Biomedical subjects

N Shimizu

Publications and source records attributed to N Shimizu.

At least 109 records · Page 6Linked to original sources

PubMed2001

Electron microscopic imaging of supercoiled DNA containing highly biased sequence.

DNA conformation of the pUC19 derivatives containing the pyrimidine/purine-biased sequence (pTIR10), highly GC-rich sequence (pTIS303) or short palindrome (pBan1), that had been shown by S1 nuclease assay to conform to unusual DNA structures under superhelical tension, was examined by an electron microscopic imaging. Under the condition of spreading of DNA on the grid that we employed, 20-50% of the molecules were shown to be nicely unfolded and the rest were highly twisted or entangled. About 70% of the unfolded molecules of pTIR10 retained the triplex-like stem of size ranging from 18 nm to 38 nm, as expected from its sequence characteristics. The plasmid pTIS303 showed slightly shorter stem structure than pTIR10, as the pyrimidine/purine-biased stretch in plasmid pTIS303 is shorter than that in pTIR10. The results suggest that the GC-rich segment may be responsible for forming unusual DNA structure in pTIS303.

DNA, Superhelical↗

PubMed2001

Analysis of the cat eye syndrome critical region in humans and the region of conserved synteny in mice: a search for candidate genes at or near the human chromosome 22 pericentromere.

We have sequenced a 1.1-Mb region of human chromosome 22q containing the dosage-sensitive gene(s) responsible for cat eye syndrome (CES) as well as the 450-kb homologous region on mouse chromosome 6. Fourteen putative genes were identified within or adjacent to the human CES critical region (CESCR), including three known genes (IL-17R, ATP6E, and BID) and nine novel genes, based on EST identity. Two putative genes (CECR3 and CECR9) were identified, in the absence of EST hits, by comparing segments of human and mouse genomic sequence around two solitary amplified exons, thus showing the utility of comparative genomic sequence analysis in identifying transcripts. Of the 14 genes, 10 were confirmed to be present in the mouse genomic sequence in the same order and orientation as in human. Absent from the mouse region of conserved synteny are CECR1, a promising CES candidate gene from the center of the contig, neighboring CECR4, and CECR7 and CECR8, which are located in the gene-poor proximal 400 kb of the contig. This latter proximal region, located approximately 1 Mb from the centromere, shows abundant duplicated gene fragments typical of pericentromeric DNA. The margin of this region also delineates the boundary of conserved synteny between the CESCR and mouse chromosome 6. Because the proximal CESCR appears abundant in duplicated segments and, therefore, is likely to be gene poor, we consider the putative genes identified in the distal CESCR to represent the majority of candidate genes for involvement in CES.

Abnormalities, Multiple↗

PubMed2001

A SNP resource for human chromosome 22: extracting dense clusters of SNPs from the genomic sequence.

The recent publication of the complete sequence of human chromosome 22 provides a platform from which to investigate genomic sequence variation. We report the identification and characterization of 12,267 potential variants (SNPs and other small insertions/deletions) of human chromosome 22, discovered in the overlaps of 460 clones used for the chromosome sequencing. We found, on average, 1 potential variant every 1.07 kb and approximately 18% of the potential variants involve insertions/deletions. The SNPs have been positioned both relative to each other, and to genes, predicted genes, repeat sequences, other genetic markers, and the 2730 SNPs previously identified on the chromosome. A subset of the SNPs were verified experimentally using either PCR-RFLP or genomic Invader assays. These experiments confirmed 92% of the potential variants in a panel of 92 individuals. [Details of the SNPs and RFLP assays can be found at http://www.sanger.ac.uk and in dbSNP.]

Base Composition↗

PubMed2001

A new neurological entity manifesting as involuntary movements and dysarthria with possible abnormal copper metabolism.

A few patients with an affected CNS involving abnormalities in copper metabolism have been described that do not fit any known nosological entities such as Wilson's disease or Menkes' disease. Three sporadic patients (two men and one woman) were examined with involuntary movements and dysarthria associated with abnormal concentrations of serum copper, serum ceruloplasmin, and urinary copper excretion. The onset of neurological symptoms occurred at the age of 15 to 17 years. The common clinical symptoms were involuntary movements and dysarthria. The involuntary movements included dystonia in the neck, myoclonus in the shoulder, athetosis in the neck, and rapid orobuccal movements. The dysarthria consisted of unclear, slow, and stuttering speech. Two of the three patients did not have dementia. A cousin of the female patient had been diagnosed as having Wilson's disease and had died of liver cirrhosis. Laboratory findings showed a mild reduction in serum copper and ceruloplasmin concentrations, whereas urinary copper excretion was significantly reduced in all three patients. Two of the three patients showed a high signal intensity in the basal ganglia on T2 weighted brain MRI. In conclusion, the unique findings of involuntary movements, dysarthria, and abnormal serum copper and urinary copper concentrations suggest that the three patients may constitute a new clinical entity that is distinct from either Wilson's or Menkes disease.

Adult↗

PubMed2001

Influence of sugar chain on fibrin affinity of recombinant t-PA.

The role of the sugar chain on the fibrin affinity property of tissue plasminogen activator (t-PA) was investigated using two variants of wild type t-PA (WT t-PA I and WT t-PA II) and mutant type t-PA (mt-PA ; Gln117 t-PA I and Gln117 t-PA II), whose sugar chains have different structures. In terms of fibrin affinity, Gln117 t-PA was higher than WT t-PA ; moreover, Type II was higher than Type I. Bindings mediated via finger domain (F mode) and kringle 2 domain (K2 mode) were distinguished using epsilon-amino caproic acid (EACA). Consequently, F mode and K2 mode bindings were inhibited by the sugar chains at Asn117 and 184, respectively. These results were assumed to be due to the steric hindrance of the sugar chains.

Aminocaproic Acid↗

PubMed2001

Two new diterpenoids from Plectranthus nummularius Briq.

Two new antioxidative diterpenoids, plectranthol A (3)[19-O-(3,4-dihydroxybenzoyl)-11,12-dihydroxy-20(10-->5)-abeo-abieta-1(10),6,8,11,13-tetraene] and plectranthol B (4)[12-O-(3-methyl-2-butenoyl)-19-O-(3,4-dihydroxybenzoyl)-11-hydroxyabieta-8,11,13-trienel along with two known diterpenoids, parvifloron E (1) and F (2) were isolated from the leaves of Plectranthus nummularius Briq. Antioxidative activities of the compounds were measured by the alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) method.

Abietanes↗

PubMed2001

Latifolosides I and J, two new triterpenoid saponins from the bark of Ilex latifolia.

Two new triterpenoid saponins, latifoloside I (1), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl 3beta,21alpha,28-trihydroxy-urs-12-ene 21-O-beta-D-glucopyranoside; latifoloside J (2), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-3beta,21alpha-dihydroxy-ursolic acid 21-O-beta-D-glucopyranoside, along with two known compounds, latifoloside C (3) and latifoloside E (4), were isolated from the bark of Ilex latifolia THUNB. Structure assignments were established on the basis of spectroscopic data and chemical evidence.

Carbohydrate Conformation↗

PubMed2001

Six new dammarane-type triterpene saponins from the leaves of Panax ginseng.

Six new minor saponins, together with known ginsenosides, were isolated from the leaves of Panax ginseng. The new saponins were named as ginsenoside-Rh5, -Rh6, -Rh7 -Rh8, -Rh9 and -Rg7, and their structures were elucidated on the basis of chemical and physicochemical evidence to be as follows: ginsenoside-Rh5: 3beta,6alpha,12beta,24zeta-tetrahydroxy-dammar-20(22),25-diene 6-O-beta-D-glucopyranoside (1), -Rh6: 3beta,6alpha12beta,20(S)-tetrahydroxy-25-hydroperoxy-dammar-23-ene 20-O-beta-D-glucopyranoside (2), -Rh7: 3beta,7beta,12beta,20(S)-tetrahydroxy-dammar-5,24-diene 20-O-beta-D-glucopyranoside (3), -Rh8: 3beta,6alpha,20(S)-trihydroxy-dammar-24-ene-12-one 20-O-beta-D-glucopyranoside (4), -Rh9: 3beta,6alpha,20(S)-trihydroxy-12beta,23-epoxy-dammar-24-ene 20-O-beta-D-glucopyranoside (5) and -Rg7: 3-O-beta-D-glucopyranosyl 3beta,12beta,20(S),24(R)-tetrahydroxy-dammar-25-ene 20-O-beta-D-glucopyranoside (6).

Chemical Phenomena↗

PubMed2001

Latifolosides K and L, two new triterpenoid saponins from the bark of Llex latifolia.

Two new triterpenoid saponins, latifoloside K (1), 3-O-beta-D-glucopyranosyl-(1-->3)-[alpha-L-rhamnopyranosyl-(1-->2)-]-alpha-L-arabinopyranosyl 3beta-hydroxy-urs-12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester and latifoloside L (2), 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->3)-[alpha-L-rhamnopyranosyl-(1-->2)-]-alpha-L-arabinopyranosyl 3beta,19alpha-dihydroxyursolic acid, were isolated from the bark of Ilex latifolia Thunb. Also isolated were two known compounds, ilekudinoside A (3) and kudinoside G (4). Structural assignments were established on the basis of spectroscopic data and chemical evidence.

Carbohydrate Conformation↗

PubMed2001

Construction of a BAC library derived from the inbred Hd-rR strain of the teleost fish, Oryzias latipes.

A large insert genomic bacterial artificial chromosome (BAC) library was constructed from the inbred Hd-rR strain of the medaka, Oryzias latipes. Approximately 92,000 clones were gridded on high-density replica filters. Insert analysis of randomly selected clones indicated a mean insert size of 210 kb and predicted a 24 times coverage of the medaka genome. The library was hybridized with a single locus DNA fragment, and the resulting positive clones were characterized and shown to be compatible with a 24-fold redundant library. This first large insert genomic library of the medaka should increase the speed of genomic analyses for this fish species.

Animals↗

PubMed2001

7-Hydroxyphthalide: a new natural salicylaldehyde analog from Oulenzia sp. (Astigmata: Winterschmitiidae).

A new salicyl lactone was detected from the unidentified Oulenzia sp. and its chemical structure was elucidated as 7-hydroxyphthalide (7-hydroxy-3H-isobenzofuran-1-one), based on its GC/MS and GC/FT-IR data and SiO2 column behavior. The compound was synthesized by NaBH4 reduction of 3-hydroxyphthalic anhydride. The GC/MS and GC/FT-IR spectra of the natural compound were consistent with those of the synthetic product. Although the compound is known as a medical material, this is the first example of its presence in nature.

Aldehydes↗

PubMed2001

Effects of dobutamine on critical capillary PO(2) and lactic acidosis threshold in patients with cardiovascular disease.

BACKGROUND: Muscle capillary PO(2) has been found to reach a minimal value, ie, a critical capillary PO(2), in the midrange of work capacity in patients with cardiovascular disease. However, it is not known if the critical capillary PO(2) can be influenced by a change in blood flow response to exercise. This study was carried out to determine the effect of changing the blood flow response to exercise, using low-dose infusion of dobutamine, on muscle end-capillary PO(2) (as approximated by femoral vein PO(2)), lactate concentration, oxygen uptake (O(2)), and the relation among these variables. METHODS: Eleven male patients with coronary artery disease performed an incremental exercise test on a cycle ergometer with and without continuous infusion of dobutamine, 6 microg/kg/min. Respiratory gas analysis was performed on a breath-by-breath basis; femoral vein blood was sampled every minute through a percutaneous catheter. RESULTS: Dobutamine increased resting O(2) and O(2) at the lactic acidosis threshold (LAT) but not peak O(2). The femoral vein PO(2) rapidly decreased toward a minimal value with increasing work rate (O(2)) irrespective of the infusion of dobutamine. After reaching its nadir (critical PO(2)), femoral vein lactate began to increase without further decrease in PO(2). Infusion of dobutamine significantly increased femoral vein resting PO(2) (27.4 +/- 4.9 mm Hg vs 32.5 +/- 3.8 mm Hg) and critical PO(2) (20.5 +/- 1.5 mm Hg vs 21.9 +/- 1.7 mm Hg), but not the PO(2) at peak O(2) (22.1 +/- 3.3 mm Hg vs 22.0 +/- 2.9 mm Hg). CONCLUSIONS: Infusion of dobutamine was found to raise the critical PO(2) and LAT but not peak O(2). These findings suggest that some of the acute increase in blood flow induced by dobutamine infusion benefits exercising muscle by increasing capillary PO(2), thereby delaying the onset of lactic acidosis.

Acidosis, Lactic↗

PubMed2001

Effects of neonatal diethylstilbestrol exposure on c-fos and c-jun protooncogene expression in the mouse uterus.

Quantitative and cell-type-specific expression of c-fos and c-jun genes after 17beta-estradiol (E2) stimulation, was investigated in the uteri of neonatally diethylstilbestrol (DES)-exposed and ovariectomized adult mice (neoDES-mice), employing Northern blot analysis, immunohistochemistry and in situ hybridization. The c-fos mRNA level before E2 injection (at baseline) was about 2.2-fold higher in neoDES-mice than in vehicle-treated control mice. In controls, E2 treatment transiently increased c-fos mRNA levels, showing a peak value (15.8-fold relative to the baseline) after 2 hours. In neoDES-mice, c-fos mRNA level reached a peak showing a 2.1-fold increase compared with its baseline value 1 hour after E2 injection. Immunohistochemistry and in situ hybridization revealed that c-fos protein (Fos) and mRNA are induced in the epithelium and vascular endothelium in both groups. Most uterine epithelia of neoDES-mice revealed low sensitivity to the c-fos expression after E2 administration compared with those of vehicle-treated controls, whereas few epithelia showed high c-fos mRNA expression even at baseline. The c-jun mRNA concentration in the neoDES-mice uteri at baseline was 70% of that in vehicle-treated controls. At 1 hour after E2 injection, c-jun mRNA levels increased 1.8-fold in controls and 1.3-fold in the neoDES-mice relative to each baseline value. There were no significant differences in the distribution pattern of c-jun protein (Jun) and mRNA in the uteri of either groups; E2 stimulated c-jun mRNA expression in the stromal and myometrial cells but suppressed it in the epithelial cells, whereas intensity of c-jun immunostaining increased in the three cell types. The permanent changes in the expression of estrogen-regulated protooncogenes, c-fos and c-jun genes, by neonatal DES exposure may be responsible for the wide range of abnormalities in the genital tract of mature animals.

Animals↗

PubMed2001

Malignant lymphoma of the bone associated with systemic sarcoidosis.

A 57-year-old woman was hospitalized with malignant lymphoma of the right talus. After treatment, complete remission was obtained. Gallium-67 scintigraphy to confirm the remission demonstrated increased uptake in the whole body skeletal muscle, especially in her thighs. Biopsy of right gastrocnemius muscle showed epithelioid granuloma. Serum angiotensin-converting enzyme activity (ACE) and lysozyme had increased to several times the normal range. We diagnosed her disease as bone-associated sarcoidosis-lymphoma syndrome. Human herpes virus 8 (HHV-8) genome was examined in the bone marrow specimen, and the relationship between sarcoidosis-lymphoma syndrome and HHV-8 was discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Pulse irradiation of low-power laser stimulates bone nodule formation.

Although low-power laser irradiation provides many anabolic effects such as acceleration of bone formation, the effects of different pulse frequencies used during laser irradiation on bone formation have not been elucidated. Osteoblastic cells isolated from fetal rat calvariae were irradiated once with a low-power Ga-Al-As laser (830 nm, 500 mW) in two different irradiation modes; continuous irradiation (CI), and 1 Hz pulsed irradiation (PI). We then investigated the effects on cellular proliferation, bone nodule formation, alkaline phosphatase (ALP) activity, and ALP gene expression. Laser irradiation in both groups significantly stimulated cellular proliferation, bone nodule formation, ALP activity, and ALP gene expression, as compared with the nonirradiation group. Notably, PI markedly stimulated these factors, when compared with the CI group. Since 1 Hz pulsed laser irradiation significantly stimulates bone formation in vitro, it is most likely that pulse frequency is an important factor affecting biological responses in bone formation.

Alkaline Phosphatase↗

PubMed2001

Microsatellite instability correlates with normal expression of cyclin E in hepatocellular carcinomas.

It has been reported that microsatellite instability (MSI) strongly correlates with carcinogenesis and cancer progression. In the present study, we studied the incidence of MSI at 5 polymorphic microsatellite markers (D5S406, D13S153, D16S402, D17S796, and poly(A) tract BAT26), the expression of G1 cyclins (cyclin A, cyclin D and cyclin E), and Ki-67 labeling index in 30 surgically resected hepatocellular carcinomas (HCCs) and their adjacent non-cancerous tissues. The results of analysis showed that 43% of HCCs exhibited MSI in one locus, 10% in two loci, and 3% in three loci. Overexpressions of cyclin E and cyclin A were observed in 57% and 83% of HCCs, respectively. MSI in HCCs, however, correlated with normal expressions of cyclin E and cyclin A and with a low labeling index of Ki-67. Thus, patients with HCCs exhibiting MSI at these 5 markers may have less involvement of G1/S disregulation and may have better prognosis than other patients with HCC.

Aged↗

PubMed2001

Reduced expression of REIC/Dkk-3 gene in non-small cell lung cancer.

Dickkopfs (Dkks) are secretory glycoproteins and are important for inducing amphibian head formation. Some Dkks have the ability to antagonize the Wnt proto-oncoprotein, which can promote cell proliferation and transformation when it is mutated or overexpressed. We recently cloned the REIC/Dkk-3 gene, one of the Dkks, and found that expression of the gene was markedly decreased in many human immortalized and tumor-derived cell lines. To further investigate the function of the REIC/Dkk-3 gene in vivo, the gene expression was quantified in 57 surgically-resected non-small cell lung cancer (NSCLC) tissues and their adjacent normal lung tissues by real-time quantitative PCR analysis based on TaqMan methodology. The REIC/Dkk-3 mRNA level was significantly lower in NSCLC tissues than in normal lung tissues. Reduced expression of REIC/Dkk-3 in NSCLC was observed in 36 (63%) of the 57 tumors. Reduced expression of REIC/Dkk-3 was frequently observed in poorly differentiated adenocarcinoma and squamous cell carcinoma. These results indicate that reduced expression of REIC/Dkk-3 may be correlated with rapid cell proliferation in human NSCLC.

Adaptor Proteins, Signal Transducing↗

PubMed2001

MR evaluation of the hippocampus in patients with congenital malformations of the brain.

BACKGROUND AND PURPOSE: Developmental changes in hippocampal formations (HFs) have been reported in association with agenesis of the corpus callosum, lissencephaly, and holoprosencephaly. The purpose of this study was to evaluate the developmental changes in HFs in patients with a variety of other congenital brain malformations. METHODS: MR images of 44 patients with congenital brain malformations associated with 11 different brain disorders were reviewed retrospectively. Five patients had more than two anomalies. Imaging and clinical findings were evaluated for the shape, size, degree of inversion, and side of abnormal HF. RESULTS: Vertically oriented or globular-shaped HFs were observed in 28 patients (64%) on coronal MR images. All patients with agenesis of the corpus callosum (n = 7), lissencephaly (n = 1), holoprosencephaly (n = 3), and Fukuyama muscular dystrophy (n = 3) had an abnormal HF. A high prevalence of abnormalities was observed in patients with polymicrogyria (11/12, 92%), heterotopia (4/5, 80%), tuberous sclerosis (2/3, 67%), and schizencephaly (2/4, 50%). Patients whose abnormalities were symmetrical had bilateral abnormal HFs, whereas those with polymicrogyria, schizencephaly, and heterotopia, whose abnormalities were localized, tended to have unilateral abnormal HFs. CONCLUSION: Hippocampal developmental abnormalities are found in a high percentage of patients with congenital malformations. Focusing on the morphologic abnormalities of the HF on coronal MR images may help in the detection of diseases associated with brain anomalies, especially subtle cortical disorders.

Adolescent↗