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Biomedical subjects

K Miyake

Publications and source records attributed to K Miyake.

At least 325 records · Page 18Linked to original sources

Activation of CD44 induces ICAM-1/LFA-1-independent, Ca2+, Mg(2+)-independent adhesion pathway in lymphocyte-endothelial cell interaction.

We have established an endothelial cell line KOP2.16 from pooled mouse lymph nodes. Resting lymphocytes avidly bound to KOP2.16 and migrated underneath the cytoplasm. The binding was partly mediated by VLA-4 and VCAM-1, but apparently independent of CD44 since anti-CD44 antibody examined failed to inhibit the binding. However, pretreatment of lymphocytes with anti-CD44 resulted in the rapid appearance of Ca(2+)-, Mg(2+)-independent, LFA-1/ICAM-1-, CD2/LFA-3, VLA-4/VCAM-1-independent lymphocyte binding, indicating that a novel adhesion pathway was induced by the anti-CD44 treatment. Interestingly, the elicited adhesion was observed only when anti-CD44 that block hyaluronate recognition of CD44 were used for lymphocyte pretreatment. Neither hyaluronate itself nor non-blocking anti-CD44 up-regulated the adhesion. Fab fragment of the blocking anti-CD44 did not induce the up-regulation unless cross-linked with a second antibody, indicating that cross-linking of surface CD44 is necessary for induction of a novel adhesion pathway. We propose that the agonistic anti-CD44 antibodies induce a novel adhesion pathway by mimicking ligand binding to CD44 on the lymphocyte surface and that non-hyaluronate ligand(s) is involved in regulation of adhesive function of CD44. Potential involvement of such a regulatory mechanism in lymphocyte homing is discussed.

Animals↗

Chemotherapy for minimally differentiated acute myeloid leukemia (AML-M0). A report on five cases and review of the literature.

With the objective of establishing the optimal therapy for minimally differentiated acute myeloid leukemia (AML-M0), we examined the therapeutic results of five AML-M0 cases and reviewed the literature. In a series of 63 patients with newly diagnosed acute leukemia who were admitted to the Main Hospital of Nippon Medical School, five patients fit the criteria for AML-M0: negative myeloperoxidase (MPO) and Sudan black B reaction by light microscopy, negative for B- and T-lineage markers, and positive for myeloid markers. They were treated by means of AdVP [adriamycin, vincristine, and prednisolone (PSL)] therapy and/or BHAC-DMP [behenoylcytosine arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP), and PSL] therapy. The AdVP therapy was unsuccessful in the two patients who received it, while a complete remission (CR) was achieved with the BHAC-DMP therapy in three of four patients. Although one patient treated with BHAC-DMP did not achieve CR, his blasts were apparently sensitive to the therapy. In assessable cases in the literature where leukemic blasts were MPO-negative, myeloid marker-positive and B- and T-lineage marker-negative, CR was achieved in 54.5% and 44.4% with anti-acute myeloid leukemia therapy and anti-acute lymphocytic leukemia therapy, respectively. Five cases in the literature were treated with a chemotherapeutic regimen containing BHAC [or cytosine arabinoside (Ara-C)], DNR, and 6-MP, and all achieved CR. The regimen containing BHAC (or Ara-C), DNR, and 6-MP may be useful as induction chemotherapy for AML-M0.

Adult↗

Expression of the DCC gene in myelodysplastic syndromes and overt leukemia.

To evaluate the molecular events in the genome that are associated with myelodysplastic syndromes (MDS) and the development of leukemia, we investigated the expression of the deleted in colorectal carcinoma (DCC) gene by the reverse transcriptase-polymerase chain reaction (RTPCR) method in 24 MDS cases and in 7 overt leukemia cases that progressed from MDS. Expression of the DCC gene was absent or extremely reduced in 2 of the 24 MDS cases, and those 2 cases developed overt leukemia within 6 months. Moreover, in 5 of the 7 cases of overt leukemia that developed from MDS, expression of the DCC gene was absent or extremely reduced. These findings suggest that inactivation of the DCC gene may be the late event that triggers the progression of MDS to leukemia.

Adult↗

Urodynamic evaluation of results of endopyelotomy for ureteropelvic junction obstruction.

We treated 13 patients with unilateral ureteropelvic junction obstruction by percutaneous endopyelotomy, and they were urodynamically evaluated by the Whitaker test and diuresis renography, in addition to excretory urography (IVP). Surgery was uncomplicated in all patients except 1 who required repeat incision 4 weeks later. Obstruction was diagnosed preoperatively by the Whitaker test and diuresis renography in 10 cases, and by IVP in 13. Postoperatively, all 10 patients (100%) with a positive Whitaker test were free of obstruction with a significant reduction in the relative renal pelvic pressure from 35.0 to 8.1 cm. water (p < 0.01). Diuresis renography revealed no obstruction in 8 patients (80%) and persistent obstruction in 2. IVP demonstrated reduced hydronephrosis in 8 of 13 patients (62%) 12 weeks after surgery and in 11 of 13 patients (85%) 19 months later. However, a marked reduction in renal pelvic size was noted in only 3 patients (23%). Flank pain disappeared in 10 of 11 patients (91%) postoperatively. Overall, surgery was successful in 11 of the 13 patients (85%). Percutaneous endopyelotomy was effective in relieving obstruction at the ureteropelvic junction with minor morbidity. The Whitaker test was more sensitive for evaluating the results of surgery than diuresis renography and IVP, although diuresis renography appears to be useful in followup evaluation of hydronephrosis.

Adolescent↗

Response of the human urinary bladder to angiotensins: a comparison between neurogenic and control bladders.

The response of the human detrusor muscle to angiotensins was investigated and compared between neurogenic and control bladders. Both angiotensin I and II induced potent contraction of the human detrusor muscle. Saralasin completely inhibited the response to both angiotensins, while verapamil and indomethacin barely suppressed the contractility provoked by angiotensin II. Captopril completely blocked the response to angiotensin I. The contractile response of angiotensin II was abolished in Ca(++)-free Krebs' solution. The contractile strength of the neurogenic bladders induced by both angiotensin I and II was significantly weaker than that of the controls. However, there was no difference in ED50 value between the 2 groups. These results support the hypothesis that angiotensin I is converted to angiotensin II by angiotensin converting enzyme in the detrusor, and that angiotensin II subsequently contracts the detrusor muscle through angiotensin II receptors. The bladder contractility induced by the angiotensins was significantly less potent in the neurogenic bladders than in the control.

Adolescent↗

Increased levels of calbindin-D in serum and urine from patients treated by extracorporeal shock wave lithotripsy.

Calbindin-D 28 kDa. is a vitamin D-dependent calcium binding protein that is found mainly in the distal renal tubules and central nervous tissue in humans. Calbindin-D was measured in the serum and urine before, and immediately, 2 hours or 24 hours after extracorporeal shock wave lithotripsy (ESWL*) in 83 consecutive patients. ESWL was performed with the Siemens Lithostar device in 61 patients and with the Dornier MPL9000 lithotriptor in 22. The serum 28 kDa. calbindin-D level was undetectable (less than 20 pg./ml.) in many samples, whereas urinary 28 kDa. calbindin-D could be detected in every sample. The serum 28 kDa. calbindin-D level was usually elevated after ESWL and the concentration in patients treated with the MPL9000 device was greater than in those treated with the Lithostar instrument. Urinary 28 kDa. calbindin-D levels were elevated significantly immediately and at 2 hours after ESWL, and they decreased to the baseline level within 24 hours after ESWL in the Lithostar group but remained consistently significantly elevated after ESWL in the MPL9000 group. This fact may be because the MPL9000 lithotriptor produces a stronger shock wave than does the Lithostar device during ESWL. These results suggest that 28 kDa. calbindin-D is released from damaged distal renal tubule cells into the serum and urine during ESWL and that 28 kDa. calbindin-D is a specific marker for renal damage by ESWL. To our knowledge this is the first clinical study using a sensitive enzyme immunoassay for human 28 kDa. calbindin-D to estimate renal damage during ESWL.

Adult↗

Spontaneous and antibody directed cytotoxicity of double-negative T cells from autoimmune mice.

MRL/Mp-lpr/lpr (MRL/lpr) mice develop a syndrome similar to systemic lupus erythematosus in humans. This strain of mice is characterized by the progressive accumulation of CD4-CD8- (double-negative; DN) T cells which express increased levels of cell adhesion molecules such as CD44 and heat stable antigen (HSA). The DN T cells exhibited a higher level of spontaneous cytolytic activity and contained a higher level of serine esterase as compared with T cells of MRL/Mp-+/+ (MRL/+) mice. We also found that mAbs against CD44, Mel-14, CD45R, and HSA could augment the cytolytic activity of DN T cells of MRL/lpr mice. Antibody-mediated augmentation of cytolytic activity of DN T cells was due to conjugate formation in which the Fc portion of mAb bound to the Fc gamma receptor on target cells and the Fab portion of mAb bound to corresponding cell surface antigens on DN T cells. The antibody-mediated augmentation of cytolytic activity was not detected in T cells of MRL/+ mice and lymphokine activated killer (LAK) cells of C57BL/6 mice. In contrast, anti-CD3 mAbs could augment the cytolytic activity of DN T cells, T cells as well as LAK cells. mAbs against LFA-1 and VLA-4 failed to augment the cytolytic activity of three different effector cells. It should be noted that anti-CD3 mAb-mediated cytolytic activity of DN T cells was substantially reduced by anti-LFA-1 mAb. However, CD44, Mel-14, CD45R as well as HSA-mediated cytolytic activity of DN T cells was not inhibited by anti-LFA-1 mAb.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Analysis of inflammatory endothelial changes, including VCAM-1 expression, in murine cardiac grafts.

We have employed a murine model of cardiac transplantation and two monoclonal antibodies, M/K-2 and MECA-32, to study the responses of graft endothelia during allograft rejection. Using immunohistologic techniques, we demonstrate that the monoclonal antibody M/K-2, which binds to the murine cellular adhesion molecule VCAM-1, reacts with an inducible endothelial epitope found in rejecting cardiac allografts, but not in cardiac isografts, normal cardiac tissues, or extracardiac vasculature from allografted mice. Similar, but focal, M/K-2 reactivity is also found in nontransplanted hearts undergoing virally induced myocarditis. M/K-2 reactivity does not develop in the nonrejecting cardiac allografts from nu/nu mice, and M/K-2 reactivity is found only in grafts that develop CD25+ graft-infiltrating cells--i.e., allografts but not isografts. PCR analyses of grafts during development of VCAM-1 expression indicate that allografts, but not isografts, contain mRNA for the cytokines IL-2 and IFN-gamma, and either of these cytokines may be associated with the expression of M/K-2 reactivity in rejecting allografts. Unlike M/K-2, MECA-32 identifies an inducible epitope that is observed on myocardial endothelia of both isografts and allografts, but not normal cardiac tissues. Further, expression of the MECA-32 epitope can occur in grafts that do not develop CD25+ infiltrating lymphocytes, since it is observed in isografts and the native hearts of transplanted or sham-operated mice. Indeed, MECA-32 reactivity may be T cell independent, since it is also found in nonrejecting allografts of nu/nu mice. PCR analyses of grafts during development of MECA-32 reactivity indicate that cardiac isografts contain mRNA for IL-1, IL-6, TNF, and lymphotoxin. One or more of these might be associated with induction of MECA-32 reactivity.

Animals↗

Up-regulation of alpha 4 integrin on activated Langerhans cells: analysis of adhesion molecules on Langerhans cells relating to their migration from skin to draining lymph nodes.

After hapten application, epidermal Langerhans cells migrate into the regional lymph nodes through dermal lymphatics. Recently, we have demonstrated that some of them take the phenotypic and functional characteristics similar to those of in vitro cultured Langerhans cells, before disappearing from the epidermis. To analyze the mechanisms underlying the migration of Langerhans cells, we studied the expression of several adhesion molecules on freshly isolated LC and cultured LC. Pgp-1 (CD44), intercellular adhesion molecule 1, and alpha 4 integrin were strongly expressed on cultured Langerhans cells. Among them, only alpha 4 integrin was strongly up-regulated by cultured Langerhans cells, because its expression by freshly isolated Langerhans cells was very weak. This up-regulation of alpha 4 integrin was also observed on in vivo activated Langerhans cells in the epidermis and draining lymph nodes after hapten application. These data suggest a possible role played by VLA-4 in the migration of Langerhans cells from the epidermis into the regional lymph nodes after hapten application.

Animals↗

Murine endothelial cell line cells, F-2: interaction with leukocytes and cytokines production.

Flowcytometry demonstrated that murine endothelial cell line F-2 expresses MHC class I antigen, FcR II, Mac-1 and vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 (ICAM-1) and class II antigen. However, co-culturing with TNF-alpha for 24 hr resulted in the increased expression of ICAM-1, and the decreased expression of VCAM-1. IL-1 alpha and IFN-gamma exerted this regulatory effect on VCAM-1 but not on ICAM-1. T (Con A blast) and B (LPS blast) cells adhered to F-2 cells at almost equal levels, and the adhesion was enhanced 20 to 50% when the cells were precultured with TNF-alpha for 24 hr. The inhibition assay using either (anti-ICAM-1 + anti-LFA-1, lymphocyte function-associated antigen-1) or (anti-VCAM-1 + anti-VLA-4, very late antigen-4) mAbs demonstrated that the ICAM-1 system was utilized more preferentially by T than B blasts when F-2 cells were stimulated with TNF-alpha, and the VCAM-1 system was vice versa under the unstimulated and stimulated conditions. Granulocytes also adhered to F-2 cells, but no mAbs could inhibit the adhesion. Although F-2 cells produced a considerable amount of IL-6, GM-CSF and neutrophil chemotactic activity, a 24 hr incubation with TNF-alpha resulted in an increase of 12 fold in IL-6 and 3 fold in neutrophil chemotactic activity production.

Animals↗

Immunohistochemical localization of calmodulin in the testes of patients with idiopathic male infertility.

The localization of calmodulin in testes of patients with idiopathic male infertility was studied using the indirect immunoperoxidase method. Specimens were obtained by testicular biopsy from 55 patients. They were divided into 26 cases of hypospermatogenesis, 11 cases of maturation arrest (8 of primary spermatocyte arrest and 3 of spermatid arrest) and 18 cases of Sertoli cell-only syndrome. Regardless of the type of testicular pathology, the types of immunoreactive cell and the intensities of staining were the same as those in the normal testis. That is, staining for calmodulin was first found to be positive in early pachytene primary spermatocytes. It became intense in late pachytene primary spermatocytes and round spermatids. By contrast, elongated spermatids and spermatozoa were not stained. Sertoli cells were stained slightly or not at all. A calmodulin-staining index (CaM-S index) was defined as the proportion of primary spermatocytes that were stained intensely for calmodulin relative to the total number of primary spermatocytes. The indices for the testes of men with complete spermatocyte maturation arrest were significantly lower than those for the testes of normal controls and of men with hypospermatogenesis. Degenerating late pachytene spermatocytes observed in the testes of men with spermatocyte arrest showed low calmodulin-specific immunoreactivity. Such a decrease in numbers of normal late pachytene spermatocytes might be responsible for the low CaM-S index in cases of complete spermatocyte arrest.

Adult↗

Response of the human neurogenic bladder to KCl, carbachol, ATP and CaCl2.

The in vitro pharmacological responses of the human neurogenic bladder to KCl, carbachol, ATP and CaCl2 have been analysed. The contractility (contractile strength and ED50) of neurogenic bladders was significantly increased when treated with carbachol, ATP and CaCl2. In contrast, there was no apparent difference in the responsiveness of neurogenic bladders when treated with KCl. There was no apparent correlation between pharmacological responsiveness and clinical parameters, such as gender, age or cystometric data, in the neurogenic bladders.

Adenosine Triphosphate↗

Beyond personality impressions: effects of physical and vocal attractiveness on false consensus, social comparison, affiliation, and assumed and perceived similarity.

We examined the effects of target persons' physical and vocal attractiveness on judges' responses to five measures: false consensus (the belief that the target shares one's behavior), choice of targets as comparison others, affiliation with targets, assumed similarity (similarity between self-ratings and ratings assigned to targets), and perceived similarity (direct questions about similarity). Higher physical attractiveness and higher vocal attractiveness were both related to higher scores on all variables. The effect of one type of attractiveness was more pronounced for higher levels of the other type of attractiveness. The joint effect of the two types of attractiveness was best described as synergistic, i.e., only targets high on both types of attractiveness elicited higher scores on the dependent variables. The effect of physical attractiveness on most dependent variables was more pronounced for subjects who were themselves physically attractive. The synergistic effect (the advantage of targets high on both types of attractiveness) was more pronounced for judges high in self-monitoring. The contribution of the study to the literature on attractiveness stereotypes is discussed.

Adult↗

Flavin-photosensitized monomerization of dimethylthymine cyclobutane dimer in the presence of magnesium perchlorate.

We have investigated the photosensitized monomerization of the cis,syn-cyclobutane dimer of 1,3-dimethylthymine using riboflavin tetraacetate and a 5-deazaflavin derivative as photosensitizer. Although little monomerization of the dimer is induced by photoexcitation of the flavins in the absence of any additives, the flavins can function as an efficient photosensitizer in the presence of magnesium perchlorate. Mechanistic studies involving spectroscopic, quantum-yield and flash-photolysis measurements demonstrated that the photosensitized monomerization exclusively proceeds through electron transfer from the dimer to the triplet flavins complexed with Mg2+. The effects of magnesium perchlorate are compared with those on the chloranil-photosensitized monomerization and also with the effects of HClO4 on the flavin-photosensitized reaction.

Flavins↗

A gene cluster involved in aerial mycelium formation in Streptomyces griseus encodes proteins similar to the response regulators of two-component regulatory systems and membrane translocators.

Mutants of Streptomyces griseus deficient in A-factor production are sporulation negative, since A-factor is an essential hormonal regulator for the induction of morphological and physiological differentiation in this bacterium. A DNA fragment which induced aerial mycelium formation and sporulation in an A-factor-deficient mutant strain, S. griseus HH1, was cloned from this mutant strain. Subcloning experiments and nucleotide sequencing showed that two open reading frames, ORF1 with 656 amino acids and ORF2 with 201 amino acids, were required in order to induce sporulation. The amino acid sequence of ORF1 significantly resembled that of the Escherichia coli HlyB protein, a member of a family of bacterial membrane proteins engaged in ATP-dependent secretion mechanisms. Conserved features of this surface translocator family, such as the transmembrane structure predicted by their hydropathy profiles and the amino acid sequence forming an ATP-binding fold, were also conserved in ORF1. The ORF1 gene appeared to constitute a transcriptional unit with an additional upstream gene encoding ORF3, which was greatly similar to ORF1 in size and amino acid sequence. The other protein, ORF2, showed significant end-to-end homology with the E. coli uhpA product, a regulatory protein for the uptake of sugar phosphates. Like UhpA as a response regulator of a bacterial two-component regulatory system, ORF2 contained a helix-turn-helix DNA-binding domain at its COOH-terminal portion and an Asp residue (Asp-54) probably to be phosphorylated at its NH2-terminal portion. An amino acid replacement from Asp-54 to Asn resulted in the loss of the ability of ORF2 to induce sporulation in strain HH1.

4-Butyrolactone↗