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Biomedical subjects

Y Kanayama

Publications and source records attributed to Y Kanayama.

At least 91 records · Page 5Linked to original sources
PubMed1991

Expression and functional role of the proto-oncogene c-kit in acute myeloblastic leukemia cells.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is thought to play an important role in hematopoiesis. In a series of human acute myeloblastic leukemia (AML), the expression of the c-kit proto-oncogene and its product was studied by means of Northern blot and immunoblot analyses. The c-kit mRNA was expressed in 20 of 25 cases of AML, and in those cases the product of the c-kit proto-oncogene was detected by immunoblotting with anti-c-kit antibody. The expression of c-kit transcripts and protein was barely detectable in normal bone marrow cells as a control. The expression of c-kit transcript did not correlate with the French-American-British classification nor clinical manifestations. In 6 of 11 cases that expressed c-kit product, AML cells were found to proliferate in response to recombinant human stem cell factor (rhSCF), the ligand for c-kit, and the synergistic stimulation of AML cells was observed by rhSCF and granulocyte-macrophage colony-stimulating factor. Immunoblotting with anti-phosphotyrosine antibody showed that the c-kit receptor protein was detectably phosphorylated in 7 of 12 cases tested before the stimulation with rhSCF, while the rhSCF treatment resulted in an increased tyrosine phosphorylation of c-kit in AML cells. These results indicate that c-kit proto-oncogene is expressed in most cases of AML and is functional in terms of supporting proliferation.

Blotting, Northern↗
PubMed1991

Angiotensin II induced biphasic inositol 1,4,5-triphosphate response in rat vascular smooth muscle cells.

We examined angiotensin II induced changes of inositol 1,4,5-triphosphate (Ins(1,4,5)P3) in cultured vascular smooth muscle cells from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) using a specific protein binding assay system. We observed a rapid biphasic Ins(1,4,5)P3 response, which peaked at 5 s and at 30 s after angiotensin II stimulation. At every period of time the Ins(1,4,5)P3 level of SHR was 2- to 5-fold higher than that of WKY. Thus, the Ins(1,4,5)P3 specific assay revealed a complex Ins(1,4,5)P3 response after angiotensin II stimulation and suggested the need for further investigation of the Ins(1,4,5)P3 metabolism following agonist stimulation in vascular smooth muscle cells.

Angiotensin II↗
PubMed1991

Hypogalactosylation of immunoglobulin G sugar chains and elevated serum interleukin 6 in Castleman's disease.

Immunoglobulin G (IgG) molecule has two N-linked complex type oligosaccharides, consisting of a mixture of at least 12 different structures. The pattern of these oligosaccharides is fairly constant in healthy individuals. In three patients with Castleman's disease, in whom serum interleukin 6 (IL-6) levels were elevated, agalactosyl species of serum IgG oligosaccharides were markedly increased as compared to those of normal healthy controls. A close relationship between increased IL-6 and altered IgG oligosaccharide structure is suggested.

Adult↗
PubMed1991

[Adult T cell leukemia/lymphoma with hyperprolactinemia: successful treatment by OK432 and PSK].

A 48-year-old woman was admitted in September 1987, because of lumbago and galactorrhea. Peripheral blood analysis showed neutrophilia and eosinophilia without abnormal lymphocytes. The antibody to adult T-cell leukemia (ATL) virus-associated antigen was detected and a hyperprolactinemia was observed. The blastogenic responses to PHA, ConA and PWM were lowered. Brain CT and MRI scannings showed no abnormalities in the hypophysis and hypothalamus, but abdomen CT revealed markedly enlarged abdominal lymph nodes. Two months after the administration of OK432 and PSK, the lymph node swellings disappeared and the responses to PHA, ConA and PWM were normalized, but hyperprolactinemia and galactorrhea persisted. After four months of the remission period, the patient developed lymph node swellings again, and was diagnosed from the biopsy specimen of the retroperitoneal lymph node as having malignant lymphoma of diffuse mixed cell type. Southern blot analysis showed a monoclonal integration of HTLV-I proviral DNA. Despite repeated combination chemotherapies, she died of pneumonia in February 1989. Autopsy revealed marked infiltrations of lymphoma cells in the liver, spleen and lungs, but no abnormality accounting for hyperprolactinemia was detected in the suprasellar regions. This case was of interest in that immunotherapy was effective in achieving a remission and in normalizing immuno-parameters in ATLL.

Adjuvants, Immunologic↗
PubMed1990

Modulation of N-acetylglucosaminyltransferase III, IV and V activities and alteration of the surface oligosaccharide structure of a myeloma cell line by interleukin 6.

The activity of N-acetylglucosaminyltransferase (GnT) III, IV and V on a myeloma cell line, OPM-1, was examined after incubation with interleukin 6 (IL-6). While augmenting cell proliferation, IL-6 resulted in a decrease of GnT III activity and an increase of GnT IV and V activities. Consistent with this, OPM-1 cultured with IL-6 showed an increased affinity to Datura stramonium lectin, which recognizes asialo-tri- and asialo-tetraantenary N-linked oligosaccharides. These results indicate that IL-6 modulates glycosyltransferase activity and the oligosaccharide structure of target cells.

Cell Membrane↗
PubMed1990

Carbohydrate analysis of immunoglobulin G myeloma proteins by lectin and high performance liquid chromatography: role of glycosyltransferases in the structures.

The carbohydrate structures and the enzymatic basis for glycosylation of IgG by bone marrow plasma cells were determined in 7 patients with monoclonal gammopathy of undetermined significance and 22 patients with IgG MM. Lectin-binding analysis showed that in all cases of monoclonal gammopathy of undetermined significance and normal controls the IgG heavy chains bound to Ricinus communis agglutinin more strongly than to concanavalin A. In contrast, the IgG in 11 of the 17 advanced cases of MM (stages II and III) studied reacted to concanavalin A more strongly. Structural analysis showed that the reduced R. communis agglutinin binding capacity of these MM IgGs was due to hypogalactosylation of IgG. The galactosyltransferase and N-acetylglucosaminyltransferase III activities of the bone marrow myeloma cells from 5 MM cases were found to have a low enzyme activity ratio of galactosyltransferase to N-acetylglucosaminyltransferase III which reflects the hypogalactosylation. This indicates that the difference in the carbohydrate moieties observed in myeloma proteins is due to variations in the activities of the two glycosyltransferases.

Carbohydrate Sequence↗
PubMed1990

Thrombin stimulates the production of immunoreactive endothelin-1 in cultured human umbilical vein endothelial cells.

The present study was designed to examine the effect of thrombin on endothelin production by cultured human umbilical vein endothelial cells (HUVEC) by radioimmunoassay. Cultured HUVEC released immunoreactive endothelin-1 (ir-endothelin-1) into the medium in a time-dependent manner. This release was inhibited completely by 10 micrograms/mL cycloheximide and is, therefore, directly related to de novo protein synthesis. Further endothelin release was stimulated by the addition of thrombin to the culture medium. Thrombin-induced ir-endothelin-1 release also was inhibited completely by 10 micrograms/mL cycloheximide. These results suggest that HUVEC in culture produce ir-endothelin-1 slowly, but continuously, and that this production is stimulated by thrombin.

Cells, Cultured↗
PubMed1990

Aberrant expression of immunoglobulin light chain isotype in B lymphocytes from patients with monoclonal gammopathies: isotypic discordance and clonal B-cell excess.

A study was made of 29 patients with monoclonal gammopathies to detect aberrations in immunoglobulin (Ig) light chain isotype expression in lymphocytes at various levels of B-cell differentiation, namely, circulating surface Ig positive (SIg+) cells, Ig-secreting cells (plaque forming cells, PFC) and mitogen-induced PFC. By using kappa-lambda analysis, two major phenotypes of aberrant Ig light chain isotype expression were found in circulating B cells at these three levels of differentiation: an absolute increase in B cells bearing the same Ig light chain isotype as that of monoclonal protein (clonal B-cell excess), and a relative decrease in those B cells (isotypic discordance). Isotypic discordance (ID) was found to be essentially negative in patients with monoclonal gammopathy of undetermined significance (MGUS) provided that they were in a stable condition. In myeloma patients, ID was found only in stage I, except for a remission case of stage III (4/7 in stage I, 0/8 in stage II, and 1/6 in stage III). ID was not restricted to a circulating SIg+ cell level but was also demonstrable at a spontaneous or pokeweed mitogen-induced PFC level. However, ID was negative at a PFC level induced by Staphylococcus aureus Cowan I. Clonal B-cell excess (CE) was frequently found in patients with active myeloma but not in stable patients (0/8 in MGUS, 1/7 in stage I, 8/8 in stage II, and 4/6 in stage III). CE was positive not only at a circulating SIg+ cell level but also at a circulating PFC level. Furthermore, patients with CE at a PFC level were found to have a higher proliferating capacity, defined as a percentage labelling index of marrow myeloma cells, than those without CE at a PFC level (P less than 0.02). ID and CE can therefore be considered as useful markers for discriminating between MGUS and myeloma, evaluating the clinical stability and predicting the clinical course.

Antibody-Producing Cells↗
PubMed1990

Alteration of membrane oligosaccharides by castanospermine, an alpha glucosidase inhibitor, enhances immunoglobulin production in Staphylococcus aureus Cowan I-stimulated lymphocyte culture.

Castanospermine (CSP) inhibits alpha-glucosidase, which is involved in the initial step of N-linked oligosaccharide processing of secretory and membrane glycoproteins. In Staphylococcus aureus Cowan I (SAC)-stimulated human lymphocyte culture, CSP at a dose of 20 micrograms/ml caused a twofold increase in immunoglobulin G (IgG) release after 7 days. An initial 48-h exposure to CSP sufficed for this enhancing effect. Plaque-forming cell assays on the seventh day disclosed that CSP caused an increase in the number of IgG-, IgA- and IgM-secreting cells. In cross-culture experiments, only a mixture of B cells pretreated with CSP and untreated T cells showed an increase in IgG production. Tritiated thymidine incorporation studies revealed that CSP enhanced B-cell responses to T cell-derived soluble factor (TSF). When incubated with CSP for 18 h, B cells showed an increased surface binding on [3H]concanavalin A (Con A). These results indicate that the alteration in B-cell membrane oligosaccharides enhances the response to TSF at an early stage of SAC culture, leading to an increase in Ig-secreting cell number at later stages. The present study provides evidence that cell-surface oligosaccharides of B cells play an important role in the responses of B cells to lymphokines.

Alkaloids↗
PubMed1990

[Actual conditions of bacterial infection associated with hematopoietic disorders--changes in 10 years. The Hanshin Study Group of Hematopoietic Disorders and Infections].

This study showed several accumulated data through ten years from our experience in hematopoietic disorders and associated infections, which has been analyzed by the Hanshin Study Group of Hematopoietic Disorders and Infections. Since 1979 to 1988, our group had evaluated the sorts of causative organisms and the efficacy of various antibiotics therapy in 2119 cases of infectious diseases associated with hematopoietic disorders. On behalf of evaluating the changes of disease profile for ten years, we divided the accumulated data into three phases; former phase the first three years, middle phase the second three years and late phase the last four years. There was no significant difference in the frequency of various hematopoietic disorders among the three phases. Each leukemia patients occupied 77% of all cases. Sepsis suspected is the most frequent infectious disease accounting for 68.8%. The other infectious diseases were 8.4% of the sepsis, 14.8% of the respiratory infections and 3.1% of the urinary tract infections. Comparing the frequency of infections among the three phases, the respiratory and urinary tract infections inclined to decrease. Of the 532 strains isolated from 2119 cases and identified as causative organisms, gram-negative bacilli occupied 62.8% and gram-positive bacteria 36.5%. In comparing the percentage of gram-negative bacilli among the three phases, it showed a decreasing tendency in order former phase 63.6%, middle phase 76.4% and late phase 43.8%. Pseudomonas, however, had been isolated at almost constant ratio through ten years. On the other hand, the ratio of gram-positive bacteria isolated were 34.5% in former phase, 23.6% in middle phase and 56.3% in late phase, showing increasing a tendency through the period. Twenty-three kinds of antibiotics were administered by intravenous drip infusion. The efficacy rate was 43.9% to 67.2%. In particular, effectiveness of antibiotic therapy often depends on the change of peripheral neutrophil counts from the onset and during the therapy. The efficacy rate, however, was 36% even neutrophil counts have not shown the tendency of increase from less than 100/microliters.

Adolescent↗
PubMed1990

Angiotensin-converting enzyme in the rat kidney. Activity, distribution, and response to angiotensin-converting enzyme inhibitors.

While it is known that angiotensin-converting enzyme (ACE) in the kidney is concentrated at the brush borders of the proximal tubule, the role of tubular ACE in renal physiology is not well understood. The active site of tubular ACE is exposed on the luminal surface of the brush borders and may hydrolyze peptides in the glomerular filtrate. However, a positive correlation between blood pressure and renal ACE activity was observed in spontaneously hypertensive rats, as well as in cases of ACE inhibition. Determination of ACE activity in different renal zones and immunohistochemistry demonstrated that ACE predominates in the inner cortex and that the proximal tubule in the outer cortex contains less ACE. Perhaps the inner cortex is the area responsible for alteration of renal ACE activity, since only ACE activity in the inner cortex increased following administration of the ACE inhibitor captopril. This would suggest that the induction of ACE occurs in the inner cortex. Renal ACE activity is also affected by oxidation. Thus, the activity increased when diamide, an oxidizing agent, was added to the crude extract of renal cortex and when oxygen was introduced into the extract. Therefore, tissue oxidation may be one factor affecting renal ACE activity.

Animals↗
PubMed1990

Corticosteroid- and furosemide-induced increase in proteinuria in nephrosis.

A corticosteroid- and furosemide-induced excessive increase in proteinuria developed in a 34-year-old nephrotic patient with focal glomerulosclerosis. The concentration of urinary protein increased almost in parallel with that of urinary glucose. This finding indicates that corticosteroids and/or furosemide can promote the disturbance of the tubular reabsorption mechanism together with increases in glomerular permeability and glomerular filtration rate.

Adult↗
PubMed1990

Chronic antihypertensive drug treatment decreases protein kinase C activity in platelets from SHR.

There is evidence that protein kinase C activity in platelets from adult SHR is significantly higher than this activity in age-matched WKY. In the present study, protein kinase C activity in the SHR was measured following antihypertensive drug treatment. Chronic administration of enalapril to SHR for 2 weeks decreased both systolic blood pressure and protein kinase C activity to the levels seen in the WKY. Similar results were obtained in case of chronic treatment of SHR with hydralazine or nifedipine. These results suggest that enhanced protein kinase C activity of SHR can be suppressed by lowering blood pressure by antihypertensive drugs.

Animals↗
PubMed1990

Amylase-producing plasmacytoma cell lines, AD3 and FR4, with der(14)t(8;14) and dic(8)t(1;8) established from ascites.

We established two human plasma cell lines, FR4 and AD3, from ascitic fluid in a patient with IgA k plasmacytoma (PC). Aberrant amylase production was found in this patient. Both AD3 and FR4 were free of Epstein-Barr virus, and both produced Ig A k in vitro. They produced amylase of the salivary type in vitro. This was confirmed by the demonstration of amylase mRNA comigrating with salivary gland mRNA. These cell lines commonly had unusual chromosomal abnormalities der(14)t(8;14) and dic(8)t(1;8). AD3 had additional chromosomal abnormalities compared with FR4. This suggests that AD3 is a subline of FR4. The oncogene c-myc is rearranged in most case of Burkitt's lymphoma with t(8;14). However, neither rearrangement nor amplification of the c-myc allele was detected in our PC lines. These lines expressed c-myc of 2.4 kb. There were no structural changes in the amylase genes of AD3 and FR4 detectable with Southern blotting analysis. As these lines were authentic PC lines, they would be useful for the future study of the relationship between the mechanism of oncogenesis and the rare tumor aberration, amylase production.

Aged↗
PubMed1989

Regulation of human tyrosine hydroxylase activity. Effects of cyclic AMP-dependent protein kinase, calmodulin-dependent protein kinase II and polyanion.

To determine the regulatory mechanism for human tyrosine hydroxylase, we examined modulations of the activity of the enzyme from human pheochromocytoma by cyclic AMP-dependent protein kinase, calmodulin-dependent protein kinase II and polyanion. The most remarkable activation was observed when the enzyme was assayed at physiological pH (pH 7) after being subjected to phosphorylation by cyclic AMP-dependent protein kinase. Calmodulin-dependent protein kinase II and polyanion also modulated the enzyme activity. The results suggest that tyrosine hydroxylase may be regulated similarly in both human and rat.

Animals↗