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Biomedical subjects

R Tanaka

Publications and source records attributed to R Tanaka.

At least 361 records · Page 20Linked to original sources

Fibrinolytic therapy for acute embolic stroke: intravenous, intracarotid, and intra-arterial local approaches.

To clarify the efficacy and limitations of the intra-arterial local infusion of a high-dose fibrinolytic agent for acute embolic stroke, we analyzed the results of 44 patients and compared them with those of 51 patients treated with intracarotid (18 patients) or intravenous (33 patients) infusion therapy. Ten megaunits of recombinant tissue plasminogen activator or 24 x 10(4) IU of urokinase were administered through a microcatheter placed into or proximal to an embolus for 20 minutes. When arterial recanalization was not achieved, a second or third infusion was performed. The rates of complete and partial recanalization just after the local infusion were 52 and 32%, respectively. They were high in middle cerebral and basilar artery occlusion and low in internal carotid artery occlusion (69, 78, and 20%, respectively). In our use, there was no difference between tissue plasminogen activator and urokinase in restoring blood flow. The mean time interval from onset to recanalization in patients with middle cerebral artery occlusion showing marked improvement was 4.8 hours, and it was 5.8 hours with basilar artery occlusion. The size of infarction was reduced, and the outcome was good in patients with complete recanalization achieved. The incidence of hemorrhagic infarction within 24 hours was 22%, and only one patient clinically deteriorated. In the intracarotid infusion group (20 x 10(4) IU of urokinase for 30 min), only two patients showed partial recanalization without clinical improvement. The incidence of hemorrhagic infarction was 28%. The outcome in this group and the intravenous infusion group (18 x 10(4) IU of urokinase a day for 1 wk) was poor compared with that in the local infusion group showing complete recanalization. This preliminary study appears to suggest that intra-arterial local fibrinolytic therapy could be a new strategy for acute embolic stroke.

Acute Disease↗

Hemostasis in spontaneous subarachnoid hemorrhage.

To comprehensively examine changes in the hemostatic systems early after spontaneous subarachnoid hemorrhage (SAH) and to assess the relationships between those changes and neurological findings, computed tomographic findings, and clinical outcomes, we reviewed 167 patients who were admitted within 24 hours of the onset of SAH. Blood was taken from all of the patients at admission for detailed examinations of the hemostatic systems. The following results were obtained: 1) the levels of the thrombin-antithrombin complex (elevation indicating the activation fo the blood coagulation system), plasmin-antiplasmin complex, and D-dimer (elevation indicating the activation of the fibrinolytic system) significantly increased with the neurological severity, amount of subarachnoid clot, and severity of clinical outcome; 2) the levels of the thrombin-antithrombin complexes and plasmin-antiplasmin complexes were significantly higher in patients with intracerebral or intraventricular hematomas than in patients without those hematomas; 3) in each of almost all the neurological and computed tomographic grades, the levels of the thrombin-antithrombin complexes were significantly higher in the patients with poor outcomes than in those with good outcomes; 4) the poor outcome rate significantly increased with neurological severity and the amount of subarachnoid clot. These data suggest that the activation of the blood coagulation system as well as of the fibrinolytic system occurred early in the course of SAH and that these systems were activated to a greater extent with the severity of neurological grades, computed tomographic findings, and clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneurysm, Ruptured↗

Blood pressure monitoring in feeding arteries of cerebral arteriovenous malformations during embolization: a preventive role in hemodynamic complications.

To study the hemodynamics of arteriovenous malformations and to avoid hemodynamic complications during and after artificial embolization, we measured arterial blood pressures in 21 feeders in 14 patients through a microcatheter system. Before embolization, the pressures were significantly low in feeders with branches terminating in the malformation (terminal divided branches) and comparatively low in arteriovenous malformations with rapid blood flow through the malformation. The pressures in feeders with brain-nutrifying branches distal to the nidus (transient branches) were significantly high. Therefore, transient branches might be distinguishable from terminal divided branches with the use of feeder pressure monitoring. A hemorrhagic complication occurred in one patient. The feeder pressure in this patient was low before embolization and showed the maximum change among the patients after embolization. It seems that the lower the feeder pressure, the more likely complications are to occur, owing to remarkable hemodynamic alterations. Feeder pressure monitoring may be useful for preventing hemodynamic complications, especially when angiographic findings show feeding arteries giving off terminal divided or transient branches or rapid blood flow through the malformation.

Adolescent↗

Effects of pentoxifylline on active oxygen-induced sister-chromatid exchange.

Active oxygens cause major tissue damages in a number of distress syndromes. Pentoxifyline (POF) and its metabolites, a methylxanthine derivative, are inhibitors of superoxide anion production in stimulated human leukocytes. Examination was made of the effects of POF on the genotoxic actions of active oxygens. The frequency of sister-chromatid exchanges (SCEs) induced by paraquat (PQ), a generator of superoxide anions was significantly reduced in cultured Chinese hamster lung cells (CHL/IU) pretreated with POF. POF metabolite samples were also effective. Superoxide anion scavenging effect of POF were found at 0.1 mM, and it was more potent than that of POF metabolite samples. POF and its metabolite sample inhibited xanthine oxidase (XOD) at 1 mM but not at 0.1 mM. POF would thus appear to protect cells from the toxic effects of active oxygens on chromosomes and tissue damage by not only inhibition of active oxygen production in leukocytes but also by scavenging activity of active oxygens.

Animals↗

Angiogenesis in microvascular endothelial cells induced by glioma cells and inhibited by tumor necrosis factor in vitro.

Neovascularization is a prerequisite for glioma growth, so inhibition of angiogenesis may achieve control of glioma growth. We examined whether glioma cells induce angiogenesis and proliferation in microvascular endothelial cells from Fisher 344 rat brains by co-culture in a physical separation system with rat C6 glioma cells or rat T9 gliosarcoma cells. Endothelial cells cultured on type 1 collagen formed capillary-like structures. C6 glioma cells co-cultured with endothelial cells promoted the formation of these capillary-like structures. However, conditioned medium from C6 cells inhibited the proliferation of endothelial cells. T9 cells had little effect on the formation of capillary-like structures and no effect on the proliferation of endothelial cells. We also examined the effects of human tumor necrosis factor (TNF)-alpha on the formation of the capillary-like structures and on the proliferation of endothelial cells. Human TNF-alpha inhibited the formation of capillary-like structures induced by C6 glioma cells at a concentration of 100 U/ml, as well as the proliferation of endothelial cells at a concentration of 1000 U/ml. These results indicate that induction of angiogenesis varies with glioma cell lines and angiogenesis does not correspond with proliferation of endothelial cells. TNF-alpha can inhibit angiogenesis in gliomas in vitro.

Animals↗

Natural history of intracranial cavernous malformations.

The authors have reviewed the clinical records of 110 patients with intracranial cavernous malformations diagnosed by histological examination and/or magnetic resonance imaging over a mean follow-up period of 4.71 years. These cases were divided, based on their presentation, into a hemorrhage group, a seizure group, and an incidentally diagnosed group. The rate of subsequent symptomatic bleeding was investigated in relation to age at onset, sex, and location of the initial lesion. A high rate of subsequent symptomatic bleeding episodes was found in the hemorrhage group, especially among younger females. The nonhemorrhagic-onset cases had a very low incidence of bleeding. The outcome was generally good, except in patients with lesions in the basal ganglia and brainstem. These findings will be helpful in planning a rational therapeutic strategy for intracranial cavernous malformations.

Adolescent↗

[Clinical significance of lymphadenopathy in the upper abdomen; ultrasound demonstration].

Little attention has been paid to the ultrasound differentiation of benign abdominal lymphadenopathy from the malignant type. We reviewed 133 ultrasound examinations of 116 patients with lymphadenopathy seen over the upper abdomen and high retroperitoneum to clarify the differences in ultrasound findings of enlarged lymph nodes caused by benign and malignant abdominal diseases. The location, number, internal texture, size, length/thickness ratio of the lymph nodes, and relation with hepatitis virus infection were evaluated. Among 75 patients with benign diseases, 63 patients showed liver dysfunction and 42/65 (65%) showed positive hepatitis C virus antibody (HCV-Ab). Enlarged lymph nodes were seen over the common hepatic artery or hepatoduodenal ligament in 84%. Most patients had fewer than 4 enlarged nodes, and 46 patients had a single enlarged node. The length/thickness ratio of nodules was more than 2.5 in 63%. In 41 patients with malignant diseases, enlarged lymph nodes tended to be more widespread in location, larger in number, and smaller in length/thickness ratio than those of benign diseases. Lymphadenopathy over the common hepatic artery or hepatoduodenal ligament may suggest the presence of chronic active hepatitis, especially relating to HCV infection, even though hepatic sonotexture is normal on ultrasound examination.

Abdomen↗

[Effect of intra-arterial and local administration of MCNU on cerebral malignant gliomas].

Twenty-six patients with cerebral malignant glioma (7 cases of astrocytoma Grade 3, and 19 of astrocytoma Grade 4) were treated by intra-arterial and local administration of MCNU. Nineteen patients were treated in combination with local radiation in a dose of 60 Gy. Intra-arterial administration of MCNU was performed by puncture of the ipsilateral common carotid artery and injection of 25mg of MCNU in 20 ml of physiological saline. Local administration of MCNU was performed by puncture of the Ommaya reservoir placed within the cavity after tumor resection. Objective tumor regression was observed on computerized tomography (CT) scans after intra-arterial and/or local administration of MCNU combined with radiotherapy in three of seven patients who had evaluable enhanced lesions on CT after surgery. It was also observed after chemotherapy alone in one of three patients with evaluable lesions. The response rate was 42.9% among patients treated with MCNU in combination with radiotherapy, and 33.3% in patients treated with MCNU alone. In two patients, local administration of MCNU induced brain edema, which was transient and caused no neurological sequelae. One patient suffered mild thrombocytopenia after seven intra-arterial doses of MCNU, however, no myelosuppression requiring administration of gamma-GCSF or blood transfusions was observed. These findings suggest that intra-arterial and local administration of MCNU can be expected to serve as effective and non-myelosuppressive chemotherapy in patients with cerebral malignant gliomas.

Antineoplastic Agents↗

The analysis of p53 tumor suppressor gene in pineal parenchymal tumors.

p53 gene mutation was examined in 9 pineal parenchymal tumors, 4 pineoblastomas and 5 pineocytomas, by the immunohistochemical and the polymerase chain reaction-mediated single strand conformation polymorphism (PCR-SSCP) analyses. In each case, immunohistochemical analysis revealed no positive staining for p53 protein with either PAb1801 or DO-1 antibody and PCR-SSCP analysis revealed no abnormal migration in exons 5 to 8 of the p53 gene. These findings suggested that p53 gene mutation is rarely related with the tumorigenesis of pineal parenchymal tumors.

Adult↗

Successful bone marrow transplantation in a child with combined IgG subclass deficiency and neutropenia.

An 8-year-old boy with combined IgG1 deficiency and neutropenia underwent allogeneic BMT from his HLA-identical, MLC-negative sister, because immunoglobulin (Ig) infusions and prophylactic antibiotics failed to prevent life-threatening infections. Conditioning was with busulfan and cyclophosphamide, MTX and CYA were given for the prophylaxis of GVHD. For 16 months after BMT no serious infections have occurred and serum IgG1 levels have returned to the normal range without Ig replacement. BMT may be appropriate treatment for patients with IgG subclass deficiency who rarely respond to conservative therapy.

Bone Marrow Transplantation↗

Clear cell variants of intracranial tumors: meningioma and ependymoma.

We report two cases of rare histological types of intracranial clear cell tumor. Case 1: The tumor, on the left frontal convexity in a 64-year-old woman, consisted largely of polygonal cells with clear cytoplasm which were divided into lobules of uneven size by abundant fibrous connective tissue. Most of the tumor cells were immunopositive for epithelial membrane antigen and vimentin. Ultrastructurally, the tumor cells showed conspicuous interdigitations of their plasma membranes with frequent junctional complexes, and contained numerous glycogen granules in the cytoplasm and its processes. Occasionally, amianthoid collagen fibers were found in the fibrous stroma. Our diagnosis of this tumor was clear cell meningioma. Case 2: The tumor, in the right cerebellar hemisphere in a 64-year-old woman, consisted of round, clear cells with a honeycomb-like pattern. The tumor cells were positive for glial fibrillary acidic protein, vimentin and S-100 protein. Ultrastructurally, the tumor was composed of round cells arranged in a cell-to-cell pattern, and the adjacent cells often formed microrosettes containing microvilli in their lumina. There were scattered cells with accumulatios of glycogen granules in their cytoplasm. Our diagnosis of this tumor was clear cell ependymoma. From the light microscopic features of these tumors, it does not necessarily seem easy to discriminate them from other intracranial tumors composed of similar clear cells, such as oligodendroglioma, central neurocytoma, hemangioblastoma and metastic renal cell carcinoma. Ultrastructural examination is crucial in the identification of the clear cell variants of meningioma and ependymoma.

Brain Neoplasms↗

Identification of a novel neutralization epitope on envelope gp46 antigen of human T-cell-leukemia virus-type-II (HTLV-II).

Having observed that multiple neutralization epitopes of human T-cell-leukemia-virus-type-I (HTLV-I) envelope gp46 clustered in a region between amino acids 187 and 199, we speculated that a region of HTLV-II gp46 corresponding to the HTLV-I-neutralization region may contain HTLV-II-specific neutralization epitopes. To test this, we immunized a NZW rabbit and BALB/c mice with a synthetic peptide containing the HTLV-II gp46 amino acids 182 to 199 (pep182-199) conjugated to OVA. The serum from the rabbit reacted to the HTLV-II gp46 and neutralized HTLV-II-mediated syncytium formation. One monoclonal antibody (MAb), M2E186N1, generated from the BALB/c mice, stained specifically the surface of HTLV-II-positive cells and reacted with HTLV-II gp46 by Western blot. This MAb was of the IgA isotype and inhibited HTLV-II- but not HTLV-I-mediated syncytium formation at a final antibody concentration of 200 micrograms/ml; it also neutralized an HTLV-II-VSV pseudotype virus specifically. Epitope mapping by ELISA using overlapping synthetic peptides indicated that the neutralization epitope recognized by the M2E186N1 MAb was located between HTLV-II gp46 amino acids 186 and 192, corresponding to the sequence Leu-Gln-His-Val-Ile-Leu-Gln-Pro. These new observations will be helpful in developing vaccines against HTLV-II infection.

Amino Acid Sequence↗

[Blood flow pattern in pulmonary atelectasis with color Doppler flow imaging].

Blood flow pattern in the lesion was evaluated in 4 patients with pulmonary atelectasis by color Doppler flow imaging synchronized electrocardiography. The pulsatile signal and triphasic signal were detected, whereas the continuous signal was not. It seemed that in pulmonary atelectasis the pulsatile signal was the blood flow signal in the pulmonary artery and the triphasic signal was the blood flow signal in the pulmonary vein.

Aged↗

Glutamate release in the gerbil hippocampus after middle cerebral artery occlusion.

In a modified version of the unilateral middle cerebral artery occlusion (MCAO) model in gerbils, both sides of hippocampus are spared from direct ischaemic insult. Using this newly employed left MCAO model in gerbils, we investigated the concentrations of extracellular amino acids in the left hippocampus by microdialysis and histological changes in both sides of hippocampus one month after ischaemia. The concentrations of glutamate and aspartate were significantly increased by more than 3.5 times basal levels after MCAO. Glutamate maintained this peak level for 40 to 120 min after the onset of ischaemia. However, hippocampal neurones were well preserved one month after MCAO. While the exact mechanism of the survival of hippocampal neurones remains to be elucidated, we suggest it may be crucial that the hippocampus be protected from ischaemic insult.

Amino Acids↗

Discharge of muscle afferents during voluntary co-contraction of antagonistic ankle muscles in man.

The discharge of 38 tibialis anterior (TA) muscle spindle endings was recorded at rest and during isometric voluntary contraction of the ankle joint in eight healthy human subjects. With the ankle joint in 110 degrees plantarflexion, 24 endings (61%) were tonically active in the resting subject. During weak voluntary dorsiflexion, seven additional endings were activated, so that a total of 31 endings were active (82%). 24 of these were either newly recruited or discharged at a faster rate than at rest (average discharge rate 6.6 Hz at rest, 9.7 Hz during contraction). At matched levels of TA EMG, one ending was newly recruited and 10 were more active during co-contraction of dorsi and plantar flexors than during isolated dorsiflexion. 26 endings were equally active during the two tasks and one ending decreased its firing rate with co-contraction. Four of the 11 endings, which had a higher discharge rate during co-contraction than during dorsiflexion, discharged faster during plantarflexion than at rest although slower than during co-contraction. Plantarflexion had no effect on the discharge of three endings. The remaining four endings were not investigated during plantarflexion. It is suggested that the increased discharge rate of muscle endings during co-contraction is caused either by small changes in the length of the TA muscle or by a disproportionately high fusimotor drive during co-contraction.

Ankle↗