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Biomedical subjects

M Takanashi

Publications and source records attributed to M Takanashi.

At least 55 records · Page 3Linked to original sources

Early effects of gamma knife radiosurgery on brain metastases: assessment by 201TlCl SPECT and 99mTc-DTPA-human serum albumin SPECT.

Thallium-201 chloride (201TlCl) single photon emission computed tomography (SPECT) was used to determine tumor viability, and the early and delayed images of technetium-99m-diethylenetriaminepenta-acetic acid-human serum albumin (99mTc-HSA-D) SPECT were used to assess tumor vascularity and permeability, respectively, in 17 patients with 18 brain metastases. SPECT was performed before, 1 week after, and 1 month after radiosurgery. The ratios of 201Tl and 99mTc-HSA-D uptake in a tumor were expressed as a ratio to uptake in the corresponding normal contralateral areas (uptake index). Magnetic resonance imaging with gadolinium was used to determine tumor volume. 201Tl index decreased significantly 1 week (p < 0.05) and 1 month (p < 0.005) after radiosurgery. In contrast, 99mTc-HSA-D indices of early and delayed images obtained at 1 week after radiosurgery were not significantly different from the pretreatment values. However, both were significantly low (p < 0.05) 1 month after radiosurgery. No change in tumor volume was detected 1 week following radiosurgery, but there was a significant decrease (p < 0.005) after 1 month. The reduction in tumor viability that occurs before the appearance of evidence of tumor shrinkage represents the early effect of radiosurgery on brain metastases. Reduction in tumor size, vascularity, and permeability occur subsequently.

Adult↗

Pharmacological profile of YM087, a novel potent nonpeptide vasopressin V1A and V2 receptor antagonist, in vitro and in vivo.

The biochemical and pharmacological profile of YM087, 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin- 6-yl)-carbonyl]-2-phenylbenzanilide monohydrochloride, a newly synthesized nonpeptide vasopressin (AVP) antagonist, was investigated in several in vitro and in vivo studies. YM087 showed high affinity for V1A receptors from rat liver and V2 receptors from rat kidney with Ki values of 0.48 and 3.04 nM, respectively. YM087 also inhibited [3H]oxytocin (OT) binding to rat uterus (OT receptors) plasma membranes with a Ki value of 44.4 nM, and at 100 microM did not affect the binding of [3H]AVP to anterior pituitary (V1B receptors) plasma membranes, which indicated that it had less affinity for these OT and V1B receptors. YM087 had no effect on cytosolic free calcium concentration ([Ca++]i) itself, but suppressed AVP-induced increase in [Ca++]i of cultured vascular smooth muscle cells at the same concentrations as the binding affinities. Furthermore, YM087 potently blocked AVP-induced cAMP production of cultured renal epithelium cells concentration dependently and had no agonistic activities. In in vivo studies, intravenous administration of YM087 inhibited the pressor response to exogenous AVP in pithed rats and produced an aquaretic effect in dehydrated conscious rats in a dose-dependent manner. These results demonstrate that YM087 is a potent and nonpeptide dual AVP V1A and V2 receptors antagonist and can be used in future studies to help clarify the physiological and pathophysiological roles of AVP.

Animals↗

Oncogenic transformation and inhibition of adipocytic conversion of preadipocytes by TLS/FUS-CHOP type II chimeric protein.

Myxoid liposarcomas are characterized by t(12; 16)(q13;p11) translocation and expression of TLS/ FUS-CHOP chimeric transcripts (types I to III). Among these, the type II transcript is expressed in the majority of cases of myxoid and round cell liposarcoma. To investigate the function of the type II chimeric protein, we obtained stable transformants of ST-13, a murine preadipocytic cell line, which express TLS/FUS-CHOP type II protein (ST-TC) or CHOP protein (ST-C) as well as vector-transfected controls (ST-V). ST-TC and ST-C cells showed almost complete or partial resistance to adipogenic conversion by insulin and thiazolidinedione, respectively. Induction by adipogenic stimulation of the adipocytic genes such as C/EBP alpha, aP2, and adipsin was almost totally suppressed in the ST-TC cells, whereas in ST-C cells C/EBP alpha alone was induced without induction of aP2 and adipsin. Transcriptional suppression of the C/EBP alpha gene in ST-TC cells was suggested by the results of chloramphenicol acetyltransferase (CAT) assay showing a significantly lower C/EBP alpha promoter activity compared with findings in ST-C and ST-V cells. Failure to rescue adipogenic conversion by ectopic expression of C/EBP alpha in ST-TC cells suggested a functional impairment of C/EBP alpha to induce expression of downstream genes. TLS/FUS-CHOP type II protein showed transforming activity, as evidenced by loss of contact inhibition of growth, anchorage-independent growth in soft agar, and tumor formation in nude mice, showing typical histological features of myxoid liposarcoma seen in humans. These findings suggest important roles for TLS/FUS-CHOP type II protein in the oncogenesis of myxoid liposarcoma.

Adipocytes↗

[A 85-year-old woman with one year history of convulsion, dementia, and consciousness disturbance].

We report a 85-year-old woman who died after one year history of convulsion, dementia, and consciousness disturbance. She was apparently well until January 6, 1995 when she was 85 year old; on that evening, she suddenly stated that some one was in her room and she became confused. A local MD gave her diazepam and she fell into sleep. At 3 o'clock in the following morning, she developed tonic-clonic convulsion in her right lower extremity which showed a march to her right upper extremity and the left lower extremity. She was admitted to our hospital. On admission, she was comatose with respiratory acidosis. She was intubated and placed on a ventilator. She was treated with intravenous phenytoin. She gradually gained consciousness and became alert. Respiration became normal. Her MRI revealed ventricular dilatation, fronto-parietal cortical atrophy, and a T1-low and T2-high signal intensity lesion in the left occipital lobe. She was discharged for out patient follow-up on February 4, 1995. Since then, she noted loss of memory and small step gait. A follow-up CT scan revealed a mass lesion which showed a ring-shaped enhancement in the left occipital lobe and was admitted again. On admission, she was alert but markedly demented. The optic fundi was unremarkable, but she appeared to have right homonymous hemianopsia. No motor weakness was noted. In Gd-DTPA enhanced MRI, the above tumor showed a ring enhancement. The diagnosis of glioblastoma was entertained, however, considering her age, she was treated with intravenous glycerol and intramuscular steroid. She was discharged for out-patient follow-up on July 15, 1995. Her gait disturbance had progressively become worse and she developed nausea and vomiting and was admitted again on October 2, 1995. On admission, she was somnolent and markedly demented. Brain stem responses were retained normally. She was unable to stand or walk. Deep tendon reflexes were slightly increased in the right upper extremity and the plantar response was extensor on the right. Her hospital course was complicated by respiratory tract infection and respiratory acidosis. She expired on November 2, 1995. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that she had a glioblastoma involving the left occipital lobe and the adjacent areas. Post-mortem examination revealed an infiltrating tumor in the left occipital lobe. On microscopic examination, the tumor was very cellular; nuclear atypism was marked and tumor cells undergoing mitosis were seen. In some areas, capillary proliferation was seen. Histologic characteristics were consistent with glioblastoma.

Aged↗

Growth stimulatory effect of thrombopoietin on the blast cells of acute myelogenous leukaemia.

Thrombopoietin stimulated blast colony formation in 11/20 acute myelogenous leukaemia (AML) patients studied. The FAB subtypes of the blasts responding to thrombopoietin were not restricted to those of the megakaryocyte lineage, but also included M1-M5 AML blasts. The morphology of colony cells produced by megakaryocytic blasts showed megakaryocytoid features, whereas colony cells produced by M1-M5 AML blasts remained myeloblasts. An increase in CD41 was observed in the cells of colonies produced by blasts from the megakaryocyte lineage involving leukaemia and chronic myeloid leukaemia in blastic crisis. Thrombopoietin receptor was observed on leukaemic blasts which formed colonies following incubation with thrombopoietin.

Cell Division↗

The effect of methylprednisolone on myocardial beta-adrenergic receptors and cardiovascular function in shock patients.

The effect of methylprednisolone on the myocardial beta-adrenergic receptors after long term ( > 72 h) catecholamine infusion was studied. In 56 patients with pulmonary arterial catheter, 10 mg/kg of methylprednisolone was given as an intravenous bolus. Significant increases could be seen in cardiac output and blood pressure in patients who were simultaneously treated with vasopressors like dopamine and/or dobutamine. In patients who were on dopamine infusion higher than 10 micrograms/kg/min methylprednisolone there was an increase in the systemic vascular resistance. Patients who were not on vasopressors but received methylprednisolone, had no similar changes in hemodynamic parameters. In an in vitro analysis of tissue from the myocardium in 12/56 patients who succumbed and in four additional patients who expired after multiple trauma, a beta-adrenergic receptor assay was performed. It was found that the long term infusion of catecholamines decreased the receptor number and the methylprednisolone abolished or caused the decrease to be less pronounced. In this study we could not control the selection of the patients; a randomized study needs to be conducted in the future.

Adult↗

Effect of Gamma Knife radiosurgery on acoustic neurinomas. Assessment by 99mTc-DTPA-human serum albumin- and 201TlCl-single photon emission computed tomography.

Single photon emission computed tomography (SPECT) was performed on 16 patients with acoustic neurinoma before and 1 and 2 years after Gamma Knife surgery. 201TICI-SPECT was used to determine tumor viability. Early and delayed images of 99mTc-DTPA-human serum albumin (99mTc-HSA-D)-SPECT were used to assess tumor vascularity and permeability, respectively. There was a statistically significant decrease in the 99mTc-HSA-D index of the early image at 1 year (p = 0.013) and at 2 years (p = 0.018) after Gamma Knife surgery. On the other hand, the 201Tl index and the 99mTc-HSA-D index of the delayed image were not significantly different from their pretreatment values. These observations demonstrate that a reduction in tumor vascularity without a decrease in tumor viability may be one of the effects of Gamma Knife surgery on acoustic neurinomas.

Adult↗

Radiosurgery of brain metastases with the Gamma Knife.

A total of 130 patients with metastatic brain tumors were treated with the Gamma Knife; 85 had multiple lesions. The marginal dose was 14-30 Gy for the initial 20 cases during the first 6 months. Thereafter, we increased the marginal dose to between 25 and 30 Gy for the last 110 cases. The follow-up period ranged from 1 to 49 months (mean 9 months). The recurrence rate fell from 20% for the early low-dose cases to 4.6% for the later 110 higher-dose cases (p = 0.043). Transient neurological deterioration developed in 7 cases (5.4%), and permanent neurological deficits were recognized in a further 6 cases (4.6%). The relatively high prescription dose of 25-30 Gy at the margin of brain metastases treated with the Gamma Knife resulted in an acceptably high control rate with a low rate of complications.

Adult↗

The positive inotropic effect and the hydrolysis of phosphoinositide induced by endothelin-3 in rabbit ventricular myocardium: inhibition by a selective antagonist of ET(A) receptors, FR139317.

Endothelin-3 (ET-3), an isopeptide of ET, had a concentration-dependent positive inotropic effect (PIE) on rabbit papillary muscle. The maximal inotropic response to ET-3 was 65% of the maximal response to isoproterenol. ET-1 elicited a PIE below 10(-9) M, namely, over a concentration range at which ET-3 did not elicit a PIE. The selective ET(A) antagonist FR139317 effectively antagonized the PIE of ET-3. FR139317 abolished the PIE induced by ET-1 (<10(-9)M) but did not inhibit the PIE induced by high concentrations of ET-1. FR139317 also antagonized the PIE of sarafotoxin S6c. ET-3 caused a time- and concentration-dependent increase in [3H]inositol phosphates (inositol monophosphate, inositol bisphosphate and inositol trisphosphate). FR139317 at 10(-5) M decreased the ET-3-induced increase in inositol phosphates by about 60%, whereas it attenuated the increase in [3H]IP1 induced by ET-1 (3 x 10(-8)M) by only 20%. Thus, in the presence of FR139317, the PIEs of ET-3 and ET-1 were partially dissociated from the PI hydrolysis that was induced by these isopeptides. FR139317 inhibited the specific binding of [125I]ET-1 and of [125I]ET-3, and it was apparent that FR139317 had a high-affinity and a low-affinity site for competing for specific binding with each ligand. These findings indicate that different subtypes of the ET receptor are involved in the induction of the PIEs of ET-3 and ET-1. The PIE of ET-3 may be mediated predominantly by ET(A1) receptors that are susceptible to FR139317 and BQ-123 and partially by ET(B) receptor that are inhibited by RES-701-1. Both ET(A1) and ET(A2) receptors may be responsible for the PIE of ET-1, depending on the concentration in rabbit ventricular myocardium.

Animals↗

[Trials and analysis of umbilical cord blood collection, separation and cryopreservation methods for transplantation].

Placental and umbilical cord blood, as an alternative course of haematopoietic stem cells for bone marrow reconstitution, have recently been showed to yield successful sibling-donor cord blood grafts children. The advantages of using cord blood are related to the high number of haematopoietic progenitors in circulation at birth. In our study there was a remarkable heterogeneity of volume, number of nucleated cells and the number of progenitors from sample to sample. Seven out of 40 samples of more than 61 ml blood volume contained 1.8 (+/- 1.0) x 10(5) CFU-GM or 6.0 (+/- 4.8) x 10(8) nucleated cells. 10 ml of whole blood was necessary for laboratory tests including ABO blood type, screening of infectious markers, HLA typing, as well as frozen sera and cells for the possible future tests. Collected cord blood of more than 70ml in volume may have sufficient numbers of CFU-GM for engraftment to pediatric patients weighing about 20 kg. A cord blood bank project is now going on by collecting blood with informed consent of the mother in cooperation with obstetrics and gynecology staff.

ABO Blood-Group System↗

Age-related changes in alpha 1-adrenoceptors in rat prostate.

The age-related changes in the density of alpha 1-adrenoceptors in the dorsolateral lobe of the rat prostate were evaluated in Wistar rats at 8, 52, and 104 weeks of age. [3H]YM617, a newly synthesized alpha 1-adrenergic blocker, was used as the ligand. The mean maximum number of binding sites, or alpha 1-adrenoceptor density (Bmax) +/- SE of 104-week-old rats (11.0 +/- 1.2 fmol/mg protein) was significantly lower than that in the 8-week-old rats (37.0 +/- 4.3 fmol/mg protein) and 52-week-old rats (37.2 +/- 3.4 fmol/mg protein) (respectively, P < 0.01). In contrast, mean affinity (Kd) values +/- SE of these groups showed no significant differences (8-week-old rats, 115.8 +/- 9.1; 52-week-old rats, 100.5 +/- 5.8; and 104-week-old rats, 116.4 +/- 9.8 pM). Mean volumes +/- SE of muscle cells of the prostate were 3.7 +/- 1.1 x 10(3) microns3 at 8 weeks, 30.0 +/- 6.2 x 10(3) microns3 at 52 weeks, and 18.6 +/- 8.2 x 10(3) microns3 at 104 weeks. Volumes for 8-week-old rats were significantly smaller than those for 52-week-old (P < 0.01) and 104-week-old rats (P < 0.05). However, the mean area density of the muscle cells showed no difference among the three groups: 20.1 +/- 2.2% at 8 weeks, 27.3 +/- 2.9% at 52 weeks and 20.3 +/- 3.4% at 104 weeks. In conclusion, the density of YM617-binding sites (alpha 1-adrenoceptors) in 104-week-old rats was lower than in 8- and 52-week-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Increased number of Epstein-Barr virus latently infected B-cells in T-cell non-Hodgkin's lymphoma tissues.

Epstein-Barr virus (EBV) is a causative agent of malignant lymphomas occurring in immunocompromised hosts. Similar lymphoid tumors can be induced in mice with severe combined immunodeficiency (SCID mice) by transplanting human B-cells with latently infected EBV. We have previously observed that when apparently EBV-negative lymphomas were engrafted into SCID mice, 11 of 18 T-cell non-Hodgkin's lymphomas (NHLs) produced EBV associated lymphomas, but only 2 of 30 engrafted with B-NHLs. Previous studies suggested that EBV-infected cell inducing lymphomas in SCID mice may preferentially exist in T-cell NHL tissues. To prove this assumption, in situ hybridization (ISH) using oligonucleotide probes for EBV-encoded small RNAs 1 (EBER1) was used in this study to demonstrate EBV-bearing lymphocytes in NHL tissues. It was found that EBV-bearing cells existe in 9 of the 10 T-cell NHL surgical specimens. By contrast, in B cell NHLs, only 2 of 10 carried EBV-bearing cells. Further semi-quantitative analysis demonstrated that apparently significantly more EBV-bearing cells were present in T-cell NHL tissues than in B-cell NHLs. Moreover, these EBV-bearing cells in lymphoma tissues were shown to be of B-cell lineage, by the combinated analysis of immunostaining with CD20 and ISH with EBER1. These results indicated the increase of EBV-bearing B-cells in T-cell NHL tissues, suggesting the activation of B-cells with latently infected EBV by neoplastic T-cells.

Animals↗

Corticosteroid effect on early beta-adrenergic down-regulation during circulatory shock: hemodynamic study and beta-adrenergic receptor assay.

OBJECTIVES: The steroid effect on critically ill patients remains controversial. The aim of this study is to characterize the effect of methylprednisolone on the heart in a beta-adrenergically down-regulated condition. DESIGN: A prospective hemodynamic study and retrospective receptor assay. SETTING: Multidisciplinary ICU in a university hospital. SUBJECTS: 42 patients who required pulmonary arterial catheters and an additional 4 corpses who were available for study within 3 h of their deaths. INTERVENTION: Intravenous methylprednisolone (10 mg/kg). MEASUREMENTS AND RESULTS: We pursued a hemodynamic study following a glucocorticoid administration. In patients who had undergone a long term (> 72 h) catecholamine treatment, the cardiac index increased. In patients who had undergone a short term (1-72 h) catecholamine treatment and in patients with no record of catecholamine administration, the cardiac index showed no remarkable change. Among the corpses, who died soon after their arrival, and the patients, who later died in the ward and were available for further study, we measured beta-adrenergic receptor density in the left ventricular myocardium. It was found that receptor density was decreased after long term catecholamine treatment. Methylprednisolone, on the other hand increased the receptor density. CONCLUSION: Methylprednisolone improved the cardiac index, intriguingly, in patients with long term catecholamine treatment in circulatory shock. Myocardial beta-adrenergic receptor also increased in number after the administration of methylprednisolone. However, the hemodynamic improvement caused by methylprednisolone was not observed in patients without beta-adrenergic down-regulation.

Adrenergic beta-Antagonists↗

Gamma knife surgery for Cushing's disease.

BACKGROUND: The efficacy of gamma knife surgery on Cushing's disease is not well known to date. In most reported cases of Cushing's disease treated with gamma knife, the area to be irradiated was determined with computed tomography or pneumoencephalography. We report two cases of recurrent pituitary-dependent Cushing's disease treated with gamma knife using stereotactic magnetic resonance imaging (MRI). MATERIALS AND METHODS: Recurrent microadenomas were visualized as hypointense areas using gadolinium-enhanced MRI after two transsphenoidal surgeries in both cases. The doses of irradiation given were 35 Gy and 20 Gy to the margin of the tumors, and less than 8 Gy and 21 Gy to the optic apparatus and cranial nerves in the cavernous sinus, respectively. RESULTS: Both patients had clinical remission with normal serum cortisol and adrenocorticotrophic hormone levels, during 2-year follow-up after radiosurgery, without endocrinologic deficiency or neurologic deterioration. CONCLUSIONS: Gamma knife surgery can be an alternative therapy for Cushing's disease when pituitary adenomas are apart from the optic apparatus and can be visualized clearly by MRI, even if tumors are recurrent after microsurgery.

Adenoma↗

Renal aging change of alpha 1-adrenoceptor in Wistar rats.

1. The aging changes of density of the alpha 1-adrenoceptors in the kidney were evaluated with Wistar rats of several ages (8, 52 and 104 weeks old). 2. [3H]prazosin and [3H]YM617 (newly synthesized alpha 1-blocker) were used for the ligand. The Bmax of [3H]prazosin was 74.0 +/- 9.5 fmol/mg/protein in 8 week, 52.1 +/- 7.3 fmol/mg protein in 52 week, and 31.3 +/- 4.2 fmol/mg protein in 104 week rats, and that of [3H]YM617 was 45.0 +/- 6.6 fmol/mg/protein in 8 week, 32.4 +/- 5.7 fmol/mg/protein in 52 week, and 19.3 +/- 5.5 fmol/mg/protein in 104 week rats. 3. The Bmax of both ligands for 104 week rats was significantly decreased compared to 8 week rats, however, 52 week rats showed no decrease of Bmax for both ligands. 4. The Kd values showed no difference in these three age groups for both ligands. 5. Autoradiographic study supported the result above mentioned. Furthermore, the binding sites of alpha 1-adrenoceptors were mainly in the cortex (vascular wall and peritubular area) and that alpha 1-adrenoceptors were chiefly chlorethylclonidine dihydrochloride (CEC) insensitive.

Adrenergic alpha-Antagonists↗

Immunoglobulin idiotypic specificity of AIDS-associated lymphomas and their experimental model.

B cell non-Hodgkin's lymphoma (B-NHL) occurring in immunocompromised hosts, such as acquired immune deficiency syndrome (AIDS) patients, is a high-grade malignancy resistant to regular chemotherapy. To determine whether immunotherapy with public anti-Ig idiotype antibodies can be used to treat these NHL, the Ig idiotype specificity of six NHL in AIDS patients (AIDS-ML) and 23 B-NHL experimentally induced in immunocompromised mice (SCID mice) was investigated. One of the six AIDS-ML and two of the 23 experimental B-NHL reacted monoclonally with a single public antibody, while one AIDS-ML and three experimental B-NHL reacted polyclonally with two or three different antibodies. The presence of Ig idiotypic polyclonality requires special consideration with regard to the introduction of anti-Ig idiotype immunotherapy in these cases.

Adult↗

Gamma Knife surgery for angiographically occult vascular malformations.

To evaluate the effect of radiosurgery on angiographically occult vascular malformations (AOVMs), 9 patients treated with Gamma Knife surgery were followed up for 21-37 months. Eight patients had bleeding episodes, 1 had uncontrollable epilepsy. Rebleeding occurred in 3 AOVMs 5 or 6 months after treatment. One patient experienced transient radiation-induced edema. One patient underwent surgical extirpation due to uncontrollable epilepsy 21 months after Gamma Knife surgery. Histological findings revealed an arteriovenous malformation (AVM) and a cavernous angioma. There was hypertrophy of the internal membrane of the AVM, but no effect on the cavernous malformation. Radiosurgery should only be considered in cases of inoperable AOVM, because there is no definite proof that radiosurgery prevents AOVMs from rebleeding.

Adolescent↗