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S Ichii

Publications and source records attributed to S Ichii.

At least 19 recordsLinked to original sources
PubMed1992

Frequent somatic mutations of the APC gene in human pancreatic cancer.

The APC (adenomatous polyposis coli) gene is responsible for familial adenomatous polyposis and is also associated with the development of sporadic tumors of the colon and stomach. To investigate whether or not mutations of APC play any role in tumors arising in other organs, we examined somatic mutations of this gene in sporadic (nonfamilial) renal cell carcinomas, hepatocellular carcinomas, and cancers of the lung and pancreas. DNAs isolated from tumors were examined by means of a RNase protection analysis, coupled with the polymerase chain reaction followed by DNA sequencing of the polymerase chain reaction products. By screening a part of the APC coding region, we detected somatic mutations in four of ten pancreatic cancers; each of these mutations would yield a truncated APC product due to a 1- or 5-base pair deletion. These results imply that mutations in APC contribute to carcinogenesis in the pancreas.

Base Sequence↗
PubMed1992

The APC gene, responsible for familial adenomatous polyposis, is mutated in human gastric cancer.

Although gastric cancer is the most common cancer in the world, genetic changes during its carcinogenesis are not well understood. Since some gastric cancers are considered to originate from the intestinal metaplasia, it is likely that the adenomatous polyposis coli (APC) gene, the mutation of which causes adenomatous polyps in the colon, is associated with carcinogenesis of gastric cancer. Based on this idea, DNAs isolated from gastric cancers were examined by means of a RNase protection analysis coupled with polymerase chain reaction followed by sequencing of the polymerase chain reaction products. By screening nearly one-half of the coding region of the APC gene in 44 tumors, somatic mutations were detected in three tumors: a missense mutation, a nonsense mutation, and a 5-base pair deletion resulting in a frame shift which causes truncation of the gene product. These results suggest that the mutation of the APC gene also plays an important role during the carcinogenesis of at least some gastric cancers.

Adenocarcinoma↗
PubMed1992

Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene.

We examined somatic mutations of the adenomatous polyposis coli (APC) gene in 63 colorectal tumors (16 adenomas and 47 carcinomas) developed in familial adenomatous polyposis (FAP) and non-FAP patients. In addition to loss of heterozygosity (LOH) at the APC locus in 30 tumors, 43 other somatic mutations were detected. Twenty-one of them were point mutations; 16 nonsense and two missense mutations, and three occurred in introns at the splicing site. Twenty-two tumors had frameshift mutations due to deletion or insertion; nineteen of them were deletions of one to 31 bp and three were a 1-bp insertion. One tumor had a 1-bp deletion in an intron near the splicing site. Hence, 41 (95%) of 43 mutations resulted in truncation of the APC protein. Over 60% of the somatic mutations in the APC gene were clustered within a small region of exon 15, designated as MCR (mutation cluster region), which accounted for less than 10% of the coding region. Combining these data and the results of LOH, more than 80% of tumors (14 adenomas and 39 carcinomas) had at least one mutation in the APC gene, of which more than 60% (9 adenomas and 23 carcinomas) had two mutations. These results strongly suggest that somatic mutations of the APC gene are associated with development of a great majority of colorectal tumors.

Adenoma↗
PubMed1992

Inactivation of both APC alleles in an early stage of colon adenomas in a patient with familial adenomatous polyposis (FAP).

To examine whether the dosage effect of germ-line mutations in patients with familial adenomatous polyposis (FAP) is sufficient to cause colorectal adenomas, or an additional somatic mutation of the normal allele is required as well, we have investigated somatic mutations of the APC gene in multiple adenomas developed in one FAP patient. In addition to a 5-bp deletion of one allele present constitutionally in this patient, the normal APC allele had been lost in five of seven DNA samples extracted from small adenomas (< 3 mm in diameter) with mild or moderate atypia. This result indicates that the inactivation of both alleles of the APC gene is probably essential for the development of an early-stage adenoma, in agreement with the two-hit mutational model underlying the concept of tumor suppressor genes.

Adenoma↗
PubMed1992

Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet-ring cell carcinoma.

We searched for somatic mutations of the adenomatous polyposis coli (APC) gene in DNA samples isolated from 57 sporadic gastric cancers, by means of a ribonuclease (RNase) protection analysis coupled with DNA amplification by the polymerase chain reaction (PCR). Examining 30% of the APC coding region, including a region where somatic mutations in colorectal tumors are known to be clustered, we detected somatic mutations in 12 tumors; seven in 17 very well differentiated adenocarcinomas, two in 19 well or moderately differentiated adenocarcinomas, and three in ten signet-ring cell carcinomas. So far, no somatic mutations have been identified in 11 poorly differentiated adenocarcinomas. Eight of the 17 somatic mutations found in 12 tumors caused truncation of the gene product due to a nonsense mutation and a 1-, 2- or 5-bp deletion; nine others were point mutations that altered amino acids. Our results suggest that inactivation of APC plays a role in development of some gastric cancers, particularly very well differentiated adenocarcinomas and signet-ring cell carcinomas.

Adenocarcinoma↗
PubMed1991

Atypical depressive symptoms possibly predict responsiveness to phototherapy in seasonal affective disorder.

Phototherapy was administered to 24 depressed patients with seasonal affective disorder (SAD), of which 62%, 24%, and 14%, respectively, showed improvements of greater than or equal to 50%, 25-50%, and less than 25% based on the Hamilton rating scale for depression for SAD (HAMSAD). No patients showed aggravation or side effects. Although the improvement rate in HAMSAD correlated significantly with the pretreatment severity of atypical symptoms of depression, it did not correlate with that of typical symptoms. This suggests that phototherapy is a useful treatment in SAD and that responsiveness to phototherapy in SAD can possibly be predicted by the atypical depressive symptoms before treatment.

Adolescent↗
PubMed1991

Re-investigation of ontogenesis of epidermal growth factor receptor mRNA in the liver of rats: quantitative evaluation of northern blot analysis.

Changes in the expression rate of epidermal growth factor receptor (EGFR) mRNA with age in the liver of rats were examined to assess the contribution of EGF to the proliferation of hepatocytes in younger animals. Northern blot analyses with a 32P-labeled probe derived from the extracellular domain of EGFR cDNA were evaluated quantitatively by normalizing the densitometric scanning data with the relative amounts of poly(A)+ RNA in the samples. The expression of EGFR mRNA was low during the early period and increased towards the adult level after 21 days of birth. In contrast, the rate of beta-actin mRNA expression was significantly higher immediately after birth and showed a tendency to decrease with time.

Actins↗
PubMed1991

Isolation and characterization of cDNA clones for castration-induced mRNAs in the rat ventral prostate.

To identify gene products involved in castration-induced involution of the rat ventral prostate, we constructed a subtraction cDNA library of the ventral prostate from rats castrated for 48 h. The library was screened with subtracted cDNA probes enriched for sequences with a low copy number expressed in intact or castrated rats. As a result of differential screening, 48 cDNA clones representing 10 different induced mRNAs were isolated. The time course of these mRNA inductions after castration was examined. Within the first 24 h after castration, the level of mRNAs for these cDNA clones was significantly increased and it reached its peak by 48-72 h after castration. Although mRNAs for these cDNA clones were expressed in various tissues from intact rats, an increase in mRNA as a response to castration was observed only in the ventral prostate. Partial sequence analyses of the 10 cDNA clones indicate that three cDNA clones represent rat glutathione S-transferase Yb-1, Yb-2 and Yb-3 subunit mRNA sequences, but for others respective homologues could not be found in a search of the GenBank database (release 67).

Animals↗
PubMed1990

Epidermal growth factor receptor mRNA in livers from newborn, adult and partially hepatectomized rats.

Epidermal growth factor (EGF) receptor mRNA expression in livers of newborn, adult control and partially hepatectomized rats 1 and 3 days post-operation was examined by Northern blot analysis. A human EGF receptor cDNA (P 64-1, Ullrich et al., 1984) was hybridized to RNA species of 10, 6 and 3 kb. These mRNAs were profoundly decreased in livers from newborn rats and relatively decreased in regenerating rat livers. beta-Actin mRNA in these tissues showed a tendency to increase over that of the adult controls.

Animals↗
PubMed1990

Growth and fecundity of Schistosoma japonicum in mice maintained at different environmental temperatures.

On weeks 7 and 9 post infection (PI), the number of Schistosoma japonicum in mice maintained at low (5 degrees C) and high (32 degrees C and 35 degrees C) temperatures did not differ from those in controls (25 degrees C), but shorter males were observed in hosts at 5 degrees C. Further, both male and female worms recovered on week 7 PI from mice kept at 35 degrees C were shorter than those recovered from controls. Staining analysis revealed that worm maturation was not affected in mice kept at 5 degrees C and 32 degrees C. However, some female worms from mice kept at 35 degrees C had no eggs in the uterus. The day of patency of worms in the temperature-stressed mice did not differ from that in controls. EPG in mice kept at 32 degrees C rose to a high level on weeks 7-8 PI which was about 10 times as many as those in control mice, while EPG in mice kept at 5 degrees C appeared to be lower than in controls. The 7-week tissue egg count revealed that the hot- and cold-stressed mice supported significantly less egg productivity per female worm than control mice. The environmental temperature could not alter the migration pattern of schistosomula from the skin to lungs in mice.

Animals↗
PubMed1990

[Acute myeloblastic leukemia associated with 46, XY, del(5)(q22)].

A 38-year-old male admitted to the Internal Medicine of Surugadai Nihon University Hospital, complaining of general fatigue and throat pain. The laboratory examinations revealed leukocytosis (83, 900/microliters) and an appearance of myeloblasts (90.2%) in the peripheral blood. The nucleated cell count was 56 x 10(4)/microliters with 85.5% myeloblasts in bone marrow. He was diagnosed as acute myeloblastic leukemia (AML). Though he received two courses of combination chemotherapy with daunorubicin, BH-AC, 6 MP and prednisone, one course of combination with mitoxantrone, etoposide and cytosine arabinoside and one course of combination with aclarubicin cytosine arabinoside and prednisone, he could not achieved remission. A chromosome analysis revealed 46, XY del(5)(q22). The amount of DNA fragments hybridized to 4.5 Kb v-fms probe in blastoid cells was approximately a half amount of normal persons. It is not defined the relationship between the decrease of fms and leukemia in this case. He was diagnosed de novo AML, since he had not been received the therapy with potential mutagenic and carcinogenic agents and had not been exposed the irradiation on his works.

Adult↗
PubMed1989

Epidermal growth factor (EGF) binding, EGF-dependent autophosphorylation and activity of tyrosine-specific protein kinase in hepatic membrane fractions from fetal, newborn, adult and partially hepatectomized rats.

The binding of 125I-epidermal growth factor (EGF) and activities of EGF-receptor autophosphorylation and of tyrosine-specific protein kinases were determined in hepatic membrane fraction from newborn, fetal and hepatectomized adult rats and compared with those of adult control rats. Although the EGF binding was decreased, there was a tendency for the activity of autophosphorylation to be higher and ligand-dependency to be lower in the membranes from growing hepatic tissues. The activity of tyrosine kinases did not differ among animal groups but a supplement of (NH4)2SO4 to the incubation mixture revealed a difference in the EGF-dependency of the activity; the salt inhibited the activity in the control more profoundly than in the newborn and fetus but the activity was partially restored in the presence of EGF, while in the newborn and fetus the activity did not respond to the added EGF. The results suggest that the higher activity with less responsiveness to the ligand of EGF-receptor autophosphorylation and protein-tyrosine kinase is one of the characteristics of growing rat hepatic tissues.

Aging↗
PubMed1988

The effects of sodium valproate on plasma somatostatin and insulin in humans.

To determine the role of gamma-aminobutyric acid (GABA) in islet tissue, sodium valproate (1600 mg/day) was administered for 6 days to 10 normal subjects and 1 patient with a somatostatinoma. Plasma valproate concentrations reached a steady state by the third day accompanied by elevation of plasma GABA concentrations. Sodium valproate administration resulted in a 40% decrease in plasma somatostatin concentrations in the normal subjects and a 63% decrease in the somatostatinoma patient, respectively, compared to the response to placebo. Plasma C-peptide concentrations did not change in any subject. Fasting blood glucose levels decreased in the somatostatinoma patient during sodium valproate administration. These results suggest that endogenous GABA may play some role in the release of somatostatin, but not in the release of insulin.

Adult↗
PubMed1988

Cloning of glucocorticoid-responsive mRNA in the rat thymus.

To elucidate the molecular mechanism of rat thymus involution induced by administration of glucocorticoid, we screened a cDNA library for polysomal poly(A)+RNA from adrenalectomized rat thymi by a differential colony hybridization method. Labeled cDNAs for mRNAs isolated from thymi of adrenalectomized rats and rats receiving dexamethasone (Dex) treatment were used as probes. Eight cDNA clones for mRNAs which had a diminished response to administration of Dex were isolated. The relative concentration of cloned mRNAs in the thymic polysomal RNA was significantly decreased 3 h after hormone administration, while changes in the nuclear RNA were not significant after Dex administration. One of the selected cDNA clones designated pRTGR-8 corresponded to mRNA of about 3,000 nucleotides, and a nuclear run-off transcription assay indicated that the rate of transcription of pRTGR-8 RNA was repressed by Dex administration. The cloned cDNAs obtained in this experiment may provide useful probes for studying the negative regulation mechanism of gene expression by glucocorticoids.

Animals↗
PubMed1988

Binding sites for epidermal growth factor in nuclear fraction from rat liver.

Binding sites for mouse epidermal growth factor (EGF) were observed in purified nuclear fraction from rat liver. The binding data yielded a curvilinear Scatchard plot which was decomposed into two binding components with different binding affinities. The binding component with higher affinity (Kd approximately 10(-10) M) represented approximately 15% of the total binding, while the high affinity binding sites were less than 5% of the total in the microsomes. The ligand-dependent autophosphorylation, one of the characteristic features of EGF receptor in the plasma membrane, was not observed at the site of the receptor (170 KDa) in the nuclear fraction. The binding characteristics for EGF fluctuated during the course of liver regeneration after partial hepatectomy; the binding capacity in the nuclear fraction increased in contrast to the decrease in the microsomes. However, the binding sites in the nuclear fraction obtained in the early period after partial hepatectomy consisted only of low affinity ones.

Animals↗
PubMed1986

Receptor binding in the rat liver nuclear matrix.

3H-Dexamethasone (Dex)-receptor complexes prepared from the rat liver cytosol efficiently bound to the nuclear matrix from the same tissue. The binding was increased with the concentration of the 3H-Dex-receptor complex added and reached a maximum plateau. However, when the partially purified 3H-Dex-receptor complex was used, saturation of the binding sites in the nuclear matrix was not observed in the range of concentration of 3H-Dex-receptor complex used. Therefore, it was considered that the apparent saturability observed in the binding of the unpurified receptor complexes is caused by the translocation inhibitor(s) in the cytosol. When the binding capacity was expressed on the basis of unit weight of DNA, the nuclear matrix exhibited 20 times more of that of the unfractionated nuclei. However, no line of evidence of enrichment of the binding sites in the DNA isolated from the nuclear matrix was observed. These observations show that the role of the nuclear matrix in the action of glucocorticoid is quite uncertain.

Animals↗