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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 649 records · Page 36Linked to original sources

[Three-dimensional analysis of regrowth pattern in recurrent supratentorial glioblastoma multiforme and anaplastic astrocytoma with special reference to prognosis].

To determine effects of surgical treatments on the quality and duration of survival following tumor recurrence and to analyze prognostic factors that may affect the outcome, we have reviewed our experience with reoperations for 43 patients having recurrence with malignant histologic findings among 188 cases of supratentorial glioblastoma multiforme (GM), anaplastic astrocytoma (AA) and low-grade astrocytoma (LGA) (27 of 77 patients with GM, and 16 of 42 patients with AA) since introduction of computed tomography (CT) in May, 1976. Using CT and/or more recent magnetic resonance imaging (MRI), the regrowth patterns of tumor recurrence were examined with aspect of local extension, non-contiguous or remote metastatic invasion, and tumor cell dissemination through cerebrospinal fluid. MRI can provide more significant informations on the selection for reoperation in terms of recognition of the developmental features. In most of the patients who underwent reoperations at recurrence, surgically accessible components of the lesion were shown to cause neurological deficits as a result of compression rather than infiltration of functionally important areas. Reoperations thus might be achieved with acceptable mortality and morbidity. In contrast, patients with tumors in inaccessible areas of the central nervous system received additional chemotherapy and/or interferon administration. Indications for re-irradiation of the recurrence is also discussed.

Adult↗

[A molecular basis for multidrug resistance and reversal of the resistance].

Multidrug-resistance is frequently characterized by enhanced drug efflux resulting from a membrane glycoprotein of 170,000 daltons (P-glycoprotein). Analysis of cloned cDNAs for the human MDR 1 gene, whose product is the P-glycoprotein, indicates that P-glycoprotein is an energy-dependent drug-efflux system for cytotoxic hydrophobic anticancer drugs. We have demonstrated that a photoanalog of a reversing agent, SDB-ethylenediamine, specifically binds to P-glycoprotein. The binding site on P-glycoprotein seems to be identical with that of anticancer agents and other reversing agents. On the other hand, the radioactive photoactive dihydropyridine calcium channel blocker, [3H] azidopine, photolabels P-glycoprotein in membrane vesicles from multidrug-resistant cells. This photolabeling is almost completely inhibited by excess dihydropyridine analogs that reverse or lower drug-resistance. In contrast, the labeling is not significantly inhibited by analogs that do not reverse resistance. These results suggest that it may be possible to quickly screen for dihydropyridine analogs that reverse multidrug resistance by measuring the inhibition of [3H] azidopine labeling of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Role of plasma histamine and neutrophil chemotactic factor in exercise-induced asthma].

The mechanism of exercise-induced asthma (EIA) is still controversial, although the role of chemical mediator is strongly suspected. In the present study, 50 asthmatic patients were observed after exercise on bicycle ergometer during dry air breathing, and changes of plasma histamine and neutrophil chemotactic factor (NCF) were measured and effect of anti-allergic drugs was examined. 31 patients developed postexertional bronchoconstriction and their % reduction of FEV1 after exercise correlated significantly with the degree of airway hyperresponsiveness to inhaled methacholine determined by Astograph. Plasma histamine levels were examined in 20 EIA positive cases and 13 EIA negative cases, but no significant changes were observed between pre- and post-histamine levels in either group. On the other hand, NCF was elevated significantly after exercise in both EIA positive and negative cases, but postexertional NCF levels were significantly higher in EIA positive than in EIA negative cases. The relationship between % increase of NCF and the % reduction of FEV1 after exercise was significant (r = 0.472, p less than 0.05). DSCG and Azelastine protected the development of EIA in 14 out on 19 cases and 7 out of 12 cases, respectively. Pretreatment with DSCG significantly reduced the increase of NCF after exercise. These results indicates that one of the chemical mediator, NCF, may play an important role in producing postexertional bronchoconstriction in asthmatic patients.

Adolescent↗

Synthetic isoprenoid photoaffinity labeling of P-glycoprotein specific to multidrug-resistant cells.

The synthetic isoprenoid N-solanesyl-N,N'-bis(3,4-dimethoxy-benzyl)ethylenediamine (SDB) is known to reverse drug resistance in human multidrug-resistant KB cells. SDB inhibits the photolabeling of P-glycoprotein with the vinblastine analog N-(pazido-(3-(125)l)salicyl)-N'-beta-aminoethylvindesine. We synthesized photoactive radioactive SDB and used it to photoaffinity label membrane vesicles from human KB cells and their multidrug-resistant subline KB-C2 cells. A 150 to 170 kDa protein in membrane vesicles from KB-C2 cells was specifically labeled by the photoanalog of SDB. The labeled band was not detectable in parenteral drug-sensitive cells. The photolabeled 150 to 170 kDa protein was immunoprecipitated with a monoclonal antibody (C219) specific to P-glycoprotein. P-glycoprotein labeling was inhibited by anticancer agents, vinblastine, vincristine, actinomycin D, and daunomycin, with half-maximal inhibition at 2.0, 2.3, 18, and 23 microM, respectively. Only 33 and 18% of the labeling was inhibited by 100 microM Adriamycin and colchicine, respectively. The labeling was also inhibited by agents that reverse multidrug resistance, such as verapamil, reserpine, cepharanthine, and SDB. The existence of other molecules that specifically bind to 125l-SDB-photoanalog was suggested in both KB and KB-C2 membrane vesicles. The fact that we could identify the synthetic isoprenoid acceptor in membrane vesicles from multidrug-resistant cells confirms that P-glycoprotein plays a role in the multidrug resistance phenotype and provides an explanation for the fact that SDB circumvents multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Experimental analysis of intracerebral natural resistance against H-2+ and H-2- lymphomas grafted into the brain].

The authors have investigated intracerebral natural resistance mechanism after tumor transplantation into the brain, by using YAC-1 (Moloney leukemia virus-induced T cell lymphoma of A/Sn mouse origin) and its H-2 negative A. H-2-. It was found that highly immunogenic H-2+ YAC-1 was less tumorigenic than A. H-2- in untreated as well as NK-depleted syngeneic mice. The variant cells were not rejected even if inoculated together with YAC-1 cells into the brain. Furthermore, in T cell-depleted, thymectomized mice YAC-1 was as tumorigenic as A. H-2-. Thus, intracerebral natural resistance was expressed against YAC-1, suggesting that T cells but not NK cells might be involved in the tumor rejection with an MHC-restricted regulation. Contrary to this, A. H-2- cells escaped from the natural resistance of the brain. In vitro cytotoxicity assays showed that in relation to the enhancement of cell surface H-2 antigens, intracerebrally passaged YAC-1 cells decreased and increased the sensitivity to NK- and CTL-mediated lysis, respectively. In contrast, A. H-2- did not alter either susceptibility to cell-mediated lysis or cell surface H-2 expression. In vivo rapid elimination assays revealed that after intravenous or subcutaneous inoculation there was a more efficient abrogation of 125I-iododeoxyuridine (IUdR) labelled YAC-1 cells in normal untreated mice compared to NK-depleted mice. After intracerebral inoculation, however, no difference in remaining radioactivity was observed between untreated and NK-depleted mice. This indicates that selective NK-mediated elimination of tumor cells might occur after intravenous or subcutaneous but not after intracerebral inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[In vivo antitumor activity of mitoxantrone and the flow cytometric analysis of its influence on cell cycle transition--comparison with doxorubicin and aclarubicin on ascitic hepatoma AH109A cells].

Mitoxantrone was compared with doxorubicin and aclarubicin of its in vivo antitumor activity and influence on cell cycle transition by use of rat ascitic hepatoma AH109A. Antitumor activity determined by the cell growth curve was similar in mitoxantrone and doxorubicin, but the sensitivity of AH109A to aclarubicin was lower than that to the other two drugs. Doxorubicin and mitoxantrone showed all phase arrests with 1/10 of maximally tolerated dose (MTD), and with lower concentrations a strong arrest at G2 phase was observed, thus, mitoxantrone appeared to have a similar antitumor activity on AH109A to that of doxorubicin. Aclarubicin, with 1/10 MTD, demonstrated only a transient arrest at G2 phase, cells arrested at G2 phase entering into the next phase. With below 1/10 MTD, there was no appearance on histograms, and the influence on AH109A cell cycle transition by aclarubicin was considered to be little in comparison with doxorubicin and mitoxantrone.

Aclarubicin↗

[Monoclonal antibodies against human erythrocyte membrane antigens and the antigens recognized by these antibodies].

Six monoclonal antibodies (KOR-E1-E6) were raised against human erythrocyte membrane antigens. Aggregating reactions of normal human erythrocytes with or without enzyme treatment and specific antigen deficient (null type) erythrocytes were used for detection of the antigens. SDS-polyacrylamide gel electrophoresis with Western blotting and immunoperoxidase methods were also used to confirm the results. The antigen recognized by KOR-E1 and KOR-E5, which was sensitive to protease, trypsin, and neuraminidase, and only expressed on human erythrocytes, was identified as Pr1h. The antigen recognized by KOR-E2 and KOR-E6 was identified as the EnaTS portion of glycophorin A, because the antigen was sensitive to protease and trypsin, but resistant to neuraminidase, and was not present on En(a-) erythrocytes. The antigen recognized by KOR-E3 that was protease-, trypsin-, and neuraminidase resistant, and absent on En (a-) erythrocytes, was identified as Wrb antigen. As KOR-E4 reacted with all erythrocytes examined, the antigen it recognizes could not be determined.

Animals↗

[Monoclonal antibodies against human erythrocyte membrane antigens and their reactivities with hematopoietic cells].

Four monoclonal antibodies against human erythrocyte membrane antigens were established. The antigenic determinants of KOR-E1, E3, E6 were Pr1h antigen, Wrb antigen, and the trypsin sensitive portion of glycophorin A (EnaTS) respectively. The antigen recognized by KOR-E4 could not be determined. The reactivities of these antibodies with normal hematopoietic cells, malignant hematopoietic cell lines (N = 31), and fresh leukemic cells obtained from 128 patients with various types of leukemias were studied. All antibodies reacted only with erythrocytes among peripheral blood cells, and also KOR-E6 reacted only with erythroid cells among bone marrow cells. KOR-E3 had no reactivity with any cell lines examined, and KOR-E1 and KOR-E4 were reactive with some lymphoid cell lines. However, KOR-E6 had specific reactivities with erythroid (HEL, K562), megakaryocytic (CMK-1), multiphenotypic (KOPM-28), and basophilic (KU-812) cell lines. The antigen (glycophorin A) recognized by KOR-E6 was expressed on a small population of mononuclear cells separated from acute lymphoblastic leukemia (3/70), acute myelogenous leukemia (2/12), monosomy 7-myeloproliferative disorder (1/1), juvenile CML (1/1), and transient myeloproliferative disorder with Down's syndrome (4/12), although it could not be determined whether these cells were leukemic cells or not. KOR-E6 was reactive with a large population of leukemic blasts in erythroleukemia (2/2) and acute megakaryoblastic leukemia (3/6). Thus, KOR-E6 appears to be an erythroid marker of leukemic cells.

Adolescent↗

[The development of spinal endoscope using a flexible optic fiber].

The development of spinal endoscope using a thin (0.75 mm in diameter) flexible fiber catheter AS-001, Fukuda-densi Co Ltd., Japan) is described in this study. This fiber catheter contains 3,000 optic fibers as imaging and illuminating fibers within its diameter. The effective length and the visual angle is 1.10 m and 53 degree, respectively. Video processor system was connected to this fiber catheter. With a patient in the lateral decubitus position under local anesthesia, this fiber catheter was introduced into the lumbar subarachnoid space in a similar manner as lumbar spinal drainage. Eight patients with myelopathy were evaluated by this spinal endoscopic study. With other radiological diagnostic modalities such as myelography, selective spinal angiography using intraarterial digital subtraction angiography (DSA), or magnetic resonance imaging (MRI), it was difficult to make definitive diagnosis in these 8 patients. In 4 patients among them, vascular tangle, or tortuous course of the dilated vessels were visualized on the dorsal surface of the spinal cord by the spinal endoscopic study, which strongly suggested the spinal arteriovenous malformation. In 3 of them, operative findings verified these preoperative endoscopic diagnoses to be correct. In the remaining case, surgical intervention was not attempted because of the personal affair of the patient. In every case, several structures around the thoracolumbar cord such as spinal dura mater, arachnoid membrane, or conus medullaris were observed under the pulsation of the cerebrospinal fluid. No complication was associated with this spinal endoscopic study. About 10 minutes were required for the whole procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Familial occurrence of intracerebral cavernous angioma].

This article reported a familial occurrence of intracerebral cavernous angioma in four members of one generation diagnosed by X-ray CT, MRI or operative specimen. Case 1, a 34-year-old female, was examined just after an episode of sudden convulsive seizure. On examination, she had a cutaneous angioma without any neurological deficit. X-ray CT revealed a high density mass lesion in the left frontal lobe, and MRI demonstrated a mass lesion in the chronic stage with an old hematoma circumscribed by hypointensity ring indicating peripheral hemosiderosis. Complete excision was carried out and a diagnosis of cavernous angioma was made after histological examination. Case 2, the 37-year-old brother of Case 1, suddenly developed left hemiparesis and hypesthesia with severe headache. X-ray CT revealed a high density mass in the right parietal lobe and two other calcifications. The right parietal lesion was excised and a histopathological diagnosis of cavernous angioma with intracerebral hematoma was made. Case 3, the 49-year-old sister of Case 1, suddenly fell into a coma and was admitted immediately. X-ray CT revealed a large pontine hemorrhage. She died on the 4th day of hospitalization without operative treatment. Necropsy was not carried out. Case 4, the 39-year-old sister of Case 1, was asymptomatic, however, she was examined on the supposition of a familial occurrence of intracerebral cavernous angioma. On examination, it was found she had multiple cavernous angioma without any neurological deficit. X-ray CT revealed parietal intracerebral calcification. MRI demonstrated a mass lesion with peripheral hypointensity ring in the right parietal lobe, and another small lesion in the pons.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Partially thrombosed radiculomeningeal arterio-venous fistula in spinomedullary junction].

A 58-year-old man was admitted to our hospital because of tetraparesis of fairly sudden onset. He had had difficulty in miction since 6 months earlier. MRI study showed a high intensity area in front of the medulla and a low intensity "vessel-like" shadow in front of the upper cervical region on T1-weighted image. The dorsal part of the medulla and cervical spinal cord showed diffuse low intensity signals in T1-weighted image. The intra-axial lesion appeared as high intensity signals in T2-weighted image. Angiography revealed a huge dilated vascular malformation fed by a third part of the right vertebral artery. The lesion in front of the medulla was not opacified. His neurological status progressively deteriorated, resulting in combined respiratory distress. Emergency surgery was performed only for posterior decompression. Although postoperative balloon catheterization was scheduled, he died of gastric perforation and pancreas necrosis one month after the operation. At the autopsy, it was found that the feeding artery of the AVM was branched from the junction of V3 and V4 of the right vertebral artery, where the artery penetrates the dura mater. The meningeal artery was engorged, and the radicular vein of C1 was markedly dilated due to the retrograde filling. The premedullary vessel was thrombosed, but the cervical part of the AVM showed eccentric hypertrophy of the wall and a partially organized thrombus. Intra-axially, the posterior funiculus was markedly destroyed and the spinal cord was edematous and subnecrotic.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Angiography↗

[Comparative study of in vitro diagnosis by the skinned fiber test and clinical diagnosis of malignant hyperthermia].

Skeletal muscles from twenty patients suspected of malignant hyperthermia during general anesthesia were examined with the skinned fiber test for abnormality in the Ca2+ release function of their sarcoplasmic reticulum, and the result was correlated with the classifications of the patients in accordance with the clinical criteria now used in Japan. Among them, fourteen patients were diagnosed as clinical malignant hyperthermia syndrome (fulminant syndrome: 4, abortive syndrome: 10). Three out of four fulminant cases showed potentiated Ca-induced Ca release mechanism of the sarcoplasmic reticulum in their skeletal muscles. The others including six patients not diagnosed as malignant hyperthermia were normal in the sarcoplasmic reticulum function. This suggests that the skinned fiber test has comparatively high sensitivity to fulminant malignant hyperthermia syndrome. The present paper discusses, based on the present results, the problems resulting from the difference in diagnostic concept between in vitro criteria by the skinned fiber test to detect a specific pathogenetical factor in the skeletal muscle of a single abnormality and clinical criteria to pick up a series of relatively non-specific symptoms and signs of a clinical syndrome.

Adolescent↗

[Experimental simulation study on EC-IC bypass: Part 2, Hemodynamics of superficial temporal artery and clinical application of the stenosis model].

In the preceding paper, Part 1, hemodynamics of the internal carotid artery stenosis and their changes after EC-IC bypass have been simulated and discussed in hydraulic and theoretical vascular models. In this study, theoretical model simulation has been advanced and applied to evaluate possible hemodynamic changes due to systemic blood pressure drop and to discuss the difference in efficacy between bypass and pressure elevation for its treatment. Dimensions of the STA have been referred to sometimes in relation to the technical problems for anastomosis but rarely for its cut bypass flow values. A hydraulic model of the STA has been manufactured with silicone and glass tubes to determine the relations between dimensions and cut bypass flow of STA. This was done because cut bypass flow is one of the important factors to be considered when speculating bypass capacity. STA main trunk is assumed to be 50 mm in length and 2 mm in inner diameter, and its branches reaching anastomosis sites about 40 mm in length. Effects of such factors as number of branches (single or double anastomosis), inner diameter and length are measured in this model to determine their effects on STA cut flow. In addition to these two problems, cortical arterial pressure and STA bypass flow are measured and compared to each other to determine in what hemodynamic conditions EC-IC bypass should be performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

[A case of radiation-induced intracranial fibrosarcoma with repeated episodes of intratumoral hemorrhage].

A fibrosarcoma developed 10 years after radiotherapy for craniopharyngioma in a 19-year-old girl is reported. The mode of presentation in this patient was unique. She had repeated episodes of intracranial bleeding which mimicked hemorrhagic cerebral infarction, and there was also an extremely rapid regrowth of the tumor after each resection. Chemotherapy with ACNU, cisplatin and adriamycin was transiently effective in the stormy course of this patient. The occurrence of radiation induced intracranial tumor should be kept in mind in the follow up study of patients with benign brain tumors who have received radiation therapy.

Adult↗

[An experimental study on subrenal capsule assay (SRCA)--problems for the use of immunosuppressive agents].

We studied whether or not cyclosporin A (CSA) has a usefulness in subrenal capsule assay (SRCA) with normal immunocompetent mice. Sixty mg/kg of CSA was given to BDF1 mice daily subcutaneously, and various dosages of adriamycin (ADR) was given intravenously on day 2. The body weight of BDF1 mice decreased over 20% within ten days when ADR was given at more than 5 mg/kg. MX-1, a human breast carcinoma line is known to be sensitive to ADR. This tumor was implanted subcutaneously in the back of BALB/c nu/nu mice and chemosensitivity was tested against ADR. ADR resulted to be positive at the dose of 8 mg/kg. On the contrary, the dose of 5 mg/kg proved to be negative, and hence the result of SRCA would be false negative, if the dose of ADR is reduced to avoid the toxicity of CSA. The tumor grew slowly when only 60 mg/kg of CSA was given daily for three weeks, and the inhibition rate was 56.2%. The toxicity of CSA was neglected because of the body weight loss was approximately 13%. CSA may have the antitumor effect by itself, and we therefore suggest that the CSA is not useful for SRCA.

Adenocarcinoma↗

[Delayed neuronal dysfunction after recirculation of cerebral ischemia].

Delayed neuronal deterioration of recovered neuronal function from cerebral ischemia was investigated in experiments using 25 cats. The neuronal function was evaluated by direct cortical response (DCR) and EEG. To induce cerebral ischemia clamps were applied to both the innominate and left subclavian arteries and were removed 15 minutes after complete loss of DCR. Following recovery of circulation, DCR and EEG were studied for at least 48 hours, along with the changes of cerebral blood flow (CBF) and intracranial pressure (ICP). In 7 of 25 cats CBF gradually or rapidly decreased after it was regained through recirculation due to the increase of ICP, resulting in no recovery of neuronal function. In the other 18 cats normal values of CBF and ICP were observed soon after the recirculation although temporary increase of ICP was found. The recovery of DCR and EEG was observed in 12 of these 18 cats, and these functions were maintained up to the end of the experiment in 9 of these 12 cats. In the other 3 cats and another 5 cats in which only DCR was recovered, these neuronal functions deteriorated 8 to 30 hours after recirculation. In one cat neither DCR nor EEE was recovered at all. Moreover, in the 9 cats mentioned ICP gradually increased before or after the deterioration of neuronal functions, and it finally reached the level of systemic blood pressure. These results indicate that the recovery of neuronal function from ischemic insults must be judged at least 48 hours after recirculation because of delayed neuronal deterioration, and pathogenesis of delayed neuronal dysfunction and delayed increase of ICP must be fully investigated thereafter.

Animals↗

[Biphenotypic leukemia in childhood--analysis of 19 cases].

The leukemic cells of 19 patients (pts) out of 180 children with acute leukemia expressed both CD 19 (B 4) and CD 13 (MY 7) antigens. These biphenotypic leukemias (BiL) were divided into 3 groups on the basis of clinical features, antigen profiles and karyotypes. GroupI pts (N = 6) were infants under one year of age with high initial white blood cell (WBC) count over 200,000/microliters. The blasts of this group did not express CD 10 (J 5) antigen. In 4 of these pts, the blasts initially did not express CD 13 antigen, however, they became strongly positive after short-term culture without stimulation. Cytogenetic analysis revealed a breakpoint at 11 q 23. Group 11 pts (N = 6) were often school age and had a high WBC count over 100,000/microliters and CD 10 positive blasts. The blasts of 4 pts did not express CD 13 antigen until short-term culture. Cytogenetic marker was Ph1 chromosome. Group III pts (N = 7) were often preschool age and the WBC count was lower than that of other groups. The blasts expressed CD 10 antigen with normal karyotypes or various karyotype abnormalities. Prognosis of pts with BiL was more poor than that of CD 13- common ALL, and among 3 groups survival of Group I and II was significantly shorter than that of group III. This study suggests that childhood BiL represents heterogeneous leukemias. It is important to distinguish BiL in childhood acute leukemia and further divide into the groups in order to establish an adequate therapy for prognostically poor BiL.

Adolescent↗