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T Inamura

Publications and source records attributed to T Inamura.

At least 91 records · Page 5Linked to original sources
PubMed1994

Intracarotid infusion of bradykinin selectively increases blood-tumor permeability in 9L and C6 brain tumors.

This study investigated the effects of bradykinin on blood-tumor barrier (BTB) permeability in transplanted 9L gliosarcomas (9L) and C6 gliomas (C6) in rats. Permeability, expressed as the unidirectional transfer constant, Ki (microliter/g/min), was measured by quantitative autoradiography. Tracers used to examined permeability included radiolabeled alpha-aminoisobutyric acid ([14C]AIB), sucrose ([14C]sucrose) and dextran ([14C]dextran). Intracarotid infusion of bradykinin (10 mg/kg/min) significantly increased the BTB permeability in both 9L and C6 tumors to [14C]AIB and [14C]sucrose, but did not increase permeability to [14C]dextran. Blood-brain barrier (BBB) permeability in normal (non-tumor) brain was not significantly increased to any of the tracers by intracarotid bradykinin infusion. Ki values for [14C]AIB, [14C]sucrose and [14C]dextran of 9L tumors in the bradykinin group versus control group were 41.6 +/- 12.6 vs. 24.8 +/- 6.30 (P < 0.02), 17.5 +/- 9.34 vs. 9.05 +/- 4.36 (P < 0.05), and 3.90 +/- 2.59 vs. 2.42 +/- 1.76, respectively (mean +/- S.D.). Ki values to [14C]AIB, [14C]sucrose and [14C]dextran of C6 tumors in the bradykinin group versus control group were 41.4 +/- 19.0 vs. 19.5 +/- 11.4 (P < 0.01), 18.0 +/- 8.88 vs. 7.06 +/- 3.05 (P < 0.01), and 4.07 +/- 1.45 vs. 2.27 +/- 1.26, respectively (mean +/- S.D.). Intracarotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect. Intracarotid infusion of bradykinin may be a useful technique for selective delivery of compounds to brain tumors.

Aminoisobutyric Acids↗
PubMed1994

Differential tissue expression of immunoreactive dehydropeptidase I, a peptidyl leukotriene metabolizing enzyme.

We previously reported that intracarotid infusion of leukotriene C4 (LTC4) causes a selective increase in vascular permeability within brain tumor capillaries in experimental rat brain tumor. Normal brain capillaries are rich in gamma-glutamyl transpeptidase (gamma-GTP), an enzyme which converts LTC4 to leukotriene D4 (LTD4), and acts as an 'enzymatic barrier' to the vasoactive effects of LTC4. Metabolism of LTD4 in brain capillaries is, however, not known. In this study, rat renal dipeptidase (dehydropeptidase-I, microsomal dipeptidase; EC 3.4.13.11), which converts LTD4 to leukotriene E4 (LTE4) in kidney, was purified from rat kidney and the distribution of immunoreactive dipeptidase in multiple rat organs was determined. Immunocytochemical multi-organ analysis in the rat, which included brain, lung, heart, liver, spleen, small intestine, and testis, was performed. The antigen corresponding to renal dipeptidase was recognized in lung, liver, and testis. There was no antigen in the brain, heart, spleen, and small intestine. In order to confirm the absence of dipeptidase activity in brain capillaries, the metabolism of LTD4 by isolated brain capillaries were examined by reversed phase high performance liquid chromatography. When LTD4 was incubated with the isolated rat brain capillary, no measurable conversion of [3H] LTD4 to LTE4 and leukotriene F4 (LTF4) by brain capillaries was observed with 30 min of incubation. These findings suggest that although gamma-GTP acts as an enzymatic barrier and inactivates LTC4, brain capillaries do not have metabolic activity against LTD4.

Animals↗
PubMed1994

Bradykinin selectively opens blood-tumor barrier in experimental brain tumors.

Bradykinin, infused in low doses (10 micrograms/kg/min) through the carotid artery ipsilateral to RG2 glioma in rats, significantly increased the permeability in tumor capillaries to six different tracers of varying molecular weights compared with intracarotid infusion of saline alone. Permeability in normal brain capillaries was not significantly increased by intracarotid bradykinin infusion. Tracers used to examined permeability included radiolabeled alpha-aminoisobutyric acid (AIB; MW 103), sucrose (MW 342.3), inulin (MW 5000), and dextran (MW 70,000), horseradish peroxidase (HRP) and Evans blue (EB). Permeability was expressed as the unidirectional transfer constant K(i) (microliter/g/min). The permeabilities (K(i)) of tumors in the bradykinin group versus the control saline group for AIB, sucrose, inulin, and dextran were 25.91 +/- 6.78 vs. 13.95 +/- 4.29 (p < 0.01), 17.90 +/- 2.65 vs. 10.75 +/- 4.55 (p < 0.01), 23.92 +/- 6.99 vs. 6.20 +/- 4.37 (p < 0.01), and 17.84 +/- 1.00 vs. 1.47 +/- 1.24 (p < 0.001), respectively (mean +/- SD). Permeability of RG2 gliomas to high molecular weight dextran (70,000) was 12-fold higher in the bradykinin group than in the saline infusion group. Intracarotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect. The permeability of normal brain capillaries was unaffected by intracarotid bradykinin infusion. The increased permeability was reversed 20 min after stopping the intracarotid infusion. Electron microscopic and gross qualitative analysis was performed using HRP and EB. Intracarotid bradykinin infusion increased HRP and EB within tumor tissue but not normal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Intracarotid histamine infusion increases blood tumour permeability in RG2 glioma.

Histamine will alter blood flow and permeability in systemic and cerebral vessels. We reported that intracarotid infusion of histamine selectively increased the blood flow in experimental brain tumours and caused extravassation of Evans blue within tumours. In this study, the effects of histamine on tumour and brain capillary permeability were quantified using autoradiography. RG2 glioma cells were implanted in female Wistar rats. Seven days after implantation, either low doses of histamine (1 or 10 micrograms kg-1 min-1) or saline as a control was infused through the carotid artery of rats. Regional permeability was measured by autoradiography using [14C] aminoisobutyric acid, and the unidirectional transfer constant, Ki (microliters g-1 min-1), was calculated. Intracarotid infusion of 10 micrograms kg-1 min-1 histamine resulted in significant increase in brain tumour permeability, compared to controls. The permeability, Ki, for the 10 micrograms kg-1 min-1 histamine group, the 1 micrograms kg-1 min-1 histamine group, and the control group was 18.8 +/- 4.6 (p < 0.05), 14.9 +/- 5.2, 13.9 +/- 3.7 microliters g-1 min-1, respectively. There was no significant change in blood brain permeability in other brain regions. The effect of increased permeability by 10 micrograms kg-1 min-1 histamine was suppressed by the H2-blocker, cimetidine. This suggests that the effect of histamine on tumour capillaries is mediated by H2-receptors. Intracarotid histamine infusion selectively increases permeability in brain tumours.

Animals↗
PubMed1994

Selective and prolonged MRI enhancement by Mn-TPPS in an experimental rat brain tumour with peripheral benzodiazepine receptors.

Synthesized Mn-TPPS, a paramagnetic metalloporphyrin, is expected to be a tumour specific contrast media for magnetic resonance (MR) imaging. We investigated the enhancing characteristics of Mn-TPPS using a transplanted rat C6 glioma model with peripheral type benzodiazepine (PBD) receptors since porphyrins are thought to possibly be endogenous ligands for PBD receptors. An Mn-TPPS enhancement study was then performed either with or without pretreatment while using peripheral and central type benzodiazepine receptor specific ligands (PK11195 and clonazepam, respectively). A signal intensity analysis disclosed the selective and prolonged enhancement of the brain tumour even at 17 h after the Mn-TPPS injection. This specific enhancement of the tumour, however, was not inhibited nor replaced by benzodiazepines. The tissue concentration of Mn-TPPS was significantly higher in the glioma tissue than the other tissues, while PK11195 pretreatment could not reduce the intratumoural Mn-TPPS concentration. A subcellular distribution study disclosed that Mn-TPPS was readily incorporated into the tumour cells. On the other hand, Mn-TPPS was not specifically distributed in the mitochondrial fraction where PBD receptors exist. The present study therefore indicates that Mn-TPPS could be incorporated into tumour cells and supports the potential use of this agent to improve the diagnostic specificity of MR imaging for brain tumours.

Animals↗
PubMed1994

Intracarotid infusion of RMP-7, a bradykinin analog: a method for selective drug delivery to brain tumors.

The bradykinin analog, RMP-7, was investigated for its ability to selectively increase uptake of molecular tracers in RG2 glial tumors. When infused in low doses (0.1 microgram/kg/min) through the intracarotid artery ipsilateral to RG2 gliomas in rats, RMP-7 significantly increased the permeability of tumor capillaries to methotrexate and to four other tracers of varying molecular weights, compared to intracarotid infusion of vehicle alone. Tracers used to examine permeability included radiolabeled alpha-aminoisobutyric acid (M(r) 103 D), sucrose (M(r) 342 D), methotrexate (M(r) 454.5 D), inulin (M(r) 5000 D), and dextran (M(r) 70,000 D). Permeability was expressed as the unidirectional transfer constant, Ki (microliters/gm/min). The permeability (Ki) of tumors in the RMP-7 group compared to the vehicle control group was as follows: alpha-aminoisobutyric acid, 35.3 +/- 9.11 versus 12.7 +/- 4.56 (p < 0.001); sucrose, 16.5 +/- 3.83 versus 9.28 +/- 3.12 (p < 0.05); methotrexate, 26.3 +/- 10.3 versus 8.98 +/- 6.78 (p < 0.005); inulin, 13.5 +/- 3.23 versus 6.55 +/- 4.32 (p < 0.005); dextran, 15.2 +/- 3.42 versus 1.47 +/- 1.24 (p < 0.001). The permeability of RG2 gliomas to high-molecular-weight dextran (70,000 D) was 10.3-fold higher in the RMP-7 group than in the vehicle control group. Intracarotid infusion of RMP-7 did not significantly increase the blood volume in tumor or brain tissue. The permeability of normal brain capillaries was unaffected by intracarotid infusion of 0.1 microgram/kg/min RMP-7 relative to that achieved in tumor. These data support the idea that intracarotid infusion of RMP-7 will be a useful technique for selective delivery of antitumor compounds to brain tumors.

Animals↗
PubMed1993

Germ cell tumor in the hypothalamo-neurohypophysial region: clinical features and treatment.

Twenty-one patients with germ cell tumors (17 germinomas and 4 teratomas) involving the hypothalamic-neurohypophysial (HN) region were reviewed retrospectively. Eleven patients were males and 10 females, and their ages ranged from 7 to 45 years (average 18.5 years). Diabetes insipidus was the initial and the most prominent symptom in most germinomas; in teratomas the most prominent symptom was visual disturbance. Fifteen patients with germinomas were treated by radiotherapy, and 4 with teratomas were treated by surgical resection alone. Two recent germinoma patients with extensive CSF dissemination were treated with systemic chemotherapy consisting of anticancer platinum drugs and etoposide, which resulted in a complete disappearance of the tumors. Patients with germinoma treated after the introduction of CT scanning had a greatly improved mortality rate, and their actual survival rate was 87.5% over 10 years. On the basis of this review, the authors consider that diagnosis at an early stage of the disease and chemotherapy, which can be an effective therapeutic alternative to radiation therapy, may improve not only the mortality rate but also the quality of life of patients with HN germ cell tumors.

Adolescent↗
PubMed1993

Expression of the B-chain of platelet-derived growth factor and proliferative activity of human brain tumors.

The expression of the B-chain of platelet-derived growth factor (PDGF) was analyzed in 29 human brain tumors (4 astrocytomas, 7 glioblastomas, 3 medulloblastomas, 3 oligodendrogliomas, 7 meningiomas, and others) using monoclonal antibody after digestion with alkaline phosphatase, and compared with proliferative activities measured by in vivo uptake of bromodeoxyuridine. Medulloblastomas contained the highest amounts of PDGF B-chain, some four to eight times more than that in control brain tissue. The most predominant PDGF molecule of the medulloblastoma was 17 kd. Astrocytomas, glioblastomas, oligodendrogliomas, and meningiomas contained predominantly 30 and/or 22-24 kd molecules. Glioblastoma and meningioma proliferative activities correlated closely to PDGF concentrations, with only a few exceptions. Tumors that contained a high level of PDGF B-chain showed high proliferative activity, while tumors with high proliferative activity did not always contain a high level of PDGF B-chain. Tumors that contain many PDGF B-chains may thus indicate malignancy.

Adolescent↗
PubMed1992

The 56 kd platelet-derived growth factor (PDGF)-related protein is phosphorylated and the most stable form in human glioma cells.

We report herein the presence of a 56 kd platelet derived growth factor (PDGF)-related protein as a phosphorylated form in human glioma cells. The phosphorylation of the 56 kd form was found to be the longest of all PDGF-related proteins. By Western blotting using a monoclonal anti-PDGF B-chain, the 80 kd, 56 kd, 40 kd, 28 kd and 17 kd PDGF-related proteins were detected, while after treatment among the nitrocellulose membrane transblotted cell extracts with alkaline phosphatase, 40 kd was the most densely observed while the 56 kd and 80 kd PDGF-related proteins were also detected. In a 32P flush labeling study, it was revealed that PDGF-related proteins incorporated with 32P were detected at 28, 32, 35, 40, 56 and 80 kd but the 17 kd monomer was not labeled. Among the labeled PDGF-related proteins, the 56 kd PDGF-related protein alone remained intracellularly for at least 16 hours. These results indicated that the PDGF-related proteins in human glioma cells are synthesized in a phosphorylated form and partly remain in a 56 kd phosphorylated form intracellularly. The 56 kd form may thus be the most stable form and likely has a substantial biological effect.

Glioma↗
PubMed1992

Natural history and choice of treatment in forty patients with medullary venous malformation (MVM).

Follow-up studies of forty patients with forty-one medullary venous malformations (MVM's) are described. The patients included nineteen males and twenty-one females in an age range from eight to seventy-two years (mean 43.4 years). All cases were diagnosed angiographically. Of the forty-one lesions, twenty-five were located in supratentorial and sixteen in infratentorial regions. In twenty-five supratentorial MVM's, thirteen had superficial drainage, eight deep drainage and three both superficial and deep drainage. Fifteen patients presented with intracranial hemorrhage and eleven patients with complaints or symptoms not related to hemorrhage. Fourteen hemorrhages were found incidentally. The mean follow-up period was three years and eleven months and the longest was sixteen years. No patient died of recurrent hemorrhage and only two had recurrent hemorrhage after a short interval. One patient died of malignant glioma. Thirty-seven out of thirty-nine patients (95%) were in an excellent or good clinical condition with a score above 80% on the Karnofsky Performance Test. This study indicates the low incidence of rebleeding in ruptured MVM's (2/15, 13.3%) and of bleeding in incidentally found unruptured MVM's (0/25, 0%). However, this evidence may be sufficient to support aggressive radical surgery for MVM's.

Adolescent↗
PubMed1992

Leukotriene C4 contents, synthase and catabolic activity in human meningiomas.

Leukotriene has been proposed as a factor of tumour induced brain oedema. Independently of its size, meningioma occasionally shows various extents of peritumoural oedema. We investigated LTC4 tissue contents, LTC4 catabolic and synthetic activity in 12 human meningiomas and their correlation with peritumoural oedema was studied. LTC4 contents were varied from 0.01 to 8.21 pg/mg tissue. When LTA4, an unstable expoxide intermediate was incubated with tumour homogenate, LTC4 was rapidly synthesized. However, LTC4 levels generated by incubating LTA4 with each homogenate were much different in each case. Degradation of LTC4 to LTD4, LTE4, and other polar materials was also rapid by incubation with tumour homogenates. Approximately 70% of added LTC4 was transformed to LTD4, LTE4 nor 6-trans LTB4 diastereoisomers during 30 min incubation at 37 degrees C. The results suggested that there were significant LTC4 tissue contents and LTC4 synthetic and catabolic activity in meningiomas. Oedema index ranged from 1.0 (no peritumoural oedema) to 67.5. No significant correlation, however, was observed not only between the LTC4 tissue contents and LTC4 synthetic or catabolic activities but also between each of these three parameters and peritumoural oedema. Thus, these results do not support a significant correlation of sulfidopeptide LTs with oedema formation in meningioma patients. Since leukotrienes are extremely unstable compounds, LTC4 tissue contents should be carefully discussed along with a consideration of rapid LTC4 synthesis and catabolism. Further role of leukotrienes in meningioma tissue should be studied.

Chromatography, High Pressure Liquid↗
PubMed1992

Peritumoral brain edema in meningiomas--influence of vascular supply on its development.

In a series of 35 patients with intracranial meningiomas, factors influencing the development of peritumoral brain edema (PTBE) were analyzed. We used numbers of the Edema Index as the extent of PTBE, which was obtained from the size of the meningioma and associated PTBE on a T2-weighted image of magnetic resonance imaging. We evaluated a relationship between the Edema Index and some factors that may play a role in the development of PTBE. Tumors in the frontal region and at the sphenoid ridge tended to be associated with larger PTBE than those in other locations (P less than 0.05). Histologically, meningotheliomatous and transitional meningiomas tended to be associated with larger PTBE than fibroblastic meningiomas (P less than 0.05). The meningiomas that had a vascular supply from the intrinsic cerebral arteries on angiography significantly correlated with severe PTBE compared with those supplied only from the meningeal side (P less than 0.01). We concluded that location, histology, and vascular supply from intrinsic cerebral arteries were the factors influencing PTBE. It is stressed that the vascular supply from the intrinsic cerebral arteries may have an influence on the extensive PTBE of meningioma.

Blood-Brain Barrier↗
PubMed1991

Cranial fasciitis: case report.

A 2-year-old boy with cranial fasciitis is described. He had a rapidly growing subcutaneous right occipital mass, which was associated with a dimple in the overlying skin. It appeared similar to a malignant subcutaneous tumor with skin invasion. Total resection of the tumor was performed, and the histological diagnosis, cranial fasciitis, was confirmed.

Child, Preschool↗