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Biomedical subjects

T Okada

Publications and source records attributed to T Okada.

At least 829 records · Page 46Linked to original sources

Analysis of site of action of a choriocarcinoma-derived immunoregulatory factor on IL-2-mediated T cell responses.

We have investigated the functional ability of a choriocarcinoma-cell-derived factor to block human T cell responses and the factor's immunoregulatory site of action on the T cell signal transduction pathway. The factor completely suppressed human T cell responses activated by phorbol ester and calcium ionophore, reagents which strongly stimulate IL-2-mediated T cell responses. It failed to inhibit CD 25 expression and IL-2 production by T cell blasts in the T cell activation phase, but completely blocked recombinant IL-2-induced proliferation of T cell blasts in the T cell proliferation phase. Absorption experiments with the factor and Con A-induced T cell blasts as well as [125I]IL-2 binding experiments with T cell blasts revealed that the factor acted on the physiological events occurring after IL-2-mediated stimulation of IL-2 receptor complexes, demonstrating no interaction of the factor with either IL-2 molecules or IL-2 receptor complexes. Moreover, it suppressed murine IL-2 dependent T cell line proliferation, suggesting the presence of common pathways in human and murine T cell proliferation. The biological and immunological significance of the factor during pregnancy and in the immunosuppressed tumor-bearing hosts are discussed.

Calcimycin↗

Effects of neuropeptide Y and calcitonin gene-related peptide on local cerebral blood flow in rat striatum.

The effects of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) on local cerebral blood flow (LCBF) were studied in vivo in rat striatum. Administration of 1 and 5 nmol NPY as a bolus into the internal carotid artery caused a dose-dependent decrease in the ipsilateral striatal LCBF. This decrease developed slowly and persisted for at least 2 h, without affecting mean blood pressure. In contrast, CGRP, at a concentration of 10 pmol, increased striatal LCBF by about 30%, and the duration of the increase was about 1 h. However, at higher doses of CGRP no increase in LCBF was observed. These results suggest that NPY and CGRP released from nerve fibers innervating blood vessels can function as long-acting modulators of CBF.

Animals↗

Are Ly1 B cells responsible for the IL2-hyperresponsiveness of B cells in autoimmune-prone NZB x NZW F1 mice?

Unlike splenic B cells from normal BALB/c mice, those from autoimmune-prone NZB x NZW (B/W) F1 young mice were hyperresponsive to interleukin 2 (IL2) and proliferated even in the absence of prior stimulation signals. We found that the B cell subpopulation responsible for this event belongs to that with 6B2 (B220)-dull, Ly1(CD5)-positive phenotypes. Cell cycle analysis revealed that the 6B2-dull, Ly1 B cell subpopulation contains a significant number of cells at stages of G1A and G1B, while the majority of 6B2-bright B cells belongs to GO. Therefore, it appears that most of the 6B2-dull, Ly1 B cells in young B/W F1 mice are already stimulated in vivo to the stage of early activation, so that they respond to IL2 without prior stimuli. Unlike other strains of mice, including parental NZB and NZW, the B/W F1 mice showed a rapid decrease in the proportion of splenic Ly1 B cells, beginning at about 6 months of age. This was associated with the hyporesponsiveness to IL2 of 6B2-dull splenic B cell population in the old B/W F1 mice. This phenomenon seems to relate to further activation and differentiation, which occur in Ly1 B cells with aging.

Aging↗

The novel murine B cell differentiation antigen Lp-3.

The unique murine lymphocyte differentiation antigen, Lp-3, with a mol. wt of approximately 125 kd, was found using a rat monoclonal antibody. The Lp-3 antigen was distributed on a wide variety of myeloid, T cell, and B cell lineages in mice. However, the expression was only found in B cells at certain stages of differentiation. The pre-B and virgin B cells in the bone marrow from 2-month-old BALB/c mice were weakly positive for Lp-3, while the resting B cells in the spleen and lymph node were Lp-3 negative. In contrast, the majority of B cells in the peritoneal cavity, mostly Ly-1 (CD5) B cells, had a brighter fluorescence for Lp-3 than did bone marrow B cells. The Lp-3 antigen could be induced in a high density in approximately one-half of lipopolysaccharide-stimulated, large, blastic spleen B cells. Cell cycle analysis showed that Lp-3 is an early B cell activation antigen which is first expressed at the G1A phase of the cell cycle. Therefore this novel B cell differentiation antigen will be useful for differentiating pre-B and virgin B cells in the bone marrow, resting B cells, and a population of activated B cells in the periphery. In contrast to findings in BALB/c mice, there was an elevated population of B cells with a bright Lp-3 expression in the spleen of autoimmune-prone NZB x NZW F1 mice.

Animals↗

Localized release of perivascular heparin inhibits intimal proliferation after endothelial injury without systemic anticoagulation.

Segmental endothelial desquamation of the common carotid artery was produced in 30 rats using a balloon catheter technique which produces consistent proliferation of intimal smooth muscle cells from 5 to 20 days after injury. Immediately after endothelial injury, 15 animals were treated with periadventitial application of heparin contained in a continuous-release drug-delivery system using the polymer polyvinyl alcohol (PVA) and PVA alone applied in a similar fashion to 15 control rats. Animals were killed at 5, 10 and 20 days, respectively, after surgery by intracardiac perfusion-fixation, and vessels were prepared for light microscopy, scanning electron microscopy, and immunohistochemistry with antibodies directed against actin. At all time periods, there was a significant reduction in intimal cross-sectional area in heparin/PVA-treated vessels compared to control vessels. Scanning electron microscopy showed complete absence of endothelial cells from the luminal surface in both control and treated arteries at all time periods without evidence of significant platelet aggregation. Immunohistochemistry demonstrated the presence of immunoreactive actin in the proliferating myointimal cells. Femoral venous prothrombin time and partial thromboplastin time were unchanged in heparin/PVA-treated animals compared to controls at 1, 5, and 10 days. Continuous-release polymer drug delivery can be used to apply heparin selectively to the adventitial surface of vessels and effect changes in the vessel wall over periods of up to 3 weeks. By this means, smooth muscle proliferation and subsequent vessel narrowing after endothelial injury were inhibited without systemic anticoagulation. This technique may be applicable to both clinical and research applications related to the pathophysiology of arterial injury.

Animals↗

Two populations of mouse lymphokine-activated killer cells separated by use of soybean agglutinin.

We separated lymphokine-activated killer (LAK) cells induced from spleen cells of BALB/c mice by culturing with recombinant interleukin-2 (rIL-2) into soybean agglutinin-positive (SBA+) and soybean agglutinin-negative (SBA-) fractions with a cell sorter at the time when LAK activity reached a maximum (day 3). We found that the cells with LAK activity were enriched in the SBA+ fraction. Analysis of cell surface phenotypes revealed that the SBA+ cells are of non-T cell origin, while the SBA- fraction consists of T cells. We also found that the large granular lymphocyte (LGL) fraction of spleen cells obtained with a Percoll gradient became SBA+ after culture for 3 days with rIL-2, whereas cells of high density did not. The change in SBA binding sites was also examined on C57BL/6 mouse spleen cells and we found that NK1.1+ non-T cells selectively acquire SBA binding sites at an early stage of activation with rIL-2. On the other hand, sorted SBA- cells gradually acquired SBA binding sites on extended culturing with rIL-2. These results suggest that the expression of SBA binding sites is related to the stage of cell activation with rIL-2, though cells of the NK-lineage became SBA+ at an earlier period of a culture with rIL-2 than cells of the T-lineage. Utilizing these findings, we separated NK-derived LAK cells by means of SBA-binding, and used the separated cells for adoptive immunotherapy for experimental pulmonary metastasis. We found that SBA(+)-NK cell-derived LAK cells showed stronger activity for the inhibition of experimental pulmonary metastasis than SBA(-)-T cell-derived LAK cells.

Animals↗

A treatment trial of delayed sleep phase syndrome with triazolam.

Triazolam causes a phase-shift of the circadian rhythm of locomotor activity in golden hamsters. We attempted to treat two patients with delayed sleep phase syndrome (DSPS) with triazolam. In one male patient we administered triazolam when the sleep phase began to delay after chronotherapy. Triazolam combined with chronotherapy enabled him to normalize and stabilize his sleep-wake cycle. But in the other female patient despite normalization of her sleep-wake cycle, she became depressive and did not continue taking the drug. In some cases triazolam is useful for the treatment of DSPS, but in others, triazolam induces a depressive state.

Adult↗

Mean cellular volume of urinary red blood cells in investigation of hematuria.

The mean cellular volume (MCV) of urinary red blood cells (RBCs) of pediatric patients with glomerular (group I; n = 52) and nonglomerular (group II; n = 21) hematuria was determined using an automated blood-cell analyzer. Group I patients had a significantly lower MCV than group II (61 +/- 8 vs. 88 +/- 15 microns 3, mean +/- SD; p less than 0.001). With a MCV of 75 microns 3 taken as the dividing line between glomerular and nonglomerular hematuria, correct assessment of the site of bleeding was made in 67 of the 73 (92%) patients studied. Determination of the MCV of urinary RBCs is a simple noninvasive test for localizing the site of hematuria in pediatric patients.

Adolescent↗

Trophoblast-derived immunoregulatory factor: demonstration of the biological function and the physicochemical characteristics of the factor derived from choriocarcinoma cell lines.

An immunosuppressive factor released by choriocarcinoma cell lines was analyzed in the present study. It inhibited the proliferative responses of human T cells stimulated by lectins or alloantigens. It also blocked the generation of alloreactive cytotoxic T cells. The suppressive activity of the factor was detected in the responses of the T cells costimulated with 1 nM 12-O-tetradecanoyl phorbol 13-acetate and 1 microM A23187, suggesting the possibility that the factor acted on the intracellular signal transduction in T cells rather than interfering with early events such as T cell receptor signal transduction through cell membranes. Moreover, the factor acted directly on T cell proliferation pathways without activation of suppressor cells but did not act on T cell activation pathways. Taken together, all these findings expanded our previous reports on a factor released by normal trophoblasts, indicating the possible identity of the two factors. The physicochemical properties of the choriocarcinoma-derived factor were examined, and the biological significance of the factor during pregnancy was discussed in this paper.

Calcimycin↗

A patch-clamp study: secretagogue-induced currents in rat peritoneal mast cells.

Ca2+ entry through plasma membrane has been considered to play a significant role in elevating cytosolic free Ca2+ concentrations during stimulus-secretion coupling in mast cells, but electrophysiological evidence of the Ca2+ channels is lacking. We examined the properties of secretagogue (compound 48/80)-induced currents in rat peritoneal mast cells, using the patch-clamp technique. In the whole cell recordings, the addition of compound 48/80 induced transient currents that were suppressed by Cd or reduced by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). In Ringer solution containing 2 mM Ca2+, the current-voltage relation was fairly linear from -100 to 50 mV and the reversal potential was 14 +/- 10.1 mV (n = 9). When the external Ca2+ was approximately 1 microM, the compound 48/80-induced currents were marginal, but readmission of Ca2+ or Ba2+ to the bath solution led to an appearance of the currents. In the cell-attached patches, the stimulation enhanced the activity of inward current mediated by Ba2+. The unitary inward Ba2+ current was characterized by the unitary conductance of 10.5 +/- 2.0 pS (n = 10) with isotonic BaCl2 pipette solution, the extrapolated reversal potential of 60.7 +/- 16.0 mV (n = 10) positive to the resting membrane potentials. The percent open time of the inward Ba2+ current channel was not appreciably changed by voltage. In some whole cell recordings, an increase in openings of the cation-selective channel (20-45 pS) was identified in the stimulated cells. When the external Na+ was completely replaced by choline+, the compound 48/80-induced currents had a fairly linear current-voltage relation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Breathing abnormalities during sleep in patients with chronic heart failure.

Polysomnography was carried out in 11 adult outpatients with stable chronic heart failure (CHF) due to valvular heart disease in order to investigate respiratory abnormalities during sleep. The subjects consisted of 6 males and 5 females and their ages ranged from 54 to 76 years. A coexisting central dominant sleep apnea syndrome (SAS) was found in 4 males, 3 of whom had evidence of nasal obstruction. A successful mitral valve replacement in one patient with central dominant SAS was associated with a reduction in the frequency of sleep apnea. The results suggest complications caused by respiratory abnormalities during sleep are common and should be considered in the management of patients with CHF.

Aged↗

[Clinical aspects of traumatic intracerebral hematomas. Pathogenesis of delayed traumatic intracerebral hematomas].

Eighty three cases of traumatic intracerebral hematomas (maximum diameter of at least 3 cm) were classified into the following two groups. Group-1 consisted of 34 cases in which intracerebral hematomas were confirmed in the initial CT scans on admission. Group-2 consisted of 49 cases in which intracerebral hematomas were found not in the initial CT scans on admission, but in the second or later CT scans. This is the so-called CT-diagnosed delayed traumatic intracerebral hematomas which have been widely reported in recent years with the increasing use of CT scans. These two groups were studied clinically and the following results were obtained. 1) Traumatic intracerebral hematomas were apt to occur in middle-aged or elderly patients, and more delayed cases increased in patients of 60 or older. 2) The times when the formation of traumatic intracerebral hematomas were judged as completed showed two peaks: within 6 hours after the trauma and 12 to 24 hours after the trauma. 3) Excluding traumatic hemorrhages in the basal ganglia, there were many hematomas in the frontal lobes in the cases of coup injuries by anteroposterior force or contre-coup injuries by posteroanterior force and in the temporal lobes in the cases of contre-coup injuries by lateral force. Traumatic hemorrhages in the basal ganglia were seen in 10 cases, six of which were in Group-1. In all six of these cases, the intracerebral hematoma was confirmed within 6 hours after the trauma and the direction of the external force was unclear. Except for the findings described in 1) to 3), there were no differences in the basic pathogenesis and characteristics between the two groups. These results indicate that there is no essential difference in pathogenesis between CT-diagnosed delayed traumatic intracerebral hematomas and other intracerebral hematomas, as far as the present clinical studies are concerned.

Adolescent↗

Effect of dextran on the stability of isolated, perfused rat heart.

Stability of cardiac function and myocardial intracellular ionic composition was examined in the Krebs-perfused isolated rat working heart. Hearts perfused by a conventional Krebs solution showed stable contraction for 2 h, but during this period, intracellular ionic environment (Na, K, Ca) substantially changed. Addition of dextran to the perfusate inhibited, though not completely, this time-dependent deterioration and made the heart less vulnerable to the hypoxia-reoxygenation.

Animals↗

Fragile X chromosome in institutionalized male adults with mental retardation.

A clinical and cytogenetical study of mentally retarded male adults with an IQ of below 35 has been carried out in the Ranzan Colony for Mental Retardates, Saitama, Japan. The study showed one fragile X-positive retardate with IQ 23 in the 53 residential retarded patients, giving a hemizygote prevalence of 1.9% (1/53). Macroorchidism and elongated ears, practical markers for the clinical diagnosis of fragile X-linked mental retardation, were also detected in this 43-year-old subject with fra(X)(q27.3). He is amiable and no autistic behavior has been observed. The subject, however, has been suffering from epilepsy since childhood and has cataract in both eyes.

Adult↗