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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 487 records · Page 27Linked to original sources

Establishment of a new cell line derived from a human gliosarcoma.

A permanent cell line, GI-1, was established from a human gliosarcoma, and its characteristics were investigated. The original tumor was a mixture of two different neoplasms which had components of both glioma and sarcoma. The established cell line expressed various mesenchymal antigens, but not neuroepithelial antigens. It was noted, however, that the cell line produced tumors with the morphological features of human glioma after inoculation in athymic mice. The contrast of the pathological characteristics in tissue culture and in xenograft was unique, and this finding suggests that the GI-1 cell line may have the features of both glioma and sarcoma.

Aneuploidy↗

Preventive effect of synthetic serine protease inhibitor, FUT-175, on cerebral vasospasm in rabbits.

The effect of the synthetic multiserine protease inhibitor FUT-175 on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated in rabbits. The SAH in rabbits was simulated by a single injection of autologous arterial blood into the cisterna magna, and, for 7 days, the caliber of each basilar artery was examined several times via angiogram. In 10 SAH rabbits, the peak of the arterial narrowing was observed on Day 2. In this model, the effect of intravenous administrations of FUT-175 was examined. Twenty-seven SAH rabbits were randomly divided into three groups, and 3 doses of 1, 2, or 3 mg of FUT-175 were administered intravenously. Angiographic arterial narrowing on Day 2 in nontreated SAH rabbits (Control) was 35% compared with 21, 5, and 14% in rabbits treated with a total of 3 (Group A; n = 9), 6 (Group B; n = 13), and 9 mg (Group C; n = 5) of FUT-175, respectively. There were statistically significant differences in the arterial calibers between Group A and the Control on Days 1 and 2, between Group B and the Control from days 1 to 4, and between Group C and the Control from days 1 to 4. In three other rabbits, after vasospasm reached its maximum on Day 2, no vasodilatory effect was observed when a total of 6 mg of FUT-175 was administered intravenously. The results indicate that the inhibition of the plasma serine protease cascades at an early stage of SAH prevents the development of cerebral vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Therapeutic trial of cerebral vasospasm with the serine protease inhibitor, FUT-175, administered in the acute stage after subarachnoid hemorrhage.

The therapeutic effect of the synthetic serine protease inhibitor, FUT-175, on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated. Twenty-three patients with severe SAH who were admitted between February and July 1990 and who underwent surgery within 48 hours of the initial aneurysmal rupture were treated with an intravenous administration of FUT-175 soon after the operation. The patients were divided randomly into three groups, each receiving a different dose of FUT-175 (Group A, 20 mg every 12 hours for 4 days; Group B, 20 mg every 6 hours for 4 days, Group C, 40 mg every 6 hours for 4 days). The results were compared with another group of twenty-two patients with severe SAH who were admitted before February 1990 and received equivalent treatment, except they were not treated with FUT-175. In 64% of all the patients treated with FUT-175 (Groups A, B, C), and in 85% of those treated with higher doses of FUT-175 (Groups B and C), there was no spasm or only mild vasospasm on the angiogram. The incidence of a delayed ischemic neurological deficit significantly decreased from 55% in the control group to 13% in all patients treated with FUT-175 and to 7% in the patients treated with higher doses (P less than 0.05). The incidence of cerebral infarction resulting from vasospasm significantly decreased from 43% in the control group to 9% in patients treated with FUT-175. In the patients treated with higher doses of FUT-175 (Groups B and C), none developed cerebral infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Human glioma-specific antigens detected by monoclonal antibodies.

Three murine monoclonal antibodies, designated GA-17, GB-4, and GC-3, were prepared by the hybridization of murine myeloma cells (NS-1) and spleen cells of BALB/c mice immunized with the crude membrane fraction of cultured human gliosarcoma cells (GI-1). Two of them (GA-17 and GB-4) reacted exclusively with the membrane of glioma cells, and the other (GC-3) reacted with the membrane of glioma cells and a T cell line (MOLT-4). Although these antibodies reacted with almost all of the gliomas, the reactions differed. GA-17 reacted equally well with all glioblastoma (17 cases) and low-grade astrocytoma (10 cases), whereas GB-4 reacted poorly with 7 cases of glioblastoma and GC-3 did not react with 7 cases of low-grade astrocytoma. The antigens, exclusively expressed on the cell surface, were analyzed by surface labeling with 125I followed by a cell lysis and immunoprecipitation with these antibodies. The findings obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that GA-17, GB-4, and GC-3 reacted with Mr 140,000-145,000, Mr 160,000, and Mr 145,000-150,000 proteins, respectively. Some evidence has been obtained indicating that these antigens are composed of the same polypeptide chain (Mr 120,000) with the carbohydrate chains being different.

Animals↗

Involvement of the external carotid arteries in moyamoya disease: neuroradiological evaluation of 66 patients.

Arterial stenoses and/or occlusions in moyamoya disease are mainly localized intracranially, although some instances of stenotic lesions of the extracranial arteries have been reported in some autopsy cases. We have reviewed the angiograms of 66 patients with moyamoya disease to investigate whether stenotic lesions are present in the external carotid artery and its branches. We noticed that 13 patients had stenoses in the branches of the external carotid artery, although no occlusions were recognized. This result indicates that the arterial stenoses and/or occlusions are not confined to the intracranial arteries and that systemic factors contribute to the pathogenesis of moyamoya disease. This result also suggests that studies on specimens of the superficial temporal artery, which can be obtained easily at surgery, may reveal the molecular mechanism of intimal thickening.

Adolescent↗

Mechanism of interferon gamma-induced protection of human gliosarcoma cells from lymphokine-activated killer lysis: division of lymphokine-activated killer cells into natural killer- and T-like cells.

The mechanism by which interferon gamma (IFN-gamma) decreases the susceptibility of the established cultured gliosarcoma line Gl-1 to lymphokine-activated killer (LAK) lysis was analyzed. The results of monolayer depletion and lectin-dependent cellular cytotoxicity assays by LAK cells revealed that the resistance to LAK lysis of IFN-gamma-treated Gl-1 cells is manifested at the stage of LAK cell target recognition alone. We have also divided LAK cells into populations of phenotypically natural killer (NK)- and T-like cells with monoclonal antibodies and complement, respectively. We have used these cells to examine the mechanism of IFN-gamma-induced protection of Gl-1 cells from LAK lysis in cold target inhibition, monolayer depletion, and direct binding assays. The results revealed that NK-like cells do not recognize IFN-gamma-treated Gl-1 cells as efficiently as they do untreated targets, whereas T-like cells show the opposite tendency. In conclusion, we have demonstrated that the IFN-gamma induced protection of tumor cells from LAK lysis is predominantly regulated by the target recognition of NK-like cells. On the other hand, IFN-gamma-treated tumor cells may bind to T-like cells but fail to trigger them to initiate further stages for lysis as effectively as NK-like cells.

Cell Division↗

Human cytochrome P450IIE1 gene: DraI polymorphism and susceptibility to cancer.

Human cytochrome P450IIE1 (CYP2E) is involved in the metabolic activation of procarcinogens such as N-nitrosodimethylamine, benzene and ethyl carbamate. We screened DNA from 28 individuals for restriction fragment length polymorphisms (RFLPs) is the human P450IIE1 gene and detected an RFLP for the restriction endonuclease DraI. The distribution of the genotypes of this polymorphisms among lung cancer patients (n = 74) differed from that among controls (n = 73) with statistical significance of p < 0.05. In addition, the distribution among patients with cancers of the digestive system (n = 38) was also different from that among controls. Our findings indicate an association between the DraI polymorphism of the IIE1 gene and susceptibility to cancers of the lung and the digestive system.

Cytochrome P-450 CYP2E1↗

Immunological studies on opportunistic infection and the development of adult T-cell leukemia.

Three patients with opportunistic infection preceding adult T-cell leukemia (ATL) are presented: a 66-year-old woman with cryptococcosis and Pneumocystis carinii pneumonia, a 46-year-old man with Pneumocystis carinii pneumonia, and a 55-year-old woman with cryptococcosis. Although, at the first examination, the first two had smoldering type ATL and the third case was an HTLV-I carrier, all three developed overt ATL 14-16 months after the onset of opportunistic infection. It is considered that there is immune suppression already present in HTLV-I carriers and in patients with smoldering ATL, and opportunistic infection is predictive of the development of ATL.

Aged↗

Aneurysm arising at the triplicate anterior communicating artery--case report.

A very rare case of triplicate anterior communicating artery associated with ruptured aneurysm in a 21-year-old female is reported. The triplicate configuration was not predicted by preoperative cerebral angiography, but found intraoperatively. The aneurysm was trapped successfully, and she recovered with no neurological deficit.

Adult↗

Rapid morphological changes in bovine brain microvascular endothelial cells on extracellular matrices.

The morphological changes in endothelial cells derived from bovine brain microvasculature, carotid artery, and aorta during growth on extracellular matrices were compared. All cells formed tubular structures on a basement membrane. Ultrastructural studies showed that the tubular structures had lumens surrounded by many endothelial cells. On type I collagen gel, brain microvascular endothelial cells still formed tubular structures, but the other two cell types formed confluent monolayers. However, when a second layer of collagen gel was laid over these cells, tubular structures developed within 2-3 days. Brain microvascular endothelial cells form tubular structures more readily than endothelial cells derived from large vessels on both basement membrane and type I collagen gel.

Animals↗

Treatment of unclippable giant posterior cerebral artery aneurysms with detachable balloons--report of three cases.

Three patients presented with rare giant posterior cerebral artery aneurysms, clinically manifesting as cerebral ischemia, mass effect, and subarachnoid hemorrhage. All aneurysms were partially thrombosed, originated at the P2 segment, and possessed broad necks. Surgical neck clipping was difficult but proximal occlusion of the parent artery was feasible. Aneurysm occlusion sparing the parent artery was attempted in all cases, but failed because the detachable balloon did not successfully block the aneurysmal neck. All patients tolerated test occlusion at the P2 segment, so the parent artery was occluded proximally with detachable balloons, leaving the important perforating arteries unaffected. Two transient ischemic attacks were associated with the procedure. Where surgical treatment is unusually difficult, and proximal ligation or trapping just feasible, embolization with detachable balloons is an acceptable substitute.

Adolescent↗

Skull base metastasis from gastric cancer--case report.

A 48-year-old male presented with a metastatic skull base tumor located on the right of the clivus and the sphenoid sinus, which originated from adenocarcinoma of the stomach. The initial symptom was abducens nerve paralysis and there were no symptoms of upper gastrointestinal tract throughout the course. This gastric cancer, which rarely metastasizes to the central nervous system or osseous system, caused multiple bone metastases which produced the neurological symptoms.

Carcinoma↗

Synthesis of radiopaque cyclophosphazene monomers, properties of bulk polymers and their application to composite resin.

A series of studies was conducted on the synthesis of polyfunctional cyclophosphazene monomers having radiopacity and a polymerization group in the same molecule, and their properties and applicability to composite resin were examined. Using octachlorocyclotetraphosphazene, P4N4Cl8 (4PNC), monomers were synthesized by replacing the 1-4 of chlorine (Cl) with p-bromophenol (BrC6H4OH, BrPh), and replacing the residual number of Cl, 7-4, with 2-hydroxyethyl methacrylate [CH2:C(CH3)COOCH2CH2OH](HEMA), so as to obtain four kinds of transparent monomer having radiopacity and a polymerization group in the same molecule. We then analyzed these monomers and examined their physical properties after bulk-polymerization. Next, we prepared an organic composite filler using 4PN-(BrPh)3-(EMA)5 monomer, which showed comparatively good radiopacity, to produce a new experimental radiopaque composite resin. Although radiopacity improved in accordance with the increase in the number of BrPh molecules replaced, the mechanical properties of the polymer became poorer. Similarly it was proved that the radiopacity of composite resin made with 4PN-(BrPh)3-(EMA)5 monomer was equivalent or even superior, compared with the radiopacity of the front tooth. Consequently, it was shown that these synthesized monomers can be applied to visible light-cured radiopaque composite resin.

Bisphenol A-Glycidyl Methacrylate↗

Classification of the callus in limb lengthening. Radiographic study of 35 limbs.

35 calluses formed during limb lengthening were classified radiographically into 6 types: external, straight, attenuated, opposite, pillar, and agenetic. The healing indexes correlated well to the intrinsic periosteal and endosteal conditions of each type. This classification enabled us to estimate the intrinsic conditions, predict the healing index, control the daily lengthening speed, and decide to apply early augmentation of the callus.

Adolescent↗

Changes in major phospholipids of mitochondria during postischemic reperfusion in rat brain.

Major mitochondrial phospholipids were examined in rat brain after 30 minutes of reperfusion following 30- or 60-minute periods of ischemia to examine their changes and explore their relationship to mitochondrial dysfunction during postischemic reperfusion. The amount of phospholipids and the percentage of polyunsaturated fatty acid chains, which tended to decrease during 30 minutes of ischemia, recovered after reperfusion. However, after ischemia lasting for 60 minutes, these parameters did not recover but decreased further, suggesting progressive disruption of phospholipids by phospholipase A2 after reperfusion. These changes were particularly notable in cardiolipin, which is contained specifically in mitochondria. The changes were also closely associated with mitochondrial respiration and respiratory enzyme (cytochrome c oxidase and F0F1-adenosine triphosphatase) activities, which have been known to correlate with the amount of cardiolipin. These results suggest that phospholipid metabolism in mitochondrial membranes is an important factor bearing on the integrity of energy metabolism during postischemic reperfusion.

Adenosine Triphosphatases↗

Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial.

With the cooperation of 60 neurosurgical centers in Japan, a prospective randomized placebo-controlled double-blind trial of a new calcium antagonist AT877 (hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, or fasudil hydrochloride) was undertaken to determine the drug's effect on delayed cerebral vasospasm in patients with a ruptured cerebral aneurysm. A total of 276 patients, who underwent surgery within 3 days after subarachnoid hemorrhage (SAH) of Hunt and Hess Grades I to IV, were entered into the study. Nine patients were excluded because of protocol violation. The remaining 267 patients received either 30 mg AT877 or a placebo (saline) by intravenous injection over 30 minutes, three times a day for 14 days following surgery. Demographic and clinical data were well matched between the two groups. It was found that AT877 reduced angiographically demonstrable vasospasm by 38% (from 61% in the placebo group to 38% in the AT877 group, p = 0.0023), low-density regions on computerized tomography associated with vasospasm by 58% (from 38% to 16%, p = 0.0013), and symptomatic vasospasm by 30% (from 50% to 35%, p = 0.0247). Furthermore, AT877 reduced the number of patients with a poor clinical outcome associated with vasospasm (moderate disability or worse on the Glasgow Outcome Scale at 1 month after SAH) by 54% (from 26% to 12%, p = 0.0152). There were no serious adverse events reported in the AT877 group. This is the first report of a placebo-controlled double-blind trial that has demonstrated a significant reduction in angiographically revealed vasospasm by intravenous drug therapy.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Correlation of basic fibroblast growth factor expression levels with the degree of malignancy and vascularity in human gliomas.

Basic fibroblast growth factor (FGF) is a mitogen, a differentiation factor for neuroectoderm-derived cells, and a potent angiogenic factor. The authors have previously demonstrated that the messenger ribonucleic acid of basic FGF is expressed in more than 90% of human gliomas. In the present study, they examined the expression of basic FGF in human glioma tissues using immunohistochemical techniques with a mouse monoclonal antibody against human basic FGF. They also correlated the basic FGF level with the histological grades of malignancy assessed by the number of nucleolar organizer regions (NOR's). Basic FGF was detected in 18 of 19 gliomas, whereas it was undetectable in two normal brains. The expression level of basic FGF peptide increased proportionally with the degree of malignancy. There was also a tendency for the number of NOR's in glioma cells to increase in glioma samples with a high level of basic FGF expression. Furthermore, most of the cases with increased vascularity demonstrated on cerebral angiograms showed a relatively high level of basic FGF expression of tumor cells and a large number of NOR's in endothelial cells in tumor tissues. These results suggest that basic FGF is actually produced in most gliomas and is involved in tumorigenesis and malignant progression as an autocrine growth factor. Moreover, basic FGF may play an important role in tumor neovascularization as a paracrine angiogenic factor.

Animals↗

Selection and combination of various endovascular techniques in the treatment of giant aneurysms.

Between April, 1989, and January, 1991, a total of 19 cases of giant aneurysm were treated by the endovascular approach. The patients included seven males and 12 females aged 15 to 72 years. Detachable balloons, occlusion coils, and ethylene vinyl alcohol copolymer liquid were used as embolic materials. In seven cases, thrombosis of the aneurysmal sac and/or base was achieved while sparing the parent arterial flow, complete obliteration of the aneurysm was achieved in four of these. Of these four patients, the thrombotic material was a detachable balloon in two, a combination of a detachable balloon and coils in one, and occlusion liquid in one. In the other three cases, complete occlusion was not achieved; one aneurysm was occluded with a detachable balloon and two with coils. In 11 patients, the parent artery was occluded either by trapping or by proximal arterial occlusion, and all patients showed complete occlusion of the aneurysms. In one patient, a combined bypass procedure and parent artery occlusion was performed. Among the 19 cases in this series there were four transient ischemic attacks, one reversible ischemic neurological deficit, and one death due to aneurysmal rupture during the procedure. Two patients died in the follow-up period, one from pneumonia 2 months postoperatively and the other from acute cardiac failure 2 weeks following surgery. Both deaths were unrelated to the endovascular procedure. It is concluded that the endovascular treatment of giant aneurysms remains difficult because of the large and irregular shape of the aneurysmal base and thrombus in the aneurysmal sac. The proper selection and combination of the available endovascular techniques is therefore of critical importance.

Adolescent↗