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Biomedical subjects

K Iwasaki

Publications and source records attributed to K Iwasaki.

At least 19 recordsLinked to original sources

Effects of the N-methyl-D-aspartate antagonists on the rise in [Ca2+]i following depolarization in aged rat brain synaptosomes.

The effects of non-competitive NMDA antagonists, MK-801 and dextrorphan in relation to the rise in intracellular Ca2+ concentrations ([Ca2+]i) after stimulation with 15 mM K+ in whole brain synaptosomes from young (3 months old) and aged (24 months old) Fisher344 rats were examined. A fluorescent chelating agent, Rhod-2, was employed to monitor any alterations of K(+)-evoked [Ca2+]i. In young rats, the rise in [Ca2+]i following depolarization was affected by neither dextrorphan (1, 10, 100 microM) nor MK-801 (0.1, 1, 10 microM), while in aged rats, 1 microM dextrorphan and 0.1 microM MK-801 brought about a significant increase in [Ca2+]i following depolarization. In low Mg2+ medium, 10 microM MK-801 and 100 microM dextrorphan significantly inhibited the rise in [Ca2+]i after stimulation with 15 mM K+ in young rats, while neither dextrorphan nor MK-801 could affect the rise in [Ca2+]i significantly in aged rats. When 100 microM NMDA was applied in a medium containing 1.2 mM Mg2+, the rise in [Ca2+]i following depolarization was slightly inhibited by 1 microM MK-801 in young rats, but it was not inhibited significantly by dextrorphan. In aged rats, both 100 microM dextrorphan and 10 microM MK-801 strongly inhibited the rise in [Ca2+]i following depolarization in the presence of 100 microM NMDA. Instead of NMDA, when 100 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), a non-NMDA receptor agonist, was applied, dextrorphan did not inhibit the rise in [Ca2+]i. In low Mg2+ medium, 100 microM NMDA potentiated the inhibitory effect of 10 microM dextrorphan in young rats, while 100 microM dextrorphan or MK-801 did not show any further inhibition by adding 100 microM NMDA. The addition of 100 microM AMPA did not affect the effect of dextrorphan in a low Mg2+ medium in young rats. These results suggest that NMDA antagonist-mediated [Ca2+]i homeostatic system may alter through aging. In addition, the findings that NMDA potentiated the inhibitory effect of NMDA antagonist, which being further potentiated by aging or lowered extrasynaptosomal Mg2+, indicate the possibility that the Mg2+ block to NMDA receptors might be attenuated through aging.

Aging

The facilitating and suppressing effects of delta 9-tetrahydrocannabinol on the rise in intrasynaptosomal Ca2+ concentration in rats.

The effects of delta 9-tetrahydrocannabinol (delta 9-THC) on the rise in intracellular Ca2+ concentrations ([Ca2+]i) after stimulation with 15 mM or 29 mM K+ in rat whole brain synaptosomes were examined. A fluorescent chelating agent, Rhod-2, was employed to monitor any alterations of K(+)-evoked [Ca2+]i. Pretreatment with 10(-10) M delta 9-THC for 3 min enhanced K(+)-evoked [Ca2+]i significantly, while 10(-9), 10(-8) or 5 x 10(-8) M delta 9-THC significantly inhibited the K(+)-evoked [Ca2+]i. These results suggest that delta 9-THC had a biphasic effect on the K(+)-evoked Ca2+ response in rat brain synaptosomes.

Animals

Survey of 1120 Japanese women with a history of recurrent spontaneous abortions.

Our recent 7-year clinical survey showed that among the 1120 women with repeated spontaneous abortions registered in this clinic, 2898 out of a total of 3216 pregnancies (90.1%) had terminated in spontaneous abortion. Among these wastages, 84.2% occurred before 12 weeks of gestation, and 11.1 percent occurred between 12 and 15 weeks. Through routine examination of reproductive wastage, 82 (9.9%) of the 825 Japanese couples examined were shown to have either a chromosomal abnormality or normal variants in the wife and/or husband, thus demonstrating no racial difference in the incidence of chromosomal abnormalities in infertile patients in comparison with studies performed in other countries. One hundred and forty-seven congenital uterine anomalies (14.7%) were found in 1000 hysterosalpingographies, and 12 of 148 examined females were positive for anti-cardiolipin antibody. 393 other females with no major abnormalities likely to induce spontaneous abortions were indicated for immunotherapy. Ample time spent on genetic counseling prevented further reproductive wastage, and ideal metroplasty resulted in a successful post-operative pregnancy course in more than 85% of cases. Immunosuppressant and anticoagulant therapy decreased the serum titer of anti-cardiolipin antibody, enabling pregnancies to be maintained to term. Immunotherapy utilizing the husband's lymphocytes also brought more than 80% of pregnancies to successful completion, with 200 deliveries achieved with this therapy. In contrast, 64.1% of pregnancies again terminated spontaneously in patients who were indicated for immunotherapy but did not receive treatment. The findings of the present study suggest that the causes of reproductive wastage, especially the etiology of early recurrent spontaneous abortion, are complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Habitual

Analysis of the close relationship between human astrocytoma-specific antigens detected by murine monoclonal antibodies and c-kit proto-oncogene product.

Tyrosine-specific phosphorylated proteins found exclusively on the cell surface of human astrocytomas were previously identified with murine monoclonal antibodies, designated as GA-17, GB-4 and GC-3. The purpose of this study was to further characterize the antigens and investigate the relationship between them and c-kit protooncogene product. We demonstrated that the antigens had protein kinase activity. Moreover, GA-17 reacted with c-kit protein expressed on the membrane of A172 human glioblastoma cells.

Antibodies, Monoclonal

HNK-1 expression pattern in normal and bis-diamine induced malformed developing rat heart: three dimensional reconstruction analysis using computer graphics.

The spatiotemporal distribution of the immunoreactivity of monoclonal antibody HNK-1 was investigated immunohistochemically in normal and bis-diamine-induced malformed rat embryonic hearts using three-dimensional reconstruction with computer graphics. First recognized in the primitive heart 11.5 days after conception, HNK-1 immunoreactivity was distributed in the atrio-ventricular and bulbo-ventricular junctional areas with incomplete ring-like appearance in the early embryonic stages. In the late embryonic stages the immunoreactive sites were rearranged and localized in the sites topographically corresponding to almost the entire pathway of the conduction system, including the three major internodal tracts connecting the right sinoatrial node and atrioventricular node. Immunoreactivity gradually decreased after the completion of the conduction system, and only a faint reactivity in the atrio-ventricular node region remained in the new-born heart. These results indicate that HNK-1 is expressed temporarily in the pathways corresponding to the conduction system during the development of the heart. In bis-(dichloroacethyl)-octamethylen-diamine (bis-diamine)-induced malformed hearts, localization of HNK-1 immunoreactivity was not remarkably altered in the early embryonic heart. In the late embryo, immunoreactive sites in the sino-atrial node region and atrio-ventricular node region deviated dorsocaudally with the poorly developed internodal tracts, and abnormal distribution was observed in the bilateral atria. We consider that these abnormalities may occur in conjunction with abnormal morphological development such as insufficient absorption of the sinus venosus.

Animals

A case of linitis plastica of the rectum treated by pelvic exenteration after aggressive immunochemotherapy.

Multidisciplinary treatment was administered to a 32 year-old man with primary linitis plastica of the rectum, which was considered inoperable due to an extensive local spread at the first operation. Thirty KE of OK-432 was injected into the tumor per week (total 90-KE) and 5 KE of OK-432 was inoculated into the intracutaneous space per week (total 125 KE). Also methotrexete (MTX 50 mg) and 5-FU (500 mg) combined were given each week by intra-arterial infusion (total 20 courses). After this immuno-chemotherapy the CEA decreased from the pretreatment value of 12.7 ng/ml to 3.6 ng/ml and the tumor size was reduced. A total pelvic exenteration could then be performed almost curatively. As a result, this patient was able to return to the society with a better quality of life and has survived for 20 months since presentation.

Adult

Bone marrow plays a role in bone metabolism: histomorphometry of iliac bone in postmenopausal women.

We conducted a histomorphometrical study on the role of the bone marrow in cancellous bone metabolism using iliac bone specimens from 79 postmenopausal women. A gradual decrease in hematopoietic tissue of the bone marrow was proportionate to the decrease in cancellous bone and the ratio of osteoid perimeter/bone perimeter regardless of age. On the other hand, the ratio of eroded perimeter/bone perimeter remained almost steady until hematopoietic tissue decreased significantly. These findings suggest that a change in the bone marrow, that is, a decrease in hematopoietic tissue, causes an imbalance in bone formation and resorption and leads to bone loss.

Aged

Accessory nerve neuroma presenting as recurrent jugular foramen syndrome.

We report a patient with spontaneous recovery and recurrence of a jugular foramen syndrome secondary to an accessory nerve neuroma. He showed sudden onset of unilateral palsy of the ninth, tenth and eleventh cranial nerves in 1982. He recovered almost fully and in 1990 the palsies recurred. MRI revealed a small mass in the right jugular foramen. The tumour was resected via suboccipital craniectomy, and diagnosed as a neuroma of the eleventh cranial nerve.

Accessory Nerve

Intraventricular craniopharyngioma: report of two cases and review of the literature.

Two unusual cases of purely intraventricular craniopharyngioma are presented. Both patients complained of headache as a sign of increasing intracranial pressure, but neither other neurological deficits nor hormonal disorders were present. Magnetic resonance images showed a mass lesion located within the third ventricle. Surgery confirmed that these two tumors were completely confined within the third ventricle, and histologically they proved to be squamous papillary craniopharyngiomas. Review of the literature demonstrates that craniopharyngiomas at this location have many common features and would appear to form a distinct entity.

Adult

Angiosarcoma of the thigh with thrombosis in the femoral artery.

We report a case of angiosarcoma with some peculiar clinical features developing on the left thigh of a 63-year-old man. The early primary lesion was erythematous with necrotic areas. The initial biopsy specimen of the lesion indicated a benign angioproliferative process. However, the necrotic area enlarged rapidly, ulcerated with severe pain, and thus was widely excised. The excised specimen had a malignant histologic appearance, particularly in the fascia, and was diagnosed as angiosarcoma. Following local recurrence, the lesion was complicated by thrombosis of the femoral artery at the affected site. A similar cutaneous lesion subsequently arose on the right lower leg, and thrombosis developed in the right femoral artery. Both legs had to be amputated. There were no distant metastases.

Amputation, Surgical

Immunohistochemical localization of gangliosides in ENU-induced rat glioma.

Biochemical studies have indicated that the structurally simple gangliosides, including GD3 and GM3, are major glycolipid components of glioma tissues. In order to clarify the localization of the gangliosides in ethylnitrosourea-induced rat glioma, an immunohistochemical study was performed using antibodies against GM1, GM3, and GD3. The results obtained in normal fetus, newborn, and adult rat brain, and also in human glioma, were compared. In fetal and newborn rat brain, GD3 was present mainly in the neuroepithelial cell surface of the matrix and subependymal layers of the ventricular wall, but GM3 and GM1 were not detected. In adult rat brain, GD3-positive cells were absent, or present in diminished number, and GM1 was found chiefly in the neuropil of the cerebral cortex. Most of the rat glioma cells were positive for GD3, but not for GM1. It was demonstrated that the ganglioside composition of glioma cells was similar to that of immature neuroectodermal cells in fetal and newborn rat brain. Furthermore, the number of GD3-positive oligodendroglioma cells increased with tumor growth. In anaplastic gliomas and gross oligodendrogliomas, most tumor cells expressed not only GD3 but also GM3. These results suggest that GD3 is a marker of proliferating neuroectodermal cells, and that activity of the key enzymes in ganglioside synthesis alters with tumor growth and anaplastic change.

Adult

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

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

Painful tic convulsif caused by a brain tumor: case report and review of the literature.

Patient with painful tic convulsif caused by a brain tumor is presented. The patient was admitted with right trigeminal neuralgia and ipsilateral facial spasm, i.e., painful tic convulsif. Preoperative computed tomography scans showed no apparent abnormalities; however, surgery revealed that these symptoms were associated with a pearly tumor located in the cerebellopontine angle. Subtotal resection for the decompression of the right trigeminal and facial nerves was performed and resulted in complete relief of the symptoms. Histological examination demonstrated the tumor to be an epidermoid cyst.

Cerebellar Diseases

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

Effects of reperfusion on left ventricular ejection fraction and volume after acute myocardial infarction.

The effects of reperfusion on left ventricular (LV) function and volume were studied in patients with evolving acute myocardial infarction (AMI). We analyzed the LV ejection fraction and volume in patients who had been admitted within 24 h of the onset of their first AMI with culprit lesion of #6, #7 and #1 (American Heart Association classification). Sixty-five patients (Re group) received successful reperfusion therapy within 6 h after the AMI. The other 60 patients (Oc group), who were admitted from 6 to 24 h after the AMI, received conservative therapy. Patients with re-obstruction of the culprit lesion after reperfusion therapy were excluded from the Re group. Patients with spontaneous recanalization following conservative therapy were excluded from the Oc group. The LV ejection fraction (LVEF), LV end-systolic volume index (LVESVI), and LV end-diastolic volume index (LVEDVI) were measured using a modified Dodge's formula by left ventriculography performed 4 weeks after the AMI. LVEF in the Re group was significantly greater than in the Oc group (57 +/- 12 vs 49 +/- 11%) (mean +/- SD, p less than 0.01). LVESVI in the Re group was significantly smaller than in the Oc group (30 +/- 13 vs 38 +/- 16 ml/m2, p less than 0.01). Although LVEDVI was not significantly different between the 2 groups, in patients with a responsible coronary lesion of segment #6, LVEDVI in the Re group was significantly smaller than in the Oc group (67 +/- 14 vs 77 +/- 18 ml/m2, p less than 0.05). Although LVEF and LV volume correlated in both groups, the correlation was weak (r = 0.40-0.42), suggesting that LV volume was not dependent solely on LV functional recovery. The incidence of ventricular aneurysm in the Re group was significantly lower than in the Oc group (15.4 vs 45.0%, p less than 0.01). Multivariate analysis selected reperfusion of the responsible coronary artery as one of the factors significantly associated with a reduction of LVEDVI, LVESVI, an improvement of LVEF, and a decrease in the rate of aneurysm formation. In summary, our results indicated that reperfusion improved EF, reduced LV volume, and decreased the rate of aneurysm formation as compared to non-reperfusion, which suggests that reperfusion therapy is beneficial for both functional recovery and ventricular remodeling.

Adult

Emergency coronary angioplasty for acute myocardial infarction--factors affecting acute restenosis in catheterization laboratory and reocclusion during hospitalization.

A total of 107 consecutive patients with acute myocardial infarction underwent emergency coronary angioplasty (PTCA). Restoration of blood flow with TIMI grade III was established by emergency PTCA in 101 patients (94.4%). "Acute restenosis" was defined as a lesion that, when dilated to less than 50%, narrowed again to more than 75% luminar reduction 5 min after the balloon inflation. Acute restenosis occurred in 39 patients (39%). Multivariate analysis selected 3 factors associated significantly with an increased rate of acute restenosis: (1) dissection, (2) small balloon/artery diameter ratio and (3) low systolic blood pressure during PTCA. Reocclusion, which was defined as a total reobstruction of the lesion during hospitalization following emergency PTCA, was examined by predischarge coronary angiography. Acute restenosis correlated significantly with an increase in reocclusion rate. The incidence of documented reocclusion was 12%. Residual stenosis, multivessel disease and irregular dilation correlated significantly with an increased rate of reocclusion. The in-hospital and postdischarge mortalities were 5.6% and 2.1%, respectively. In summary, emergency PTCA produced a high angiographic success rate. Use of adequate balloon size and sufficient dilation correlated significantly with angiographic outcome in emergency PTCA. Patients with acute restenosis, high residual stenosis, irregular dilation, and multivessel disease would have a relatively high risk of reocclusion.

Adult

Effect of nebracetam on the disruption of spatial cognition in rats.

Central cholinergic hypofunction causes the disruption of spatial cognition, while cholinomimetics improve this disruption in rats. Scopolamine (0.5 mg/kg, i.p.) has also been reported to disrupt radial maze performance in rats. Nebracetam (WEB 1881 FU), a new nootropic candidate, was able to correct this scopolamine-induced disruption of spatial cognition at the dose of 10 mg/kg, p.o. Furthermore, nebracetam enhanced oxotremorine-induced tremors in mice. These results indicate that nebracetam has a cholinergic enhancing effect. The scopolamine-induced disruption of spatial cognition has been previously reported to improve not only by cholinomimetics but also by brain noradrenergic drugs such as L-threo-DOPS and amantadine. Nebracetam reversed the change of brain noradrenaline contents in the frontal cortex and hippocampus in which the noradrenaline content decreased by treatment with scopolamine. Nebracetam also decreased the delta 9-tetrahydrocannabinol (6 mg/kg, i.p.)-induced disruption of spatial cognition, which was reported to be related to the lymbic noradrenergic function. These results suggest that the cognitive enhancing effect of nebracetam involves not only cholinergic mechanisms but also involves lymbic and hippocampal noradrenergic mechanisms.

Animals