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Biomedical subjects

T Honma

Publications and source records attributed to T Honma.

At least 55 records · Page 3Linked to original sources
PubMed2000

The Arabidopsis floral homeotic gene PISTILLATA is regulated by discrete cis-elements responsive to induction and maintenance signals.

PISTILLATA is a B-class floral organ identity gene required for the normal development of petals and stamens in Arabidopsis. PISTILLATA expression is induced in the stage 3 flowers (early expression) and is maintained until anthesis (late expression). To explore in more detail the developmentally regulated gene expression of PISTILLATA, we have analyzed the PISTILLATA promoter using uidA (beta)-glucuronidase gene) fusion constructs (PI::GUS) in transgenic Arabidopsis. Promoter deletion analyses suggest that early PISTILLATA expression is mediated by the distal region and that late expression is mediated by the proximal region. Based on the PI::GUS expression patterns in the loss- and gain-of-function alleles of meristem or organ identity genes, we have shown that LEAFY and UNUSUAL FLORAL ORGANS induce PISTILLATA expression in a flower-independent manner via a distal promoter, and that PISTILLATA and APETALA3 maintain PISTILLATA expression (autoregulation) in the later stages of flower development via a proximal promoter. In addition, we have demonstrated that de novo protein synthesis is required for the PISTILLATA autoregulatory circuit.

Arabidopsis↗
PubMed2000

4-Sulfenyl-2-carbamoyl-4-isoxazolin-3-ones: biological isostere to 4-chloro-2-carbamoyl-4-isoxazolin-3-ones.

4-Sulfenyl-2-carbamoyl-4-isoxazolin-3-ones (4) were designed on the basis of biological isosterism and prepared in four steps. Some of these compounds showed sufficient pre-emergent herbicidal activities against various kinds of weeds. Among the synthesized compounds, 2-(N-(4-chlorophenyl)-N-isopropylcarbamoyl)-4-ethylthio-5-methyl-4 -isoxazolin-3-one (4cd) exhibited the most promising activity.

Carbamates↗
PubMed2000

Detection and measurement of urinary 2-hydroxyestradiol 17-sulfate, a potential placental antioxidant during pregnancy.

BACKGROUND: Preeclampsia is associated with a quantitative imbalance between lipid peroxide and an antioxidant coproduced in the placenta. To investigate our hypothesis that 2-hydroxyestradiol 17-sulfate (2-OH-ES) is the placental antioxidant during pregnancy, we developed an assay for 2-OH-ES in urine and studied samples from women with and without preeclampsia. METHODS: The detection and measurement of 2-OH-ES in the urine of pregnant women were performed by RIA using highly specific antiserum to 2-OH-ES. To confirm the reliability of the RIA method, the same samples were analyzed by HPLC using an electrochemical detector. RESULTS: Urinary 2-OH-ES values obtained by RIA showed a close relationship to those obtained by HPLC (y = 1.1x - 0.01; r = 0.96). The urinary 2-OH-ES concentrations during the first, second, and third trimesters were 2. 0 +/- 0.6 (mean +/- SE, n = 13), 5.3 +/- 1.3 (n = 21), and 15.3 +/- 2.0 microg/mg creatinine (n = 54), respectively, and <0.15 microg/mg creatinine (n = 10) at 2-24 h after delivery. The concentrations in preeclamptic women during the third trimester were significantly lower, 3.9 +/- 1.9 microg/mg creatinine (mean +/- SE, n = 12). CONCLUSIONS: RIA can be used to measure urinary 2-OH-ES during pregnancy. The increase in urinary 2-OH-ES during gestation, its decrease after delivery, and the lower values in preeclampsia are consistent with a role of 2-OH-ES as a placental antioxidant.

Adolescent↗
PubMed2000

Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly.

We investigated the molecular basis of holoprosencephaly in a sporadic patient and identified a novel missense mutation in the signal sequence of the sonic hedgehog (Shh) gene. Magnetic resonance imaging of the head showed a lobar type of holoprosencephaly and partial agenesis of the anterior corpus callosum. He was treated for craniosynostosis at 7 months of age. All three exons of the Shh gene were amplified by polymerase chain reaction from genomic DNA of the patient and controls. Sequencing analysis of the polymerase chain reaction fragments, screened by single-strand conformation polymorphism analysis, revealed a heterozygous mutation of a T-to-C substitution at nucleotide position 50. This mutation predicted an amino acid replacement of leucine to proline at codon 17 located in the signal peptide of SHH protein. It probably disturbs the translocation of the protein into the endoplasmic reticulum and may lead to holoprosencephaly because of haploinsufficiency of Shh.

Adult↗
PubMed2000

[Regional cerebral blood flow of the basal ganglia and thalamus measured using Xe-CT].

Cerebral blood flow (CBF) images obtained using Xe-CT have a much higher spatial resolution than SPECT or PET images. The regional CBF (rCBF) of deep brain regions, the basal ganglia and thalamus, was able to be measured using Xe-CT in 6 subjects. Average rCBF was 87.1 +/- 20.7 ml/100 g/min in the caudate nucleus, 83.5 +/- 15.8 ml/100 g/min in the putamen, 50.0 +/- 8.7 ml/100 g/min in the globus pallidus and 88.9 +/- 12.4 ml/100 g/min in the thalamus. The average rCBF value of the globus pallidus was lower than the values of the caudate nucleus, putamen and thalamus. These observations may be explained by reduced cellularity of the globus pallidus in comparison to the other regions. SPECT and PET are not able to clearly demonstrate the globus pallidus on CBF images. However, precise rCBF values can be measured in the globus pallidus using Xe-CT.

Adult↗
PubMed1999

Synthesis and biological activities of NB-506 analogues: Effects of the positions of two hydroxyl groups at the indole rings.

In the course of a study of 6-N-amino-substituted analogues of NB-506 (1), a more potent anticancer drug, J-109,404 (2), in which the formyl group of NB-506 was replaced with a 1,3-dihydroxypropane group, was reported. A study of further modification in the positions of two hydroxyl groups at the indole rings of 2 resulted in the discovery of a 2,10-dihydroxy analogue, J-107,088 (3), which is a promising anticancer agent with a broader therapeutic window than J-109,404.

Animals↗
PubMed1999

Trichloroethylene inhibits aldehyde dehydrogenase only for aliphatic aldehydes of short chains in rats.

The effects of trichloroethylene (TCE) administration on aldehyde dehydrogenase (ALDH) and cytochrome P450 isozymes were studied in rats and compared with those of methanol. Intragastric administration of TCE to rats at 0.05 or 0.2 ml/kg for 1 week significantly inhibited ALDH activity for aliphatic aldehydes of short chains in the mitochondrial and cytosolic fractions of rat liver, respectively, but had no effect on the activity for long chain aliphatic aldehydes. ALDH activity catalyzing the metabolism of some aromatic aldehydes was even induced by TCE. Microsomal ALDH activity was not decreased by TCE treatment. A kinetic study showed that the low-Km isozyme of ALDH for propionaldehyde in mitochondrial and cytosolic fractions was inhibited by TCE treatment. Addition of TCE, trichloroethanol or trichloroacetic acid to the in vitro assay system did not affect the activity for acetaldehyde, but chloral hydrate at 0.02 mM decreased the activity by 42 and 35% in cytosol and the 700 x g supernatant, respectively. Methanol treatment, on the other hand, had no effect on any ALDH activity. Both TCE and methanol significantly induced CYP2E1 in rat liver. The combined effects of TCE on ALDH and cytochrome P450 may account for the degreasers' flush. Exposure to TCE and methanol may result in a change in the metabolism and toxicity of other chemicals.

Alcohol Dehydrogenase↗
PubMed1999

Diffuse pachygyria with cerebellar hypoplasia: a milder form of microlissencephaly or a new genetic syndrome?

We report on 2 families with diffuse pachygyria and cerebellar hypoplasia, who presented hypotonia, ataxia, seizures, and developmental delay since infancy. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed decreased gyral formation in the cerebral cortex and marked hypoplasia in the cerebellum. Cerebellar hypoplasia is often associated with type 2 lissencephaly; however, our cases showed no polymicrogyria, and their clinical findings were quite mild compared with those of microlissencephaly. Their characteristic phenotype suggested a new genetic syndrome, which was possibly inherited as an autosomal recessive trait.

Cerebellar Diseases↗
PubMed1999

Regional differences on production of chemokines in gastric mucosa between Helicobacter pylori-positive duodenal ulcer and gastric ulcer.

It is well known that antrum-predominant gastritis and pan-gastritis occurs in the patients with Helicobacter pylori-positive duodenal ulcer (DU) and gastric ulcer (GU), respectively. However, the role of chemokines in the pathogenesis of these pathologies is unclear. We examined the regional differences in mucosal chemokine production in patients with DU and GU. The production of interleukin-8 (IL-8), growth-related gene (GRO) alpha, and macrophage inflammatory protein (MIP)-1alpha was greater in the antrum than in the corpus in DU patients. In the patients with GU, monocyte chemoattractant protein (MCP)-1 levels in the mucosa adjacent to ulcer were greater than those away for the ulcer in the corpus. The reduction in chemokine production occurring in association with the eradication of H. pylori differed between DU and GU patients in the antrum (IL-8, P = 0.0394; GROalpha, P = 0.0149; MIP-1alpha, P = 0.0246; MCP-1, P = 0.0087). The data imply a different pathogenesis may exist for the gastritis present in patients with DU and GU occurring in H. pylori-positive individuals.

Adult↗
PubMed1999

HLA genotyping of 5,000- and 6,000-year-old ancient bones in Japan.

We used polymerase chain reaction (PCR)-based DNA typing to identify HLA class II alleles of two individuals from ancient human remains. Genomic DNAs were isolated from two ancient human skeletons excavated from the Sanganji and Kitakogane sites in the main and northern islands of Japan, respectively. They were archaeologically estimated to be approximately 5,000 and 6,000 years old respectively, representing the remnants from the Jomon era. High molecular weight DNA was extracted by the standard proteinase K-phenol extraction method followed by purification with a Centricon-30 micro concentrator. Several rounds of PCR successfully gave rise to amplification of the HLA-DRB1 and -DQA1 genes. The PCR-restriction fragment length polymorphism (PCR-RFLP) and sequencing based typing (PCR-SBT) methods revealed that those ancient individuals possessed the DRB1 and DQA1 alleles which are highly prevalent among the modern north Asian as well as Japanese populations.

Alleles↗
PubMed1999

Clinicopathological study of recurrent uterine cervical squamous-cell carcinoma.

OBJECTIVE: To improve prognoses of patients with recurrent uterine cervical squamous-cell carcinoma. PATIENTS AND METHODS: We clinicopathologically analyzed 464 patients with uterine cervical squamous-cell carcinoma (126 positive, 338 negative pelvic lymph-node metastasis) who were treated at the Saitama Cancer Center from January 1, 1976 to December 31, 1991. RESULTS: The recurrence rates of negative pelvic lymph-node metastasis patients were 14. 2% (39/274) in pT1b and 32.8% (21/64) in pT2b. But for positive lymph-node metastasis patients the rates were 39.0% (23/59) in pT1b and 58.2% (39/67) in pT2b. The interval to recurrence was shorter in positive pelvic lymph-node patients than in negative patients. The 5-year survival rates after relapse of negative lymph-node patients with intrapelvic, extrapelvic, and both-sites recurrence were 53, 12, and 40%, respectively. But among distant recurrent sites, lung metastasis in negative lymph-node patients and lymphatic tract metastasis brought relatively fair prognoses. CONCLUSIONS: Regular long-term checks are necessary and active retreatments are recommended for patients with local recurrences, lung metastasis, or lymphatic vessel metastatic lesions.

Bone Neoplasms↗
PubMed1999

Genotypes of alcohol-metabolizing enzymes in relation to alcoholic chronic pancreatitis in Japan.

Long-term consumption of large amounts of alcohol is the main cause of chronic pancreatitis. All heavy drinkers, however, do not contract chronic pancreatitis. Although genetic predisposition to alcoholism and alcoholic liver disease has been reported, genetic susceptibility to alcoholic pancreatitis is still a matter of debate. To determine the relation between genotypes of alcohol-metabolizing enzymes and chronic alcoholic pancreatitis, we examined genotype patterns of aldehyde dehydrogenase 2 (ALDH 2), alcohol dehydrogenase 2 (ADH 2) and cytochrome P-4502E1 (CYP2E1) in 54 patients with chronic alcoholic pancreatitis who were diagnosed in general hospitals in all over Japan and compared with those in 30 patients with chronic nonalcoholic pancreatitis or in 46 alcoholics with normal pancreatic function. There were no significant differences in the distribution of genotypes of ALDH 2 and CYP2E1 among those three groups. As for the ADH 2 genotype, distribution of 2(1)/2(1), 2(1)/2(2), and 2(2)/2(2) was 35%, 30%, and 35% in alcoholics with normal pancreatic function; 4%, 39%, and 57% in the chronic alcoholic pancreatitis group; and 0%, 50%, and 50% in the chronic nonalcoholic pancreatitis group, respectively. The frequency of ADH 2(2) allele was significantly higher in the chronic alcoholic pancreatitis group, compared with alcoholics with normal pancreatic function; but, it was not significantly different from that in the chronic nonalcoholic pancreatitis group. We also examined the relation between pancreatic fibrosis or pancreatitis histologically diagnosed and genotypes of alcohol-metabolizing enzymes in alcoholic autopsy cases. Twenty of 31 cases showed moderate or severe pancreatic fibrosis and showed intralobular + interlobular fibrosis, which is characteristic in alcoholic pancreatitis or intralobular fibrosis. ADH 2(2) allele tended to show a high frequency in the intralobular + interlobular fibrosis group, compared with that in the intralobular fibrosis group (75.0% vs. 41.7%, p < 0.1). The chronic pancreatitis group had a significantly higher frequency of the ADH 2(2) allele than that in cases without such findings (87.5% vs. 58.7%, p < 0.05). However, the ALDH 2 and CYP2E1 genotypes showed no significant relation to the findings of pancreatic fibrosis or histological pancreatitis. These data suggest that the risk of chronic alcoholic pancreatitis diagnosed clinically and pathologically seems to be associated with the ADH 2(2) allele in the genotypes of alcohol-metabolizing enzymes.

Alcohol Dehydrogenase↗
PubMed1999

Synthesis and structure-activity relationship of a new series of potent angiotensin II receptor antagonists: pyrazolo[1,5-a]pyrimidine derivatives.

We have already reported 7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid derivatives, which are potent in vitro angiotensin II (AII) antagonists, but have no oral antihypertensive activity. Removal of the carboxylic acid and replacement of the heteroaromatic system afforded potent in vitro antagonists. Removal of the carbonyl oxygen and changing the position of the biphenyltetrazole substituent were critical to the display of oral activity. To improve the in vitro and oral activities, modifications were made of the substituents at the 3- and 5-positions of the pyrazolo[1,5-a]pyrimidine. Structure-activity studies showed the methyl substituent at the 3-position to be essential for potent in vivo activity. We present the design, syntheses, and biological data of a series of pyrazolo[1,5-a]pyrimidine derivatives, which are orally active AII receptor antagonists.

Angiotensin II↗
PubMed1999

Effects of toluene on regulation of adenylyl cyclase by stimulation of G-protein-coupled receptors expressed in CHO cells.

We determined the effects of toluene exposure on activation or inhibition of adenylyl cyclase by stimulating human beta2-adrenergic receptors (beta2-AR) and muscarinic acetylcholine receptor (mAChR) m2 subtypes, respectively, expressed in CHO cells. The formation of cAMP via beta2-AR stimulation was slightly but not significantly facilitated in the presence of 3.7 microM toluene. On the other hand, the inhibition of adenylyl cyclase by 10 microM of carbamylcholine stimulation of mAChR m2 subtypes was attenuated in the presence of toluene. These results strongly suggest that toluene affects activation of Gi rather than Gs.

Adenylyl Cyclase Inhibitors↗
PubMed1999

The contribution of acute toxicity in animals to occupational exposure limits of chemical substances.

The correlations of lethal doses of various industrial chemicals for rats and mice with occupational exposure limit values were investigated. 50% lethal dose (LD50) values obtained by oral (p.o.) and intraperitoneal (i.p.) injection and 50% lethal concentration (LC50) values obtained by inhalation exposure were collected from Registry of Toxic Effects of Chemical Substances (RTECS). Threshold Limit Value (Time-Weighted Average) (TLVs-TWA) and Threshold Limit Value (Short Term Exposure Limit) (TLVs-STEL) recommended by American Conference of Governmental Industrial Hygienists (ACGIH) were used as exposure limits. TLVs-TWA or TLVs-STEL and LD50 or LC50 values obtained for the rats were plotted on logarithmic scales on the ordinate and abscissa, respectively. High correlations were obtained between these parameters. The order of correlations was: TLVs-STEL vs. LC50s > TLVs-TWA vs. LC50s > TLVs-TWA vs. LD50s i.p. > TLVs vs. LD50s p.o. The same calculations for the relationship between TLVs and lethal doses in mice were also performed. The order of the three types of correlations was same as that of the rats; however, correlation coefficients for TLVs-STEL vs. LC50s and for TLVs-TWA vs. LC50s obtained in mice were smaller than those in rats. TLVs-TWA are, therefore, well correlated with LC50 values rather than LD50 values, particularly with those in rats. High correlations between TLVs-STEL vs. LC50s were also obtained, as had been expected before calculation. The equation: TLV-TWA = 10b x (LC50)a can be obtained from these plottings, where the values a and b are taken from each linear regression line. TLV-TWA for each chemical can be calculated by using LC50 and the equation. The upper and lower 95% confidence limits for calculated TLV-TWA were TLV-TWA (calculated from LC50) x 22.9 and TLV-TWA (calculated)/22.9, respectively, where LC50 for rats expressed in ppm x hr was used.

Animals↗
PubMed1999

Different change patterns of the isozymes of cytochrome P450 and glutathione S-transferases in chemically induced liver damage in rat.

In this experiment, we studied the different changes in activities and protein levels of each subform of hepatic cytochrome P450 and glutathione S-transferase (GST), in chemical-induced liver injury in rats. Rats were administered 1,1-dichloroethylene (DCE), allyl alcohol (AA), bromobenzene (BB) and N,N-dimethylformamide (DMF) p.o. once every two days for 7 times, and decapitated 18 hr after the last administration. DCE and AA showed stronger hepatic toxicity than BB and DMF, as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were higher in DCE and AA treated rats than in BB and DMF groups. Anti-cytochrome P450 inhibitable activity of toluene metabolism and/or immunoblot analysis showed that CYP2E1 and CYP2B1/2 were induced by BB and DMF, but not by the other two chemicals; CYP2C11 was greatly decreased by all of the four toxicants; and CYP1A1/2 was slightly reduced by the four treatments. These changes were reflected in testosterone metabolism. Formation of 6 beta- and 7 alpha-hydroxytestosterone from testosterone was enhanced only in DMF-treated rats, whereas that of 2 alpha- and 16 alpha-hydroxytestosterone was reduced by all of the four chemicals. Serum GST activity was increased only in BB and DMF treated rats, but liver cytosolic GST activity was enhanced by all of the four hepatotoxicants, with higher values in BB and DMF groups than in DCE and AA groups. Immunoblot analysis demonstrated that GST Yp was induced by BB and DMF treatments, and Ya and Yc were increased only by BB. GST Yk and Yb1 were not affected by the treatments. The different change patterns of enzymes by a specific toxin and the similar modifying effect on a specific enzyme by different toxins were discussed in relation to the liver damage and to the heterogeneous distribution of enzymes in liver.

Administration, Oral↗
PubMed1999

[A case of sleeve resection of the left main bronchus for tuberculous bronchial lesion].

A 31-year-old woman was admitted to our center with left chest pain and dyspnea after treatment of pulmonary tuberculosis. Chest X-ray film showed atelectasis of left lower lobe and left deviation of the mediastium. Bronchofiberscopy revealed obstruction of the left main bronchus. Chest MRI showed intermediate intensity at the left main bronchus and very high intensity at the peripheral bronchus. We performed sleeve resection of the left main bronchus and anastomosed end to end with absorbable monofilament sutures. Postoperative course was uneventful. Bronchoplasty for tuberculous obstructive lesion is a useful procedure.

Adult↗