Biomedical subjects

K Tomoda

Publications and source records attributed to K Tomoda.

At least 19 recordsLinked to original sources

PubMed2001

Direct binding of the signal-transducing adaptor Grb2 facilitates down-regulation of the cyclin-dependent kinase inhibitor p27Kip1.

Ectopic expression of Jab1/CSN5 induces specific down-regulation of the cyclin-dependent kinase (Cdk) inhibitor p27 (p27(Kip1)) in a manner dependent upon transportation from the nucleus to the cytoplasm. Here we show that Grb2 and Grb3-3, the molecules functioning as an adaptor in the signal transduction pathway, specifically and directly bind to p27 in the cytoplasm and participate in the regulation of p27. The interaction requires the C-terminal SH3-domain of Grb2/3-3 and the proline-rich sequence contained in p27 immediately downstream of the Cdk binding domain. In living cells, enforcement of the cytoplasmic localization of p27, either by artificial manipulation of the nuclear/cytoplasmic transport signal sequence or by coexpression of ectopic Jab1/CSN5, markedly enhances the stable interaction between p27 and Grb2. Overexpression of Grb2 accelerates Jab1/CSN5-mediated degradation of p27, while Grb3-3 expression suppresses it. A p27 mutant unable to bind to Grb2 is transported into the cytoplasm in cells ectopically expressing Jab1/CSN5 but is refractory to the subsequent degradation. These findings indicate that Grb2 participates in a negative regulation of p27 and may directly link the signal transduction pathway with the cell cycle regulatory machinery.

3T3 Cells↗

PubMed2001

Prevention of accelerated presbycusis by bone marrow transplantation in senescence-accelerated mice.

A substrain of the senescence-accelerated mouse (SAM), the SAMP1 mouse, is an animal model for accelerated senescence including the age-related acceleration of both immunological dysfunction and hearing loss caused by the impairment of spiral ganglion cells. In the present study, we examine whether the accelerated presbycusis can be prevented by allogeneic BMT. Young SAMP1 (H-2(k)) mice were irradiated with 9 Gy and then reconstituted with bone marrow cells from normal BALB/c (H-2(d)) mice. Allogeneic BMT was found to prevent the development of immunological dysfunction, hearing loss, and apoptosis of spinal ganglion cells in SAMP1 mice. These findings indicate that some types of accelerated presbycusis do not result from defects in the cochlea, but do from defects in the hematopoietic stem cells (HSC) and immunocompetent cells derived from the HSC. If this is the case, either allogeneic BMT, which replaces abnormal HSC with normal HSC and reconstructs a normal immune system in the recipients, or autologous BMT using genetically modified bone marrow cells, could become a new strategy for the treatment of presbycusis.

Age Factors↗

PubMed2001

Mycobacterium kansasii arthritis of the foot in a patient with systemic lupus erythematosus.

Mycobacterium kansasii, an atypical Mycobacterium, may cause serious illness in humans. We describe a M. kansasii infection of the foot joint, which was diagnosed in a 46-year-old woman with systemic lupus erythematosus. The diagnosis was based on a positive culture from degenerative tissue and histological diagnosis of a synovium. We reviewed the literature regarding M. kansasii infection of the joint, bone, and periarticular structures focusing on the complication of rheumatic diseases.

Arthritis, Infectious↗

PubMed2001

[Clinical study on mortality of rheumatoid arthritis compared with malignant rheumatoid arthritis].

OBJECTIVE: To determine how the mortality of patients with rheumatoid arthritis (RA) behave in comparison with that of patients with malignant rheumatoid arthritis (MRA). METHODS: The mortality of RA patients selected at randam identified in 1991-2000 (n = 104) was compared with that of 18 MRA patients. Hazard ratios of death were calculated with a multivariate survival analysis. A clinical study of patients with both RA and MRA was performed in mortality. RESULTS: Excess mortality was seen in MRA patients in Kaplan-Meier survival curves (p = 0.02 by log-rank test). MRA patients were treated more often with cytostatic and immunosuppressive drugs. Infection was the main cause of death in both RA and MRA patients. Vasculitis was not reported as the cause of death in MRA patients. Secondary amyloidosis played an important role in RA death rather than MRA. CONCLUSION: There remained an excess mortality in MRA patients compared with RA, and infection was attributable to the key cause of death in both RA and MRA suggesting therapeutic side effects.

Aged↗

PubMed2000

Full three-dimensional photonic bandgap crystals at near-infrared wavelengths

An artificial crystal structure has been fabricated exhibiting a full three-dimensional photonic bandgap effect at optical communication wavelengths. The photonic crystal was constructed by stacking 0.7-micrometer period semiconductor stripes with the accuracy of 30 nanometers by advanced wafer-fusion technique. A bandgap effect of more than 40 decibels (which corresponds to 99.99% reflection) was successfully achieved. The result encourages us to create an ultra-small optical integrated circuit including a three-dimensional photonic crystal waveguide with a sharp bend.

Journal Article↗

PubMed2000

Prevention of autoimmune hearing loss in MRL/lpr mice by bone marrow transplantation.

We examined the effects of bone marrow transplantation (BMT) on immune-mediated inner ear diseases in MRL/Mp-lpr/lpr (MRL/lpr) mice, which manifest not only lupus nephritis but also sensorineural hearing loss (SNHL) at the age of 20 weeks. These mice were treated with cyclophosphamide (CY) and irradiation (5 Gy x 2), followed by the transplantation of bones plus bone marrow cells from allogeneic normal C57BL/6 mice at the age of 12 weeks. Hematolymphoid cells were reconstituted with donor-derived cells 3 months after BMT. Thus-treated MRL/lpr mice showed neither lupus nephritis nor SNHL even 24 weeks after BMT. No pathological findings were observed in either glomeruli or cochleae. These findings suggest that BMT can be used to prevent the development of autoimmune SNHL in MRL/lpr mice.

Animals↗

PubMed2000

Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable by computed tomography during arterial portography.

Recent advances in imaging modalities enable the identification of small hepatocellular nodules. Among the imaging techniques currently used for detecting hepatocellular carcinomas (HCC), computed tomography (CT) during arterial portography (CTAP) is one of the most sensitive techniques available for detecting hemodynamic change. Even so, well-differentiated HCCs that display only limited hemodynamic change, a feature shared with nonmalignant hepatocellular nodules, are not always detectable by CTAP. To improve our ability to distinguish well-differentiated HCCs from nonmalignant hepatocellular nodules, we have attempted to clarify how the characteristics of the nodules are shown by each imaging technique. We studied the imaging and pathological characteristics of 31 nodules (in 22 patients) detected by ultrasonography (US), but not by CTAP. Histological diagnoses were as follows: HCC, 17 of 31 nodules (55%); high-grade dysplastic nodules, 1 of 31 (3%); and nonmalignant nodules, 13 of 31 (42%). Neither digital substraction angiography (DSA) nor CT arteriography (CTA) were able to detect any of the nodules. Detection rates for plain CT were: 5 of 17 (29%) HCC, 1 of 1 (100%) high-grade dysplastic nodules, and 1 of 13 (8%) nonmalignant nodules. Detection rates for T1/T2-weighted magnetic resonance imaging (MRI) were: 4 of 17 (24%) HCC, 1 of 1 (100%) high-grade dysplastic nodules, and 3 of 13 (23%) nonmalignant nodules. Dynamic CT and dynamic MRI provided no additional information. In conclusion, there is some probability that hepatocellular nodules detected by US, but not by CTAP, are HCC. Presently, it is difficult to distinguish between benign nodules and malignant ones with these imaging techniques, and our findings indicate that biopsy may be advisable for nodules detected under these conditions.

Adult↗

PubMed2000

Consecutive imaging of the facial nerve using high-resolution magnetic resonance imaging.

This study examined the signal intensity of the facial nerve on T1-weighted images using the multiplanar reconstruction (MPR) method of the high-resolution magnetic resonance imaging technique. The facial nerves of 12 sides in 6 normal adults were consecutively observed from the mastoid area to the intraparotid area. Results indicated that facial nerves showed similar or relatively high signal intensity compared with the intensity of the parotid parenchyma. Although previous studies have indicated that the intraparotid facial nerve had a low signal intensity, facial nerves were probably confused with the intraparotid ductal system or vessels which show low signal intensity on T1-weighted images or with low signal lines due to chemical artifacts. All facial nerve trunks were clearly identified; however, 33% (4/12) of second branches of the nerves shifted or curved too strongly to be detected in the parotid parenchyma with this method.

Adult↗

PubMed2000

Extracellular adenosine 5'-ATP-induced calcium signaling in isolated vestibular ganglion cells of the guinea pig.

Extracellular adenosine 5'-triphosphate (ATP)-induced intracellular calcium concentration ([Ca2+]i) changes in acutely isolated vestibular ganglion cells (VGCs) of the guinea pig were investigated using the Ca2+ -sensitive dye Fura-2. Extracellular ATP induced an increase in [Ca2+]i in VGCs in a dose-dependent manner. ATP induced an increase in [Ca2+]i even in the absence of extracellular Ca2+ (1 mM Ethylene Glycol-bis (beta-aminoethyl Ether) N,N,N',N'-Tetraacetic Acid (EGTA)), thus suggesting that ATP induces Ca2+ release from the intracellular stores. The P2-receptor antagonists suramin and reactive blue 2 inhibited the ATP-induced [Ca2+]i increase in a dose-dependent manner. The P1-receptor agonist adenosine did not induce any changes in [Ca2+]i. These results suggest that VGCs may possess a P2-purinergic receptor but not a P1-purinergic receptor. La3+, a receptor-mediated calcium channel blocker, inhibited the ATP-induced [Ca2+]i increase but, in contrast, nifedipine, a L-type calcium channel blocker, did not. These results suggest that ATP induces both a Ca2+ -release from the intracellular stores and a Ca2+ influx from the extracellular space through La3+ -sensitive and nifedipine-insensitive Ca2+ channels in VGCs. Our results also suggest that extracellular ATP may act as a neurotransmitter or neuromodulator of the vestibular peripheral system in the guinea pig.

Adenosine Triphosphate↗

PubMed1999

Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1.

The proliferation of mammalian cells is under strict control, and the cyclin-dependent-kinase inhibitory protein p27Kip1 is an essential participant in this regulation both in vitro and in vivo. Although mutations in p27Kip1 are rarely found in human tumours, reduced expression of the protein correlates well with poor survival among patients with breast or colorectal carcinomas, suggesting that disruption of the p27Kip1 regulatory mechanisms contributes to neoplasia. The abundance of p27Kip1 in the cell is determined either at or after translation, for example as a result of phosphorylation by cyclinE/Cdk2 complexes, degradation by the ubiquitin/proteasome pathway, sequestration by unknown Myc-inducible proteins, binding to cyclinD/Cdk4 complexes, or inactivation by the viral E1A oncoprotein. We have found that a mouse 38K protein (p38) encoded by the Jab1 gene interacts specifically with p27Kip1 and show here that overexpression of p38 in mammalian cells causes the translocation of p27Kip1 from the nucleus to the cytoplasm, decreasing the amount of p27Kip1 in the cell by accelerating its degradation. Ectopic expression of p38 in mouse fibroblasts partially overcomes p27Kip1-mediated arrest in the G1 phase of the cell cycle and markedly reduces their dependence on serum. Our findings indicate that p38 functions as a negative regulator of p27Kip1 by promoting its degradation.

3T3 Cells↗

PubMed1999

MR imaging of non-squamous vaginal tumors.

We reviewed the MR images and pathologic findings of five cases of primary vaginal neoplasms of non-squamous origin. Histologic types consisted one case each of adenocarcinoma, adenosarcoma, melanoma, lymphoma, and neurilemoma. Magnetic resonance imaging was found useful for evaluating the type and the extension of vaginal tumors.

Adult↗

PubMed1999

T cells infiltrating from the systemic circulation proliferate in the endolymphatic sac.

It has been reported that autoimmune mechanisms are involved in the development of inner ear disorders such as Meniere's disease and steroid-responsive sensorineural hearing loss. In the present study, using an animal model for graft-versus-host disease, we investigated the immune regulatory mechanism in the endolymphatic sac and demonstrated that donor T cells injected into the systemic circulation of recipients infiltrate and proliferate in the perisaccular region. These findings suggest that immunocompetent cells are supplied from the systemic circulation through blood-labyrinth and blood-endolymph barriers into the endolymphatic sac, and that the endolymphatic sac allows these cells to proliferate locally as a local immune defense. It therefore seems likely that the endolymphatic sac plays a crucial role in not only graft-versus-host disease but also autoimmune inner ear disorders.

Animals↗

PubMed1998

Induction of immune-mediated hearing loss in SCID mice by injection of MRL/lpr mouse spleen cells.

Induction of immune-mediated hearing loss in SCID mice by injection of MRL/lpr mouse spleen cells The MRL/lpr mouse, which has a mutation in the Fas gene encoding a cell-surface receptor for apoptosis, shows an accumulation of abnormal immunocompetent cells and SLE-like disease. It has recently been reported that this mouse also manifests sensorineural hearing loss (SHL) with cochlear pathology at 20 weeks of age. We examined the effects of injecting MRL/lpr spleen cells on the development of SHL in severe combined immunodeficient (SCID) mice, which originally develop neither SHL nor cochlear pathology. Immune-mediated SHL and cochlear pathology were, indeed, transferred to the SCID mice by the injection of spleen cells from the MRL/lpr mice. These findings suggest that cell-mediated immunity is involved in the development of SHL and cochlear pathology.

Animals↗

PubMed1998

Sensitivity in detection of hypervascular hepatocellular carcinoma by helical CT with intra-arterial injection of contrast medium, and by helical CT and MR imaging with intravenous injection of contrast medium.

PURPOSE: To determine the effectiveness of i.a. contrast-enhanced helical CT and of i.v. contrast-enhanced helical CT and MR imaging, in detecting hypervascular hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Fifty patients with 125 hypervascular HCC nodules underwent helical CT both during arterial portography (CTAP) and during hepatic arteriography (CTHA). Helical CT and MR imaging of the entire liver with i.v. administration of contrast medium were also performed. Helical CT images were obtained at 30-33 s (arterial-phase CT) and at 5 min (equilibrium-phase CT) after the initiation of an i.v. bolus injection of contrast medium. After T1- and T2-weighted spin-echo MR imaging, gradient-echo images during breath-holding were obtained prior to and 20 s, 1 min, and 2 min after the bolus administration of 0.1 mmol/kg of gadopentetate dimeglumine (dynamic MR). The sensitivity and positive predictive value of the various techniques were evaluated and compared. RESULTS: In terms of sensitivity for hypervascular HCC nodules of less than 1 cm in diameter, CTAP (90%) and CTHA (88%) were significantly superior to dynamic MR imaging (44%), arterial-phase CT (39%), spin-echo MR imaging (20%), and equilibrium-phase CT (7%) (p < 0.001). However, there was no significant difference in the techniques with regard to the detection of lesions equal to or more than 2 cm in diameter. CONCLUSION: For detecting small hypervascular HCCs, helical CT with i.a. contrast enhancement is superior to helical CT and MR imaging with i.v. enhancement.

Adult↗

PubMed1998

Preoperative staging of endometrial carcinoma: diagnostic effect of T2-weighted fast spin-echo MR imaging.

PURPOSE: To evaluate the usefulness of T2-weighted fast spin-echo magnetic resonance (MR) imaging with a 512 x 256 matrix for assessment of the preoperative stage of endometrial carcinoma. MATERIALS AND METHODS: Twenty-eight women with histopathologically proved endometrial carcinoma underwent preoperative T2-weighted fast spin-echo, dynamic T1-weighted fast spin-echo, and postcontrast T1-weighted spin-echo MR imaging with a phased-array surface coil. The uterine long-axis planes in each sequence were reviewed at separate sessions by three radiologists blinded to the histopathologic data. RESULTS: For the diagnosis of myometrial invasion, no statistically significant differences were found among T2-weighted imaging, dynamic imaging, and postcontrast T1-weighted imaging. For the diagnosis of deep myometrial invasion, T2-weighted and dynamic images showed higher specificity than postcontrast T1-weighted images (T2-weighted, 89%; dynamic, 88%; and postcontrast T1-weighted, 80%). For cervical invasion, T2-weighted and dynamic images showed larger areas under receiver operating characteristic curves than did postcontrast T1-weighted images (T2-weighted, 0.78; dynamic, 0.71; and postcontrast T1-weighted, 0.67). CONCLUSION: T2-weighted imaging is useful for identifying the stage of endometrial carcinoma.

Carcinoma↗

PubMed1998

Effects of injection rates of contrast material on arterial phase hepatic CT.

OBJECTIVE: Our goal was to assess the effects of the i.v. injection rate of contrast material on arterial phase hepatic CT. SUBJECTS AND METHODS: One hundred patients were randomly divided into four groups of 25 with different injection rates of 90 ml of contrast material: 2, 3, 4, or 5 ml/sec. Single-level serial CT was performed at the level of the middle section of the main portal vein before injection and every 2 sec from 12 sec to 60 sec after injection of contrast material. The enhancement value was calculated as the difference in attenuation value between the unenhanced and contrast-enhanced images for the aorta and liver parenchyma. The duration of the arterial phase was defined as the interval beginning when the enhancement value for the aorta reached 100 H and ending when the value for the liver parenchyma reached 20 H. RESULTS: Faster injection rates increased the maximum enhancement of the aorta. Although faster injection rates decreased the time from injection to the beginning and the end of the arterial phase, faster injection rates did not decrease the duration of the arterial phase itself. CONCLUSION: A faster injection rate increases arterial enhancement of the liver, and the duration of the arterial phase remains the same as that occurring with a slower injection rate. We hypothesize that faster injection rates can provide better results using CT to reveal hypervascular liver tumors.

Adult↗

PubMed1998

[Evaluation of transcatheter hepatic segmental or subsegmental infusion of SMANCS for treatment of hepatocellular carcinoma].

A total of seventeen patients with hepatocellular carcinoma (HCC), nineteen HCCs, who underwent as an initial treatment transcatheter hepatic segmental or subsegmental arterial administration of SMANCS alone for hepatocellular carcinoma (HCC), were studied to evaluate the efficacy and complication of that treatment. The initial treatments provided CR in eight patients (47%), and repeat administrations of SMANCS achieved CR in an additional four patients (24%). The initial treatment provided a dense deposit of Lipiodol in the twelve tumors (63%), in five of which Lipiodol was thereafter washed out in some portions of the tumor. Complete necrosis was obtained in nine (75%) of fourteen hypervascular tumors, and in two (40%) of five intermediately vascular or hypovascular tumors. Segmental or subsegmental administration of SMANCS was well tolerated with self-controlled abdominal pain or fever well responding to medication. Ascites was seen in three cases, and atrophy of the segment infused occurred in five patients. Cholinesterase significantly reduced at one week and one month, then recovered to baseline two to three months after initial treatment. The cumulative survival rates were 77% at 1 year, 66% at 2 years, and 53% at 5 years in the whole patients. The survival rate was 100% at 5 years in the Child A group. In the patients who obtained CR using SMANCS alone, the survival rates were 89% at 1 year, 74% at 2 years and 56% at 5 years. Although this method may transiently deteriorate hepatic function, segmental or subsegmental administration of SMANCS may be an excellent therapeutic method for treatment of HCC and promising for use in properly selected patients.

Adult↗

PubMed1998

[Three-dimensional gadolinium-enhanced dynamic MRI of whole liver using spectrally selected enhanced fast gradient recall sequence].

Three-dimensional gadolinium-enhanced dynamic MRI of whole liver using the spectrally selected enhanced fast gradient recall sequence (spec IR-efgre3d) was performed in five patients with HCC. Ten HCC nodules were confirmed by CTA, CTAP and Lipiodol CT, and all of them were detected with dynamic MRI. MIP images reconstructed from 3D gadolinium-enhanced dynamic MR studies clearly showed the main portal vein and its branches in all cases. Portal vein thrombosis was also demonstrated with the MIP images.

Carcinoma, Hepatocellular↗