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Biomedical subjects

I Nagata

Publications and source records attributed to I Nagata.

At least 235 records · Page 13Linked to original sources

Effects of opioid peptides on the cellular immunity in spleen cells from intact nude mice or nude mice bearing human ovarian carcinoma.

The present study was designed to explore the effects of opioid peptides on the lytic activity of spleen cells from intact nude mice or nude mice bearing human ovarian cancer cells (KF). When the spleen cells from intact nude mice were incubated with various concentrations of opioid peptides, the ability of the spleen cells to lyse the KF cells was significantly stimulated between 0.05 nM and 50 nM concentrations of all opioid peptides used in this study. The degree of stimulation was most marked at 5 nM opioid peptides and the most marked stimulatory effect was obtained by alpha-endorphin. On the other hand, the lytic activity of spleen cells from nude mice challenged with the KF cells was about two-fold higher than that of intact nude mice, suggesting that spleen cells from nude mice challenged with KF cells have KF-cell-specific cytotoxicity. Even if the spleen cells were incubated with any concentration of alpha-endorphin or [Met]enkephalin indicated, the lytic activity remained unchanged. In contrast, only beta-endorphin resulted in a significant increase of the lytic activity between 0.5 nM and 50 nM. These results suggest that opioid peptides play a crucial role in immune surveillance mechanisms.

Animals↗

Restorative effects of calmodulin antagonists on reduced cisplatin uptake by cisplatin-resistant human ovarian cancer cells.

In the present study, we attempted to determine effects of calmodulin antagonists (W-7 and W-5) on cisplatin uptake by human ovarian cancer cells, using KF cells derived from serous cystadenocarcinoma of the ovary and cisplatin-resistant cells (KFr). The degree of cisplatin resistance of the KFr cells was about 3.7-fold higher than that of the parent KF cells, with regard to the concentration of cisplatin required for 50% inhibition of cell proliferation (IC50). When KF and KFr cells were incubated with 10 micrograms/ml cisplatin for 4 hr, cisplatin-content in the KF cells was significantly higher than that in the KFr cells. When KF cells were incubated in the presence of W-7 (but not W-5), cisplatin uptake significantly increased, compared to cells treated with cisplatin alone. On the other hand, when KFr cells were incubated in the presence of 5 micrograms/ml W-7 or W-5, cisplatin uptake was significantly higher than uptake by KFr cells treated with cisplatin alone, being comparable to that by KF cells treated with cisplatin alone. Such an increase in cisplatin uptake seemed to bring about adjuvant effects to cisplatin of KFr cell proliferation in vitro. The KF tumor grown in nude mice took up 24.8 ng/g dry wt of cisplatin 4 hr after intraperitoneal administration. When cisplatin was administered with calmodulin antagonists, cisplatin uptake by the KF and KFr tumors was significantly increased, compared to that after treatment with cisplatin alone. In particular, the cisplatin uptake by the KFr tumor was about 2.5-fold higher than that by the KFr tumor treated with cisplatin alone. These results suggest that coadministration of calmodulin antagonists and cisplatin may be of use in patients with refractory ovarian cancer.

Biological Transport↗

Treatment of a giant aneurysm of the cavernous internal carotid artery associated with a persistent primitive trigeminal artery: case report.

A case of an unruptured giant aneurysm of the cavernous portion of the left internal carotid artery associated with a persistent primitive trigeminal artery (PTA) is presented. The usual surgical approach to giant aneurysms at this site, including ligation of the ipsilateral internal carotid artery (ICA) and an extracranial-intracranial (EC-IC) bypass, was inadequate because of continued blood supply to the aneurysm via the PTA from the vertebrobasilar system. The patient was successfully treated with a combination of EC-IC bypass surgery, ICA ligation, and simultaneous intravascular balloon obliteration of the ICA just distal to the junction of the PTA and immediately proximal to the aneurysmal neck. Follow-up radiological investigations showed thrombosis of the aneurysm.

Carotid Artery, Internal↗

Effects of a dopamine antagonist (metoclopramide) on the release of LH, FSH, TSH and PRL in normal women throughout the menstrual cycle.

To obtain further insight into the role of endogenous dopamine on the adenohypophyseal hormones secretion in normal women, responses of the adenohypophyseal hormones to a dopamine antagonist, metoclopramide, were evaluated in 7 normal women during the early follicular, late follicular and mid-luteal phases of the menstrual cycle. PRL increments following metoclopramide were similar in all phases. During the early and late follicular phases, metoclopramide induced no significant change in circulating LH levels. However, a significant rise in serum LH was observed following metoclopramide during the mid-luteal phase. No significant changes in serum FSH levels were observed after metoclopramide during any of the 3 phases of the cycle. Following metoclopramide, serum TSH levels significantly rose in all phases. TSH increments following metoclopramide were significantly lower in the mid-luteal phase than in the early follicular phase. These results suggest that the modulatory effect of endogenous dopamine on adenohypophyseal hormones secretion is variable and selective throughout the normal menstrual cycle.

Adult↗

Glucose consumption and rate constants for 18F-fluorodeoxyglucose in human gliomas.

To investigate the value of direct measurement of the rate constants by performing 18F-labeled fluorodeoxyglucose (FDG) studies of glucose consumption in human gliomas in vivo, a kinetic method with 3- and 4-parameter rate constant models for FDG uptake was used to analyze data from dynamic scans obtained by positron emission tomography after injection of FDG into 14 patients with glioma. The results were compared with those obtained by the autoradiographic method using 3- and 4-parameter rate constant models. There were no significant differences in the glucose consumption calculated by the four different methods both in the gliomas and in the contralateral intact cortex. It was found that the rate constant k4* could be neglected in calculation of glucose consumption in gliomas as well as in the contralateral intact cortex. The rate constant k3*, an index of hexokinase function, was higher in malignant gliomas than in benign gliomas and was close to that in the contralateral cortex. This study indicates that the 3-parameter autoradiographic method, which is the most common one used in clinical practice, is reliable for the calculation of glucose consumption in human gliomas. Furthermore, direct measurement of the regional rate constants for FDG by the kinetic method was found to be useful for evaluation of the biochemical and physiological characteristics of human gliomas in vivo.

Adult↗

Choriocarcinoma with brain metastasis: report on two cases with long-term survivals.

Choriocarcinoma is a potentially curable neoplasm. Although the presence of brain metastases worsens the ultimate prognosis, aggressive therapeutic intervention is sometimes justified for brain metastases of a potentially curable neoplasm. In the present clinical report, we present two cases of choriocarcinoma with brain metastasis manifesting neurological deterioration, and discuss treatment strategies. From the results of treatment, we conclude that surgical removal of the lesion, followed by chemotherapy combined with irradiation, should be the treatment of choice in patients with progressive neurological deterioration.

Adult↗

[Intraluminal thrombosis and growth-mechanism of giant intracranial aneurysms].

12 giant intracranial aneurysms were studied by MRI. Intraluminal thrombosis was observed in 9 aneurysms. Thrombosis was found more frequently in larger aneurysms. Thrombi were formed posteriorly or inferiorly in the lumen of 4 among 5 IC-cavernous aneurysms. Location of the neck of the aneurysms and stagnation of blood flow influenced by gravity may be causative factors determining the location of thrombi. In 6 aneurysms intraluminal thrombi were inhomogeneous on MRI, suggesting that the thrombi had been formed at different times. New thrombi were formed between the aneurysmal wall and the old thrombus in 3 cases. Dissection of the aneurysmal wall by residual blood flow in the lumen or hemorrhage in the aneurysmal wall may be one of the growth mechanisms of giant intracranial aneurysms.

Adolescent↗

[Therapeutic values of prostaglandin D2 in nude mice bearing human ovarian carcinoma].

In vitro and in vivo effects of prostaglandin D2 on human ovarian cancer growth were examined by using a cell line, designated HR, derived from ascites of patient with serous cystadenocarcinoma of the ovary. The HR cell proliferation in vitro was dose-dependently inhibited at prostaglandin D2 concentrations between 0.1 and 4.0 micrograms per ml. The results of a 51Cr-release assay seemed to indicate that the inhibition resulted from a direct cytotoxic effect exerted by prostaglandin D2. All DNA, RNA, and protein synthesis by the HR cells was also inhibited in a dose-dependent manner with 48 hr exposure to prostaglandin D2. When nude mice were inoculated with 5 X 10(5) HR cells, the 50% survival time in the untreated group was 52 days. The 50% survival time of nude mice treated with 12 mg (but not 4 mg) of prostaglandin D2 per kg was significantly prolonged to 67 days, in addition to a significant inhibition of the tumor growth. Adjuvant effects of prostaglandin D2 on cisplatin in relation to tumor growth were also studied. Combinations of 0.2 or 0.4 microgram cisplatin per ml and 0.05 or 0.1 microgram prostaglandin D2 per ml, which did not affect the HR cell proliferation alone, resulted in a significant inhibition of cell proliferation. In addition, the tumor take of HR cells by nude mice in groups treated with a combination of cisplatin and prostaglandin D2 was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Improvement in the mechanical properties of artificial blood vessel suitable for the extracranial cerebral artery].

Saphenous vein interposition grafts have been commonly used for the reconstruction of occlusive lesions in the extracranial cerebral vessels, such as carotid or vertebral arteries. In contrast, cerebral revascularization using an artificial blood vessel has not been so common. This is due to the fact that conventional artificial blood vessels have been too firm or too rigid for use in the neurosurgery. Another reason is that the long term patency rate of small caliber artificial blood vessels has usually been inferior to that found in autologous vein grafts. The purpose of this study was to develop a soft and compliant artificial blood vessel suitable for cerebrovascular surgery. This new artificial blood vessel is made of polyurethane, porous in structure (porous polyurethane). Thus, multiple small-sized pores exist both in the inner and outer surfaces, and in the wall of the porous polyurethane graft. To test its mechanical properties, we evaluated stress-strain curves and compliance. In comparison to expanded polytetrafluoroethylene graft (Goretex), which has been one of the most commonly used artificial blood vessels in the cardiovascular surgery, the mechanical properties of the porous polyurethane graft more closely resembled those of the common carotid artery in dogs. Thus, porous polyurethane graft was shown to be a soft and compliant new artificial blood vessel. This means not only that it can be maneuvered with technical ease for anastomosis but also that there is a reduction of compliance-mismatch between the host vessel and the artificial vessel. Compliance mismatch has been documented as a major factor in the inducement of intimal hyperplasia, which causes a delayed occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibition of human ovarian cancer cell proliferation by calmodulin inhibitors and the possible mechanism.

Direct inhibitory effects of calmodulin inhibitors on human ovarian cancer cell proliferation in vitro were examined. All calmodulin inhibitors used in this study inhibited proliferation of HR cells derived from human serous cystadenocarcinoma of the ovary in a dose-dependent manner. The degree of inhibition by melittin and W-5 was most marked and was followed by that of W-7, R24571, and bepridil. HR cell proliferation was dose-dependently stimulated by epidermal growth factor (EGF). The stimulatory effects seemed to be a result of the binding of EGF to HR cells. Binding of EGF was significantly inhibited by W-5, R24571, and melittin. These results suggest that inhibition by calmodulin inhibitors of cancer cell proliferation may result in part from the interference in the binding of EGF to the cells.

Biomechanical Phenomena↗

Paradoxical perpendicular contact guidance displayed by mouse cerebellar granule cell neurons in vitro.

In order to study migration of neurons in vitro, we cultured microexplants of the newborn mouse cerebellum outer layer, which is rich in immature granule cells, on a substratum double-coated with poly-L-lysine and laminin. The granule cells first migrated away from the explant along radially oriented parallel bundles of their neurites, thus displaying typical contact guidance. Then, in almost all explants, they changed their orientation by 90 degrees to extend cell processes and translocate perpendicular to the radial neurites. Orientation and migration of neurons perpendicular to the aligned parallel structure is a novel type of contact-guided cell behavior, and may have interesting implications in migration of neurons in the cerebellum and other parts of the nervous system.

Animals↗

Regional cortical blood flow during extra-intracranial bypass surgery in young patients with moyamoya disease.

Regional cortical blood flow (rCBF) was measured with a thermal diffusion flow probe in 14 cortical regions of 12 young patients with moyamoya disease before and after completion of superficial temporal-middle cerebral artery anastomosis. The prebypass rCBF value was low in most patients, especially in the frontal regions. On temporary occlusion of the cortical artery during the surgical procedure, no significant drop in rCBF occurred. rCBF increased immediately after anastomosis in all but one region and continued to increase for 5-10 minutes in four of the eight regions measured. In the other four regions, rCBF declined gradually after the initial increase, and the final increase was slight. The average increase in rCBF was significant at 1-2 minutes and at 5-10 minutes after anastomosis. However, the latter increase did not bring the flow into the normal range. It may be that the initial increase in postbypass rCBF is determined solely by the pressure gradient between the donor and recipient arteries, and that subsequent rCBF is controlled by other factors within the brain. In one patient who underwent double anastomoses to the frontal and temporal lobes, neither anastomosis increased rCBF in the non-corresponding lobe to recipient artery. This suggests that there is no direct connection between supra- and infra-Sylvian arteries and supports the concept of nonuniform epicerebral microcirculation in moyamoya disease.

Adolescent↗

Comparison of dynamic and xenon computed tomography in the evaluation of cerebrovascular ischemia.

Dynamic computed tomographic (DCT) scans with iodine contrast enhancement were compared with simultaneously obtained xenon CT studies of cerebral blood flow (CBF) in 15 patients with subacute or chronic cerebrovascular ischemic disease. Specifically, the width and corrected first moment (cMT1), as demonstrated by DCT, were compared with the regional CBF (rCBF) data and the rCBF map obtained with xenon CT. The DCT and rCBF images were well correlated in patients without, but poorly correlated in those with, leptomeningeal anastomotic collateral circulation. The correlation of rCBF and 1/width with 1/cMT1 was significant (r = 0.78, p less than 0.01) in the former, but not in the latter. These data were thought to reflect a difference in the tracer inflow pattern between the patients with and those without leptomeningeal anastomoses. Our series did not include patients with acute cerebral infarction or recanalization, which are thought to be associated with marked changes in cerebral blood volume in the affected region. However, the influence of cerebral blood volume should be studied in detail in our subacute or chronic series.

Brain Ischemia↗

[The application of vascular endoscope for the extracranial cerebrovascular occlusive disease: the development of the endoscopic system].

Flexible thin fiber catheter is applied as vascular endoscope for occlusive lesions in the extracranial cerebral arteries. This fiber catheter is introduced transfemorally through 6 or 7 french-sized double lumen balloon catheters. Vascular endoscope clearly demonstrates the internal surface of these vessels by transient occlusion of the proximal side of the vessel through balloon inflation. The occlusive lesions in the subclavian artery or in the proximal vertebral artery were revealed as round smooth-surfaced mass to be treated by the percutaneous transluminal angioplasty.

Aged↗

[The mechanism of resistance and its circumvention of cisplatin-resistant human ovarian cancer cells].

In this study, we attempted to elucidate the mechanisms of cisplatin resistance and circumvent the resistance with calmodulin antagonists using a cisplatin-resistant human ovarian cancer cell line (KFr). It was assumed that the cisplatin resistance resulted from impairment of cisplatin transport systems. In particular, we considered that a reduced cisplatin transport function caused by some amino acids had an effect on the resistance mechanism. Reduced uptake of cisplatin as well as cisplatin analogues to KFr cells was observed. Four cisplatin analogues used in this study had cross-resistance to cisplatin. However, the concentration of drugs incorporated into cells was not always correlated with the degree of resistance. Therefore, it is possible that, in addition to the reduced influx function, an other mechanism is involved in the resistance. Combined treatment with cisplatin and calmodulin antagonists significantly increased the uptake of cisplatin by KFr cells and maintained the cellular level. Thus, a combination therapy of cisplatin and calmodulin antagonists seemed to be of clinical use.

Animals↗

[Effects of lymphokine-activated killer cells and interleukin-2 on the ascites formation and the survival time of nude mice bearing human ovarian cancer cells].

Effect of intraperitoneal instillations of interleukin-2 (IL-2) and/or lymphokine-activated killer (LAK) cells on the ascites formation and the survival time was examined by using a nude mice model with malignant ascites by intraperitoneal inoculation of human ovarian cancer cells (HRA) derived from ascites of a patient with serous cystadenocarcinoma of the ovary. On 28 days after tumor inoculation, all nude mice in both untreated and spleen cells only treated groups formed ascites. Two of 10 nude mice treated with IL-2 only after tumor inoculation survived without forming ascites during the experimental period. On the other hand, all nude mice treated with LAK cells only formed ascites by 14 days after tumor inoculation. When LAK cells and IL-2 were combined 5 of 10 mice survived without forming ascites during the experimental period. The survival time of the IL-2 only treated group was significantly prolonged, compared to that of medium only, spleen cells only and LAK cells only treated groups. When administration of LAK cells was followed by IL-2, the survival time was further prolonged.

Animals↗