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Biomedical subjects

M Katoh

Publications and source records attributed to M Katoh.

At least 19 recordsLinked to original sources
PubMed1997

MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase.

c-Jun N-terminal kinases/stress-activated protein kinases (JNKs/SAPKs) are mitogen-activated protein kinase (MAPK)-related protein kinases that are involved in several cellular events, including growth, differentiation, and apoptosis. Mixed lineage kinases (MLKs) form a family of protein kinases sharing two leucine zipper-like motifs and a kinase domain whose primary structure is similar to both the tyrosine-specific and the serine/threonine-specific kinase classes. We have reported that a member of the MLK family, MUK/DLK/ZPK, can activate JNK/SAPK in vivo, and here we show that another member of the MLK family, MST/MLK2, activates JNK/SAPK. Both MUK/DLK/ZPK and MST/MLK2 cause a slight activation of p38/Mpk2 when overexpressed in COS-1 cells, whereas MST/MLK2, but not MUK/DLK/ZPK, activates extracellular response kinase (ERK) to a certain degree. The activity of SEK1/MKK4/JNKK, a MAPK kinase class protein kinase designated as a direct activator of JNK/SAPK, is also induced by MUK/DLK/ZPK or MST/MLK2 overexpression. Furthermore, recombinant MST/MLK2 produced in bacteria directly phosphorylates and activates SEK1/MKK4/JNKK in vitro, showing that MST/MLK2 acts like a MAPK kinase kinase. Taken together, these results suggest that MLK family members are MAPK kinase kinases preferentially acting on the JNK/SAPK pathway.

Animals↗
PubMed1997

Cloning of human bone morphogenetic protein type IB receptor (BMPR-IB) and its expression in prostate cancer in comparison with other BMPRs.

Bone metastasis is a common event in prostate cancer, and it is known that some of the bone morphogenetic proteins (BMPs) are expressed in prostate cancer cells, while no study on the expression of their receptors, BMPRs, has been reported. Here we report cloning and sequence analysis of the human BMPR-IB cDNA. We also analysed the expression of transcripts of three types of the BMPR genes in human tissues and prostate cancer cell lines. The BMPR-IB mRNA was present in various organs, but the highest level was found in the prostate. Moreover, the amount of BMPR-IB mRNA was significantly low in prostate cancer tissues after androgen withdrawal and was also low in prostate cancer cell lines. RT-PCR analysis showed that the BMPR-IB message was upregulated by androgen stimulation in the LNCaP cell line which expresses the androgen receptor. By contrast, the mRNA levels of BMPR-IA and BMPR-II were not significantly different among non-cancerous and cancerous prostate tissues. It was also suggested that human BMPR-IA and BMPR-IB might have different biological functions in the prostate, although their sequences were 85.3% identical in the serine-threonine kinase domain.

Amino Acid Sequence↗
PubMed1997

Role of myocyte nitric oxide in beta-adrenergic hyporesponsiveness in heart failure.

BACKGROUND: The positive inotropic response to beta-adrenergic stimulation is attenuated at the isolated myocyte level in heart failure. Nitric oxide (NO) has a negative inotropic effect and attenuates the response to isoproterenol. It has been suggested that NO synthesis is increased in failing myocytes. However, the pathophysiological consequences after induction of NO in myocyte contractility are less clear in the setting of heart failure. METHODS AND RESULTS: We examined the effects of an NO synthase (NOS) inhibitor on contractile function in myocytes isolated from 11 dogs with rapid pacing-induced heart failure (ejection fraction, 29 +/- 2%) and 8 control dogs (ejection fraction, 74 +/- 3%). Sarcomere shortening velocity was measured as an index of contractility under four experimental conditions: at baseline, after adding isoproterenol (ISO; 1 nmol/L), after an NOS inhibitor (N pi-nitro-L-arginine methyl ester [L-NAME], 0.1 nmol/L), and after L-NAME plus ISO. L-NAME alone had no effects on basal sarcomere shortening velocity in either control or heart failure myocytes. However, L-NAME significantly augmented the inotropic response to isoproterenol in heart failure myocytes (107.1 +/- 7.3% [ISO alone] versus 140.6 +/- 10.7% [ISO plus L-NAME] increase from baseline; P < .05) but not in control myocytes (135.5 +/- 9.9% [ISO alone] versus 137.1 +/- 11.4% [ISO plus L-NAME]; P = NS). Myocardial NOS activity measured by the conversion of arginine to citrulline was significantly increased in dogs with heart failure compared with that in control dogs. CONCLUSIONS: The increased NO induction in failing myocytes does not alter baseline sarcomere mechanics but attenuates the positive inotropic response to isoproterenol. Thus, myocyte NO plays an important role in the autocrine regulation of the contractile function of myocytes in congestive heart failure.

Adrenergic beta-Agonists↗
PubMed1997

Mutations induced in male germ cells after treatment of transgenic mice with ethylnitrosourea.

The present study was undertaken to clarify whether the transgenic mouse mutagenesis assay system can be used instead of dominant lethals or specific locus test after treatment of male germ cells in mouse with ethylnitrosourea (ENU). Male Big Blue transgenic mice (BB) carrying a lacI target gene were given a single intraperitoneal injection of 150 mg/kg ENU. Vasa deferential sperm, caudal epididymal sperm or whole testes were assayed for mutation at 3, 14, 22 and 93 days after treatment with ENU. The average of background lacI- mutant frequencies was 2.05 x 10(-5). The MF observed in post spermatogonial stage after treatment with ENU were slightly increased over background. On the other hand, ENU induced high MF in the spermatogonial stage. MF detected after treatment of BB male germ cells with ENU were lower than those detected in the mouse visible specific-locus mutations in previous reports. Nevertheless, it is clear that this assay is a practical alternative to the specific locus test for detecting mutations induced in spermatogonial stage.

Animals↗
PubMed1997

Analysis of vascular anatomy and lymph node metastases warrants radical segmental bowel resection for colon cancer.

To determine the indications for limited colon cancer surgery in each location, we reviewed the arterial branching patterns and lymph node metastases along the course of specific vascular trunks in 344 colon cancer patients who had undergone preoperative angiography and colectomy with lymph node dissection. Our conclusions are follows: Because the ileocecal artery always arises from the superior mesenteric artery and lymph node metastases of cecum cancer were limited to nodes along the ileocolic artery, cecum cancer can be cured by ileocecal resection. The right colic artery has various origins, and ascending colon cancer shows various patterns of lymph node metastases. Therefore a right hemicolectomy should be performed for ascending colon cancer. The middle colic artery forks into right and left branches, and each branch has different branching variations. If the right colic and middle colic arteries have a common trunk, a right hemicolectomy should be performed for transverse colon cancer on the right side. If the left branch of the middle colic artery has an independent replaced origin, lymph node dissection should be modified according to the variant origin. If the left colic artery and the first sigmoidal artery have a common trunk, the lymph nodes along the common trunk should be removed for sigmoid colon cancer and for descending colon cancer. Of the patients with sigmoid colon cancer, 6.3% also had lymph node metastases along the superior rectal artery. Given that the lymph nodes along the superior rectal artery are skeletonized, sigmoid colon cancer can be also cured by partial sigmoidectomy.

Arteries↗
PubMed1997

[Study on the surgical treatment for pulmonary metastasis from renal cell carcinoma].

BACKGROUND: Pulmonary resection for metastatic renal cell carcinoma were studied to assess the indication of surgical management. METHODS: Between January, 1981 and December 1994, 17 consecutive patients (14 men and 3 women) underwent complete pulmonary resection for metastatic renal carcinoma. Median age was 61 years (range, 45 to 73 years). Eleven were appeared lung metastasis after resection of primary tumor. Median time between nephrectomy and pulmonary resection was 32 months (range, 0 to 127 months). RESULTS: There were no operative deaths. One patient had solitary metastasis, 4 had two, 2 had three, 2 had four, one had seven, one had eight and 6 had more than twenty-two. Segmental resection was performed in 12 patients, lobectomy in 2, lobectomy and segmentectomy in 3 and segmentectomy for total lobes in 3. Four patients had another site operation of renal metastasis, brain tumor resection, chest wall and ribs resection, contra-lateral adrenalectomy and contralateral partial nephrectomy. Median follow-up was 44 months (range, 10 to 129 months). The cause specific survival rate and disease free survival after pulmonary resection was 55 and 48 percent at 5 years and 27 and 14 percent at 10 years, respectively. CONCLUSION: Pulmonary resection for metastatic renal cell carcinoma was considered effective in some selected slow-growing cases. Multiple and both lungs metastases is not contraindication and the patients under 10 metastatic focuses had good prognosis.

Aged↗
PubMed1997

[Single stage excision for an intractable brain abscess and free rectus abdominis flap for reconstruction of the anterior skull base].

A case is presented of the frontal brain abscess following resection of squamous cell carcinoma of the maxillary sinus who had undergone reconstruction of the anterior skull base using a free rectus abdominis muscle flap. Local flap, ex. galeal flap, can be used for separating the cranial space from the paranasal sinuses and the nasopharynx, but it cannot provide reliable separation and protection of the brain from bacterial flora of the upper airway and it is too weak to support the brain in cases where orbital exenteration has been performed. The distant flaps such as the pectoralis major musculocutaneous flap, on the other hand, can provide a good alternative for reconstruction of the anterior skull base in such difficult cases, but frequently requires a secondary division of the pedicle. The free flap can circumvent such problems. We used the free rectus abdominis muscle flap and the postoperative course was uneventful. A bone graft was not necessary to reconstruct the anterior skull base.

Brain Abscess↗
PubMed1997

[Combined deficiency in neutrophil functions after bone marrow transplantation and the in vitro effect of granulocyte colony-stimulating factor].

In order to investigate the mechanism of susceptibility to bacterial infection after bone marrow transplantation (BMT), we evaluated the neutrophil functions at 1, 3, 6, and 12 months after hematological reconstitution in a 29-year-old AML patient who received allogeneic bone marrow transplantation. Acute graft-versus-host disease (GVHD) was grade I, and chronic GVHD was not present. The patient exhibited complications of upper and lower respiratory infections several times after BMT, all of which subsided within a month. Chemotactic responses toward all three chemotactic factors, random mobility, phagocytosis, superoxide (O2-) release and bactericidal activity were severely impaired early after reconstitution. These neutrophil functions gradually improved with time after BMT, and all normalized at 12 months after reconstitution of transplanted bone marrow. Both O2- release and bactericidal activity of neutrophils were significantly enhanced at 6 and 12 months after marrow reconstitution following pretreatment of 50 ng/ml of granulocyte colony-stimulating factor (G-CSF) in vitro. These findings suggest that the combined disorders in neutrophil functions in early phase after BMT may play an important role in susceptibility to bacterial infections until one year after BMT. Administration of G-CSF, which potentiates the bactericidal activity of neutrophils, is recommended for preventing infectious complications and for treating prolonged and unmanageable infections after BMT.

Adult↗
PubMed1996

Cloning, expression and chromosomal localization of Wnt-13, a novel member of the Wnt gene family.

The Wnt genes, encoding structurally-related secreted glycoproteins, are implicated in mammary carcinogenesis induced by mouse mammary tumor virus. In search of the Wnt gene(s) expressed in human gastric cancer, a WTGC1 cDNA fragment sharing 66.9% amino-acid homology with human and mouse Wnt-2 was isolated by degenerate polymerase chain reaction. The human gene corresponding to WTGC1 was designated as Wnt-13 and overlapping Wnt-13 cDNAs were cloned. Nucleotide sequence analysis indicated that the Wnt-13 gene encodes the protein of 372 amino acids, including a signal peptide, two potential N-glycosylation sites and 24 cystein residues highly conserved among members of the Wnt gene family. The Wnt-13 mRNA of 2.5 kb in size was detected in heart, brain, placenta, lung, prostate, testis, ovary, small intestine and colon of adult human and also in brain, lung and kidney of fetal human. Among various cancer cell lines, the Wnt-13 mRNA was detected in HeLa (cervical cancer), MKN28 and MKN74 (gastric cancer). The Wnt-13 gene has been mapped to human chromosome 1p13. These results suggest that the Wnt-13 gene may be involved in normal human development or differentiation as well as in human carcinogenesis.

Adult↗
PubMed1996

Molecular cloning of rabbit matrix metalloproteinase-2 and its broad expression at several tissues.

We have cloned cDNA encoding rabbit matrix metalloproteinase-2 (MMP-2, 72 kDa type IV collagenase) by a combination of conventional library screening, the 'single strand ligation to single-stranded cDNA (SLIC)' method and 'long and accurate PCR (LA-PCR)'. Deduced amino acid sequence was highly conserved through mammalian species. Northern blot analysis revealed that rabbit MMP-2 had 2 species of mRNA, 2.8 kbp and 3.5 kbp, and were expressed constitutively in all the tissues tested. This was totally different from mRNA expression of rabbit MMP-1, -3 and -9.

Amino Acid Sequence↗
PubMed1996

Effect of neonatal exposure to diethylstilbestrol and tamoxifen on pelvis and femur in male mice.

BACKGROUND: Permanent abnormalities have been reported in reproductive and non-reproductive organs of mice and humans exposed perinatally to a synthetic estrogen, diethylstilbestrol (DES). Recent studies demonstrated that sex hormones affected the shape of the innominate bone in mice. Therefore, we analyzed the long-term effects of neonatal exposure of DES and tamoxifen, an anti-estrogen, in mouse bones. METHODS: Changes in the pelvis and femur were examined in 1- to 15-month-old C57BL/Tw male mice given 5 daily injections of 3 micrograms DES or of 100 micrograms tamoxifen beginning on the day of birth by measuring contents of calcium (Ca) and phosphorus (P), and the numbers of osteoblasts and osteoclasts. RESULTS: The ash weight of pelvis and femur in neonatally DES- and tamoxifen-treated mice was lower than that in the controls at 2-15 months of age. Contents of Ca and P of pelvis and femur in neonatally tamoxifen-treated mice were lower than in the controls and neonatally DES-treated mice. In neonatally DES-treated mice at 6-12 months, Ca and P contents in the pelvis were lower than in controls, but not different in the femur. The number of osteoblasts per unit length of endocortical surface of the femur in 2- and 3-month-old DES- and tamoxifen-treated mice was lower than that in the controls. The osteoclast number in the femur in DES-treated mice at 2 to 12 months was not different from that in the controls; however, in tamoxifen-treated mice, the number was higher than in the controls. An epiphyseal line was clearly detected in the femur of 12- and 15-month-old DES- and tamoxifen-treated male mice, whereas the line in the controls disappeared after 12 months. CONCLUSIONS: The present results indicate that in male mice, neonatal exposure to DES and tamoxifen induced permanent changes in the pelvis and the femur, and that tamoxifen had a greater effect on bone tissue than did DES.

Age Factors↗
PubMed1996

A new transgenic mouse mutagenesis test system using Spi- and 6-thioguanine selections.

A new transgenic mouse mutagenesis test system has been developed for the efficient detection of point mutations and deletion mutations in vivo. The mice carry lambda EG10 DNA as a transgene. When the rescued phages are infected into Escherichia coli YG6020-expressing Cre recombinase, the phage DNA is converted into plasmid pYG142 carrying the chloramphenicol-resistance gene and the gpt gene of E. coli. The gpt mutants can be positively detected as colonies arising on plates containing chloramphenicol and 6-thioguanine. The EG10 DNA carries a chi site along with the red and gam genes so that the wild-type phages display Spi- (sensitive to P2 interference) phenotype. Mutant phages lacking both red and gam genes can be positively detected as plaques that grow in P2 lysogens of E. coli. These mutant phages are called lambda Spi-. The spontaneous gpt mutation frequencies of five independent transgenic lines were 1.7 to 3.3 x 10(-5) in bone marrow. When the mice were treated with ethylnitrosourea (single i.p. treatments with 150 mg/kg body weight; killed 7 days after the treatments), mutation frequencies were increased four- to sevenfold over the background in bone marrow. The average rescue efficiencies were more than 200,000 chloramphenicol-resistant colonies per 7.5 micrograms bone marrow DNA per packaging reaction. In contrast to gpt mutation frequencies, spontaneous Spi- mutation frequencies were 1.4 x 10(-6) and 1.1 x 10(-6) in bone marrow and sperm, respectively. No spontaneous Spi- mutants have been detected so far in spleen, although 930,000 phages rescued from untreated mice were screened. In gamma-ray-treated animals, however, induction of Spi- mutations was clearly observed in spleen, at frequencies of 1.4 x 10(-5) (5 Gy), 1.2 x 10(-5) (10 Gy), and 2.0 x 10(-5) (5O Gy). These results suggest that the new transgenic mouse "gpt delta" could be useful for the efficient detection of point mutations and deletion mutations in vivo.

Animals↗
PubMed1996

A promiscuous T cell hybridoma restricted to various I-A molecules.

In a previous study, we identified T cell receptor and major histocompatibility complex (MHC) contact sites on the pigeon cytochrome c p43-58 peptide. Positions 46 and 54 of p43-58 were shown to be the MHC-binding sites. Specific amino acids were identified on the MHC-binding sites which bound to the relevant I-A molecule. In the present study, using NOD (I-Ag7) mice, we established a T cell hybridoma specific for a p43-58 analog 46R50E54A with arginine (R) and alanine (A) at positions 46 and 54, respectively. Interestingly, NOE 33-1-2 recognized 46R50E54A in the presence of not only I-Ag7, but also I-Ad, s, u and v. In contrast to previous reports that promiscuous T cells were able to recognize peptide antigens with various HLA-DR or I-E molecules consist of monomorphic alpha and polymorphic beta chains, the promiscuous T cell clone NOE33-1-2 recognized peptides with various I-A molecules lacking the monomorphic chain.

Amino Acid Sequence↗
PubMed1996

Determination of the allele-specific antigen-binding site on I-Ak and I-Ab molecules.

Residues 46 and 54 on a pigeon cytochrome c 43-58 analog, 50E, function as major histocompatibility complex class II contact sites. A peptide, 46F50E54A, with phenylalanine (F) at position 46 and alanine (A) at 54 on 50E bound to Ab and a peptide, 46D50E54A, with aspartic acid (D) at 46 and alanine at 54, bound to Ak. To determine the allele-specific peptide contact sites on I-A molecules corresponding to the I-A contact sites of the peptides, we analyzed responses of Ak- and/or Ab-restricted T cell hybridomas to 46F50E54A or 46D50E54A using L cell transfectants expressing recombinant I-A molecules between Ak and Ab or point mutants of Ak as antigen presenting cells. It was shown that the N-terminal half of the alpha helix of the A alpha chain determined the allele-specific T cell responses. Furthermore, with arginine (k type amino acid) or alanine (b type amino acid) at position 56 of the Ak alpha chain, these T cell hybridomas were stimulated predominantly by 46D50E54A (Ak binding peptide) or 46F50E54A (Ab binding peptide), respectively. Thus, the amino acid at position 56 of the A alpha chain determines allele-specific antigen presentation. This postulate was confirmed by direct binding analysis of 50E analogs of various I-A molecules. A single amino acid change (arginine to alanine) at position 56 of the Ak alpha chain altered the peptide binding specificity (46D50E54A to 46F50E54A).

Alleles↗
PubMed1996

Teratology study of erythritol in rabbits.

The effect of maternal ingestion of the reduced energy sweetener erythritol was investigated in KBL:JW strain pregnant rabbits. Animals received 1.0, 2.24, or 5.0 g/kg intravenously once daily from Days 6 to 18 of gestation. Maternal effects (auricular edema, and bradypragia) were observed in the high-dose group. No deaths or significant abnormalities occurred in animals given 1.0 or 2.24 g/kg. No effect was observed in the reproductive performance of the dams or in fetal development from ingestion at any of the treatment levels.

Abnormalities, Drug-Induced↗
PubMed1996

Overexpression of bone morphogenic protein (BMP)-4 mRNA in gastric cancer cell lines of poorly differentiated type.

Gastric cancer is classified as the poorly differentiated and the well differentiated type, depending on its histological, biological, and genetic characteristics. Bone metastasis is more frequently detected in the poorly differentiated type than in the well differentiated type. The prognosis of patients with diffuse osteoplastic bone metastasis of gastric cancer is extremely poor. In this study, we examined the mRNA expression of bone morphogenic proteins (BMPs) in seven gastric cancer cell lines: OKAJIMA, TMK1, MKN45, and KATO-III derived from the poorly differentiated type; and MKN7, MKN28, and MKN74, derived from the well differentiated type. BMP-2 was expressed only in TMK1. BMP-4 mRNA was over-expressed in OKAJIMA, MKN45 and KATO-III, weakly expressed in MKN7, MKN28, and MKN74, but was not expressed in TMK1. Although the biological roles of BMP-2 and BMP-4 expression in gastric cancer remain to be elucidated, these results indicate that BMP-4 mRNA is preferentially overexpressed in the poorly differentiated type of gastric cancer.

Blotting, Northern↗
PubMed1996

Enhanced expression of manganese superoxide dismutase mRNA and increased TNFalpha mRNA expression by gastric mucosa in gastric cancer.

Manganese superoxide dismutase (Mn-SOD), a mitochondrial enzyme, is a cytokine-regulated acute-phase protein that protects cells from free radicals. The current investigations examined the in vivo regulation of the expression of Mn-SOD mRNA and tumor necrosis factor alpha (TNFalpha) mRNA in gastric carcinoma tissue. The expression of these transcripts in breast carcinoma tissue also was examined because breast cancer is a much more TNF-sensitive tumor than gastric cancer. TNFalpha mRNA was markedly increased in gastric carcinoma tissue (p < 0.005). There were significantly higher levels of Mn-SOD mRNA in gastric carcinoma tissue than in noncancerous tissue (p < 0.0001). The level of Mn-SOD mRNA in gastric carcinoma tissue was higher than that in breast carcinoma tissue (p < 0.005). Up-regulation of Mn-SOD mRNA in gastric carcinoma tissue most likely serves as a protective mechanism against superoxide radicals and TNF cytotoxicity.

Adult↗