Biomedical subjects

S Tada

Publications and source records attributed to S Tada.

At least 109 records · Page 6Linked to original sources

PubMed1996

Enhancing effect of the liver extract and flavin adenin dinucleotide mixture on anti-viral efficacy of interferon in patients with chronic hepatitis C.

A combined preparation of liver extract and flavin adenin dinucleotide (FAD) (Adelavin) has been widely used in patients with chronic liver diseases in Japan. One milliliter of this agent contains 15 microliters of phenol-soluble phase of liver nucleic acid fraction and 10 mg of FAD. To examine the advantages of using this preparation in the elimination of hepatitis C virus (HCV) from patients with chronic hepatitis (CH)-C receiving interferon (IFN), 2 ml of this preparation was intravenously (n = 9) or intramuscularly (n = 8) administered daily for 5 days before 6 million units of IFN-alpha was intramuscularly injected once. Before and 48 hours after the injection of IFN, serum ALT, 2'5'-oligoadenylate synthetase (2'5-AS) activity, and HCV RNA levels were measured. The daily administration of this preparation alone for 5 days did not significantly change serum ALT, 2'5-AS activities, and HCV RNA levels. The 2'5-AS activities were significantly increased by IFN after the intravenous injection of this preparation (p < 0.01), while an injection of IFN alone of this dose did not change its activities (n = 10). HCV RNA levels were significantly decreased by IFN only after the administration of the preparation (intramuscular, p < 0.01; intravenous, p < 0.01). The effect of intravenous injection of this preparation was also elicited in patients with HCV genotype II and with HCV more than 10(5) copies/ml. These results suggest that this preparation may enhance the 2'5-AS production by IFN as a result of the increase in mitochondrial adenosin triphosphate production and may be a potent agent to enhance the anti-viral efficacy of IFN in patients with CH-C.

Adult↗

PubMed1996

Reduction of LAK-sensitivity and changes in antigen expression on hepatoma cells by sodium butyrate.

We demonstrated that sodium butyrate (SB) induced differentiation of functions in human hepatocellular carcinoma (HCC) cell lines. To investigate relationship between the sensitivity for cellular cytotoxicity and the cellular differentiation of HCC cells, the effect of SB on lymphokine-activated killer (LAK) sensitivity and antigen expression of a human HCC cells were studied. SB induced LAK-resistance of human HCC cell lines, HCC-T and HCC-M, time-dependently. A flowcytometric analysis of cell surface antigens revealed that SB markedly reduced the expression of laminin and fibronectin and increased the expression of liver-specific antigen defined by a mouse monoclonal antibody time-dependently, but did not modify that of major histocompatibility complex antigens, intercellular adhesion molecule (ICAM)-1, or CEA. Leukocyte function-associated antigen (LFA)-3 expression on HCC-T was reduced slightly by SB treatment. LAK sensitivity was inhibited by anti-laminin, but not with anti-beta 2-microglobulin, anti-HLA DR, anti-ICAM-1, anti-fibronectin, or anti-CEA. Anti-LFA-3 reduced LAK sensitivity of HCC-T, but not HCC-M, although the reduction was less than that obtained by anti-laminin treatment. These results provided evidence that SB induced LAK-resistance of human HCC cells according to cellular differentiation and extracellular matrix functionality played an important role in this LAK-mediated cell killing. Moreover, the structure expressed on HCC cells, which contributed to LAK cytolysis, was different for each HCC cell.

Animals↗

PubMed1996

[Double-dose Gd-DTPA: detectability of intraparenchymal brain metastasis].

PURPOSE: The aim of this study was to assess the efficacy of double-dose (0.2 mmol/kg cumulative dose) gadopentetate dimeglumine (Gd-DTPA) in patients with intraparenchymal brain metastasis. MATERIALS AND METHODS: We studied 119 patients using an incremental-dose technique. After precontrast T1- and T2-weighted spin-echo studies were performed, each patient received an initial injection of 0.1 mmol/kg body weight and an additional dose of 0.1 mmol/kg 6-8 minutes later. RESULTS: Fifty-five cases (65 examinations) showed abnormal findings suggestive of intraparenchymal metastatic brain tumor and were included in the efficacy analysis. More enhancing lesions were detected with double-doses than with a single dose in 39 of 65 examinations (60%). With a single dose of Gd-DTPA. 562 definite and 111 equivocal lesions were found in brain parenchyma, and with an additional dose. 923 definite and 145 equivocal lesions were detected. In three cases, intraparenchymal metastatic brain tumors were detected only with double doses, and in five cases the lesion was solitary with a single dose but multiple after double doses. Based on our results. MR imaging with double doses had a statistical advantages over 0.1 mmol/kg examination in detecting early and/or small metastases. There is no statistical difference between at 0.5T and 1.0-1.5T in improving detectability of metastatic brain tumors after a double dose. We have not experienced any adverse effects of Gd-DTPA in this patient series. CONCLUSION: In surveying brain metastatsis, contrast-enhanced MR imaging with double doses is more useful in detecting lesions than with a single dose of Gd-DTPA.

Adult↗

PubMed1995

Stimulation of DNA synthesis by mouse DNA helicase B in a DNA replication system containing eukaryotic replication origins.

A number of DNA helicases have been isolated from mammalian cells, but their abilities to stimulate DNA replication accompanied with DNA unwinding have not been addressed so far. We constructed a model DNA replication system using the yeast autonomously replicating sequence (ARS) as the replication origin. In this system, SV40 T antigen as a DNA helicase assembles to the replication origin where the DNA duplex is unwound by torsional stress due to the negative supercoiling of template DNA, which leads to bidirectional DNA replication from the origin. We report here that DNA helicase B isolated from mouse FM3A cells can greatly stimulate DNA synthesis in this replication system in place of SV40 T antigen. DNA synthesis was dependent on the presence of single-stranded DNA binding protein (RP-A), DNA polymerase alpha/primase from mouse cells, and Escherichia coli DNA gyrase. DNA gyrase was required not only at elongation as a DNA swivelase but also at initiation to increase negative superhelical density of template DNA with the assistance of RP-A. A mammalian DNA fragment containing a replication initiation zone upstream of the c-myc gene as well as the yeast ARS fragment acted as a cis-element in this system using DNA helicase B. Both DNA helicase B and SV40 T antigen have the ability to extensively unwind the template DNA in the presence of RP-A and DNA gyrase, which may be crucial for stimulation of DNA synthesis in this system.

Adenosine Triphosphatases↗

PubMed1995

Stimulation of mouse DNA primase-catalyzed oligoribonucleotide synthesis by mouse DNA helicase B.

Many prokaryotic and viral DNA helicases involved in DNA replication stimulate their cognate DNA primase activity. To assess the stimulation of DNA primase activity by mammalian DNA helicases, we analyzed the synthesis of oligoribonucleotides by mouse DNA polymerase alpha-primase complex on single-stranded circular M13 DNA in the presence of mouse DNA helicase B. DNA helicase B was purified by sequential chromatography through eight columns. When the purified DNA helicase B was applied to a Mono Q column, the stimulatory activity for DNA primase-catalyzed oligoribonucleotide synthesis and DNA helicase and DNA-dependent ATPase activities of DNA helicase B were co-eluted from the column. The synthesis of oligoribonucleotides 5-10 nt in length was markedly stimulated by DNA helicase B. The synthesis of longer species of oligoribonucleotides, which were synthesized at a low level in the absence of DNA helicase B, was inhibited by DNA helicase B. The stimulatory effect of DNA helicase B was marked at low template concentrations and little or no effect was observed at high concentrations. The mouse single-stranded DNA binding protein, replication protein A (RP-A), inhibited the primase activity of the DNA polymerase alpha-primase complex and DNA helicase B partially reversed the inhibition caused by RP-A.

Adenosine Triphosphatases↗

PubMed1995

Solid Tubular Carcinoma of the Breast: MR Imaging and Pathologic Correlation.

PURPOSE: Solid tubular carcinoma of the breast is a recognizable histologic type of invasive ductal carcinoma, characterized by rare axillary lymph nodal metastases and a good prognosis. The purpose of this study is to describe the magnetic resonance (MR) characteristics of solid tubular carcinoma and to emphasize the spotty appearance on the MR subtraction images. MATERIALS AND METHODS: We reviewed the MR findings of seven patients with biopsy-proven solid tubular carcinoma. Two of the 7 cases were of the pure type (more than 85% solid tubular component) and the remaining 5 were of the mixed type (50% to 85% solid tubular component). The mean age of the patients was 56 years. RESULTS: The mean size of the lesions was 28 mm. On T1-weighted images four of the lesions were visible and three were not identified. After Gd-DTPA all the lesions were enhanced. On the subtraction images, g" popcorn" appearence areas were noted in the stained mass. CONCLUSION: Our preliminary results suggest that solid tubular carcinomas have a characteristic apperarence on the subtraction MR images.

Journal Article↗

PubMed1995

Differential effects of [3H]nemonapride and [3H]spiperone binding on human dopamine D4 receptors.

We compared some binding parameters of [3H]nemonapride and [3H]spiperone in human dopamine D4 (hD4) receptors with three different numbers of tandem repeat units. Although both of the radioligands showed similar affinity constants for each hD4 receptor variant, the maximal number of binding sites labeled by [3H]nemonapride was approximately 1.35-fold higher than that by [3H]-spiperone for all variants. Estimated Ki values for the inhibition of [3H]nemonapride binding by a series of dopaminergic ligands were highly correlated to respective values obtained for the inhibition of [3H]spiperone binding to each hD4 receptor. These results suggest that the hD4 receptor, as shown for the D2 receptor, may exist in multiple molecular forms as a monomer-dimer equilibria, and that [3H]spiperone may discriminate in the multiple molecular forms.

Benzamides↗

PubMed1995

Polymorphic tandem repeats in dopamine D4 receptor are spread over primate species.

The human dopamine D4 receptor has polymorphic tandem repeats in the third cytoplasmic loop. However, these repeats are not present in the rat counterpart. To determine whether the tandem repeats are specific to humans or not, we analyzed genomic DNA sequences for the D4 receptor of six primate species (human, chimpanzee, gorilla, orangutan, macaque, marmoset). Sequencing data revealed that all primates have the 48-bp tandem repeats in the D4 receptor gene. This finding suggests that these repeats originated before the separation of the New World monkey lineage from the Old World monkey and ape-human lineages.

Amino Acid Sequence↗

PubMed1995

Endoscopic evaluation of gastric inflammatory fibroid polyp.

Clinical and endoscopic manifestations of 18 gastric inflammatory fibroid polyps (IFP) in 16 patients who underwent endoscopic or surgical removal were retrospectively analyzed. All of the lesions were located within the pyloric antrum, and the sizes varied from 0.8 to 7.0 cm. On endoscopy, six polyps which measured 1.0 cm or less uniformly seemed to be sessile or intramural tumors, whereas four of the nine polyps between 1.1 and 2.0 cm in size were additionally accompanied by a central depression. The remaining three, which measured more than 2.0 cm, showed characteristic polypoid growth with ulcerations. Three polyps more than 1.0 cm in size occasionally prolapsed into the duodenal bulb. Three patients with these prolapsing polyps and two with polyps accompanied by ulcerations experienced abdominal pain, nausea, or severe anemia. Two polyps (11%) were precisely diagnosed as IFP by means of conventional forceps biopsy. Histological examinations revealed that all of the polyps proliferated within the submucosa. Therefore, this type of polyp may be subject to endoscopic removal to enable a precise diagnosis and treatment.

Adult↗

PubMed1995

Rat Kupffer cell-derived nitric oxide modulates induction of lymphokine-activated killer cell.

BACKGROUND & AIMS: Nitric oxide is now recognized to regulate immune responses and cell viability in various organs. The present study was designed to clarify whether NO released from Kupffer cells modulates the lymphokine-activated killer (LAK) activity of interleukin 2 (IL-2)-treated splenocytes. METHODS: Splenocytes and Kupffer cells were isolated from male Wistar rats and cocultured for 48 hours in the presence of lipopolysaccharide (1 microgram/mL). The splenocyte LAK activity and expression of IL-2 receptor were determined. RESULTS: Kupffer cells with lipopolysaccharide reduced the IL-2 receptor expression and LAK activity of splenocytes. The addition of either NG-monomethyl-L-arginine, an inhibitor of NO synthesis, or aminoguanidine, an inhibitor of inducible NO synthase, to the medium reversed the suppression of IL-2 receptor expression and LAK activity by lipopolysaccharide-stimulated Kupffer cells. 8-bromoguanosine 3',5'-cyclic monophosphate and NO donors decreased the splenocyte LAK activity and IL-2 receptor expression. Treatment with lipopolysaccharide increased the inducible NO synthase activity as well as the nitrite and nitrate levels in the culture medium of Kupffer cells but not in splenocytes. CONCLUSIONS: The results of this study suggest that NO produced by the inducible NO synthase of Kupffer cells in response to lipopolysaccharide modulates the IL-2 receptor expression and LAK activity of splenocytes.

Analysis of Variance↗

PubMed1995

Effect of Clostridium perfringens-derived wound healing substance as compared with epidermal growth factor on the growth and morphological transformation of BALB/3T3 A31-1-1 cells.

Clostridium perfringens-derived wound-healing substance (WHS), having growth-stimulating activity, was examined to determine its effect on the growth and morphological transformation of BALB/3T3 A31-1-1 cells. WHS accelerated the cell growth at the exponential growth phase, shortening the doubling time by 8-18%. The maximum cell density of the treated cultures was slightly higher than that of the control culture, and the cell number decreased in the same way as the control cells did. On the other hand, the cells treated with epidermal growth factor (EGF) or insulin showed growth rates similar to that of the control cells during the exponential growth phase, and after the control cells attained the maximum cell number, the number of the treated cells continued to increase gradually for more than 4 days and then decreased. Under the experimental conditions of the two-stage transformation assay, application of WHS at the tumor-initiation or promotion stage did not accelerate the formation of transformed foci. Although treatment with EGF at the initiation stage induced no enhancement, marked enhancement of morphological transformation was observed in the treatment at the promotion stage. These results indicate that the mode of action between WHS and EGF or insulin is different on the growth-stimulating activity and morphological transformation of BALB/3T3 A31-1-1 cells.

3T3 Cells↗

PubMed1995

Full-length cDNA cloning and distribution of human dopamine D4 receptor.

Dopamine D4 receptor is the focus of interest in terms of pharmacological profile and possible relation to the disease. Using poly A+RNA from human retina as a template, we succeeded in cloning of full-length cDNA of the human dopamine D4 receptor by improved reverse transcription-polymerase chain reaction (RT-PCR). From the RT-PCR products, two polymorphic variants which had two and four tandem repeats in the putative third cytoplasmic loop were obtained. Transient expression of the full-length cDNA in COS-1 cells produced [3H]spiperone binding sites with a high affinity. These results confirmed the existence of the D4 receptor mRNA containing a different number of polymorphic tandem repeats in native human tissues. The RT-PCR method demonstrated the restricted distribution of the D4 mRNA in human tissues and brain regions. The mRNA was detected at the highest level in the retina, followed by the brain, placenta, and kidney. Among brain regions, relatively low levels for mRNA of the human D4 receptor were observed in the nigrostriatal pathway compared with the mesolimbic system. The distribution of the mRNA in human brain suggests that the D4 receptor plays a different role in the central nervous system compared with the D2 receptor.

Base Sequence↗

PubMed1995

Small nonpolypoid neoplastic lesions of the colon: endoscopic features with emphasis on their progression.

We investigated the endoscopic and histologic features of 74 nonpolypoid neoplasias of the colorectum measuring 15 mm or less in diameter. Colonoscopically, they were characterized by flat growth, being either slightly elevated with a central depression or else completely flat against the surrounding mucosa. Of the 54 lesions measuring 5 mm or less in diameter, 3 (7%) were diagnosed as cancer, whereas the remaining 51 (93%) were diagnosed as adenomas with moderate epithelial atypia. The lesions measuring more than 5 mm were fewer in number (20), and they were more frequently given the histologic diagnosis of severe epithelial atypia (20%) and cancer (70%). Whereas the endoscopic features of the cases of adenoma with moderate atypia included both complete flatness and flat-topped elevation with a central depression, the lesions diagnosed as adenoma with severe atypia were endoscopically recognized as flat or slightly depressed lesions, and a deep central depression or prominent elevation was noted in the lesions diagnosed as cancer. These findings suggest that some minute nonpolypoid neoplasias may transform to nonpolypoid cancers and invade the submucosa, whereas others do not manifest rapid growth.

Adenoma↗

PubMed1995

Small flat cancer of the rectum: clinicopathologic and endoscopic features.

The clinicopathologic and endoscopic features of 15 patients with small flat cancer of the rectum were investigated. Whereas 4 patients had hematochezia, the remaining 11 patients were asymptomatic, and stool positive for occult blood was the only remarkable clinical feature in 8 of them. Endoscopic features were slight elevation with central depression in 8 lesions, flat-topped elevation in 4, and shallow depression with irregular margin in 3. The surface of the tumor was often faint red in color and frequently characterized by mucosal friability. Five flat rectal cancers were missed during initial endoscopy, and they were found by repeated endoscopic examination. Three flat cancers were not identified in the distal rectum until retroflexed colonoscopic observation was performed. Although all tumors were smaller than 2 cm in diameter and 6 of them were under 1 cm, 9 lesions had deeply invaded the submucosal layer and 7 tumors showed lymphovascular permeation. Two lesions of 1 cm or greater had metastasized to perirectal lymph nodes. These results suggest that careful observation during endoscopy is necessary to detect flat rectal cancers, and a U-turn to examine the anorectal junction should be routinely done in the appropriate age group.

Adenocarcinoma↗

PubMed1995

Metal-mediated oxidative damage to cellular and isolated DNA by certain tryptophan metabolites.

The tryptophan metabolites 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxykynurenine (3-HKyn) are carcinogens. DNA damage by 3-HAA and 3-HKyn in the presence of metal ions was investigated as a potential mechanism of their carcinogenicity. Pulsed field gel electrophoresis showed that in the presence of Mn(II), 3-HAA and 3-HKyn induced DNA double-strand breaks in cultured human cells. DNA single-strand breaks were observed with alkali treatment. The enhancing effect of catalase inhibitor and the inhibitory effect of o-phenanthroline on the strand breakage indicated the involvement of H2O2 and endogenous transition metal ion. Damage to DNA fragments obtained from c-Ha-rds-1 protooncogene was investigated by a DNA sequencing technique. 3-HAA and 3-HKyn induced piperidine-labile sites frequently at thymine and guanine residues in the presence of Cu(II). The inhibitory effects of bathocuproine and catalase on Cu(II)-mediated DNA damage suggest that Cu(I) and H2O2 have important roles in the production of active species causing DNA damage. The Cu(II)-mediated DNA damage was enhanced by preincubation of 3-HAA with Mn(II). UV-visible spectroscopy showed that Mn(II) and Cu(II) enhanced the rate of autoxidation of 3-HAA in different ways. These results suggest that in the presence of Mn(II) or Cu(II), these tryptophan metabolites produce H2O2, which is activated by transition metal ion to cause damage to DNA both in the case of isolated DNA and cultured cells.

3-Hydroxyanthranilic Acid↗

PubMed1995

Insect cell expression of recombinant imidazoleglycerolphosphate dehydratase of Arabidopsis and wheat and inhibition by triazole herbicides.

Imidazoleglycerolphosphate dehydratase (IGPD; EC 4.2.1.19), which is involved in the histidine biosynthetic pathway of Arabidopsis thaliana and wheat (Triticum aestivum), has been expressed in insect cells using the baculovirus expression vector system. N-terminal amino acid sequencing indicated that recombinant IGPDs (rIGPDs) were produced as mature forms via nonspecific proteolytic cleavages in the putative transit peptide region. The wheat rIGPD contained one Mn atom per subunit, and the Mn was involved in the assembly of the subunits to form active IGPDs. Protein-blotting analysis, using antibodies raised against the wheat rIGPD, indicated that IGPD was located in the chloroplasts of wheat. The rIGPDs of Arabidopsis and wheat, which were 86% identical in their primary structures deduced from the cDNAs, exhibited similar properties in terms of the molecular mass, pH optimum, and the Km for the substrate, imidazoleglycerolphosphate. However, the nonselective herbicides 3-amino-1,2,4-triazole and a newly synthesized triazole [(1R*, 3R*)-[3-hydroxy-3-(2H-[1,2,4]triazole-3-yl)-cyclohexyl]- phosphonic acid], inhibited Arabidopsis and wheat IGPDs in a mixed-type and a competitive manner, respectively.

Amino Acid Sequence↗

PubMed1995

Characterization of DNA synthesis and DNA-dependent ATPase activity at a restrictive temperature in temperature-sensitive tsFT848 cells with thermolabile DNA helicase B.

A temperature-sensitive mutant defective in DNA replication, tsFT848, was isolated from the mouse mammary carcinoma cell line FM3A. In mutant cells, the DNA-dependent ATPase activity of DNA helicase B, which is a major DNA-dependent ATPase in wild-type cells, decreased at the nonpermissive temperature of 39 degrees C. DNA synthesis in tsFT848 cells at the nonpermissive temperature was analyzed in detail. DNA synthesis measured by incorporation of [3H]thymidine decreased to about 50% and less than 10% of the initial level at 8 and 12 h, respectively. The decrease in the level of thymidine incorporation correlated with a decrease in the number of silver grains in individual nuclei but not with the number of cells with labeled nuclei. DNA fiber autoradiography revealed that the DNA chain elongation rate did not decrease even after an incubation for 10 h at 39 degrees C, suggesting that initiation of DNA replication at the origin of replicons is impaired in the mutant cells. The decrease in DNA-synthesizing ability coincided with a decrease in the level of the DNA-dependent ATPase activity of DNA helicase B. Partially purified DNA helicase B from tsFT848 cells was more heat sensitive than that from wild-type cells. Inactivation of DNA-dependent ATPase activity of DNA helicase B from mutant cells was considerably reduced by adding DNA to the medium used for preincubation, indicating that the DNA helicase of mutant cells is stabilized by binding to DNA.

Animals↗

PubMed1995

Simple reaction times and timing of serial reactions of adolescents with mental retardation, autism, and Down syndrome.

The purpose of this study was to examine the serial information processing in adolescents with mental retardation, autism, and Down syndrome by using a serially patterned tracking task. Analyses indicated that 7 adolescents with mental retardation, 8 with autism, and 3 with Down syndrome had significantly slower and more variable simple reaction times than did 10 college students. Also, the autistic adolescents had significantly faster mean simple reaction time than those with Down syndrome. On a task of tracking serial light stimulation, mentally retarded adolescents had significantly faster reaction time than college students. The autistic subjects excessively had faster anticipatory reaction time than did the subjects in the other three groups. On the other hand, adolescents with Down syndrome had markedly slower and more variable reaction time than did adolescents with non-Down-syndrome mental retardation. As for motor organization of keystrokes on the tracking task, mentally retarded adolescents responded with six movements, in which these individuals pressed a series of keys 1, 2, 3, 4, 5, and 6, as a chunk, as exhibited by college students. Adolescents with autism and Down syndrome, however, did not produce this movement-output chunking.

Adolescent↗