping for the ruptured VA dissecting aneurysms using the double microcatheters technique. METHODS: We treated 11 patients who presented with subarachnoid haemorrhage (SAH) due to rupture of a VA dissecting aneurysm which did not involve the posterior inferior cerebellar artery at the site of dissection. All patients tolerated the balloon occlusion test. Within 3 days of the SAH, the dissection site was trapped with a Guglielmi detachable coil (GDC) using the double microcatheters technique. The proximal and distal sites of the dissecting aneurysm were embolized simultaneously. FINDINGS: GDC trapping at the affected site was successful in all 11 patients. Radiographic findings showed complete occlusion of the dissection site and patency of the unaffected artery. Although one patient experienced transient dysphagia, there were no major complications. INTERPRETATION: The double microcatheters technique is effective for coil trapping of ruptured VA dissecting aneurysms in selected patients. The risks posed by this simple technique are minimal, even in the acute stage.
Acute Disease↗