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Biomedical subjects

Y Ishida

Publications and source records attributed to Y Ishida.

At least 505 records · Page 28Linked to original sources

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↗

Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16.

Forty cultured human leukemia and lymphoma cell lines never exposed to anticancer agents in culture, apart from doxorubicin (ADM)-resistant K562/ADM, were examined for reactivity with a monoclonal antibody, MRK16 in F(ab')2 form [MRK16-F(ab')2], which recognizes P-glycoprotein (P-gp). The relative resistance index to various drugs was calculated by dividing the 50% growth inhibitory concentration (IC50) of the test cell line by IC50 of K562, which was the negative control in the antibody experiment. MRK16-F(ab')2 reacted with four cell lines, K562/ADM, KYO-1, HEL and CMK, which had relative resistance index values of 2 or more to vincristine (VCR), vindesine, vinblastine, ADM, daunorubicin, mitoxantrone (MIT), etoposide (VP-16) and actinomycin-D (ACT-D). The level of resistance to VCR and ADM in these cell lines decreased significantly in the presence of 10 microM verapamil in vitro. Significant expression of mRNA of P-gp gene was also detected in K562/ADM, KYO-1 and HEL. MRK16-F(ab')2 did not react with 36 other cell lines. Among them, three cell lines, PL-21, P31/FUJ and KOPM-28, had relative resistance index values of 2 or more to anthracyclines, MIT and VP-16, but not to vinca alkaloids or ACT-D. The level of ADM-resistance in these cell lines did not decrease significantly in the presence of 10 microM verapamil. Five cell lines, ATL-1K, HL-60, KMOE-2, ML-1 and U266, had relative resistance index values of 2 or more to some of the drugs, but not to the others, and 19 other cell lines did not. These results indicate that the reactivity of MRK16-F(ab')2 correlates with a relative resistance index of 2 or more to all these drugs in cultured human leukemia and lymphoma cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A novel multidrug resistance in cultured leukemia and lymphoma cells detected by a monoclonal antibody to 85-kDa protein, MRK20.

A monoclonal antibody, MRK20, in F(ab')2 form [MRK20-F(ab')2], which reacts with 85-kDa membrane protein in a doxorubicin (ADM)-resistant subline (K562/ADM) of human myelogenous leukemia cell line, K562, was examined for reactivity with 41 cultured human leukemia and lymphoma cell lines. None of these cell lines had ever been exposed to any anticancer agent in vitro except K562/ADM. The relative resistance index to various drugs was calculated by dividing the 50% growth-inhibitory concentration (IC50) of the test cell line by IC50 of K562 (the negative control in the antibody experiment). MRK20-F(ab')2 reacted with seven cell lines, KYO-1 derived from chronic myelogenous leukemia in blastic crisis (CMLbc), CMK from acute megakaryoblastic leukemia, HEL from erythroleukemia, P31/FUJ from acute monocytic leukemia, KOPM-28 from CMLbc, PL-21 from acute promyelocytic leukemia and K562/ADM. MRK20-F(ab')2 did not react with 34 other cell lines. All seven MRK20-F(ab')2-positive cell lines had relative resistance index values of 2 or more to anthracyclines (ADM, pyrarubicin, daunorubicin), mitoxantrone, etoposide, bleomycin, and pepleomycin. There was no distinct correlation between the reactivity to MRK20-F(ab')2 and a higher relative resistance index than 2 to vinca alkaloids, actinomycin-D, cisplatin, 4-hydroperoxycyclophosphamide, nimustine hydrochloride, methotrexate or cytarabine. These results indicate that MRK20-F(ab')2 detects a novel multidrug resistance to anthracyclines, mitoxantrone, etoposide, bleomycin and pepleomycin in cultured human leukemia and lymphoma cells.

Antibiotics, Antineoplastic↗

Isolation of human megakaryocytes by immunomagnetic beads.

A simple method was developed to purify human megakaryocytes to homogeneity from normal bone marrow aspirates. An initial separation of marrow between 1.020 and 1.050 g/ml. Percoll density cut was used to enrich megakaryocytes. After washing, the cells were suspended with immunomagnetic beads which were coated with sheep anti-mouse IgG antibody and treated with anti-human glycoprotein (GP) IIb/IIIa monoclonal antibody, or the cells were treated with human platelet GP IIb/IIIa monoclonal antibody and suspended with the immunomagnetic beads which were coated with sheep anti-mouse IgG antibody. Megakaryocytes were selectively separated using a magnet. All of the isolated cells were morphologically recognizable megakaryocytes. 1.5-3.1 x 10(4) megakaryocytes were obtained from 1.7-4.5 x 10(8) bone marrow nuleated cells. These cells were all positive in immunoenzymatic staining for GP IIb/IIIa. Megakaryocytes obtained by this method responded to recombinant human GM-CSF (rhGM-CSF) showing an increased 3H-thymidine (3H-dT) incorporation. These data show that this method is useful for obtaining pure megakaryocyte populations which can be submitted to comprehensive biological studies.

Antibodies, Monoclonal↗

Regulation of mammalian melanogenesis by tyrosinase inhibition.

Melanocyte stimulating hormone (MSH) specifically induces differentiation of mammalian melanocytes. To further define the biochemical events elicited by this stimulus, we have cloned murine melanoma cells which are either highly responsive or nonresponsive to MSH, and have examined their ultrastructural appearance, their melanogenic activities, and also their expression of tyrosinase. We have found that the basal levels of melanogenic activity in pigmented and nonpigmented cells correlate with expression of surface MSH receptors rather than with production of tyrosinase. Nonpigmented cells produce a potent, highly stable inhibitor of melanogenesis; this inhibitor acts directly on tyrosinase to dramatically and abruptly suppress melanin production. This posttranslational control of tyrosinase activity may represent a critical regulatory point in mammalian pigmentation.

Animals↗

Interferons modulate the expression of hormone receptors on the surface of murine melanoma cells.

The effects of IFN-alpha, IFN-beta, and IFN-gamma on the differentiation of murine melanoma cells has been studied, in the presence and absence of melanocyte-stimulating hormone (MSH); the cells were highly responsive to treatment with MSH, which increased the rate of melanin production 25-fold and tyrosinase activity 6-fold within 4 d. Treatment of melanoma cells with IFN-alpha, IFN-beta, or IFN-gamma alone had no stimulatory effect on melanin production, but when the cells were cultured with IFN in the presence of MSH, pigment production was significantly and synergistically increased relative to cells cultured with MSH only. Flow cytometric analysis revealed that levels of tyrosinase in the cells were not affected by MSH or by IFN, which suggests that stimulation of melanogenic activity occurred by activation of a preexisting cellular enzyme. Scatchard analyses showed that the number of MSH receptors on IFN-treated cells was significantly increased (approximately 2.5-fold) relative to untreated cells (approximately 61,000/cell). These findings demonstrate that IFN stimulate differentiation (that is, pigmentation) of melanocytes by increasing the expression of surface MSH receptors; this in turn suggests that such a mechanism may in part be responsible for postinflammatory skin pigmentation, and provides an additional basis for action in the clinical responses of melanoma to IFN treatment.

Animals↗

Critical analysis of extensive cervical laminectomy.

Conventional extensive laminectomy has been widely performed to reduce spinal cord compression, and is greatly facilitated by the use of an air drill. Laminectomy is recognized, however, as the occasional cause of problems after surgery, such as spinal instability or deformity, acceleration of spondylotic change, constriction of the dura mater caused by extradural scar formation, and lack of posterior bony protection for the spinal cord. In an effort to eliminate these negative aspects of conventional laminectomy, a surgical technique called suspension laminotomy has been used. Fifty-five patients treated with conventional extensive laminectomy and 55 others treated with suspension laminotomy were followed up clinically and compared. Flexibility and alignment of the cervical spine were assessed by plane radiographs, and dural configuration by computed tomographic scans. Neurologic improvement was also evaluated. Decrease of spinal movement after laminectomy was observed, notably during extension, probably as a result of functional insufficiency of paraspinal muscles. The incidence of postoperative spinal deformity was lower and the relief of dural constriction better in the patients treated with suspension laminotomy than in those treated with conventional laminectomy. Neurological recovery was significantly better in fully decompressed cases than in insufficiently decompressed cases.

Adult↗

Redundant nerve roots of the cauda equina: clinical aspects and consideration of pathogenesis.

In order to investigate the clinical significance of redundant nerve roots of the cauda equina (RNR) and their pathogenesis, the following studies were performed: 1) examination of 1,256 myelograms of patients with lumbar disease; 2) clinical analysis of 55 patients with RNR and 75 without RNR; 3) electrophysiological examination of 9 patients with RNR; and 4) anatomical and histopathological examination of 6 autopsy cases. RNR were found in 42% of patients with severely constricted spinal canals. In comparing patients with RNR and those without RNR, RNR were found in older patients, these patients exhibited a longer period from the onset of the symptoms to the time of myelographic manifestation, and they caused more severe signs and symptoms. The spatial distribution of redundant nerve roots and the extent of degeneration of nerve fibers in redundant nerve roots indicated the close causal relationship between RNR and constriction of the spinal canal. As the pathogenesis of RNR, the authors suggest a squeezing force from the constricted spinal canal acting on the nerve roots.

Adolescent↗

[Antihypertensive effect of bopindolol on stroke-prone spontaneously hypertensive rats (SHRSP)].

The antihypertensive effect of bopindolol, a long-acting beta-adrenoceptor blocking agent, was investigated in stroke-prone spontaneously hypertensive rats (SHRSP). One group received tap water during the period of 8 to 32 weeks of age. The average dose of bopindolol administered was calculated from water intake to be approximately 1.4 mg/kg/day. The lowering effect in blood pressure of bopindolol was apparent at the age of 14 weeks, and this continued up to the end of the experiment. Bopindolol significantly reduced the heart rate. Plasma levels of urea nitrogen (BUN), triglyceride, and phospholipid of SHRSP treated with bopindolol were lower than those of the control SHRSP. One of the 8 control SHRSP died, and no rats treated with bopindolol died during the experiment. The histopathological study revealed that three of the control SHRSP had cerebral apoplexy, whereas there was no evidence of cerebral apoplexy in the treated SHRSP. Chronic treatment of bopindolol clearly alleviated myocardial fibrosis and hypertrophic changes in the left ventricular wall of the heart. Decreases in the incidence of proliferative arteritis and malignant nephrosclerosis in the kidney and necrotizing arteritis of the mesenteric arteries were observed in SHRSP treated with bopindolol. The data presented indicate that bopindolol is a powerful antihypertensive agent.

Administration, Oral↗

[Cystic pineocytoma successfully treated with synchronized chemoradiotherapy. Case report].

A case of pineocytoma associated with intraventricular and meningeal metastasis is reported. The patient, a 25-year-old female, was admitted complaining of headache. Computed tomography revealed an irregular-shaped pineal lesion enhanced by contrast medium and accompanied by a cyst. An intraventricular cystic metastatic lesion and meningeal metastasis were also suggested. Biopsy of the pineal region proved the lesion to be a pineocytoma without neuronal or glial differentiation. Ventriculoperitoneal shunting was performed, and radiation therapy combined with chemotherapy (ACNU and vincristine) was administered. This treatment apparently destroyed both the primary and metastatic lesions, and the patient returned to her normal life. In 4 years of follow-up there has been no recurrence of the tumor. Pineocytoma with meningeal metastasis usually has a poor prognosis, but in this case combined radiation therapy and chemotherapy was curative. Although pineocytoma is rarely accompanied by a cyst, in cases of a pineal lesion coexistent with a cyst, a diagnosis of pineocytoma should be considered.

Adult↗

[Estimation of myocardial viability in left ventricular regions with akinetic wall motion by postextrasystolic potentiation using list-mode radionuclide ventriculography in an interesting case with silent ischemia and with premature ventricular complexes (quadrigeminy)].

For determining an indication of percutaneous transluminal angioplasty (PTCA), a 73-year-old-man with silent ischemia and with ventricular premature complexes (quadrigeminy) were performed cardiac nuclear studies. This case had 99% stenosis in LCX (#11) and 90% stenosis in RCA (#1), and demonstrated akinetic wall motion in left ventricular (LV) inferior and posterior regions. Exercise-redistribution Tl-201 studies indicated myocardial viability in a portion of the inferior wall but not in the posterior wall. To estimate the potential contractile function in the regions with akinesis, from the list-mode data of radionuclide ventriculography, those of postsinus beats and postextrasystolic beats were separately selected and were analyzed for investigating LV wall motion and LV ejection fraction (EF). With the post-extrasystolic potentiation, LVEF increased from 36% to 45% and the systolic wall motion was augmented in the inferior wall but not in the posterior wall. From these findings we recognized the existence of myocardial viability in a portion of the inferior wall. After PTCA for the RCA lesion, improvements of the myocardial Tl-201 distribution and LV wall motion in the inferior wall were definitely observed and hence LVEF increased by 16% to contribute to an increase in exercise performance. Thus, this case indicates that the postextrasystolic potentiation is useful for determining an indication of PTCA in patients with LV asynergy, demonstrating the myocardial viability and the potential LV function.

Aged↗

[Autopsy cases of glioblastoma multiforme: treatment results of high-dose fractionated radiation therapy and CT scan findings].

Six autopsy cases of glioblastoma multiforme in cerebral hemisphere were examined by large histological preparations. They were treated by surgery and high-dose fractionated radiation therapy (5 Gy twice weekly). Their morphological changes were compared to the last CT and radiation field and total doses. Four out of six cases showed small residual tumor. One case showed extensive necrosis of the tumor and brain. The other case exhibited no tumor tissue at all. Spongy degeneration of the white matter associated with astrocytosis and macrophage infiltration extended sometimes beyond the local irradiation field. These white matter changes were easily occurred in the previous peritumoral edema where tumor cell infiltration was frequently observed. Residual tumor cells consisted of small anaplastic cells, which might be radioresistant and recur. Enhancement effect of CT scan showed tumor tissue and radiation necrosis with vascular proliferation.

Adult↗

[Noninvasive diagnosis of cardiac involvement by technetium-99m-pyrophosphate (Tc-99m PYP) myocardial scintigraphy in 2 cases of familial amyloid polyneuropathy and 1 case of secondary amyloidosis].

To validate the significance of technetium-99m-pyrophosphate (Tc-99m PYP) myocardial scintigraphy in diagnosing cardiac amyloidosis, 2 patients with familial amyloid polyneuropathy (FAP) and 1 patient with amyloidosis secondary to chronic rheumatic arthritis were studied. All three patients had echocardiographic abnormalities, which were increased wall thickness of the interventricular septum and the left ventricular posterior wall, and granular sparkling appearance in the septum. In 2 patients with FAP, abnormal myocardial uptake of Tc-99m PYP was diffusely detected in Tc-99m PYP SPECT. In the remaining 1 patient with secondary amyloidosis, however, Tc-99m PYP SPECT showed no abnormality, although we had confirmed the presence of myocardial amyloid deposits (type AA amyloid protein) with high amount in the histological examination. Thus, these results indicate that Tc-99m PYP scintigraphy may have a limitation in detecting cardiac involvement in secondary amyloidosis although it is useful in FAP.

Adult↗

[Detection of multidrug resistant cells in human malignant diseases by monoclonal antibodies and strategy to eradicate resistant malignant cells].

Two monoclonal antibodies of F (ab')2 form, MRK 16 and MRK 20 that recognize P-glycoprotein and P85 kD protein respectively, were useful to detect multidrug resistant cells in human lymphoma, leukemia and gastrointestinal cancer cell lines. They were classified into 4 groups: Group I (4 cell lines) was insensitive to vinca alkaloids, anthracyclines, etoposide (VP-16) and actinomycin-D (ACT-D), and reactive to MRK 16 and MRL 20. Group II (2 cell lines) was insensitive to vincristine (VCR), but not reactive to both antibodies. Group III (3 cell lines) was insensitive to anthracyclines and VP-16, but sensitive to vinca alkaloids and ACT-D, and reactive to MRK 20 but not to MRK 16. Group IV (all other cell lines) was sensitive to these drugs, and not reactive to both antibodies. MRK 16 detects P-glycoprotein-associated multidrug resistance (MDR), while MRK 20 detects P 85kd-associated novel MDR. These monoclonal antibodies were useful for detection of MDR cells in clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Radial long-axis tomography: a new reconstructing algorithm for thallium-201 myocardial SPECT].

The long-axis (L-A) tomograms of the heart in thallium-201 SPECT have been conventionally reconstructed as those parallel to the midventricular vertical or horizontal L-A plane. We developed a new algorithm for reconstructing the rotated L-A tomograms around the L-A to longitudinally observe thallium-201 myocardial distribution and to provide an optimal view of the cardiac apex. After determining the orientation of the L-A and reconstructing the short-axis (S-A) tomograms using standard techniques, the coordinates of the S-A planes were transformed to the polar coordinates whose origin is located at the position of the L-A in each plane. Then, "radial L-A tomograms", i.e. midventricular L-A planes oriented at the angle of every 6 degrees to the midventricular horizontal L-A plane, were reconstructed. Also, we developed a new technique for analyzing thallium-201 distribution of the L-A tomograms. For the basal 2/3 regions, two profiles which consist of the pixels with maximum count on the upper and lower myocardial portions of the lines (spaced at 1 pitch) vertically to the L-A were computed. For the remaining apical 1/3 regions, the semi-circumferential maximum-count profile from the values of 30 radii spaced at 6 degrees interval were computed. Based on these profiles, a 2D polar representation was then generated. From the study using a cardiac phantom with an apical small infarction, the usefulness of this new tomographic method for the detection of apical myocardial ischemia was demonstrated. The application to the exercise/redistribution studies in patients with effort angina indicated that radial long-axis tomography provides precise information about the longitudinal extent of perfusion defects, particularly in the apical regions.

Algorithms↗

[Massive intracerebral hemorrhage due to convexity meningioma].

Intracranial meningioma usually present with the typical symptomatology of a progressive neurological deficit. Sudden spontaneous intracerebral hemorrhage from an asymptomatic meningioma is exceedingly rare. A case of 81-year-old woman with convexity meningioma manifested suddenly by massive intracerebral hemorrhage is reported with the findings of computed tomography and angiography.

Aged↗