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T Igarashi

Publications and source records attributed to T Igarashi.

At least 91 records · Page 5Linked to original sources
PubMed2001

Involvement of granule-mediated apoptosis in the cyclic changes of the normal human endometrium.

Our objective is to investigate the involvement of granule-mediated apoptosis in the cyclic changes of the endometrium. We demonstrated the localization of CD56, perforin, granzyme B and caspase-3 in the endometrium by immunohistochemistry. We also confirmed the localization of perforin by immuno-electron microscopy, and demonstrated apoptosis in endometrial glandular cells by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and electron microscopy. Uterine CD56-positive natural killer (NK) cells expressed perforin and granzyme B in its cytoplasm. Uterine NK cells increased significantly in the endometrial stroma during the secretory phase, and peaked during the late secretory phase. These cells started decreasing in number during the menstrual period. In endometrial glandular cells, caspase-3 and TUNEL-positive cells increased significantly from the late secretory phase, with apoptosis reaching a peak during the menstrual period. Using electron microscopy, we observed uterine NK cells with chromatin rich, segmented nuclei and intracytoplasmic granules in the stroma obtained from late secretory phase endometria. These cells extended projections to the lining of endometrial glandular cells and attached to form a cell-to-cell contact. In addition, nuclear chromatin was observed to have already cohered and small cytoplasmic organelles were beginning to disappear, suggesting that these endometrial glandular cells were undergoing apoptosis. Utilizing immuno-electron microscopy, intracytoplasmic granules in uterine NK cells were stained with anti-perforin antibody. The findings of this study suggest that granule-mediated apoptosis in endometrial glandular cells induced by NK cells expressing perforin and granzyme B may be associated with the onset of menstruation.

Adult↗
PubMed2001

Retinoic acids repress the expression of ETS-1 in endothelial cells.

The transcription factor ETS-1 expressed in endothelial cells (ECs) regulates angiogenesis by inducing MMP-1, MMP-3, MMP-9, u-PA and integrin beta3 in endothelial cells (ECs). Here, we examined whether antiangiogenic retinoic acids affect the expression of ETS-1 in ECs. The expression of ets-1 mRNA was up-regulated in sparse to subconfluent ECs and down-regulated in confluent ECs. When confluent ECs were stimulated with basic fibroblast growth factor (bFGF), ets-1 mRNA was induced. All-trans retinoic acid (ATRA) as well as 9-cis retinoic acid reduced the augmented expression of ets-1 mRNA in both subconfluent ECs and bFGF-treated confluent ECs. This inhibitory effect of ATRA was dose dependent and was evident at a concentration as low as 10(-7) M. ATRA did not alter the stability of ets-1 mRNA. Moreover, promoter analysis indicated that ATRA repressed the expression of ets-1 mRNA at transcriptional level. As a result, ATRA reduced the binding of ETS-1 protein to the ETS binding motif. These results indicate that the anti-angiogenic effect of retinoic acids is mediated at least in part by the transcriptional repression of ets-1 mRNA in ECs.

Alitretinoin↗
PubMed2001

An inferior mesenteric-caval shunt via the internal iliac vein with portosystemic encephalopathy.

We report here a case of an unusual extrahepatic portosystemic venous shunt in a 37-year-old woman without liver cirrhosis or portal hypertension, who developed portal systemic encephalopathy. Angiography demonstrated an inferior mesenteric-caval shunt characterized by the presence of direct communication of the inferior mesenteric vein with the left internal iliac vein. After the treatment with percutaneous transcatheter embolization of the shunt via a femoral vein approach using coils, she had no episode of portal systemic encephalopathy.

Adult↗
PubMed2001

Assessment of gadolinium-enhanced time-resolved three-dimensional MR angiography for evaluating renal artery stenosis.

OBJECTIVE: The purpose of this study was to assess the image quality of gadolinium-enhanced time-resolved three-dimensional (3D) MR angiography and to evaluate its accuracy in revealing renal artery stenosis. SUBJECTS AND METHODS: Thirty-nine patients underwent MR angiography using an ultrafast 3D Fourier transform spoiled gradient-recalled acquisition in the steady state (TR/TE range, 2.6/0.7--0.8). Five seconds after administration of 15--20 mL gadodiamide hydrate, four or five consecutive data sets with imaging times of 7.0--7.6 sec were acquired during a single breath-hold. A timing examination was not performed. Image quality was assessed using quantitative analysis (signal-to-noise, contrast-to-noise, and venous-to-arterial enhancement ratios) and qualitative analysis (presence of venous overlap, presence of artifacts, and degree of renal arterial enhancement). MR angiography depiction of the renal artery stenosis was evaluated using conventional angiography as the standard of reference. RESULTS: On the best arterial phase, average aortic signal-to-noise ratio (+/-SD) was 74.5 +/- 24.4, aorta-to--inferior vena cava contrast-to-noise ratio was 70.8 +/- 23.4, and inferior vena cava--to-aorta venous-to-arterial enhancement ratio was 0.03 +/- 0.04. No venous overlap was seen in 38 of 39 patients. Substantial enhancement of renal arteries was seen in all patients without any noticeable artifacts. MR angiography correctly depicted the degree of stenosis in 44 of 47 normal arteries, 13 of 16 mildly stenotic arteries, five of five moderately stenotic arteries, three of four severely stenotic arteries, and one of one occluded artery. Sensitivity and specificity for revealing greater than 50% stenosis was 100%. CONCLUSION: Time-resolved 3D MR angiography can provide high-quality arteriograms. Its performance in revealing renal artery stenosis is comparable with that of conventional angiography.

Adult↗
PubMed2001

The impact of a 4 cm. cutoff point for stratification of T1N0M0 renal cell carcinoma after radical nephrectomy.

PURPOSE: The 1997 TNM classification defines T1 tumors as those smaller than 7 cm. Recently, a cutoff point of 4 cm. has been proposed to create a subclass of T1 tumors. We evaluated the validity of this cutoff point by assessing the pathological findings and prognoses of patients with T1N0M0 renal cell carcinoma following radical nephrectomy. MATERIALS AND METHODS: We reviewed the hospital charts of 333 patients with T1N0M0 tumors, followed as long as 282 months (median 63) after radical nephrectomy. The validity of tumor size cutoff point for predicting survival outcome was tested in relation to other prognostic factors, including patient age, tumor position, nuclear grade, tumor histopathology and degree of microscopic venous invasion. RESULTS: During followup 32 patients (9.6%) had tumor recurrence and 21 (6.3%) died of renal cell carcinoma. A 5 cm. cutoff point maximized the differences in cancer specific survival rates and a 4 cm. cutoff point maximized the differences in disease-free survival rates. Tumor size was directly related to microscopic venous invasion and nuclear grade, which are significant prognostic factors, and a 4 cm. cutoff point enhanced these relationships. CONCLUSIONS: Tumor size is an important prognostic factor for patients with T1N0M0 renal cell carcinoma. A cutoff point of 4 cm. is practical for dividing the T1N0M0 classification into T1a and T1b subclasses.

Adult↗
PubMed2001

Phase I and pharmacological study of a new camptothecin derivative, exatecan mesylate (DX-8951f), infused over 30 minutes every three weeks.

PURPOSE: A Phase I study of exatecan, a new water-soluble camptothecin derivative, was conducted to determine the maximum tolerated dose and a recommended dose, according to an internationally standardized core protocol. Pharmacological profiles of lactone and total (lactone + carboxylate) exatecan were also investigated. PATIENTS AND METHODS: Fifteen patients with advanced solid malignancies were treated with 3, 5, and 6.65 mg/m(2) of exatecan infused over 30 min every 3 weeks. Concentrations of lactone, total drug, and a metabolite in plasma and urine were determined during the first course. RESULTS: Dose-limiting neutropenia and liver dysfunction were observed in two of six patients at 6.65 mg/m(2), but no grade 3 or worse diarrhea was observed. Emesis was moderate, and no grade 3 or worse nausea and vomiting were observed at a recommended dose of 5 mg/m(2), with prophylactic use of granisetron. Pharmacokinetics were linear and had moderate variability; clearances of lactone and total drug were 6.8 +/- 2.8 and 2.1 +/- 1.1 (mean +/- SD) l/h/m(2), respectively. The ratio of lactone concentration to total drug concentration in plasma decreased from 0.81 +/- 0.06 at the end of infusion to 0.15 +/- 0.06 10 h after the infusion. The lactone:total ratio of drug exposure was 0.30 +/- 0.08, ranging from 0.16 to 0.43. Neutropenia was related to the drug exposure of both lactone and total drug. CONCLUSIONS: The recommended dose of exatecan infused over 30 min every 3 weeks is 5 mg/m(2), with a favorable toxicity profile of mild and infrequent diarrhea. Interpatient variability of pharmacokinetics was similar to or smaller than that with other camptothecin derivatives.

Adult↗
PubMed2001

Fetal DNA diagnosis from maternal blood: PEP-TaqMan PCR analysis of a single nucleated erythrocyte (NRBC).

Development of a real-time quantitative TaqMan PCR assay permits the high-quality analysis of DNA or RNA. This study demonstrates the successful detection of single locus genes from single NRBCs, retrieved by micromanipulation of cells on a blood smear slide. Quantitative data in relation to the concentration of a single locus DNA amplified by PEP from a single NRBC are also provided. In summary, a PEP-TaqMan system can potentially be a powerful tool for noninvasive fetal DNA diagnosis through the use of maternal blood.

Cell Nucleus↗
PubMed2001

[Epiduroscopy in patients with chronic low back pain without remarkable findings on magnetic resonance imaging].

Two patients with chronic low back pain and sciatica failed to respond to conservative treatments. In these patients, magnetic resonance imaging (MRI) showed no remarkable findings corresponding to their symptoms. We treated these patients using epiduroscopy. Epiduroscopic visualization of the spinal canal permits efficient adhesiolysis and irrigation. One patient got better after two epiduroscopic procedures, and the other did not. Epiduroscopy may be an effective, minimally invasive treatment as well as examination for patients with chronic low back pain without remarkable findings on MRI.

Adult↗
PubMed2000

2000 Volvo Award winner in basic science studies: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats.

STUDY DESIGN: This study tested the hypothesis that the 17-kDa form of tumor necrosis factor-alpha is the pathophysiologic agent expressed by herniated nucleus pulposus in vivo that is primarily responsible for the histologic and behavioral manifestations of experimental sciatica associated with herniated lumbar discs. OBJECTIVE: The authors determined the molecular weight and concentration of active tumor necrosis factor-alpha in rat herniated disc and used exogenous tumor necrosis factor-alpha at the same molecular weight to study its neuropathologic effect on rat nerve root and dorsal root ganglion preparations in vivo. SUMMARY OF BACKGROUND DATA: Expressed by herniated nucleus pulposus in culture, tumor necrosis factor-alpha causes neuropathologic injury in nerve roots and neuropathic pain states in which mechanical allodynia is seen in response to peripheral stimuli. METHODS: Western blotting was used to identify the molecular weight of the operative tumor necrosis factor-alpha protein form, and measures of optical density were used for semiquantitative determination of concentration. Plastic-embedded nerve roots and dorsal root ganglion were used for neuropathologic evaluation, and von Frey stimulation was used to quantify mechanical allodynia. RESULTS: The 17-kDa form of tumor necrosis factor-alpha is expressed by herniated nucleus pulposus at a concentration of approximately 0.48 ng per herniated rat lumbar disc. Exogenous tumor necrosis factor-alpha applied in vivo to rat nerve roots produced neuropathologic changes and behavior deficits that mimicked experimental studies with herniated nucleus pulposus applied to nerve roots. CONCLUSIONS: The data reinforce other evidence that tumor necrosis factor-alpha is involved in mechanisms of neuropathic pain.

Animals↗
PubMed2000

Activation of coagulation in C57BL/6 mice given verotoxin 2 (VT2) and the effect of co-administration of LPS with VT2.

To obtain better insight into the pathogenesis of verotoxin-producing Escherichia coli-associated diseases, in this study, we explored the effect of verotoxin 2 (VT2) on coagulation in an animal model. After being given VT2 (50 ng/kg, lethal dose), C57BL/6 mice showed progressively increasing expression of TF mRNA in the kidney and brain and elevated plasma levels of thrombin-antithrombin III complex (TAT), normotest, fibrinogen, and PAI-1 paralleling the disease course over 24 hours; platelet counts were decreased at 48 hours with hemorrhage in the kidney and brain. Co-administration of lipopolysaccharide (LPS, 0.5 mg/kg) with VT2 (50 ng/kg) exhibited more prominant and/or prolonged increase in not only expression of TF and PAI-1 mRNAs in the kidney and brain but also plasma levels of TAT, fibrinogen, and PAI-1 and was associated with more remarkable hemorrhage in the tissues. Although VT2 (5 ng/kg) was not a lethal dose, co-administration of LPS (0.5 mg/kg) with VT2 (5 ng/kg) enhanced the susceptibility to VT2, resulting in more prolonged elevation of TAT levels during the first 24 hours than that in the LPS group and a second elevation at 72 hours, followed by death. Plasma IL-1beta level reached a maximum at 24 hours after VT2 (50 ng/kg) injection prior to the increase in TAT levels, whereas the increase in TNFalpha level immediately after injection was associated with the increase in PAI-1 mRNA. These observations indicate that the activation of coagulation by VT2 may occur through a mechanism different from that used by LPS, since plasma TAT levels rose in the mice immediately after LPS injection and returned to normal over 36 hours.

Animals↗
PubMed2000

Targeted and stable gene delivery into muscle cells by a two-step transfer system.

We developed a muscle-specific gene delivery system based on two-step gene transfer. The first step involved adenovirus-mediated transfer of the ecotropic retrovirus receptor (EcoRec) gene driven by the muscle-specific desmin promoter. Both human primary myoblasts and fibroblasts were efficiently transduced with this adenovirus vector. However, expression of EcoRec was detected only in myoblasts. In the second step, EcoRec-expressing myoblasts could be stably transduced with the ecotropic retroviral vector with the beta-galactosidase gene. Approximately 15% of myoblasts were transduced by this two-step strategy. When the transduced myoblasts were differentiated into myotubes, extensive cell-cell fusion occurred, and the apparent number of beta-galactosidase-positive cells increased to 28%. These results indicate that our two-step gene delivery system could be used for targeted and stable gene transfer into muscle cells.

Adenoviridae↗
PubMed2000

Simple method for determination of the active metabolite of the inotropic drug pimobendan in rat liver microsomes.

A rapid and sensitive high-performance liquid chromatographic method for quantitation of the O-demethylated active metabolite formed in a liver microsomal assay system has been developed. The metabolite was separated on an Inertsil ODS-2 column and quantitated by fluorescence detection (excitation at 338 nm, emission at 405 nm). The retention times for pimobendan and its metabolite were 5.6 and 2.8 min, respectively. The intra- and inter-assay relative standard deviations in the measurement of pimobendan O-demethylase activity at the substrate concentrations of 1 microM and 500 microM were 2.0%, 6.8%, 2.1% and 5.6%, respectively, and the limit of detection was 0.1 ng for the demethylated metabolite.

Animals↗
PubMed2000

Application of nucleus pulposus to the nerve root simultaneously reduces blood flow in dorsal root ganglion and corresponding hindpaw in the rat.

STUDY DESIGN: An experimental study to clarify the effects of nucleus pulposus on blood flow in the dorsal root ganglion and hindpaws. OBJECTIVES: To investigate the effects of application of nucleus pulposus to nerve root on blood flow in the dorsal root ganglion and the corresponding hindpaw. SUMMARY OF BACKGROUND DATA: It has been reported experimentally that application of nucleus pulposus into the epidural space induces morphologic and functional changes in the nerve roots and induces compartment syndrome in the dorsal root ganglia. However, it has not been clarified which of these changes induces symptoms in the lower limbs. METHODS: Sixteen adult, female Sprague-Dawley rats had the left L5 nerve root and associated dorsal root ganglions exposed. Autologous nucleus pulposus was applied to the L5 nerve root, just proximal to the dorsal root ganglion (NP group). For control, the same volume of muscle tissue was applied similarly to the neural tissue (control group). Blood flow in the dorsal root ganglion, corresponding hindpaw, and the contralateral hindpaw was continuously monitored by two-channel laser Doppler flowmeter for 3 hours. After measurement of blood flow, the nerve root and dorsal root ganglion were processed for histology and evaluated by light microscope. RESULTS: Blood flow in the NP group was reduced, not only in the dorsal root ganglion, but also in the corresponding hindpaw. These reductions were statistically significant compared with the control group (P < 0.01). Edema was the principal pathologic finding seen consistently in the nerve roots and in many of the associated dorsal root ganglia from nucleus pulposus-treated animals. CONCLUSION: Application of nucleus pulposus to nerve root decreased blood flow in the dorsal root ganglion and corresponding hindpaw. These basic pathophysiologic changes are associated with compression injuries caused by herniated discs and are accepted neuropathologic mechanisms of injury associated with painful neuropathies. These acute observations in the dorsal root ganglion and the hindpaw may be important initial factors in the pathogenesis of radicular leg pain (sciatica) due to disc herniation.

Animals↗
PubMed2000

Quantification of thymic function by measuring T cell receptor excision circles within peripheral blood and lymphoid tissues in monkeys.

The thymus is the primary organ responsible for the production of mature TCR alpha / beta T cells. Quantification of a DNA excision circle that is produced during TCR rearrangement, termed a signal joint TCR rearrangement excision circle (sjTREC) can be used as a measure of thymic function. Here sjTREC measurement has been applied to two monkey species used as animal models of human disease, rhesus macaques (Asian origin) and sooty mangabeys (African origin). Initial PCR analysis determined that the TCR deltaRec-PsiJalpha rearrangement leading to sjTREC formation occurs in both species. Primers to a DNA sequence conserved in macaques, mangabeys and humans were used in a quantitative competitive PCR assay to quantify sjTREC. We found that as in humans, sjTREC in these two monkey species decline with age. sjTREC are first generated in thymocytes during the early stages of TCR rearrangement. Lymph node CD4(+) and CD8(+) T cells contain more sjTREC than peripheral blood T cell populations, suggesting that recent thymic emigrants home to the lymphoid tissues. The sjTREC level is significantly higher within the peripheral blood CD4(+) and CD8(+) T cells of mangabeys compared to macaques. Removal of the thymus in four macaques led to a profound decrease in peripheral blood sjTREC level by 1 year post-thymectomy, indicating the lack of a significant extra-thymic source of peripheral naive T cells in macaques. Our results indicate that production, trafficking, and proliferation of recent thymic emigrants in these two monkey species represents a useful animal model system for understanding human immunological disorders.

Aging↗