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K Sagawa

Publications and source records attributed to K Sagawa.

At least 19 recordsLinked to original sources

Epitopes for CD1a, CD1b, and CD1c antigens are differentially mapped on Langerhans cells, dermal dendritic cells, keratinocytes, and basement membrane zone in human skin.

BACKGROUND: CD1 antigens are classified serologically into at least three groups, CD1a, CD1b, and CD1c, and many kinds of monoclonal antibodies are available for each subgroup of CD1 antigens. CD1a, CD1b, and CD1c antigens have been shown to be selectively and differentially expressed on epidermal Langerhans cells and dermal dendritic cells in normal human skin. OBJECTIVE: The objective was to further delineate the localization of epitopes of CD1 antigens in human skin. METHODS: We examined the immunoreactivity of 14 different CD1 antibodies (seven CD1a, five CD1b, and two CD1c antibodies) with the immunoperoxidase technique. We also studied the reactivity of NU-T2 (CD1b) antibody by immunogold electron microscopy. RESULTS: The epitopes for CD1a, CD1b, and CD1c antigens were differentially mapped on epidermal Langerhans cells, dermal dendritic cells, keratinocytes, the luminal portion of eccrine gland ducts, and the basement membrane zone in human skin. CONCLUSION: These CD1 antibodies may be useful to analyze the phenotypic alteration of immune and nonimmune cells in various skin diseases.

Antigens, CD

Epitope mapping of CD1a, CD1b, and CD1c antigens in human skin: differential localization on Langerhans cells, keratinocytes, and basement membrane zone.

CD1 antigens are classified into at least three groups, CD1a, CD1b, and CD1c. In order to delineate the localization of epitopes of CD1 antigens in human skin, we examined the immunoreactivity of fourteen different CD1 antibodies (seven CD1a, five CD1b, and two CD1c antibodies). The epitopes for CD1a, CD1b, and CD1c are differentially localized on epidermal Langerhans cells, dermal dendritic cells, keratinocytes, the luminal portion of eccrine gland ducts, and the basement membrane zone in normal human skin.

Antibodies

[Clinical analysis of 10 patients with chronic lymphoid leukemia].

Ten patients with chronic lymphoid leukemia were analyzed for clinical characteristics, morphology and phenotype of leukemic cells. There were 3 patients with T-chronic lymphocytic leukemia (CLL), 2 with T-prolymphocytic leukemia (PLL), 2 with B-CLL, 1 with B-PLL, 1 with non-T-non-B-CLL and 1 with Waldenström's macroglobulinemia. Although chronic lymphoid leukemia is usually characterized by proliferation of B-lymphocytes, our study revealed that 5 of 10 patients had T-cell phenotype. A peripheral blood specimen of T-CLL showed small lymphocytes with a mature appearance and an irregular nuclear margin. Most of the cells lacked large azurophilic granules in the cytoplasm and nucleoli were also inconspicuous in the nucleus by light and electron microscopic examinations. In PLL, a majority of the cells were large lymphocytes with a prominent nucleolus and abundant basophilic cytoplasm which were more clearly observed by transmitted electron microscopic examination. The patients were treated with cyclophosphamide and prednisolone, but response to treatment was transient. The median survival time was 7 months for all patients, while that of T-cell lineage cases was only 1 month. Therefore, new modalities of treatment must be investigated in the future.

Aged

[Usefulness of monoclonal antibodies for immunophenotyping in leukemia].

Clinically useful monoclonal antibodies, applied for immunophenotyping of leukemias, are reviewed. With a combination of 15 antibodies, including CD2, CD3, CD4, CD5, CD7, and CD8 for T cell marker analysis, CD10, CD19, CD20, surface immunoglobulins, and cytoplasmic mu chain for B cell marker analysis, CD13 and CD33 for myeloid marker analysis, and HLA-DR and CD25 for other marker analysis, acute lymphoblastic leukemias of T cell type, cALL type, pre-B cell type and B cell type, acute myeloid leukemias, acute unclassified leukemias and adult T cell leukemias could be clearly diagnosed by immunophenotyping of cell membrane molecules. By using additional CD11b, CD14, and CD15 monoclonal antibodies, subclassification of acute myeloid leukemia was partially possible.

Antibodies, Monoclonal

Simultaneous occurrence of myelomonocytic leukemia and multiple myeloma: involvement of common leukemic progenitors and their developmental abnormality of "lineage infidelity".

We investigated the origin of leukemic progenitors in a case of the simultaneous occurrence of myelomonocytic leukemia and multiple myeloma (IgG-kappa). At presentation, myeloperoxidase and nonspecific esterase-positive myelomonocytic cells had proliferated up to 12.2 x 10(9)/liter in the peripheral blood. Bone marrow cell differentials revealed the coexistence of myelomonocytic cells (30%) and atypical plasmacytoid cells (26%). Myelomonocytic cells in peripheral blood expressed both myeloid antigens (CD11b, CD13, CD14, CD15, CD33) and T/B-lymphoid antigens (CD2, CD4, CD5, CD7, CD10, PCA-1). Bone marrow mononuclear cells (BMMC) could be divided into PCA-1 strongly positive and PCA-1 weakly positive populations, which were considered to represent myeloma cells and myelomonocytic cells, respectively; the former were CD2-positive (CD2+), CD14-, and CD15-, whereas the latter were CD2+, CD14+, and CD15+. Immunohistochemical analysis revealed that, in addition to plasmacytoid cells, a minority of myelomonocytic cells showed a positive reaction for IgG staining, and production of IgG was observed in the culture supernatant of CD14+ myelomonocytic cells in peripheral blood. Southern blot analysis revealed the presence of two identical rearrangement bands of immunoglobulin heavy chain gene in both BMMC containing myeloma cells and myelomonocytic cells and CD14+ myelomonocytic cells in peripheral blood. In a long-term methylcellulose assay, peripheral blood mononuclear cells produced large compact colonies consisting of macrophages and IgG+ plasmacytoid cells (M phi/P colonies), while BMMC produced a different type of colonies consisting of CD14+ myelomonoblasts, macrophages, and IgG+ plasma cells (Mb/M phi/P colonies) in addition to M phi/P colonies. Recloning experiments showed that primary Mb/M phi/P colonies gave rise to both secondary M phi/P and Mb/M phi/P colonies. These observations strongly suggest that common leukemic progenitors provide both myeloma and myelomonocytic leukemia cells, and the mechanism of "lineage infidelity" is probably involved in the development of their "bilineal" differentiation.

Antigens, CD

A patient of CD4-/CD8+ chronic T-cell leukemia associated with hypercalcemia.

A patient with chronic T-cell leukemia characterized by a suppressor phenotype is reported. A 71-year-old woman presented with symptoms and signs of hypercalcemia. Peripheral blood specimen showed abnormal lymphoid cells with an oval to cleaved nucleus, rather condensed chromatin, occasional prominent nucleolus, and basophilic cytoplasms with vacuoles which seems to be a T-cell counterpart of B-cell chronic lymphocytic leukemia with mixed cell types. The phenotype of these cells was CD4-, CD8+, CD5+, CD6+ with poor expression of CD3, CD7, and CD25. Southern blot analysis of T-cell receptor beta-chain gene revealed one allele rearranged band. The serum antibodies were positive against human T-cell leukemia virus, type I-associated antigens, but monoclonal integration of proviral DNA was not detected in the leukemic cells suggesting that she was just a carrier of this virus. Interestingly, serum PTH-related peptide (PRP) was elevated. The combination therapy with vincristine and prednisolone for leukemia decreased not only the number of leukemic cells but also the serum PRP levels. The clinical course was aggressive. She only responded transiently to treatments, and died of renal failure due to uncontrollable hypercalcemia six weeks after admission.

Aged

Dynamic properties of left ventricular response to changes in coronary perfusion.

To determine the dynamic property of cardiac function response to alterations in coronary perfusion, we varied coronary arterial pressure (CAP) sinusoidally around one of four mean CAP levels with a constant amplitude at several frequencies in isolated, isovolumically contracting canine heart preparations. From the frequency spectrum of the peak left ventricular pressure (PLVP) response, we arrived at a phenomenological model with two components coupled in parallel and estimated the parameter values. One component is a first-order delay system having a short time constant (approximately 1 s) and a small gain (range 0.08-0.16); it probably represents a hydraulic effect of coronary perfusion. The other component is a second-order delay system with longer time constants (approximately 15 and 6 s) and a larger gain (range 0.14-0.69); this probably represents a metabolic effect. The gain value of the slow component varied inversely with the mean CAP level, and studies with adenosine suggested that this dependence was due to the coronary autoregulation. The model prediction of the transient responses of PLVP to step changes in CAP agreed reasonably well with those experimental data of transient responses obtained in the identical hearts but not used to determine the model parameter values.

Adenosine

Nonlinearity and load sensitivity of end-systolic pressure-volume relation of canine left ventricle in vivo.

The effects of mechanical changes in loading conditions on the left ventricular end-systolic pressure-volume relation (ESPVR) were studied in nine open-chest dogs, including three dogs studied before and after beta-adrenergic blockade. Left ventricular pressure was measured with a micromanometer, and left ventricular volume was measured with a conductance catheter. ESPVRs were obtained by increasing left atrial inflow over wide volume ranges (as much as threefold) under three different conditions: control or high or low aortic impedance. High impedance was obtained by occlusion of the descending aorta, and low impedance was obtained by a shunt between the subclavian artery and the left atrium. In the unblocked animals in 21 of 28 runs, a second-order polynomial equation gave a better fit for the ESPVR than a linear relation. To quantify the effects of the changes in aortic impedance on the ESPVR, we calculated from the quadratic equation its volume intercept (V18) and its local slope (E18) at an end-systolic pressure (Pes) of 18 kPa. In the unblocked animals, a statistically significant difference was found in V18 between low impedance (21.50 +/- 6.27 ml) and high impedance (14.10 +/- 8.98 ml; p less than 0.005) and between control (19.14 +/- 9.58 ml) and high impedance (p less than 0.05). In most dogs, E18 was increased at high and decreased at low impedance, but not significantly. In the additional experiments with beta-blockade, the nonlinearity diminished somewhat, but the load dependency of the ESPVR remained present after beta-blockade because the same leftward shift of the ESPVR with high aortic impedance was found. Two other relations, namely, of dP/dtmax and of stroke work versus end-diastolic volume, were also investigated, which on the whole showed the same behavior as the ESPVR. These results indicate that the ESPVR and dP/dtmax-Ved and stroke work-end-diastolic volume relations, when studied over a wide volume range, are nonlinear and that changes in loading conditions influence indexes of contractility derived from these relations, especially the volume intercepts, in such a way that an increase in aortic impedance may be interpreted as an increase in contractility. Blocking the beta-adrenergic receptors did not influence the load dependency of the ESPVR but, in some cases, tended to decrease the nonlinearity in concordance with the relation between contractility and nonlinearity in isolated hearts.

Adrenergic beta-Antagonists

[A comparison of sudden near maximal exercise test (dash method) and Bruce protocol for pediatric patients].

We examined 24 pediatric patients to evaluate the usefulness of sudden near maximal exercise test (dash method), where the subjects began to run at Bruce protocol of the last stage. 1) No considerable differences between two protocols were found in maximal oxygen consumption (V O2max), maximal heart rate (HRmax), maximal systolic blood pressure, and findings of electrocardiography. 2) The sudden maximal exercise test could be completed during a shorter period compared to Bruce protocol. 3) The sudden maximal exercise protocol reached 84% of HRmax and 47% of V O2max at one minute after the onset of the protocol, and produced 96% of HRmax and 89% of V O2max at two minutes after the onset. We considered that sudden maximal exercise protocol was useful to obtain a response similar to Bruce protocol at maximal exercise within a short period. We have to pay attention to the safety of the patients because their cardiopulmonary response to sudden maximal exercise protocol is dramatic.

Adolescent

[A case of pustulotic arthro-osteitis with secondary amyloidosis].

A 63-year-old man with a history of Pustulosis Palmaris et Plantaris since 1960 was suffered from lumbago and anterior chest pain in 1973. Chest X-ray film showed inter-sterno-costo-clavicular ossification. Spondylodiscitis, Syndesmophyte of lumbal spine, Sacro-iliitis were seen by abdominal X-ray film. He was admitted to near hospital with generalized edema and urinary protein (10-20 g/day) in April 1986. Laboratory studies showed hypoproteinemia, positive C-reactive protein, high serum amyloid A protein(240 ng/100 microliters) and negative HL-A B27. He was diagnosed Pustulotic arthro-osteitis and Secondary Amyloidosis by renal biopsy and rectal biopsy in 1987. He was treated with high-dose oral prednisolone(60 mg/day)and dimethyl sulfoxide. After treatment, Edema and Nephrose improved. Increasement of renal function was not observed.

Amyloidosis

Immunological and virological status of a hemophiliac infected with human T cell lymphotropic virus type 1 and human immunodeficiency virus type 1, and results of therapy.

The immunological and virological status of three hemophiliacs infected with human immunodeficiency virus type 1 (HIV-1) was monitored for 11 months. One of these patients was also infected with human T cell lymphotropic virus type 1 (HTLV-1), and HIV-1 could be isolated only from this patient among the three subjects. The doubly infected subject had the fewest T4 (helper) lymphocytes and the highest proportion of T8 lymphocytes with DR human leukocyte antigens (DR-Ag). The serum level of HIV-1 antigen increased in this patient during the observation period, and this increase was accompanied by a decrease in the proportion of DR-Ag-positive cells among the T8 lymphocytes. This patient was treated with 800 mg of zidovudine daily for 50 days. With treatment, the nonspecific clinical symptoms improved and the proportions of DR-Ag positive cells among the T8 lymphocytes decreased. Serum levels of HIV-1 antigen decreased immediately when therapy was started but later increased during therapy. In persons infected with both HTLV-1 and HIV-1, HIV-1 seems to proliferate readily.

Adolescent

Preservation of ventricular function by treatment of ventricular fibrillation with phenylephrine.

Epinephrine promotes resuscitation from ventricular fibrillation because of its peripheral vasoconstrictive effects. However, the beta-adrenergic effects of epinephrine may be detrimental because of the stimulation of myocardial oxygen demand. To test whether functional recovery from fibrillation in hearts treated with a selective alpha-adrenergic agent is greater than in hearts treated with epinephrine, ventricular fibrillation was induced in eight isolated dog hearts while coronary perfusion pressure was maintained at 30 mm Hg. In random order, epinephrine (5 micrograms/min), phenylephrine (50 micrograms/min) or no drug was infused for 5 min. The heart was then defibrillated, the drug infusion stopped and coronary perfusion pressure increased to 100 mm Hg. Coronary blood flow (ml/min per 100 g), arteriovenous oxygen difference (ml O2/dl) and myocardial oxygen consumption (ml O2/min per 100 g) measured after 4 min of ventricular fibrillation were greater with epinephrine (mean +/- SD 30.9 +/- 11.7, 17.5 +/- 1.6 and 5.4 +/- 1.9, respectively) than with phenylephrine (24.4 +/- 6.0, 15.7 +/- 2.6 and 3.8 +/- 1.1, respectively) or no drug (19.8 +/- 5.2, 12.8 +/- 1.8 and 2.6 +/- 0.7, respectively) (p less than 0.05, p less than 0.05 and p less than 0.05, respectively). The slope of the end-systolic pressure-volume relation 10 min after defibrillation and restoration of normal coronary perfusion pressure was depressed (percent of prefibrillation value) most by epinephrine infusion (72 +/- 17%, n = 6), less by no drug infusion (82 +/- 12%, n = 4) and was increased after phenylephrine infusion (143 +/- 17%, n = 6) (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hemodynamic dependence of myocardial oxygen consumption indexes.

We tested the afterload and contractile state dependency of three indexes of myocardial oxygen consumption (MVO2): total energy requirement (Et), pressure work index (PWI), and pressure-volume area (PVA). MVO2 was measured in seven isolated canine hearts at four or five different end-diastolic volumes at each of three settings of afterload resistance and with the hearts contracting isovolumically. In several hearts, contractility was also varied by dobutamine infusion. Measured MVO2 (MMVO2) was compared with values predicted (PMVO2) by each index. There was always a high degree of correlation between MMVO2 and PMVO2 for each of the indexes. However, there was a large degree of variability in the coefficients of the MMVO2-PMVO2 relation from one heart to another. We also observed a statistically significant influence of both afterload and contractile state on the predictive power of each of the indexes. Thus each index that we tested had shortcomings in being able to predict MVO2 accurately over a wide range of hemodynamic conditions.

Animals

Down-regulation of KOLT-2 antigen (CD28) by interleukin 2; role of IL-2R (p70).

Using KOLT-2 monoclonal antibody (mAb) recognizing a 44,000 molecular weight (MW) T-cell activation antigen (CD28), we observed the co-expression of KOLT-2 (CD28) antigen and Tac (CD25) antigen, associated with a 55,000 MW chain of the interleukin-2 receptor (IL-2R) complex. IL-2R (p55), on several T-cell lines transformed by human T-lymphotropic virus-I (HTLV-I), as well as several subclones of the natural killer (NK)-like cell line YT. When YT cells (YTC3T, YT5.1) and IL-2-dependent HTLV-I+ T-cell line cells (ED, ATL35C) expressing both IL-2R (p55) and IL-2R (p70) chains were cultured with recombinant IL-2 (rIL-2), KOLT-2 antigen was down-regulated in 24 hr. However, KOLT-2 antigen on HPB-ALL (Kurume) cells expressing neither of the IL-2R chains was unaffected by IL-2. IL-2 also failed to down-regulate KOLT-2 antigen on MT-1 cells bearing IL-2R (p55)/Tac without IL-2R (p70). To clarify the role of IL-2R (p70) in the IL-2-induced down-regulation of KOLT-2 antigen, we analysed the effect of IL-2 on a Tac- subclone of YT (YT2C2) that expresses IL-2R (p70). As was the case with Tac+ YT cells, KOLT-2 antigen was down-regulated by IL-2, and this down-regulation was inhibited by anti-IL-2R (p70) mAb but not by anti-Tac mAb. These results show that the signalling through the IL-2/IL-2R system down-regulates KOLT-2 (CD28) antigen by way of the interaction between IL-2 and IL-2R (p70), irrespective of IL-2R (p55)/Tac. Possible involvement of the IL-2/IL-2R system in the CD28-mediated mitogenic mechanism is discussed.

Antigens, Differentiation, T-Lymphocyte

Poorly expressed CD2 antigen on the leukemic cells of adult T-cell leukemia and chronic lymphocytic leukemia of T-cell lineage.

Adult T-cell leukemia (ATL) and T-cell chronic lymphocytic leukemia (T-CLL) are hematologic neoplasms in differentiated stages of peripheral mature T cells. This is suggested by the presence of CD2 (E rosette receptor) and mature and/or pan-T cell membrane surface antigens on their leukemic cells. We recently encountered one patient with ATL and another with T-CLL; their leukemic cells poorly expressed CD2 antigens, but clinical presentation, morphology of the leukemic cells and other marker studies were characteristic of either ATL or CLL. The clinical significance of the poor expression of CD2 remains to be further studied. The two patients reported here died of severe complications 4 and 9 weeks after diagnosis. The poor expression of CD2 in the peripheral T cells in these neoplasms is likely to indicate an aggressive nature of the disease.

Aged

Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts.

Stretch of excised myocardial tissue causes electrophysiological and potentially arrhythmogenic changes in transmembrane action potentials but corresponding data of the intact mammalian heart are lacking. The effects of increases in ventricular volume and pressure on epicardial monophasic action potentials were therefore investigated in isolated, cross circulated and in situ canine hearts. In seven isolated hearts, increases in ventricular volume and pressure resulted in (1) a linearly related decrease in action potential amplitude (r = 0.988; slope = 0.41% amplitude.ml-1; volume intercept = 17.6 ml), mainly due to a decrease in maximum diastolic potential; (2) a decrease in action potential plateau duration (at 20% repolarisation) by 19 (SD 8)%; and (3) appearance of early afterdepolarizations, reaching up to 18% of total action potential amplitude. Afterdepolarizations occurred only when ventricular outflow was obstructed at end diastole but not at end systole. In eight in situ hearts, increase in left intraventricular pressure produced by transient occlusions of the ascending aorta was also accompanied by decrease in maximum diastolic potential and action potential plateau duration, and by appearance of early afterdepolarizations. In both isolated and in situ intact ventricles, the loading induced electrophysiological changes were associated with occurrence of ectopic ventricular beats. These data show that mechanical overload produces significant electrophysiological changes in the intact canine ventricle which may lead to arrhythmia.

Action Potentials

Establishment and characterization of a clonal human T-cell line, MKB-1 derived from a patient with acute myeloblastic leukemia.

A human T-cell line, designated as MKB-1, was established by cloning procedures in a suspension culture from a peripheral blood of a 17-year-old female patient with acute myeloblastic leukemia. The immunological marker profile of MKB-1 indicated that unlike a myeloid phenotype of the original leukemic cells, the cells were positive for CD3 (both cell surface and cytoplasm), T cell receptor (TcR) alpha/beta heterodimer, CD4, CD5, CD7, CD10, CD57 (Leu7), SN-1 and the cytoplasmic TcR beta chain. These findings indicate the T cell nature of the established cells. Terminal deoxynucleotidyl transferase (TdT) was also detected in 60%. We did not detect markers of human myeloid and B cell associated antigens, HLA-class II or immunoglobulin chains. Cytogenetic study revealed that the MKB-1 cells had a female hypo-tetraploid karyotype with chromosomal abnormalities including a translocation between chromosomes 10 and 14. The breakpoint of chromosome 14 of this translocation, 14q11.2, is known to be the location of TcR alpha and delta genes; t(10; 14) (q26; q11.2) is a variant type of a T cell neoplasm-associated translocation, t (10; 14) (q24; q11.2). The MKB-1 cell line is unusual in that its T cell characteristics are phenotypically and cytogenetically distinct from the original myeloid leukemia cells.

Adolescent