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J Kato

Publications and source records attributed to J Kato.

At least 235 records · Page 13Linked to original sources
PubMed1996

The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2.

Cyclin D-Cdk4/6 and cyclin A/E-Cdk2 are suggested to be involved in phosphorylation of the retinoblastoma protein (pRB) during the G1/S transition of the cell cycle. However, it is unclear why several Cdks are needed and how they are different from one another. We found that the consensus amino acid sequence for phosphorylation by cyclin D1-Cdk4 is different from S/T-P-X-K/R, which is the consensus sequence for phosphorylation by cyclin A/E-Cdk2 using various synthetic peptides as substrates. Cyclin D1-Cdk4 efficiently phosphorylated the G1 peptide, RPPTLS780PIPHIPR that contained a part of the sequence of pRB, while cyclins E-Cdk2 and A-Cdk2 did not. To determine the phosphorylation state of pRB in vitro and in vivo, we raised the specific antibody against phospho-Ser780 in pRB. We confirmed that cyclin D1-Cdk4, but not cyclin E-Cdk2, phosphorylated Ser780 in recombinant pRB. The Ser780 in pRB was phosphorylated in the G1 phase in a cell cycle-dependent manner. Furthermore, we found that pRB phosphorylated at Ser780 cannot bind to E2F-1 in vivo. Our data show that cyclin D1-Cdk4 and cyclin A/E Cdk2 phosphorylate different sites of pRB in vivo.

Amino Acid Sequence↗
PubMed1996

The untranslated first exon 'exon 0S' of the rat estrogen receptor (ER) gene.

Recently, we have isolated the untranslated first exon 'exon ON' of the rat estrogen receptor (ER) gene from the liver by the use of the 5'-rapid amplification of cDNA ends (5'-RACE) method. To investigate the existence of other untranslated first exon(s), we further analyzed the 5'-untranslated region (UTR) of ER mRNA in the rat liver in this study. Total RNA from the livers of 8-week-old male Wistar rats was subjected to 5'-RACE with the antisense primers located in exon 1 of the rat ER gene. The inserts of four clones (clones 3, 4, 7 and 8) were sequenced. The nucleotide sequences of the clones revealed the existence of a previously unidentified untranslated first exon (we termed it 'exon OS') which was spliced onto exon I of the rat ER mRNA. The distribution of ER mRNA containing 'exon OS' (ER mRNA (OS-1)) in several brain regions and various peripheral tissues of 8-week-old male and female Wistar rats was further analyzed by the use of the reverse transcription-polymerase chain reaction. ER mRNA (OS-1) was found to be widely distributed in the rat brain and peripheral tissues. The distribution of the message was different from that of ER mRNA containing exon 0 (the first reported 5'-UTR form of rat ER mRNA) or of ER mRNA with exon ON which was reported in our recent report. These results indicate that (1) 'exon OS' is a novel untranslated first exon of the rat ER gene, (2) rat ER mRNAs possess at least three forms of 5'-UTRs which are exon 0, exon ON, and exon OS, (3) the tissue specific expression of ER is regulated, at least in part, by the usage of differential promoters in the rat.

Alternative Splicing↗
PubMed1996

The novel untranslated first exon "exon 0N" of the rat estrogen receptor gene.

The 5'-untranslated region (UTR) of the estrogen receptor (ER) mRNA in the rat liver was analyzed by the use of the 5'-rapid amplification of the cDNA ends (5'-RACE) method. The nucleotide sequence of one of the positive RACE clones (clone 9) revealed that the existence of the novel untranslated first exon (termed "exon N") being spliced onto the exon 1 of the rat ER mRNA. We further analyzed the distribution of the ER mRNA containing the "exon 0N" (ER mRNA (0N-1)) and the ER mRNA containing the previously reported exon 0 (ER mRNA (0-1)) in the rat brain and peripheral tissues. In contrast to the wide distribution of the ER mRNA (0-1), the distribution of the ER mRNA (0N-1) was almost limited in the peripheral tissues. These results indicate that the "exon 0N" is the novel untranslated first exon of the rat ER gene, and the tissue specific expression of the ER is regulated, at least in part, by differential promoter usage in the rat.

Animals↗
PubMed1996

Hepatic iron deprivation prevents spontaneous development of fulminant hepatitis and liver cancer in Long-Evans Cinnamon rats.

Several clinical studies have suggested that excess hepatic iron accumulation is a progressive factor in some liver diseases including chronic viral hepatitis and hemochromatosis. However, it is not known whether iron-induced hepatotoxicity may be directly involved in hepatitis, cirrhosis, and liver cancer. The Long-Evans Cinnamon (LEC) rat, which accumulates excess copper in the liver as in patients with Wilson's disease, is of a mutant strain displaying spontaneous hemolysis, hepatitis, and liver cancer. We found previously that LEC rats harbored an additional abnormality: accumulation of as much iron as copper in the liver. In the present study, we compared the occurrence of hepatitis and liver cancer in LEC rats fed an iron-deficient diet (ID) with those in rats fed a regular diet (RD). The RD group showed rapid increments of hepatic iron concentrations as the result of hemolysis, characteristics of fulminant hepatitis showing apoptosis, and a 53% mortality rate. However, no rats in the ID group died of fulminant hepatitis. Hepatic iron, especially "free" iron concentration and the extent of hepatic fibrosis in the ID group were far less than those of the RD group. At week 65, all rats in the RD group developed liver cancer, whereas none did in the ID group. These results suggest that the accumulation of iron, possibly by virtue of synergistic radical formation with copper, plays an essential role in the development of fulminant hepatitis, hepatic fibrosis, and subsequent hepatocarcinogenesis in LEC rats.

Animals↗
PubMed1996

Cloning of the Pseudomonas aeruginosa gene encoding CDP-diglyceride synthetase.

The CDP-diglyceride synthetase (CDS)-encoding gene (cds) from Pseudomonas aeruginosa PAO1 was cloned and sequenced. The gene possessed an open reading frame of 813 bp capable of encoding a putative polypeptide of 271 amino acids (aa) (28 699 Da). The deduced aa sequence of CDS revealed a 67% similarity (45% identity) to Escherichia coli CDS.

Amino Acid Sequence↗
PubMed1996

Hdf1, a yeast Ku-protein homologue, is involved in illegitimate recombination, but not in homologous recombination.

Hdf1 is the yeast homologue of the mammalian 70 kDa subunit of Ku-protein, which has DNA end-binding activity and is involved in DNA double-strand break repair and V(D)J recombination. To examine whether Hdf1 is involved in illegitimate recombination, we have measured the rate of deletion mutation caused by illegitimate recombination on a plasmid in an hdf1 disruptant. The hdf1 mutation reduced the rate of deletion formation by 20-fold, while it did not affect mitotic and meiotic homologous recombinations between two heteroalleles or homologous recombination between direct repeats. Hence Hdf1 participates in illegitimate recombination, but not in homologous recombination, in contrast to Rad52, Rad50, Mre11 and Xrs2, which are involved in both homologous and illegitimate recombination. The illegitimate recombination in the hdf1 disruptant took place between recombination sites that shared short regions of homology (1-4 bp), as was observed in the wild-type. Based on the DNA end-binding activity of Hdf1, we discuss models in which Hdf1 plays an important role in the late step of illegitimate recombination.

Base Sequence↗
PubMed1996

Tyrosine phosphorylation of ACK in response to temperature shift-down, hyperosmotic shock, and epidermal growth factor stimulation.

The mammalian Cdc42 protein regulates various kinds of cellular responses, including formation of filopodia, polarization of T cells, and cell cycle progression. A non-receptor tyrosine kinase ACK, which specifically binds to the GTP-bound form of Cdc42, was isolated as a putative target of Cdc42. Here we show the induction of tyrosine phosphorylation of ACK in response to temperature shift-down to 25 degrees C, and hypertonic shock, as well as stimulation with epidermal growth factor (EGF) in human embryonic kidney (HEK) 293 cells. The increased tyrosine phosphorylation level upon temperature shift-down was sustained for at least 60 min, whereas reversion of the temperature to 37 degrees C caused rapid tyrosine dephosphorylation to the initial level. The responses to EGF and the high osmolarity were transient. Furthermore, we observed association of ACK with an adaptor protein Grb2, which may suggest the involvement of Grb2 in EGF receptor-mediated tyrosine phosphorylation of ACK.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Distribution and possible origin of galanin-like immunoreactive nerve fibers in the mammalian dental pulp.

Human, dog, cat and rat dental pulps were investigated for the presence and distribution of galanin-like immunoreactive (-IR) nerve fibers, and the possible origin of pulpal galanin-IR nerve fibers in the rat was examined. Galanin-IR nerve fibers were present in the dental pulps of all species examined. Two types of galanin-IR nerve fibers were distinguished with regard to morphology; thin varicose nerve fibers and thick smooth-surfaced nerve fibers. Thin varicose galanin-IR nerve fibers were seen to run along the blood vessel in the human, dog and cat root pulp. In the coronal pulp, galanin-IR nerve fibers ran toward the odontoblastic layer but they did not form the subodontoblastic nerve plexus. In rat molar pulp, few galanin-IR nerve fibers were observed; the distribution of these nerve fibers was similar to those in human, dog and cat pulp. In contrast, many thick smooth-surfaced galanin-IR nerve fibers were observed near the blood vessels in incisor pulp of the rat; occasionally a few varicose galanin-IR nerve fibers were also observed. Transection of the inferior alveolar nerve or mandibular nerve caused complete disappearance of galanin-IR nerve fibers in rat dental pulp, while surgical sympathectomy of the superior cervical ganglion did not affect their distribution. The present results indicate that galanin-IR nerve fibers are present in the mammalian dental pulp, and that the intrapulpal galanin-IR nerve fibers in the rat originate from the trigeminal ganglion and are primary afferents.

Animals↗
PubMed1996

Construction of beta-lactamase-encoding ApR gene cassettes for rapid identification of cloned genes.

We have constructed two Escherichia coli plasmids, pYK18 and pYK19, from which the BamHI, SmaI or EcoRI DNA fragments containing the ApR gene, conferring resistance to ampicillin, can be excised. The ApR cassettes have an annealing site for the sequencing primer of pUC plasmids at each end. Therefore, when the cassette is inserted into a gene, we can determine the nucleotide sequence of the gene from the insertion site using the sequencing primers of the pUC plasmids. This method is useful for identifying a cloned gene.

Ampicillin Resistance↗
PubMed1996

Molecular analysis of the phosphate-specific transport (pst) operon of Pseudomonas aeruginosa.

The organization of the phosphate-specific transport (pst) operon in Pseudomonas aeruginosa has been determined. The gene order of the pst operon is pstC, pstA, pstB, phoU, and a well-conserved Pho box sequence (16/18 bases identical) exists in the promoter region. The most striking difference from the known Escherichia coli pst operon is the lack of the pstS gene encoding a periplasmic phosphate (Pi)-binding protein. Even though the three pst genes were absolutely required for P(i)-specific transport, expression of the pst operon at high levels did not increase P(i) uptake in P. aeruginosa. DNA sequences for the pstB and phoU genes have been determined previously. The newly identified pstC and pstA genes encode possible integral membrane proteins of 677 amino acids (M(r) 73,844) and 513 amino acids (M(r) 56,394) respectively. The amino acid sequences of PstC and PstA predict that these proteins contain a long hydrophilic domain not seen in their E. coli counterparts. A chromosomal deletion of the entire pst operon rendered P. aeruginosa unable to repress P(i) taxis under conditions of P(i) excess. The phoU and pstB genes are essential for repressing P(i) taxis. However, mutants lacking either PstC or PstA alone were able to repress P(i) taxis under conditions of P(i) excess.

ATP-Binding Cassette Transporters↗
PubMed1996

Neuropeptide Y-immunoreactive primary afferents in the dental pulp and periodontal ligament following nerve injury to the inferior alveolar nerve in the rat.

The distribution of neuropeptide Y (NPY)-immunoreactive (IR) primary afferents in the dental pulp and periodontal ligament of the rat mandible were examined following combined chronic constriction injury (CCI) of the inferior alveolar nerve (IAN) and sympathectomy of the superior cervical ganglion (SCG). NPY-IR nerve fibers were observed around the blood vessels in the trigeminal ganglion, dental pulp and periodontal ligament in normal animals. Following combined CCI of the IAN and sympathectomy of SCG (SCGx), perivascular NPY-IR nerve fibers originating from SCG disappeared completely, but many NPY-IR nerve fibers coming from the trigeminal ganglion appeared in the dental pulp and periodontal ligament. In the molar dental pulp, thick NPY-IR nerve fibers were observed within the nerve bundle, and some thin NPY-IR nerve fibers ran towards the odontoblast layer; very few NPY-IR nerve fibers were observed in the incisor pulp. In the periodontal ligament of molar, thick NPY-IR nerve fibers appeared at the alveolar part following combined CCI of IAN and SCGx. In the lingual portion of the periodontal ligament of the incisor, many thick NPY-IR nerve fibers were observed. These occasionally showed a tree-like appearance, resembling immature Ruffini endings; slowly adapting mechanoreceptors. The present results indicate that periodontal mechanoreceptors are among the main targets of injury-evoked NPY following IAN injury.

Afferent Pathways↗
PubMed1996

A case of small cell carcinoma of the uterine cervix presenting Cushing's syndrome.

A proportion of small cell carcinoma of the uterine cervix is known to secrete a neuroendocrine substance. However, cases presenting Cushing's syndrome due to ACTH secreted from a cervical small cell carcinoma are extremely rare. Here, we report a case of small cell carcinoma of the uterine cervix that ectopically secreted ACTH and presented Cushing's syndrome. A 42-year-old woman was initially admitted to the endocrine unit for investigation of ectopic ACTH syndrome. Serum cortisol and plasma ACTH levels were elevated with no diurnal variation. After gynecologic examination, her original disease was found to be a stage IIb cervical small cell carcinoma. She underwent a radical hysterectomy and pelvic lymphadenectomy. The entire tumor was excised and post-TNM classification was T2bN1M0. Immunohistochemically, tumor cells stained strongly for ACTH and chromogranin. Electronmicroscopic pictures showed typical neurosecretory granules. Although plasma ACTH returned to normal after surgery, liver metastasis appeared during the course of postoperative irradiation. She died 9 months after operation in spite of vigorous systemic chemotherapy.

Adrenocorticotropic Hormone↗
PubMed1996

Protein gene-product 9.5 in developing mouse circumvallate papilla: comparison with neuron-specific enolase and calcitonin gene-related peptide.

The present study was made to investigate the ontogeny of protein gene-product 9.5 (PGP 9.5)-like immunoreactivity (-LI) in the developing mouse circumvallate papilla (CVP), and its distribution was compared to that of neuron-specific enolase (NSE) and calcitonin gene-related peptide (CGRP). In adult CVP, PGP 9.5-LI was observed in the subgemmal nerve plexus; some thin PGP 9.5-like immunoreactive (-IR) nerve fibers penetrated taste buds and apical epithelium. PGP 9.5-LI was also observed in the spindle-shaped cells in taste buds, and a small number of round- or oval-shaped ganglionic cells in the lamina propria. The distribution of NSE-LI was comparable to that of PGP 9.5-LI. CGRP-LI was observed in the nerve fibers only; distribution of CGRP-IR nerve fibers was similar to that of PGP 9.5-IR nerve fibers, although the number of CGRP-IR nerve fibers was smaller than that of PGP 9.5-IR nerve fibers. At least six developmental stages were defined with regard to the developmental changes in the distribution of PGP 9.5-LI from embryonic day (E) 12 to adulthood: Stage I (E12-13)-a dense nerve plexus of PGP 9.5-IR nerve fibers was detected in the lamina propria beneath the core of newly-formed papilla. Stage II (E14-16) - thin PGP 9.5-IR nerve fibers penetrated the apical epithelium, and a few round-shaped cells in the apical epithelium also displayed PGP 9.5-LI. Stage III (E17-18) - thin PGP 9.5-IR nerve fibers penetrated the inner lateral epithelium of the trench. Stage IV [Postnatal day (P) 0-3] - many PGP 9.5-IR nerve fibers penetrated the outer lateral epithelium of the trench; later in this stage, taste buds appeared. Stage V (P5-10) - a small number of PGP 9.5-IR cells in the taste buds appeared, and their number increased gradually. Stage VI (P14-adult) - the number of PGP 9.5-IR taste cells increased and reached the adult level, while the number of PGP 9.5-IR nerve fibers decreased. The development of NSE-LI was similar to that of PGP 9.5-LI. CGRP-IR nerve fibers were detected at E12 in the lamina propria, and the development of the intraepithelial CGRP-IR nerve fibers was similar to that of PGP 9.5-IR nerve fibers. The present results indicate that invasion by nerve fibers of the epithelium of lingual papillae occurs in a complex manner, and that these nerve fibers may participate in the formation of the taste buds.

Age Factors↗
PubMed1996

The effectiveness of medroxyprogesterone in the treatment of multiple metastasizing leiomyosarcomas: report of a case.

A 51-year-old woman was admitted to our hospital for further investigation of chest X-ray films which showed multiple shadows that had been growing slowly over 2 years. Her only symptom was hemosputa. The lesions were suspected of being metastasizing leiomyoma due to her past history of uterine leiomyoma. Just 1 week before undergoing scheduled open lung biopsy, the lung lesions increased remarkably in size and number. A thoracotomy was performed and six of the numerous nodules were removed. The resected specimens were pathologically diagnosed as metastasizing leimyosarcoma which was positive for the progesterone and estrogen receptors. Thus, 1 month postoperatively, a course of medroxyprogesterone (MPA), 600 mg daily, was commenced. The residual lesions in her chest started to diminish, shortly afterward. She has remained well on this MPA regimen for 45 months. The prognosis of patients with metastasizing leiomyosarcoma is poor because of its low sensitivity to chemotherapy; however, some types of leiomyosarcoma are hormone-sensitive. It is therefore important to examine the hormone receptors of excised tumors from patients suspected of having metastasizing leiomyoma or leimyosarcoma.

Antineoplastic Agents, Hormonal↗
PubMed1996

Recovery of impaired left ventricular function in patients with acute myocardial infarction is predicted by the discordance in defect size on 123I-BMIPP and 201Tl SPET images.

A discrepancy between myocardial perfusion defect and wall motion abnormalities is frequently found early after coronary reperfusion in patients with acute myocardial infarction. The purpose of this study was to assess recovery of impaired left ventricular function by reference to the discordance in defect size between myocardial fatty acid uptake and myocardial perfusion using combined single-photon emission tomographic (SPET) imaging early after coronary perfusion therapy. In 37 patients with acute myocardial infarction, iodine-123 15-(p-iodophenyl)-3(R, S)-methylpentadecanoic acid (BMIPP) and thallium-201 SPET scans were performed early after coronary reperfusion. A severity score was determined from the extent of the imaging defect with each tracer. Left ventricular wall motion score (WMS) and ejection fraction (EF) were obtained at admission and at 4 weeks after the onset of infarction. In 32 of the 37 patients, discordance in defect sizes delineated with the two SPET studies was found during the acute stage. The severity score for BMIPP was larger than that for 201Tl during the acute stage (7. 7+/-2.4 vs 4.4+/-2.5, P <0.001). There was a fair correlation between the severity score for BMIPP and WMS (r=0.82, P <0.0001), but a poor correlation between that for 201Tl and WMS. The extent of discordance in severity scores between BMIPP and 201Tl during the acute stage correlated well with the extent of the improvement in WMS (r=0.86, P <0.0001) and that of EF (r=0.85, P <0.0001). We conclude that the discordance in defect size on BMIPP and 201Tl SPET images during the acute stage of infarction is an early predictor of the viability of the myocardium at risk of infarction.

Fatty Acids↗
PubMed1996

Fulminant hepatitis caused by hepatitis C virus during treatment for multiple sclerosis.

A 55-year-old woman was treated at our hospital for multiple sclerosis. Therapy consisted of glucocorticosteroids and cyclosporin. In the 7th week after these drugs were discontinued the patient developed acute liver failure due to fulminant hepatitis (FH) and died. Post-mortem examination showed massive liver necrosis. Serologic examination was negative for hepatitis B virus-related markers. Antihepatitis C virus (anti-HCV) antibody and serum HCV RNA were negative on admission, but HCV RNA appeared concurrently with the onset of FH. Although HCV infection rarely causes FH, it was considered to be the cause of FH in this patient, since there were no other causes of acute liver injury. We suspect that underlying immunologic abnormalities in conjunction with HCV infection may have precipitated the FH.

Anti-Inflammatory Agents↗
PubMed1996

Existence and expression of the untranslated first exon of aromatase mRNA in the rat brain.

Tissue-specific expression of aromatase activity and mRNA occurs by alternative utilization of multiple untranslated first exons and promoters in the human. The major transcript in the human brain contains the brain-specific first exon, "exon I-f". However, few reports on the untranslated first exon of aromatase mRNA in the rat brain have been available so far. In the present study, we investigated the existence and expression of exon I-f in the rat brain to elucidate the mechanism of the tissue-specific expression of the brain aromatase. Total RNA extracted from amygdala (AMY) was subjected to a reverse transcription-polymerase chain reaction (RT-PCR). The nucleotide sequence of the RT-PCR product had 89.4% homology to the corresponding region of exon I-f of the human aromatase cDNA. It was indicated that the major transcript in the rat AMY contained exon I-f by the use of a rapid amplification of cDNA ends (RACE). Furthermore, in order to determine the distribution of the aromatase mRNA with exon I-f, total RNAs from the hypothalamus-preoptic area (HPOA), AMY, testis and ovary were analysed by RT-PCR using the primers specific for the mouse exon I-f and the primers for the rat exon III-V. Significant levels of PCR products were found in all tissues with the highest level being in the ovary, using the primers for exon III-V. On the other hand, using the primers for exon I-f, the levels of signals from HPOA and AMY were higher than those from the testis and ovary. These results suggest that tissue-specific expression of aromatase mRNA occurs by an alternative utilization of multiple promoters in the rat, as in the human. It should be noted that minor transcripts containing exon I-f were observed in the testis and ovary.

Animals↗