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Biomedical subjects

T Yamagami

Publications and source records attributed to T Yamagami.

At least 109 records · Page 6Linked to original sources

Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders.

gp130 is a ubiquitously expressed signal-transducing receptor component shared by interleukin 6, interleukin 11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1. To investigate physiological roles of gp130 and to examine pathological consequences of a lack of gp130, mice deficient for gp130 have been prepared. Embryos homozygous for the gp130 mutation progressively die between 12.5 days postcoitum and term. On 16.5 days postcoitum and later, they show hypoplastic ventricular myocardium without septal and trabecular defect. The subcellular ultrastructures in gp130-/- cardiomyocytes appear normal. The mutant embryos have greatly reduced numbers of pluripotential and committed hematopoietic progenitors in the liver and differentiated lineages such as T cells in the thymus. Some gp130-/- embryos show anemia due to impaired development of erythroid lineage cells. These results indicate that gp130 plays a crucial role in myocardial development and hematopoiesis during embryogenesis.

Animals↗

Influence of ovariectomy at the time of mastectomy on the prognosis for canine malignant mammary tumours.

The two-year prognosis for malignant mammary tumours seen in 175 bitches in the Tokyo metropolitan area was assessed based on the extent of mastectomy and on whether an ovariectomy was carried out at the time of mastectomy. The prognosis for the bitches was not influenced by the excision size of the affected mammary glands. Ovariectomy had no effect on the two-year survival rate of the dogs that underwent the tumour excision. There was no significant difference in the two-year survival rate between the dogs ovariectomised prior to mastectomy and those ovariectomised at the time of mastectomy. These results suggest that ovariectomy at the time of mastectomy has no effect on the prognosis in dogs with established neoplasms of the mammary gland.

Animals↗

Limited proteolysis and reduction-carboxymethylation of rye seed chitinase-a: role of the chitin-binding domain in its chitinase action.

By a limited proteolysis with thermolysin, rye seed chitinase-a (RSC-a) was separated into a N-terminal cysteine-rich chitin-binding (CB-) domain (48 residues) and a catalytic (Cat-) domain (254 residues). The hydrolytic activity of the isolated Cat-domain toward soluble glycolchitin, was similar to that of RSC-a, but that toward insoluble colloidal chitin was 28% of that of RSC-a. Five disulfide bonds in the CB-domain were reduced with 2-mercaptoethanol (2-ME) in the absence of denaturing agents by an "all-or-none" process, that is, once the disulfide bond between Cys15 and Cys42 in the CB-domain was cleaved, the remaining four disulfide bonds were reduced very easily. The reduced and carboxymethylated RSC-a completely lost the chitin-binding ability, but retained 50% of the hydrolytic activity toward colloidal chitin of RSC-a. From these results, it was shown that RSC-a consists of a CB-domain and a Cat-domain connected by a flexible linker, and it was suggested that the CB-domain increases the hydrolytic action of Cat-domain toward insoluble chitin derivatives by binding to them.

Amino Acid Sequence↗

Prognosis for canine malignant mammary tumors based on TNM and histologic classification.

The 2-year prognosis of malignant mammary tumors seen in 175 bitches in the Tokyo metropolitan area was assessed based on their TNM clinical staging and histological classification. The larger the tumor size became (T category), the poorer was the clinical prognosis. The 2-year survival rates of the animals with regional lymph node metastasis of tumor cells (N1, N2 category) and/or distant metastasis (M1 category) were markedly lower than those of the animals without such involvement. As the grade of TNM staging increased, the prognosis was poorer, however, there were no significant differences in survival rates among subtypes of adenocarcinomas (tubular, papillary and papillary cystic) determined by WHO histological classification. It was also noticed that animals having carcinomas without tubular formation or myoepithelial cell proliferation had a lower survival rate than animals having carcinomas with those characteristics; and invasive carcinomas into adjacent skin or lymphatic/vascular vessels implied a poorer prognosis than non-invasive ones. The results suggest that a combined practice of TNM system and our evaluation on the above-mentioned 4 histologic features could be useful for prognostic determination of canine mammary cancers.

Adenocarcinoma↗

Cervical osteoplastic laminotomy using autogenous bone.

Cervical foraminotomies are performed from the fifth to the eighth cervical nerve roots on both sides. On the side with more marked radiculopathies the laminae are osteotomized to the full extent, but not so completely on the other side. The mass of laminae from C-3 to C-7 is lifted up using the incompletely severed side of the laminae as the fulcrum. The removed spinous processes of C-6 and C-7 are adjusted and fixed between the articular joints and the lifted laminae from C-4 to C-6. This procedure prevents extradural scar formation, there are no complications caused by foreign bodies, postoperative neuroimaging is possible because no metallic artifact is formed, and extensive decompression is achieved for the cervical cord and nerve roots.

Adult↗

The expression of IL-6 and its related genes in acute leukemia.

Acute myeloid leukemia (AML) blast cells frequently produce interleukin-6 (IL-6) and other cytokines such as colony-stimulating factors (CSF: G-CSF, M-CSF, and GM-CSF), tumor necrosis factor (TNF)-alpha, and IL-1. The AML blast cells that produced IL-6 alone could not form autonomous in vitro colonies, whereas the blast cells that coexpressed CSF in addition to IL-6 were able to form such colonies. This suggests that IL-6 acts as a costimulator to enhance CSF-induced clonogenicity of AML blast cells. TNF-alpha and IL-1 that are produced from the blast cells may stimulate the growth of the AML blast cells by inducing production of CSF in bone marrow stromal cells or in the blast cell population itself. Improvement of clinical manifestations by the administration of an anti-IL-6 murine monoclonal antibody in a patient with AML-M5B confirmed an important role of IL-6 in in-vivo growth of the blast cells. The mRNA expression of IL-6 and its related genes in AML and acute lymphoid leukemia (ALL) blast cells was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). IL-6 mRNA expression was common in AML, but rare in ALL, whereas the IL-6 receptor (IL-6R) mRNA was expressed in almost all cases of AML and in more than half of the cases of ALL. In contrast, gp130 was ubiquitously expressed in both AML and ALL. A significant correlation between the levels of IL-6R expression and the responsiveness of the blast cells to exogenous IL-6 was observed. This suggests the possibility of the rapid prediction of the responsiveness of leukemic cells to exogenous IL-6 (IL-6 administration for therapy) by rapid measurement of IL-6R mRNA by RT-PCR.

Acute Disease↗

Does an allergy skin test on school-children predict respiratory symptoms in adulthood?

BACKGROUND: It is interesting from the correct point of preventive health care whether allergy skin tests at entry have the positive relationship with common respiratory symptoms such as persistent cough, persistent phlegm and wheeze with colds at end point in longitudinal studies. OBJECTIVE: The purpose of this study is to investigate this relationship in subjects followed from when they were school-children until they were young adults. METHODS: Young adults aged 18-31 years who had participated in an allergy skin test and a health survey for common respiratory symptoms during primary and junior high school were asked about their respiratory symptoms at the end-point in the follow-up study. Three cohort groups were employed in the follow-up study. RESULTS: According to a multiple logistic analysis with adjustments made for sex, symptoms at entry in childhood, and age and smoking habits at the end-point, young adults with a positive skin test to an extract of house dust as school-children showed a higher prevalence of wheeze with colds compared with those with a negative skin test. However, this relationship was not found for persistent cough or persistent phlegm, indeed, the latter symptom was significantly associated with negative skin tests in one cohort group. CONCLUSION: The respective symptoms at entry in childhood were also predictors of their occurrence in young adults. The results show that the common respiratory symptoms such as persistent phlegm and wheeze with colds in childhood are related to those in young adults rather than is an allergy skin test to an extract of house dust in childhood.

Adolescent↗

Interphase and metaphase detection of the breakpoint of 14q32 translocations in B-cell malignancies by double-color fluorescence in situ hybridization.

The breakpoint of 14q32 translocations found in B-cell malignancies was delineated specifically in both metaphase spreads and interphase nuclei by double-color fluorescence in situ hybridization (FISH) using bacteriophage clones containing the human immunoglobulin gamma chain gene locus (Ig gamma) and a cosmid clone, CY24-68, containing VH segments. CY24-68 is more telomeric than Ig gamma, separated by approximately 1 megabase (Mb). FISH studies were performed on four patients with non-Hodgkin's lymphoma (NHL), one with acute lymphoblastic leukemia (ALL), one with plasma cell leukemia (PCL), and three cell lines. In each patient with t(8;14), t(14;18), and t(3;14), the signal of Ig gamma gene was observed on der(14) and that of CY24-68 at respective partner sites of these translocations, 8q24.1, 18q21.3, and 3q27. Interphase nuclei with a signal of Ig gamma clearly separated from that of CY24-68 were more frequently encountered in all of the patients (45% to 74%) than those in normal controls (4% to 5%). Even in cases where only interphase nuclei were available for FISH studies, 14q32 translocations are detected as shown in two patients each with NHL and t(11;14)-carrying PCL. In two cell lines, HS-1 derived from ALL carrying t(8;14) and FR4 derived from a plasmacytoma carrying a complex form of t(8;14), the signal of Ig gamma was observed at the breakpoint region 8q24.1 of the der(8) in addition to the der(14), indicating that translocation event occurred within the Ig gamma locus. Intense Ig gamma signal was found at the breakpoint region on the der(14)t(11;14) in HBL-2 derived from NHL, indicating amplification of the Ig gamma gene, and presumably the resultant chimeric DNA between Ig gamma and DNA sequences at 11q13. The present approach allowed us to unequivocally detect tumor-specific breakpoints of 14q32 translocations. Furthermore, interphase FISH provides a rapid diagnostic procedure to detect 14q32 translocations in B-cell malignancies.

Burkitt Lymphoma↗

Sequence of the canine c-yes proto-oncogene.

Cloning of the canine yes oncogene was attempted from a cDNA library derived from a healthy canine spleen using a human c-yes-1 probe. The nucleotide and amino acid sequences revealed that the canine yes gene contained an open reading frame consisting of 539 amino acids. Its product had a molecular mass of 60,368 Daltons and showed 95.9 per cent and 90.4 per cent homology with human and chick p61c-yes, respectively. Moreover, the product had a myristylation signal, src homology region (SH) 3, SH2, and tyrosine kinase domains showing 98.8 per cent and 96.0 per cent homology with those of human beings and chickens, respectively. These findings indicate that the products of the canine yes gene may have non-receptor-type tyrosine kinase activity on the cell membrane, as is the case in human and chick p61c-yes.

Amino Acid Sequence↗

Purification and characterization of two chitinases from the leaves of pokeweed (Phytolacca americana).

Two chitinases, designated PLC-A and PLC-B, were purified from the leaves of pokeweed (Phytolacca americana) using DEAE-cellulose column chromatography followed by gel filtration on Sephadex G-75, hydrophobic column chromatography, and ion-exchange FPLC. PLC-A and PLC-B are acidic and basic proteins having molecular masses of 25 and 29 kDa, and isoelectric points of 3.7 and 9.5, respectively. On the basis of their partial amino acid sequences, it was seen that PLC-A and PLC-B belong to class II and class III chitinases, respectively. The optimal pH of PLC-A toward glycolchitin is pH 4.5 and hydrolyzed (GlcNAc)4 into 2(GlcNAc)2, and (GlcNAc)5-6 into (GlcNAc)2 and (GlcNAc)3. on the other hand, PLC-B has two optimal pHs at 3 and 7 toward glycolchitin and hydrolyzed (GlcNAc)5 into GlcNAc and (GlcNAc)4, and (GlcNAc)6 into GlcNAc, (GlcNAc)2, and (GlcNAc)4.

Amino Acid Sequence↗

The complete amino acid sequence of chitinase-B from the leaves of pokeweed (Phytolacca americana).

The complete amino acid sequence of pokeweed leaf chitinase-B (PLC-B) has been determined by first sequencing all 19 tryptic peptides derived from the reduced and S-carboxymethylated (RCm-) PLC-B and then connecting them by analyzing the chymotryptic peptides from three fragments produced by cyanogen bromide cleavage of RCm-PLC-B. PLC-B consists of 274 amino acid residues and has a molecular mass of 29,473 Da. Six cysteine residues are linked by disulfide bonds between Cys20 and Cys67, Cys50 and Cys57, and Cys159 and Cys188. From 58-68% sequence homology of PLC-B with five class III chitinases, it was concluded that PLC-B is a basic class III chitinase.

Amino Acid Sequence↗

Regression of hypertrophic osteopathy following removal of intrathoracic neoplasia derived from vagus nerve in a dog.

Surgical removal of an intrathoracic tumor derived from a vagus nerve was undergone in a dog with hypertrophic osteopathy. The tumor was pathologically diagnosed as malignant schwanoma. Soft tissue swelling, lameness, and itchiness in four limbs disappeared within 7 days after surgery. The proliferated periosteal osteophytes of the four limbs was progressively reduced with time by follow-up radiography on the 58th day after surgery. On the 710th day after surgery, these osteophytes were greatly decreased as osteopathy, malignant schwanoma.

Animals↗

Ventral spinal subdural hematoma--case report.

A 26-year-old male presented with a very rare spinal subdural hematoma which developed 3 days after minor trauma. Magnetic resonance imaging showed the very large hematoma, extending from the C-1 to the T-11 levels, ventral to the spinal cord. An attempt to remove the hematoma via a posterior approach on the next day failed. On the 3rd hospital day, the hematoma was partially removed at the C7-T1 intervertebral level through an anterior approach. Neurological signs of paraplegia, and urinary and bowel disturbances did not improve postoperatively.

Adolescent↗

Effects of taurine on depletion of erythrocyte membrane Na-K ATPase activity due to ozone exposure or cholesterol enrichment.

The objective of this study was to investigate the interrelationship between taurine and erythrocyte-membrane Na-K ATPase activity. A comparison was conducted to test whether taurine or uric acid (a water-soluble scavenger of free radicals) prevents or recovers the depletion in membrane ouabain-sensitive Na-K ATPase activity resulting from ozone exposure or cholesterol enrichment of the erythrocyte membrane. A depletion of 44% and 27% in ouabain-sensitive Na-K ATPase activity was respectively caused by ozone exposure and cholesterol enrichment. Taurine as well as uric acid partially prevented the activity loss from ozone exposure. In addition, taurine at high concentrations (from 1.5 to 4.5 mM) restored the depletion of erythrocyte-membrane Na-K ATPase activity due to ozone exposure and prevented the depletion of the enzyme activity due to cholesterol enrichment. In contrast, although the same high concentrations were used, uric acid failed to show either of the above effects. These results suggest that taurine acts (1.5-4.5 mM) polyvalently as not only an antioxidizing agent but also as a membrane stabilizer to maintain the functions of membrane Na-K ATPase, a membrane-bound protein.

Adult↗

WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia.

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.

Acute Disease↗

Expression of the interleukin-6 (IL-6), IL-6 receptor, and gp130 genes in acute leukemia.

Expression patterns of interleukin-6 (IL-6), IL-6 receptor (IL-6R), and gp130 genes in 39 patients with acute myeloid leukemia (AML), in 23 patients with acute lymphoblastic leukemia (ALL), and in 7 patients with acute mixed lineage leukemia (AMLL) were studied by quantitative reverse transcriptase-polymerase chain reaction. Significant levels of IL-6 were expressed in 8 (21%) of 39 AML patients and in 2 (29%) of 7 AMLL patients, whereas in ALL, the expression of IL-6 was almost negligible. IL-6R was expressed in all patients with AML and AMLL, whereas only half of ALL patients expressed low levels of IL-6R as compared with those with AML and AMLL. However, gp130 was ubiquitously expressed in all the leukemia patients, and there was no significant difference in gp130 expression among AML, ALL, and AMLL. Significant correlation was observed between the expression of IL-6R and gp130 in AML. When tested for in vitro response to IL-6, the leukemic cells from 3 of 7 AML, none of 3 ALL, and both of 2 AMLL patients significantly responded to IL-6, showing the correlation between the expression levels of IL-6R and gp130 and the responsiveness of leukemic cells to IL-6. These results showed that quantitation of IL-6R and gp130 expression by reverse transcriptase-polymerase chain reaction is useful for the rapid prediction of the responsiveness of leukemic cells to IL-6, especially in cases of administration of IL-6.

Adolescent↗