Biomedical subjects

T Machida

Publications and source records attributed to T Machida.

At least 19 recordsLinked to original sources

PubMed2006

Increased expression of proapoptotic BMCC1, a novel gene with the BNIP2 and Cdc42GAP homology (BCH) domain, is associated with favorable prognosis in human neuroblastomas.

Differential screening of the genes obtained from cDNA libraries of primary neuroblastomas (NBLs) between the favorable and unfavorable subsets has identified a novel gene BCH motif-containing molecule at the carboxyl terminal region 1 (BMCC1). Its 350 kDa protein product possessed a Bcl2-/adenovirus E1B nineteen kDa-interacting protein 2 (BNIP2) and Cdc42GAP homology domain in the COOH-terminus in addition to P-loop and a coiled-coil region near the NH2-terminus. High levels of BMCC1 expression were detected in the human nervous system as well as spinal cord, brain and dorsal root ganglion in mouse embryo. The immunohistochemical study revealed that BMCC1 was positively stained in the cytoplasm of favorable NBL cells but not in unfavorable ones with MYCN amplification. The quantitative real-time reverse transcription-PCR using 98 primary NBLs showed that high expression of BMCC1 was a significant indicator of favorable NBL. In primary culture of newborn mice superior cervical ganglion (SCG) neurons, mBMCC1 expression was downregulated after nerve growth factor (NGF)-induced differentiation, and upregulated during the NGF-depletion-induced apoptosis. Furthermore, the proapoptotic function of BMCC1 was also suggested by increased expression in CHP134 NBL cells undergoing apoptosis after treatment with retinoic acid, and by an enhanced apoptosis after depletion of NGF in the SCG neurons obtained from newborn mice transgenic with BMCC1 in primary culture. Thus, BMCC1 is a new member of prognostic factors for NBL and may play an important role in regulating differentiation, survival and aggressiveness of the tumor cells.

Amino Acid Sequence↗

PubMed2006

Reversible splenial lesion with restricted diffusion in a wide spectrum of diseases and conditions.

OBJECTIVE: Reversible lesion in the central area of the splenium of the corpus callosum (SCC) is a unique phenomenon occurring particularly in patients with encephalitis or encephalopathy and in patients receiving antiepileptic drugs (AED). We report MR imaging findings, clinical courses, and outcomes in eight patients with various diseases and conditions. MATERIALS AND METHODS: Eight patients with a reversible SCC lesion with transiently restricted diffusion were reviewed retrospectively. Diseases and conditions that were associated with a reversible lesion included epilepsy receiving AED (n=1), seizure from eclampsia receiving AED (n=1), mild infectious encephalitis (n=2), hypernatremia resulting in osmotic myelinolysis (n=1), and neoplasm (n=3) such as acute lymphocytic leukemia, spinal meningeal melanocytoma, and esophageal cancer. We evaluated MR imaging findings and clinical findings. RESULTS: Seven patients had isolated SCC lesions; one patient with osmotic myelinolysis showed additional parenchymal lesions. The reversible SCC lesion shape was oval (n=6) or extended (n=2). The mean apparent diffusion coefficient value of the splenial lesion was 0.40+/-0.16 x 10-3 mm2/s, ranging from 0.22 to 0.64 x 10-3 mm2/s. In a patient with osmotic myelinolysis, additional white matter lesions, shown as restricted diffusion, were revealed as not reversible on follow-up MR imaging. Neurological courses and outcomes were good in seven patients with isolated SCC lesions, but poor in one with osmotic myelinolysis. CONCLUSION: Reversible SCC lesion with restricted diffusion is apparent in a wide spectrum of diseases and conditions. Neurological courses and outcomes are good, particularly in patients with isolated SCC lesions. Knowledge of MR imaging findings and the associated spectrum of diseases and conditions might prevent unnecessary invasive examinations and treatments.

Adolescent↗

PubMed2003

Leiomyosarcoma of the kidney in a dog.

A leiomyosarcoma that occurred in the right kidney of a dog (7-year-old female Labrador retriever) was studied pathologically. On histological examination, tumour cells were spindle-shaped, the cell density was high, and complex fasciculated tumour cells showing longitudinal and transverse cross-sections were observed. Both ends of the nuclei were rounded, the nucleoli were clear and many images of nuclear division were observed. Immunohistochemically, tumour cells reacted intensely with anti-vimentin antibody and anti-actin smooth muscle antibody, and mildly with anti-desmin antibody. On electron microscopy, the nuclei of tumour cells were rounded at both ends and elongated elliptically, and a large number of microfibrils with focal density and dense patches were observed in the cytoplasm. This is a case report of a very rare leiomyosarcoma of the dog kidney.

Animals↗

PubMed2003

Physical characteristics of low and medium energy collimators for 123I imaging and simultaneous dual-isotope imaging.

Septal penetration of high energy photons may degrade 123I images obtained with a low energy collimator. We evaluated the physical characteristics of a low energy, high resolution (LEHR) collimator, special LEHR (SLEHR) collimator, and medium energy collimator for 123I studies. The cross-talk of 99mTc and 123I into the 201Tl window was also examined. Sensitivity and spatial resolution were measured with each collimator. Point sources of 99mTc and 123I were imaged at various source-collimator distances using multiple energy windows, and the effects of collimator choice on energy spectrum and spatial distribution of photopeak counts were assessed. For 99mTc, both sensitivity and resolution were similar with the low energy collimators, and higher sensitivity and lower resolution were observed with the medium energy collimator. For 123I, the full width at tenth maximum was larger for 123I than for 99mTc when using the LEHR collimator. Acquisitions with multiple energy windows revealed severe degradation due to septal penetration in imaging 123I with the LEHR collimator, especially at short distances. The degradation was reduced with the SLEHR collimator and further with the medium energy collimator. In both 99mTc and 123I imaging, cross-talk into the 201Tl window was larger at shorter distances and the largest with the LEHR collimator. In conclusion, variation in collimator geometry causes differences in the effect of septal penetration on 123I images and in cross-talk into the 201Tl window. The SLEHR collimator may be suitable for use in high resolution 123I imaging and simultaneous 99mTc/201Tl imaging. Use of the medium energy collimator appears to be preferable in quantitative 123I studies.

Equipment Failure Analysis↗

PubMed2001

Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design.

As a first step in structure-based design of highly selective and potent Cdk4 inhibitors, we performed structure-based generation of a novel series of Cdk4 inhibitors. A Cdk4 homology model was constructed according to X-ray analysis of an activated form of Cdk2. Using this model, we applied a new de novo design strategy which combined the de novo design program LEGEND with our in-house structure selection supporting system SEEDS to generate new scaffold candidates. In this way, four classes of scaffold candidates including diarylurea were identified. By constructing diarylurea informer libraries based on the structural requirements of Cdk inhibitors in the ATP binding pocket of the Cdk4 model, we were able to identify a potent Cdk4 inhibitor N-(9-oxo-9H-fluoren-4-yl)-N'-pyridin-2-ylurea 15 (IC(50) = 0.10 microM), together with preliminary SAR. We performed a docking study between 15 and the Cdk4 model and selected a reasonable binding mode which is consistent with the SAR. Further modification based on the proposed binding mode provided a more potent compound, N-[(9bR)-5-oxo-2,3,5,9b-tetrahydro-1H-pyrrolo[2,1-a]isoindol-9-yl]-N'-pyridin-2-ylurea 26a (IC(50) = 0.042 microM), X-ray analysis of which was accomplished by the soaking method. The predicted binding mode of 15 in Cdk4 was validated by X-ray analysis of the Cdk2-26a complex.

CDC2-CDC28 Kinases↗

PubMed2001

Neural recognition molecule NB-2 of the contactin/F3 subgroup in rat: Specificity in neurite outgrowth-promoting activity and restricted expression in the brain regions.

NB-2, a neural cell recognition molecule of the contactin/F3 subgroup, promoted neurite outgrowth of the cerebral cortical neurons but not the hippocampal neurons. NB-2 in rat became apparent after birth at protein level, reaching a maximum at postnatal day 14 in the cerebrum and postnatal day 3 in the cerebellum. NB-2 in the cerebellum declined abruptly thereafter. In situ hybridization demonstrated that NB-2 mRNA was highly expressed in regions implicated in the central auditory pathway, including the cochlear nuclei, superior olive, inferior colliculi, medial geniculate nuclei, and auditory cortex. In addition, a high level of NB-2 expression was observed in the accessory olfactory bulb, thalamic nuclei, facial nucleus, and inferior olive. By immunohistochemistry, intense immunoreactivity against NB-2 was also detected in the auditory pathway. Thus, NB-2 is expressed in highly restricted brain regions, including the auditory system, suggesting that it plays specific roles in the development and/or maturation of the regions.

Aging↗

PubMed2001

Crystallographic approach to identification of cyclin-dependent kinase 4 (CDK4)-specific inhibitors by using CDK4 mimic CDK2 protein.

Genetic alteration of one or more components of the p16(INK4A)-CDK4,6/cyclin D-retinoblastoma pathway is found in more than half of all human cancers. Therefore, CDK4 is an attractive target for the development of a novel anticancer agent. However, it is difficult to make CDK4-specific inhibitors that do not possess activity for other kinases, especially CDK2, because the CDK family has high structural homology. The three-dimensional structure of CDK2, particularly that bound with the inhibitor, has provided useful information for the synthesis of CDK2-specific inhibitors. The same approach used to make CDK4-specific inhibitors was hindered by the failure to obtain a crystal structure of CDK4. To overcome this problem, we synthesized a CDK4 mimic CDK2 protein in which the ATP binding pocket of CDK2 was replaced with that of CDK4. This CDK4 mimic CDK2 was crystallized both in the free and inhibitor-bound form. The structural information thus obtained was found to be useful for synthesis of a CDK4-specific inhibitor that does not have substantial CDK2 activity. Namely, the data suggest that CDK4 has additional space that will accommodate a large substituent such as the CDK4 selective inhibitor. Inhibitors designed to bind into this large cavity should be selective for CDK4 without having substantial CDK2 activity. This design principle was confirmed in the x-ray crystal structure of the CDK4 mimic CDK2 with a new CDK4 selective inhibitor bound.

Crystallography, X-Ray↗

PubMed2001

Acetylsalicylic acid reduces ischemia-induced proliferation of dentate cells in gerbils.

Transient global ischemia causes neurogenesis in the dentate gyrus of adult rodents. Ischemic insults to rodents also induce cyclooxygenase-2 (COX-2), an isoform of cyclooxygenases (COXs) and a rate-limiting enzyme for prostanoid synthesis. In the present experiments, adult Mongolian gerbils were chronically treated with acetylsalicylic acid (ASA), a non-selective COX inhibitor, and the proliferation of cells in the dentate gyrus was examined under ischemia. It was proved that BrdU-labeled cells in the dentate gyrus were significantly reduced in number following ASA treatment after 10 min global ischemia. The result strongly suggests that COX, probably COX-2, and prostanoids play an important role in the proliferation of neural cells after ischemia in gerbils.

Animals↗

PubMed2001

Synthesis and structure--activity analysis of novel dihydropyridine derivatives to overcome multidrug resistance.

The structure activity relationships were studied on newly synthesized 1,4-dihydropyridine derivatives possessing a 1-pentyl group at the 4-position, and 3-pyridylpropylester was found to be one of the effective fragments for overcoming P-glycoprotein mediated multidrug-resistance (MDR) in cultured human cancer cells, in vitro. 3-Pyridylpropylester was also found to be one of the effective fragments for increasing the life span of P-glycoprotein overexpressing MDR P388 leukemia-bearing mice, in vivo. All compounds had weak calcium antagonistic activities, but there appeared no relationship between MDR reversing effect and calcium antagonistic activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

[Clinical experience of in situ extracorporeal shock wave lithotripsy using ESL-500A for bilateral ureteral stones and ureteral stones in a solitary, or a functionally solitary kidney].

Extracorporeal shock wave lithotripsy (ESWL) using ESL-500A was performed for the treatment of 18 cases of bilateral ureteral stones and 3 cases of a solitary or a functionally solitary kidney with ureteral stones from September 1991 to February 2000. Sixteen cases of the former and all 3 cases of the latter were treated by in situ ESWL, and the other 2 cases of bilateral ureteral stones were treated with auxiliary procedures. No residual stones were observed in any cases except for one of bilateral ureteral stones treated by in situ ESWL. The results show that in situ ESWL using ESL-500A seems to be useful for the treatment of bilateral ureteral stones and ureteral stones in a solitary kidney, including a functionally solitary kidney. However, auxiliary treatment will be needed in cases of urinary tract infection, undetectable stones by ultrasonography, or bilateral large stones.

Adolescent↗

PubMed2001

[A case of papillary adenocarcinoma of the prostate which was difficult to diagnose].

We report a case of papillary adenocarcinoma of the prostate found by urethroscopy. An 84-year-old male visited our hospital complaining of initial hematuria in July 1997. No abnormal findings were detected despite repeated urological examinations until endoscopic examination revealed fine papillary tumors in the prostatic urethra along with benign prostatic hyperplasia-like prominent left lobe of the prostate in June 2000. Serum prostate specific antigen (PSA) level was 4.1 ng/ml. He underwent transurethral resection of the urethral tumors and the prominent lobe, which was found to contain packed papillary tumors. Both of these tumors were well differentiated papillary adenocarcinoma most likely originating from the prostate because PSA immunostaining was positive. The prostate was irradiated postoperatively. Papillary adenocarcinoma localized in the prostate is difficult to diagnose preoperatively.

Adenocarcinoma, Papillary↗

PubMed2001

[Transitional cell carcinoma of the ureter with inverted proliferation accompanied with papillary bladder tumor: a case report].

An 85-year-old female was referred to our hospital with chief complaints of right flank pain and gross hematuria. Ultrasonography demonstrated right hydroureteronephrosis and a thumb head-sized solid mass in the lower third of the right ureter. Cystoscopy revealed papillary tumors near the right ureteral orifice. Under the preoperative diagnosis of right ureteral tumor and bladder tumor, transurethral resection of bladder tumor, right nephroureterectomy and partial cystectomy were performed. The gross specimen of the ureter contained a 5 x 3 x 1 cm, polypoid and smooth-surfaced tumor. The pathological diagnosis of the ureteral tumor was transitional cell carcinoma with inverted proliferation, grade 1 >> grade 2. On the other hand, the bladder tumor was papillary transitional cell carcinoma, grade 1. This is a case in which tumor development showed two different types.

Aged↗

PubMed2000

Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line.

Loss of heterozygosity of the distal region of chromosome 1p where tumor suppressor gene(s) might harbor is frequently observed in many human cancers including neuroblastoma (NBL) with MYCN amplification and poor prognosis. We have identified for the first time a homozygously deleted region at the marker D1S244 within the smallest region of overlap at 1p36.2-p36.3 in two NBL cell lines, NB-1 and NB-C201 (MASS-NB-SCH1), although our genotyping has suggested the possibility that both lines are derived from the same origin. The 800-kb PAC contig covering the entire region of homozygous deletion was made and partially sequenced (about 60%). The estimated length of the deleted region was 500 kb. We have, thus far, identified six genes within the region which include three known genes (DFF45, PGD, and CORT) as well as three other genes which have been reported during processing our present project for the last 3(1/2) years (HDNB1/UFD2, KIAA0591F/KIF1B-beta, and PEX14). They include the genes related to apoptosis, glucose metabolism, ubiquitin-proteasome pathway, a neuronal microtubule-associated motor molecule and biogenesis of peroxisome. At least three genes (HDNB1/UFD2, KIAA0591F/KIF1B-beta, and PEX14) were differentially expressed at high levels in favorable and at low levels in unfavorable subsets of primary neuroblastoma. Since the 1p distal region is reported to be imprinted, those differentially expressed genes could be the new members of the candidate NBL suppressor, although RT-PCR-SSCP analysis has demonstrated infrequent mutation of the genes so far identified. Full-sequencing and gene prediction for the region of homozygous deletion would elucidate more detailed structure of this region and might lead to discovery of additional candidate genes. Oncogene (2000) 19, 4302 - 4307

Carrier Proteins↗

PubMed2000

Analysis of dose distribution in gamma knife radiosurgery for multiple targets.

PURPOSE: The aim of this study is to evaluate the actual effect of irradiation for other targets in dose planning for the treatment of multiple metastases with Gamma Knife. METHODS AND MATERIALS: We analyzed dose distributions for 51 targets in 10 patients with metastatic brain tumors who underwent radiosurgery with Gamma Knife for the treatment of more than one target in one session. We made dose plans with every attempt to include as many targets as possible and calculate dose distributions separately for each dose matrix. We also calculated the composite dose distribution by including the effect of all shots used. We compared these noncomposite and composite dose distributions. RESULTS: The differences in the mean target dose between the noncomposite dose distribution and the composite one ranged from 0.0 to 4.5 Gy with a mean of 1.5 Gy and was more than 2 Gy in 12 (24%) targets. The difference tended to be larger when targets were small in volume and/or the number of targets was large. CONCLUSIONS: The effect of irradiation from the shots for other targets was not negligible in some cases. This difference of dose distribution should be considered in the analysis of clinical outcomes of cases with multiple targets treated in one session.

Brain Neoplasms↗

PubMed2000

A strong source of methyl chloride to the atmosphere from tropical coastal land.

Methyl chloride (CH3Cl), the most abundant halocarbon in the atmosphere, has received much attention as a natural source of chlorine atoms in the stratosphere. The annual global flux of CH3Cl has been estimated to be around 3.5 Tg on the grounds that this must balance the loss through reaction with OH radicals (which gives a lifetime for atmospheric CH3Cl of 1.5 yr). The most likely main source of methyl chloride has been thought to be oceanic emission, with biomass burning the second largest source. But recent seawater measurements indicate that oceanic fluxes cannot account for more than 12% of the estimated global flux of CH3Cl, raising the question of where the remainder comes from. Here we report evidence of significant CH3Cl emission from warm coastal land, particularly from tropical islands. This conclusion is based on a global monitoring study and spot measurements, which show enhancement of atmospheric CH3Cl in the tropics, a close correlation between CH3Cl concentrations and those of biogenic compounds emitted by terrestrial plants, and OH-linked seasonality of CH3Cl concentrations in middle and high latitudes. A strong, equatorially located source of this nature would explain why the distribution of CH3Cl is uniform between the Northern and Southern hemispheres, despite their differences in ocean and land area.

Arctic Regions↗

PubMed2000

Identification of the homozygously deleted region at chromosome 1p36.2 in human neuroblastoma.

BACKGROUND: We have identified for the first time a homozygously deleted region within the smallest region of overlap at 1p36.2-3 in two neuroblastoma cell lines. PROCEDURE: The 800-kb PAC contig covering the entire homozygously deleted region was made and sequenced. To date, approximately 70% of sequencing has been accomplished, and the estimated length of the deleted region was 500 kb. RESULTS: Currently, we have found six genes within the region, which include three known genes as well as three other genes that have been reported during processing of our present project for the last 3(1/2) years. We report here the results of expression and mutation analyses of those genes. CONCLUSIONS: Full sequencing for the region of homozygous deletion as well as further analyses of the genes mapped within the region may reveal whether or not there is a neuroblastoma suppressor gene as proposed by the Knudson's two-hit hypothesis.

Child, Preschool↗

PubMed2000

Analysis of loss of heterozygosity at 16p12-p13 (familial neuroblastoma locus) in 470 neuroblastomas including both sporadic and mass screening tumors.

BACKGROUND: Neuroblastoma (NBL) in children usually occurs in a sporadic form. However, it rarely occurs in families. Recently, the familial neuroblastoma (FNB) locus has been mapped to 16p12-p13 by linkage analysis. PROCEDURE: Here we show the result of loss of heterozygosity in the region spanning 16p12-p13 (D16S406-D16S409, 46 cM) in 470 NBLs including both sporadic and mass screening cases. RESULTS: Allelic loss was found in 61(13%) tumors. Deletion of 16p was associated with mass screening tumor (P = 0.035) and <1 year of age at diagnosis (P = 0.048). We found two commonly deleted regions: the sizes of the region were approximately 2 cM and approximately 6 cM. CONCLUSIONS: Our data suggested that allelic loss of 16p was common in favorable NBLs, and there may be at least two candidate loci within the region of FNB.

Child↗

PubMed2000

[Clinical statistics on patients and operations during a 20-year period (1978-1997) at Department of Urology, Jikei University School of Medicine].

A statistical analysis was made of diseases, patients, and operations at our department in the four affiliated hospitals of Jikei University School of Medicine from 1978 through 1997. Our findings were as follows. Newly diagnosed urogenital malignancies, except testicular tumors, have been increasing in the last two decades among both outpatients and inpatients. Urogenital infections, including tuberculosis, have gradually been decreasing in the last two decades. The treatment of urinary stone diseases was markedly altered by the induction of extracorponeal shock wave lithotripsy.

Female Urogenital Diseases↗