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Biomedical subjects

N Tominaga

Publications and source records attributed to N Tominaga.

At least 55 records · Page 3Linked to original sources
PubMed1990

Demonstration of high-affinity interleukin-2 receptors on B-chronic lymphocytic leukemia cells: functional and structural characterization.

Functional and structural characteristics of interleukin 2 (IL-2) receptors on B-cell chronic lymphocytic leukemia (B-CLL) cells were analyzed by a proliferation assay, IL-2 binding assay and cross-linking study. In the 3H-thymidine incorporation assay, purified B-CLL cells from four out of sixteen cases, in which the percentage of Tac antigen (Tac Ag) positive cells in peripheral blood lymphocytes ranged from 0 to 48.8%, responded to IL-2 (100 U/ml) after both 3- and 6-day incubation. No relationship was found between the responsiveness to IL-2 and the percentage of Tac Ag positive cells. In the radiolabeled IL-2 binding assay, however, B-CLL cells from all seven cases examined, including three cases with mitogenic response to IL-2 and four cases without mitogenic response, were shown to have both high- and low-affinity receptors. The number of high- and low-affinity receptors per cell ranged from 29-186 and from 420 to 1,800, respectively. Furthermore, with the affinity cross-linking method p55 (Tac Ag) and p70/75 were found even in cases without mitogenic response in their B-CLL cells. In conclusion, the B-CLL cells so far examined possessed high-affinity IL-2 receptors consisting of p55 and p70/75; nevertheless, this was not sufficient to respond to the mitogenic signal of IL-2.

B-Lymphocytes↗
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

Effective purification of human chorionic gonadotropin and its subunits from pregnant women's urinary peptides absorbed on reverse-phase resin.

Human chorionic gonadotropin (hCG) was extracted and purified by reverse-phase resin (Sepralyte C8 resin) adsorption and Sephadex G-100 column chromatography from urine of pregnant women. Approximately 15000 IU of hCG was recovered from 1000 ml of urine by C8 resin adsorption. hCG from the gel-filtration step stimulated testosterone production in rat Leydig cells and had a specific activity of approximately 8000 IU/mg, a value which was higher than those of commercial hCGs. Furthermore, hCG purified to near-homogeneity was separated effectively into its subunits by reverse-phase high-performance liquid chromatography using an acetonitrile gradient in the presence of 0.1% trifluoroacetic acid with no special pretreatment for dissociation of subunits. The separated subunits were able to re-associate. The techniques used are simple and may be suitable for not only laboratory but also industrial production of hCG and its subunits.

Animals↗
PubMed1989

Angioimmunoblastic lymphadenopathy. Review of 44 patients with emphasis on prognostic behavior.

In order to investigate the relationship between histologic findings and clinical behavior in angioimmunoblastic lymphadenopathy (AILD), 44 patients with AILD were reviewed. These patients comprised 24 men and 20 women with age range from 25 to 84 years of age (median, 64 years). Lymphadenopathy was observed in all patients, systemic in 37, and localized in seven. Polyclonal hypergammaglobulinemia was present in 64% of patients. Histologically clear cells or convoluted cells were observed in 36% and 48% of the patients, respectively. Univariate analysis (log-rank test) for prognostic factors revealed age, appetite, presence of clear cells, or convoluted cells were important factors. However, multivariate analysis revealed that there were no independent factors for prognosis. The presence of clear cells and/or convoluted cells were histologic signs for poor prognosis; autopsy showed that patients with the clear cells with or without convoluted cells mostly died of active disease of AILD with two cases progressing to non-Hodgkin's lymphomas and those with convoluted cells alone died of lung infection. From these findings, AILD could be divided into three groups: AILD with (1) clear cells with or without convoluted cells, (2) convoluted cells alone, or (3) neither cells. The first two groups showed poor prognosis, and the last a favorable prognosis.

Adult↗
PubMed1989

Existence of associated, non-associated, and oligomeric forms of human chorionic gonadotropin subunits in placental extracts.

The molecular sizes of human chorionic gonadotropin (hCG) subunits in the native state in normal first trimester placental extracts were determined by gel filtration on Sephacryl S-300, followed by SDS-polyacrylamide gel electrophoresis, protein blotting, and immunobinding analysis using anti-alpha and - beta antibodies. Mature forms of hCG subunits in the extracts were only found in the same fraction as that which contained standard urinary hCG, indicating an alpha beta dimer. On the other hand, immature forms were detected with a wide range of molecular weights, which were higher than that of standard hCG, suggesting oligomerization of associated or non-associated immature subunits. In order to determine the associated state of these subunits, various forms of associated subunits (hCG alpha beta) in placental extracts were immunoprecipitated with anti-hCG antiserum, which only recognized hCG alpha beta, and Protein A-Sepharose. They were then analyzed by SDS-polyacrylamide gel electrophoresis under reducing and non-reducing conditions, followed by immunobinding assaying. It has been suggested that there are three kinds of hCG alpha beta S (one mature and two immature). To confirm the above results and to clarify the existence of free subunits, placental extracts were subjected to two-dimensional SDS-polyacrylamide gel electrophoresis. With this technique, high molecular weight forms of immature hCG subunits were found to be present in placental cells as an oligomer of not only the alpha beta dimer but of each subunit as well.

Chorionic Gonadotropin↗
PubMed1989

Analysis of surface antigen expression of human immunoglobulin-secreting cells: phenotypic heterogeneity in normal counterparts of myeloma cells.

Human myeloma cells are malignant counterparts of plasma cells which represent the most differentiated B cells. Myeloma cells are, however, heterogeneous in their surface antigen expression (Katagiri et al, 1984, 1985), which may reflect that normal plasma cells have a spectrum of differentiation. To test this hypothesis, immunoglobulin-secreting cells (ISC) of non-neoplastic nature were studied with regard to their surface antigen expression by using a combination of reverse haemolytic plaque assay and complement-dependent cytolysis. Non-neoplastic ISC were found to have a broad spectrum of differentiation stages from the immature type of CD20+, HLA-DR+, CD38+ in the peripheral blood to the mature type of CD20-, HLA-DR-, CD38+ in the bone marrow. In patients with polyclonal B cell activation (PBA), ISC showed a more immature antigen expression in comparison with ISC in normal controls or patients without PBA. The surface antigen development of ISC was clearly demonstrated throughout the stages in the analysis of mitogen-induced ISC in vitro. No significant difference in the surface phenotype of ISC was found among heavy chain classes. Thus, non-neoplastic ISC show a spectrum of differentiation similar to that of myeloma cells, depending on the site where ISC are located, and on the degree of PBA in vivo.

Antibody-Producing Cells↗
PubMed1989

[CALLA-positive leukemic multiple myeloma of IgA-kappa type].

A 73-year-old man was admitted into the hospital because of lumbago in October, 1986. Laboratory examination on admission showed anemia, an IgA-kappa Bence Jones proteinemia. The bone marrow picture disclosed a marked involvement by the neoplastic cells, followed by leukemic conversion 2 weeks later. The leukemic cells displayed a lymphoblastoid appearance on light microscopy, but rather compatible with plasma cells on electron microscopy, showing some strands of rough endoplasmic reticulum and a prominent Golgi apparatus in the cytoplasm. The cells expressed a wide spectrum of surface markers, including those of plasma cell (PCA-1, OKT10), B cell (B1, sIg) and CALLA. Reverse hemolytic plaque assay disclosed the immunoglobulin production of monoclonal kappa chain, but a heavy chain production was recognized only in a small proportion of the cells. Under the diagnosis of multiple myeloma, he was treated with vincristine, cyclophosphamide, and prednisolone. But he died of renal failure complicating hypercalcemia after only three months of the admission in accordance with previous reports that CALLA-positive myeloma was associated with poor prognosis. This case may also represent the clinical, morphological and phenotypic diversity in multiple myeloma.

Aged↗
PubMed1989

[A case of anti-phospholipid antibody syndrome presenting chorea as an initial manifestation].

A 20 year old female patient with anti-phospholipid antibody syndrome who presented chorea as an initial symptom is described. At the age of 14, she noticed involuntary movements of upper and lower extremities bilaterally. The CT scan revealed the presence of low density areas in the right caudate nucleus and left putamen. The result of the laboratory tests included antibodies to nuclear antigens (positive FANA and anti-DNA), prolonged PT and APTT, biological false positive for syphilis. Her serum contained antibodies to cardiolipin and phosphatidylserine as demonstrated by specific ELISA assay method. The clinical diagnosis of chorea was made and haloperidol was administered with partial symptomatic improvements. The patient reported here is the first well documented case of anti-phospholipid antibody syndrome presenting chorea as an initial manifestation in the Japanese literature.

Adult↗
PubMed1989

[The roles of macrophage on the mechanism of development of periapical lesion. The response of macrophage stimulated with bacteria isolated from infected root canals].

It has been proposed that bacteria in infected root canals are most important agents to pathogenesis of the periapical lesion. The aim of the present study was to examine the roles of macrophage on the mechanism of development of periapical lesion. Therefore the influences of bacteria isolated from infected root canals to macrophage functions and the effects of products from macrophage stimulated with bacterial components to periodontal tissue were investigated. In this study, sonic extracts prepared from Bacteroides buccae predominantly isolated from root canals were tested for its capacity of induction of chemotaxis and production of prostaglandin E2 and collagenase from human peripheral monocyte. Furthermore prostaglandin E2, collagenase production and alkaline phosphatase activity of fibroblasts from human periodontal ligament (HPLF), pulp (HPF) and gingiva (Gin 1) stimulated with macrophage conditioned medium (MCM) stimulated with B. buccae sonic extracts were examined. The results obtained were as follows. The sonic extract of B. buccae showed capacity to induce macrophage chemotaxis directly and by activation of serum complement, and the serum activated with sonic extract of B. buccae was more active than the serum activated with LPS of Salmonella typhimurium. Prostaglandin E2 production of macrophage was increased when the cells were stimulated by sonic extracts of B. buccae, but collagenase activity. toas not increased. MCM stimulated with sonic extracts of B. buccae fot 48 hours strongly induced PGE2 and collagenase production from HPLF and HPF, at the same time sonic extract showed the similar capacity of induction of the PGE2 production of MCM. But, HPF stimulated with sonic extract showed the low activity of induction of the PGE2 production. On the other hand, Gin 1 cell produced a few amount of the PGE2 when it was stimulated with MCM, but not produced collagenase. Alkaline phosphatase activity of HPLF and HPF had been inhibited by addition of MCM stimulated with B. buccae sonic extract.

Macrophage Activation↗
PubMed1989

[Therapeutic effects of imipenem/cilastatin sodium against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

One hundred ninety-eight patients with severe infections associated with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 182 patients in whom efficacies are evaluable, responses were excellent in 50 patients, good in 52, fair in 21 and poor in 59, and the efficacy rating was 56.0%. 2. The efficacy rating in 87 patients who had failed to respond to prior treatment with other antibiotics was 58.6%. 3. There were significant differences in efficacy ratings when patients were grouped according to differences the number of neutrophils after treatment, less than 100, 101 approximately 500 and over 501/mm3. 4. The eradication rate in 38 patients from whom causative organisms were isolated was 75.8%. 5. Out of 197 patients in whom the safety was evaluable, side effects were observed in 19 patients (9.6%) and abnormal laboratory test values in 15 (7.6%).

Adolescent↗
PubMed1988

Quantitative evaluation of the factors affecting the process of fibroblast-mediated collagen gel contraction by separating the process into three phases.

Kinetics of collagen gel contraction by fibroblasts cultured in vitro was examined in detail for quantitative analysis. The process of collagen gel contraction was not expressed by a simple function of time. It appeared to consist of three distinct phases; a lag phase before the initiation of contraction, a rapid contraction phase and a slow contraction phase. Factors affecting the gel contraction can be classified into four groups. The first group includes increase in cell number, in culture temperature or in serum concentration, which strengthened the contraction in all the three phases, suggesting that they affected cellular activity particularly in interacting with collagen. The second group repressed the later two phases of contraction but not the first lag phase, typically increase in collagen concentration and a low dose of nocodazole or colcemid. Increasing population doubling levels of fibroblasts belongs to the third group which caused a reduced lag time but no change in the later two phases. Cytochalasin D at a low dose (0.03-0.1 microgram/ml) is another example of the third group which shortened the lag time. The last group did not change the contraction curves. Donor age of fibroblasts isolated from the skin is an example of this group. The rate of rapid contraction in the second phase was always found to be closely correlated with the degree of contraction at the end of the third phase, in a whole set of the factors above mentioned. The results suggest that the extent of the later two phases might be a reflection of the same cellular activity, particularly cytokinetical one. The lag time is directly related to the time for cells to become elongate in shape as observed by using the video-microscopy, suggesting that the lag phase is also governed by cytokinetical activity. The two cytokinetical activities are closely related, but may be distinct, since the factors affecting the collagen gel contraction can be differentiated into four groups.

Adult↗
PubMed1988

Plasma cell leukaemia of non-producer type with missing light chain gene rearrangement.

A case of plasma cell leukaemia of non-producer type is described. The patient presented with typical clinical features of plasma cell myeloma, including multiple osteolytic lesions, hypercalcaemia, renal failure and reduced polyclonal immunoglobulins, except that M-component was not detected in either the serum or urine. Morphological examinations showed a plasmacytoid appearance of the neoplastic cells, while immunological studies failed to detect cytoplasmic immunoglobulin or secretory capacity. The surface phenotype of CD38+, PCA-1+, DR-, CD20-, CD24-, CD9-, CD10- and surface immunoglobulin- was compatible with mature plasma cells. Chromosomal analysis showed the 14q+ marker due to translocation (6;14) and deletion of the short arm of chromosome 1. Analysis of immunoglobulin genes revealed the presence of heavy chain gene rearrangement, but the light chain genes, both kappa and lambda, remained in germline configuration. Such defective immunoglobulin gene rearrangement may be responsible for the failure of immunoglobulin biosynthesis and secretion by the neoplastic plasma cells. Furthermore, it is suggested that the morphological and phenotypic development of B cells may not necessarily depend on immunoglobulin light chain gene rearrangement, and that the oncogenic event in myeloma may occur at an earlier stage of B cell differentiation.

Chromosome Aberrations↗
PubMed1988

Metabolism of a new positive inotropic agent, 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212) in the rat, mouse, dog, monkey and human.

1. After OPC-8212 was orally given to rats, mice, dogs, monkeys and humans, its metabolites were identified by n.m.r. and mass spectrometry, and their concentrations in the plasma, urine and faeces of these species were measured by high-performance liquid chromatography (h.p.l.c.). 2. Hydrolysis of the amide group, oxidation and cleavage of the piperazine ring, O-demethylation of the methoxy group, and conjugation were proposed as metabolic pathways of OPC-8212. 3. In rats, mice and monkeys given OPC-8212 orally, metabolites M-1 to M-6 were detected in the plasma, urine and faeces, while M-1, -4, -5 and M-6 were detected in dogs, and M-1, M-3, M-4, M-5 and M-6 were detected in humans. 4. Conjugates of metabolites M-6 and M-7, with glucuronic acid and sulphuric acid, were observed in the urine of rats and humans.

Adult↗
PubMed1987

Electrophoretic separation of proteins on agarose gel--application for direct immunization with a gel piece containing an antigen.

An efficient method of separating proteins by electrophoresis with agarose gels containing sodium dodecyl sulfate is described. The separated proteins were then used to make antibodies. The separation of proteins in the molecular weight range 25K to 94K on 4 to 5% agarose gels showed good resolution which was comparable to that obtained by electrophoresis with polyacrylamide gels containing sodium dodecyl sulfate. The subunits of human chorionic gonadotropin were separated by the preparative agarose gel electrophoresis and the gel bands containing the subunits were used directly to raise antibodies against these proteins. The degree of solubilization of the proteins from the gel slices was found to be complete.

Antibody Formation↗
PubMed1987

Subcellular localization of intracellular forms of human chorionic gonadotropin in first trimester placenta.

To determine the subcellular sites for synthesis and processing of human chorionic gonadotropin subunits in cells, first trimester placental cells were fractionated subcellularly on sucrose density gradients. Analysis of the subcellular fractions by immunobinding techniques revealed that the rough endoplasmic reticulum-rich fraction contained only intermediates having high-mannose oligosaccharides, but the Golgi-rich fraction contained not only intermediates but also mature forms which were resistant to endoglycosidase H but sensitive to neuraminidase. These results show that human chorionic gonadotropin subunits are synthesized in the rough endoplasmic reticulum as forms containing high-mannose oligosaccharides, and their maturation occurs in the Golgi apparatus by trimming with endogenous glycosidases. They are then modified by addition of complex oligosaccharides and terminal sialic acid through glycosyltransferases.

Acetylglucosaminidase↗
PubMed1987

[Cross-sectional visualization of regurgitant jet by color flow mapping to evaluate aortic regurgitation].

In the noninvasive evaluation of aortic regurgitation by Doppler echocardiography, flow mapping of the aortic regurgitant jet using the long-axis approach is of limited value in cases of combined mitral stenotic lesions. This is because the transmitral flow yields flow disturbances in the left ventricle, making it difficult to identify the extent of the aortic regurgitant jet. To overcome these limitations, the severity of aortic regurgitation was evaluated using the cross-sectional area of the aortic regurgitant jet at the level of the aortic valve as visualized by color flow imaging technique. The study population consisted of 16 patients with aortic regurgitation (10 with pure aortic regurgitation, five with superimposed mitral stenosis, and one with mitral valve replacement). Three normal subjects served as controls. The cross-section of the aortic regurgitant jet was visualized as a mosaic of yellow and blue in all patients with aortic regurgitation, but not in any of the controls. Planimetric measurements of the cross-sectional area of the regurgitant jet (J) and the aortic annulus area (Ao) were performed, and the Doppler parameter, J/Ao, was calculated. As a reference, the aortic regurgitant fraction (RF) was calculated from Doppler measurements of systolic aortic and pulmonary flows (AF and PF); RF (%) = (AF - RF)/AF x 100. The Doppler parameter, J/Ao, correlated well with the Doppler measurement of RF (r = 0.82, p less than 0.005), irrespective of the presence of associated mitral lesions. Thus, the cross-sectional area of the aortic regurgitant jet determined by color flow imaging technique would be a useful estimate of the severity of aortic regurgitation, even in the presence of associated mitral stenotic changes.

Adolescent↗