Search PubMed⌕ Search

Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 757 records · Page 42Linked to original sources

Detection of Epstein-Barr virus DNA and EBV-determined nuclear antigen in angioimmunoblastic lymphadenopathy with dysproteinemia type T cell lymphoma.

Six cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like T cell lymphoma were analyzed by immunohistochemical staining, polymerase chain reaction (PCR) and Southern blot analysis. Five cases out of six showed gene rearrangements of the T cell receptor beta chain, indicating the existence of a clonal T cell proliferation. Epstein-Barr virus (EBV) DNA was detected in all six AILD type cases by PCR amplifying the sequence located in the internal repeat I, and confirmed by Southern blot hybridization, using a BamHI-W fragment as a probe. Detection of the EBV genome occurred more frequently as compared with other types of lymphoid disorders. Furthermore, EBV determined nuclear antigen (EBNA) was detected in UCHL-1 (CD45RO, pan-T cell marker) positive cells by immunostaining. These results suggest that a significant number of AILD type cases are T cell origin lymphomas and EBV infection may be relevant to the biological features of this type of lymphoma.

Adolescent↗

Expression of the Hermes-1 (CD44) and ICAM-1 (CD54) molecule on the surface of thyroid cells from patients with Graves' disease.

From studies of binding of 51Cr-labeled T cells to human thyroid monolayers, we have postulated the existence of tissue "homing-like" receptors on thyroid cells in patients with Graves' disease (GD). In this study we have investigated whether the CD44 (Hermes-1) protein, well known as a putative human lymphocyte homing receptor, is expressed on thyroid cells in patients with GD, and if so whether its expression is influenced by interferon-gamma (IFN-gamma). Cell surface CD44, as well as CD54 (ICAM-1), another putative homing receptor, antigens were analyzed by flow cytometry and immunohistochemistry. CD44 and CD54 were both expressed on thyroid cells from untreated patients with GD, which, in the case of CD44, appeared as two peaks. IFN-gamma treatment enhanced the expression of the CD54 protein on Graves' thyroid cells and inhibited the expression of the larger of the two CD44 peaks, but not the other. Only small amounts of CD44 and CD54 were detected on normal thyroid cells, neither of which was affected by IFN-gamma. The CD44 protein was also demonstrated on both GD and normal thyroid cells by immunohistochemistry. These findings suggest that CD44, and possibly CD54, may induce putative adhesion pathways that lead to the homing of lymphocytes to the thyroid in patients who develop Hashimoto's thyroiditis and Graves' disease.

Adult↗

Alterations in activities of protein phosphatases PP1 and PP2A in T and B lymphocytes of autoimmune MRL/MpJ-lpr/lpr mice.

Activities of protein phosphatases PP1 and PP2A were determined in T and B lymphocytes of autoimmune-prone MRL/MpJ-lpr/lpr mice (MRL/lpr mice) and two control strains, MRL/MpJ-(+)/+ mice (MRL/+/+ mice) and C3H/HeJ mice. Potential PP1 activity, which was measured after treatment of cell extract with Co(2+)-trypsin, was much higher in T lymphocytes than B lymphocytes. However, no difference in the activity was observed between MRL/lpr mice and the controls. Spontaneous PP2A activity showed similar levels in T and B lymphocytes from normal mice, but potential PP2A activity, which was measured after treatment with 2-mercaptoethanol, was significantly higher in T lymphocytes from MRL/lpr mice than those from controls. No differences were detected in PP1 or PP2A activities in B lymphocytes. From these results, our previous data [Matsuzawa, S. et al. (1992) J. Biochem. 111, 472-477] demonstrating increases in potential activities of PP1 and PP2A in lymphoid tissues from autoimmune MRL/lpr mice can be interpreted as follows. 1) The increase in potential PP1 activity of the lymphoid tissues from MRL/lpr mice is caused by replacement of B lymphocytes by abnormal T lymphocytes, which accumulate in enormous numbers. 2) The increase of potential PP2A activity in the lymphoid tissues from MRL/lpr mice is caused by the increase in this activity in their T lymphocytes.

Animals↗

Increases in protein phosphatase 2B activity in lymphoid tissues and T-lymphocytes of autoimmune MRL/MpJ-lpr/lpr mice.

The assay conditions for protein phosphatase 2B (PP2B) in crude extracts from mouse lymphoid tissues and lymphocytes were extensively investigated. Under the conditions elucidated, the PP2B activity was measured in autoimmune-prone MRL/MpJ-lpr/lpr mice (MRL/lpr mice) and two control strains, MRL/MpJ- +/+ mice (MRL/+/+ mice) and C3H/HeJ mice. In the control mice, PP2B activity was distinctly higher in spleen and thymus than brain and liver. PP2B activity was further elevated in spleen of MRL/lpr mice than in the controls. Furthermore, we observed a specific increase in PP2B activity in T lymphocytes from MRL/lpr mice as compared with in those from control mice. On the other hand, no alteration was observed in PP2B activity in B lymphocytes. These results suggest the involvement of PP2B in the abnormal signal transduction and proliferation of T lymphocytes in MRL/lpr mice.

Animals↗

Functional and phenotypical analysis of subsets of rat CD4+ T cells.

Rat CD4+ T cells were divided into two distinct subsets by a monoclonal antibody RTH-1 recognizing a unique epitope on rat CD45R. Cellular distribution of OX-22- and RTH-1-defined antigens was the same. However, OX-22 and RTH-1 recognized different epitopes that exist on rat CD45R. The expression of IL-4 gene was detected only in RTH-1low CD4+ T cell subset upon various stimulations. In contrast, the expression of IL-2 and IFN-gamma gene varied depending upon the nature of stimuli. The increased cell surface expression of CD44 was detected in RTH-1high CD4+ T cell subset. Conversely the increased expression of CD2 was detected in RTH-1low CD4+ T cell subset. The expression of CD3 and LFA-1 was not significantly different between RTH-1high and RTH-1low subsets.

Animals↗

Cellular stress- and transformation-associated cell surface antigens expressed on human and rodent tumor cells.

Stress-induced proteins may have significant roles in anti-tumor resistance. To clarify the immunobiological roles of these proteins, we first developed monoclonal antibody (mAb) H1A that detects the HeLa cell-surface antigens whose expression was enhanced by treatment of the cells with physico-chemical stressors, such as heat, H2O2 and tumor necrosis factor. H1A (IgM) detects several molecules with mol. wt. 30, 43, 75, 90, 100, 120 and 150 kDa in Western blot analysis of HeLa cell lysates. Although the antigen was constitutively expressed on the HeLa cell surface, the cell-surface expression of H1A-defined antigen was rapidly enhanced (within 1 h) after heat treatment of HeLa cells. H1A antigens were also transformation-associated, since 1) the activated oncogene-transformed fibroblasts expressed the antigens, but parental nontransformed cells did not, and 2) certain human neoplastic but not normal cells strongly expressed the antigens. Furthermore, H1A mAb also partly blocked the cytotoxicity of purified protein derivatives-stimulated human T cell receptor gamma delta-type T cells towards HeLa cells. Taken together, these data indicate that H1A-defined stress-inducible proteins may play a vital role in anti-tumor resistance by cytotoxic T cells.

Adenosine Triphosphate↗

Brefeldin A blocks the cytotoxicity of T cell receptor alpha/beta and gamma/delta cytotoxic T lymphocyte clones reacting against human autologous cancer cells.

We studied the effector mechanism of T cell receptor (TCR) alpha/beta- and gamma/delta-type cytotoxic T lymphocyte (CTL) clones that react with human autologous tumor cells. Treatment of tumor cells with a fungal antibacterial reagent, brefeldin A (BFA), resulted in the inhibition of cytotoxicity of an autologous tumor (HST-2)-specific CD8+ TCR alpha/beta-type CTL, TcHST-2. Other anti-metabolites such as chloroquine, cycloheximide and colchicine did not affect the cytotoxicity. The cell-surface antigen expression, including MHC class I molecules, was not influenced by BFA treatment. Furthermore, BFA did not influence the cytotoxicity of lymphokine-activated killer cells and natural killer cells. Since BFA blocks the transport of peptides from endoplasmic reticulum to the Golgi apparatus, the above data suggest that BFA could affect washing out of the peptide fragments from the MHC class I groove. Consequently, target tumor cells were protected from killing by CTL. Moreover, we obtained a CD4-, 8-, TCR gamma/delta-type (V delta 1+) CTL clone, TcHOT, that reacts against an autologous ovarial carcinoma, HOT. BFA could also inhibit this cytotoxicity, and it is likely that different presenting molecules other than MHC class I proteins participate in the cytotoxicity of this TCR gamma/delta-type CTL. These studies suggest that both TCR alpha/beta- and gamma/delta-type CTL may require antigenic peptides that are most likely derived from the BFA-sensitive, intracellular endogenous target proteins.

Brefeldin A↗

Functional analysis of mononuclear cells infiltrating into tumors: establishment of T cell hybridomas exhibiting distinct interacting abilities with endothelial cells and extracellular matrix components.

We have established eleven T cell hybridoma cell lines to investigate mechanisms controlling interaction of T lymphocytes with endothelial cells as well as extracellular matrix (ECM) proteins at the clonal level. T cell hybridomas were characterized and subdivided into four groups on the basis of their interaction behavior with high endothelial venules (HEV). Group 1 (G1) exhibited strong adhesiveness. The binding was temperature- and divalent cation-dependent. Group 2 exhibited both adhesiveness and transendothelial migration (TEM, i.e., transmigration beneath the cytoplasm of endothelial cells). Group 3 exhibited strong TEM. G2 and G3 hybridomas exhibited temperature-independent and divalent cation-independent binding to HEV. Group 4 exhibited nonspecific adhesiveness to the surface of a slide glass. BW 5147, a parent of T cell hybridomas, was classified as G4. TEM was dependent on both the nature of T cell hybridomas and endothelial cells. TEM was completely temperature-dependent. TEM of G3 hybridomas was not divalent cation-dependent. Each group of T cell hybridomas interacted with various ECM components.

Amino Acid Sequence↗

Cardiac atrial natriuretic peptide in monocrotaline-induced pulmonary hypertensive rats.

To determine the time course and potential triggers for synthesis of atrial natriuretic peptide (ANP) in right ventricle during the development of right ventricular hypertrophy (RVH), we measured mean right atrial pressure, right ventricular systolic pressure (RVSP), immunoreactive ANP (iANP) concentrations in plasma, and cardiac iANP concentrations and contents of monocrotaline (MCT)-induced pulmonary hypertensive rats treated with a subcutaneous injection of MCT (40 mg/kg). Following the development of RVH and pulmonary hypertension, iANP concentrations in plasma and iANP concentrations and contents in ventricular tissues increased with time. At the third week after treatment, iANP concentrations in MCT rats increased 6-fold in plasma, 57-fold in the right ventricular free wall, 20-fold in the ventricular septum and 10-fold in the left ventricular free wall compared with those in controls. At the third week, iANP contents of total ventricular tissues in MCT and control rats were 29% and 0.8%, respectively, of the corresponding atrial contents. The iANP concentrations and contents of right ventricular free walls in MCT rats were greater than those of any other parts of ventricular tissues. The iANP concentrations in right ventricular free walls were very closely related to RVSP (r = 0.93, P < 0.001). In MCT rats, iANP concentrations in right atrial tissues decreased with time. This study shows that ventricular ANP contributes to the amount of ANP stored within the heart in MCT rats and that pressure overload may be one of the triggers for ANP synthesis in the right ventricle.

Animals↗

31P nuclear magnetic resonance studies on the glycogenolysis regulation in resting and contracting frog skeletal muscle.

1. Regulation of glycogenolysis in frog skeletal muscle at rest and following contraction was studied by measuring the concentration of phosphate-containing metabolites and the intracellular pH (pHi) in CN-treated muscles, in which oxidative phosphorylation was inhibited by NaCN, using the 31P nuclear magnetic resonance (NMR) technique. 2. When CN-treated muscles were kept at rest, the phosphocreatine (PCr) concentration very slowly decreased with time with a corresponding increase of the inorganic phosphate (Pi) concentration, while the ATP concentration remained unchanged. The pHi changed in the alkaline direction for the first 3 h, and then started to change in the acidic direction. 3. When CN-treated muscles were tetanized for 10 s, the PCr concentration decreased with a corresponding increase of the Pi concentration and acidification of pHi, while the ATP concentration remained unchanged. 4. When CN-treated muscles were tetanized repeatedly (each for 2 s) at constant intervals, the pHi changed in the alkaline direction following the first and the second tetani, and then changed in the acidic direction following the subsequent tetani, indicating that the consumed ATP is first replenished by the Lohmann reaction, while glycogenolysis starts only when the total amount of contractile activity exceeds a critical value. 5. Irrespective of whether CN-treated muscles were kept at rest or tetanized repeatedly, the Pi concentration increased to about 8 mM (mmol/kg wet muscle) when glycogenolysis started, suggesting that the onset of glycogenolysis in CN-treated muscles is regulated by the Pi concentration. 6. The 'internal' buffering power of muscle cytosol was estimated to be 35 mM H+/pH unit in anaerobic muscles and 25 mM H+/pH unit in CN- and iodoacetic acid (IAA)-treated muscles. The 'internal' buffering power contains a contribution due to flux of carbon dioxide and lactic acid across the cell membrane. Evidence indicated that lactic acid flux is small.

Animals↗

Epithelial myoepithelial tumour of the tracheal gland.

A case of epithelial myoepithelial tumour originating from the tracheal gland in a 57 year old woman is described. The tumour was removed by segmental tracheal resection and end-to-end anastomosis. Histologically, the tumour comprised clear cells and presented a monophasic pattern. Immunohistochemical analysis showed that the tumour cells were positive for both S-100 protein and smooth muscle actin. suggesting that this tumour resembles a subtype of epithelial-myoepithelial carcinoma described in the 1990 WHO international classification of salivary glands. Although some reports describe a clear cell dominant epithelial myoepithelial carcinoma, in this case local invasiveness or regional lymphnode metastasis was not proved through investigation. It is therefore concluded that this was an epithelial myoepithelial tumour rather than a carcinoma.

Female↗

Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats.

To study mechanisms for attenuated endothelium-dependent vasorelaxation in hypertension, we examined the effects of acetylcholine (ACh) on renal vascular resistance (RVR) and release rates of endothelium-derived relaxing factor (EDRF) in kidneys isolated from spontaneously hypertensive rats (SHR), deoxycorticosterone acetate (DOCA) salt-hypertensive (DOCA salt) rats, and Dahl salt-sensitive (Dahl S) rats. Decreases in RVR by ACh were smaller in hypertensive rats than in their normotensive controls. The release rate of nitric oxide into the perfusate, which was estimated using nitrite-nitrate as an index, did not differ between SHR and Wistar-Kyoto rats (WKY). However, the release rate of EDRF was markedly decreased in both DOCA salt rats and Dahl S rats compared with their normotensive controls (10(-7) M ACh: DOCA salt 45 +/- 6 vs. control 410 +/- 60 pmol.min-1.g-1 kidney wt, P < 0.001). In SHR, high-K+ perfusion or pretreatment with glibenclamide, inhibitors of endothelium-derived hyperpolarizing factor (EDHF), significantly reduced ACh-induced vasorelaxation only in WKY, resulting in no differences in the RVR reduction between SHR and WKY. Thus attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF, but to a decrease in EDRF in DOCA salt rats and Dahl S rats.

Acetylcholine↗

Detection of tracheal stenosis by frequency analysis of tracheal sounds.

To develop a simple noninvasive method for detecting tracheal stenosis, tracheal sounds were analyzed using fast-Fourier transform. The subjects were all female and included 5 normal volunteers and 13 patients with tracheal stenosis mostly secondary to thyroid cancer (11 extrathoracic and 2 intrathoracic lesions). Tracheal sounds were recorded during spontaneous breathing and were digitized with an analog-to-digital converter. Pulmonary functions, including forced expiratory volume in 1 s (FEV1) expressed as percentage of vital capacity, peak expiratory flow rate (PEFR), the ratio of FEV1 to PEFR (Empey's index), and the ratio of expiratory to inspiratory flow rates at 50% vital capacity, were measured. A computed tomography scan was used to obtain the tracheal minimum cross-sectional area. Whereas PEFR demonstrated a weak correlation with the stenotic area, FEV1%, Empey's index, and the ratio of expiratory to inspiratory flow rates at 50% vital capacity did not. The power of the fast-Fourier transform spectrum of normal tracheal sounds decreased as the frequency increased up to 500 Hz. A small spectral peak was observed at approximately 1 kHz. Patients with significant tracheal stenosis demonstrated an increase in the peak spectral power at approximately 1 kHz and in the mean spectral power from 600 to 1,300 Hz in their tracheal sounds. In patients with extrathoracic lesions, the peak and mean spectral powers correlated well with the area of the stenosis as defined by computed tomography scan. In patients with intrathoracic lesions, abnormalities in the pulmonary functions as well as tracheal sound spectra appeared more evident despite milder stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Urinary growth hormone excretion in preterm neonates.

We measured urinary growth hormone (U-GH), beta 2-microglobulin (U-B2) and serum growth hormone (S-GH) in preterm neonates on days 1, 4, 7, 14 and 28 of age. U-GH as well as U-B2 were high, particularly in the more premature and sick neonates with respiratory failure requiring mechanical ventilation. U-GH showed significant positive correlations with U-B2 throughout the study but with S-GH only on day 7. Therefore, we conclude that in preterm neonates, U-GH mainly reflects the degree of renal proximal tubular function, which is determined by the degree of renal maturation of the subject and of tubular injury due to disease states such as respiratory failure.

Aging↗

Coexistence of morphea and systemic sclerosis.

While the association of morphea and systemic sclerosis (SSc) is considered to be a rare condition, we observed well-demarcated sclerotic skin changes indistinguishable from morphea in 9 of 135 SSc patients who visited our clinic during the last decade. We consider this rate of incidence (6.7%) to be high enough to consider morphea to be one of the skin involvements of SSc. There was a significantly (p < 0.01) higher incidence of morphea in males (3 of 5) than in females (6 of 130). Only 3 of 111 SSc patients positive for antinuclear antibody (ANA) also showed morphea, whereas 6 of 9 patients negative for ANA showed morphea (p < 0.01). Although the mechanism underlying the development of morphea in SSc patients remains unknown, our observations suggest a heterogeneous pathogenesis related to SSc gender and ANA type.

Adult↗

An enzymological profile of the production of lactic acid in caries-associated plaque and in plaque formed on sound surfaces of deciduous teeth.

Specific activities of lactate dehydrogenase (LDH) and its fructose 1,6-bisphosphate (FBP) dependency in the small amount of plaque formed on deciduous teeth were determined and compared between those from carious lesions and from sound surfaces. Although the caries-associated plaque showed a higher production of lactic acid than the plaque formed on sound surfaces, it occurred only when sufficient FBP was present. The proportion of activity of FBP-dependent LDH relative to that of total LDH varied much more in the caries-associated plaque than in the plaque formed on sound surfaces. Hence, the varying activity of FBP-dependent LDH might be a distinguishing feature of caries-associated plaque compared with plaque formed on sound surfaces.

Child↗

Thyroxine 5-deiodinase in human brain tumors.

To determine whether human brains contain deiodinating pathways, we studied the activity of T4 5-monodeiodinase (5-D) in 20 human brain tumors obtained intraoperatively, including astrocytoma (10), meningioma (4), oligodendroglioma (2), glioblastoma (2), medulloblastoma (1), and malignant lymphoma (1). Mitochondrial-microsomal fractions prepared from these tumor tissues were used as the source of T4 5-D. Each sample was incubated with 32.2 nmol/L T4 and 30 mmol/L dithiothreitol at 37 C for 90 min. T4 5-D activity was measured by the production of rT3 from T4 with a RIA. T4 5-D activity was found in 6 of 10 astrocytomas, 2 oligodendrogliomas, 1 of 2 glioblastomas, and 1 malignant lymphoma. This activity depended on protein concentration, incubation time, incubation temperature, and pH of the incubation mixture. It was also heat labile. T4 5-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited by iopanoic acid and aurothioglucose in a dose-dependent manner. The apparent Km and maximum velocity for T4 5-D at 30 mmol/L dithiothreitol were 106.6 nmol/L and 22.7 pmol/mg protein.h, respectively. These data suggest that human gliomas (and probably malignant lymphomas) contain T4 5-D activity, which is similar to type III enzyme activity in the rat. T4 5-D may regulate the intracellular concentration of thyroid hormone in gliomas.

Adult↗