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Biomedical subjects

K Takakura

Publications and source records attributed to K Takakura.

At least 289 records · Page 16Linked to original sources

Effect of cyclooxygenase and lipoxygenase inhibitors on delayed neuronal death in the gerbil hippocampus.

The purpose of our study was to examine whether cyclooxygenase and lipoxygenase inhibitors ameliorate delayed neuronal death in the hippocampal CA1 sector in Mongolian gerbils after 5 minutes of forebrain ischemia. Gerbils were injected intraperitoneally with cyclooxygenase inhibitors piroxicam and flurbiprofen or with lipoxygenase inhibitors AA-861 and BW-755C. Seven days after ischemic insult, the animals were perfusion-fixed, and the neuronal density in the hippocampal CA1 sector was estimated. The average neuronal density in unoperated normal gerbils was 247 +/- 9/mm (mean +/- SEM). In ischemic gerbils with vehicle administration, the average neuronal densities were 13 +/- 2, 14 +/- 2, 13 +/- 2, and 13 +/- 1 for piroxicam, flurbiprofen, AA-861, and BW-755C, respectively. The average neuronal densities in ischemic gerbils treated with 1.5 and 10 mg/kg piroxicam and 1.5 and 10 mg/kg flurbiprofen were 13 +/- 2, 194 +/- 9, 19 +/- 5, and 143 +/- 12, respectively. In ischemic gerbils treated with 15 and 100 mg/kg AA-861 and 30 mg/kg BW-755C, the average neuronal densities were 12 +/- 1, 13 +/- 1, and 14 +/- 2, respectively. At their higher doses, both piroxicam and flurbiprofen significantly (p less than 0.01) ameliorated delayed neuronal death in the hippocampal CA1 sector. Our results suggest that cyclooxygenase products play an important role in the development of delayed neuronal injury after cerebral ischemia.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats.

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.

Animals↗

Interleukin-1 stimulates growth and inhibits progesterone secretion in cultures of porcine granulosa cells.

Interleukin-1 (IL-1) significantly inhibited basal progesterone secretion and influenced the cell number in high density cultures of porcine granulosa cells harvested from small (1-2 mm) or medium (3-5 mm) follicles. These two effects of IL-1 showed similar but inverse dose-response relationships: Significant effects were observed at concentrations higher than 50 pg/ml, and the maximal effective concentration was 5 ng/ml, which reduced progesterone secretion by 53.5 +/- 2.1%. In contrast, IL-1 neither inhibited progesterone secretion nor did it influence cell number in cultures of fully mature granulosa cells harvested from the largest (8-11 mm) follicles. The growth-promoting effect of IL-1 on granulosa cells was further examined in the low density cultures, which revealed that IL-1 significantly stimulated proliferation of the less mature granulosa cells at concentrations higher than 50 pg/ml, and that at a maximal stimulatory concentration (25 ng/ml) it increased cell number to 206 +/- 11% of control. Although IL-1 increased cell number and reduced progesterone secretion of fully mature granulosa cells after 5 days in low density cultures, it seemed that the proliferating population were not the cells with luteinized morphology and positive 3 beta-hydroxysteroid dehydrogenase staining. The proliferating population of cells appeared to have less mature morphology and were negative for 3 beta-hydroxysteroid dehydrogenase staining.

3-Hydroxysteroid Dehydrogenases↗

Inhibitory effects of interleukin-1 on luteinizing hormone-stimulated adenosine 3',5'-monophosphate accumulation by cultured porcine granulosa cells.

To elucidate the mechanisms of the inhibitory effect of interleukin-1 (IL-1) on LH-stimulated progesterone secretion by cultured porcine granulosa cells, we examined which steps of the LH-stimulated, cAMP-mediated, progesterone biosynthetic pathway were affected by IL-1. Pretreatment of the cells for 48 h with IL-1 reduced intra- and extracellular cAMP accumulation in response to LH by 73% and 83%, respectively. The inhibitory effects of IL-1 were time and concentration dependent. Significant inhibition was observed at as low as 50-250 pg/ml, and the effect was maximal at 100 ng/ml (ID50; 2 ng/ml). The lowest concentration of IL-1 used (0.5 pg/ml), in contrast, showed a tendency to stimulate LH-induced cAMP accumulation. Effect of IL-1 on the specific binding of [125I]LH to granulosa cells was then examined, which showed that IL-1 (100 ng/ml) significantly reduced the specific binding by 36%. IL-1 also significantly reduced intra- and extracellular cAMP accumulation by the cells in response to forskolin (50, 150 microM) by 28-46%, indicating that IL-1 can directly inhibit adenylate cyclase activity. Contrary to these inhibitory actions of IL-1 on LH-stimulated cAMP generation, IL-1 did not significantly reduce progesterone secretion induced by (Bu)2cAMP. These results indicate that the inhibitory effect of IL-1 on LH-stimulated progesterone secretion is due to its actions at at least two different sites along the LH-stimulated, cAMP-mediated, progesterone biosynthetic pathway, the LH receptor level and adenylate cyclase systems. The post-cAMP steps of progesterone production, in contrast, did not seem to be affected by IL-1.

Animals↗

Interleukin-2 receptor/p55(Tac)-inducing activity in porcine follicular fluids.

Very recently, it has been reported that interleukin-1 (IL-1) has an inhibitory effect on progesterone production by porcine granulosa cells in vitro. In the present study we investigated the presence of IL-1 or IL-1-like activity in porcine ovarian follicular fluids (FF) as the first step in elucidating the physiological role of IL-1 in follicular growth and maturation. Since IL-1 and IL-1-like substances have interleukin-2 receptor (IL-2R)/p55(Tac)-inducing activity (TIA), we determined the TIA in the FF by means of a highly sensitive TIA assay using flow cytometry. TIA was significantly higher (P less than 0.01) in the FF of small follicles than in those of medium-sized and large follicles. A significant negative correlation (P less than 0.05) was apparent between TIA and 17 beta-estradiol concentration in the FF. The conditioned media of porcine granulosa cells also showed TIA. Of these conditioned media, those from small follicles exhibited higher TIA than those from medium-sized and large follicles. TIA in the conditioned media decreased rapidly as the culture period was extended. Sex steroids such as 17 beta-estradiol, progesterone, testosterone, and androstenedione had no effect on IL-2R/p55(Tac) induction. These results indicate that porcine granulosa cells produce the IL-2R/p55(Tac)-inducing factor, the activity of which decreases in association with the maturation of the follicles. Because of the heterogeneity of IL-2R-inducing factors, the relationship between TIA in the FF and IL-1 should be elucidated. We discuss the possibility that this factor may play a role in follicular maturation and that enhancement of IL-2R/p55(Tac) expression by this factor may contribute to the local defense mechanism in ovarian follicles.

Androstenedione↗

Successful combination chemotherapy (cisplatinum, vinblastine, and bleomycin) in the treatment of medulloblastoma disseminated by cerebrospinal fluid: case report.

A case of successful combination chemotherapy using cisplatinum, vinblastine, and bleomycin (PVB therapy) to treat medulloblastoma disseminated by cerebrospinal fluid is presented. In this case, a locally recurrent tumor and several disseminated tumors were seen to decrease in size on CT examinations. Pain in the lower extremities and urinary incontinence improved during three courses of PVB therapy administered during a period of 9 weeks. These results suggest that combination PVB therapy may offer one of the treatments of choice for recurrent or disseminated medulloblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical course and surgical prognosis of 33 cases of intracranial epidermoid tumors.

Thirty-three cases of intracranial epidermoid tumors treated during the past 25 years were analyzed with regard to clinical manifestations, recurrence rates related to the extent of surgery, and long-term survival rates. Epidermoid tumors caused various symptoms, especially in the cerebellopontine angle (15 cases), of which a transient remission of symptoms was observed in 4 cases (23.5%). The average time from initial symptoms to surgery was much shorter in suprasellar region and third ventricular locations (average of 11 months) than in other locations (average of 7 years). In 28 patients (84.9%), the tumor was removed totally or subtotally. Most of the patients could lead an independent and useful life after operation (93.1%). Among the 29 patients in a long-term follow-up survey, seven tumors recurred after an average interval of 8 years and 10 months (from the first to second operation) and 12 years and 6 months (from the second to third operation). Patients with recurrent tumors were successfully treated, and excellent functional prognosis was observed even after the second or third operation. The 20-year survival rate was 92.8% (Kaplan-Meier method).

Adolescent↗

Aggravation of inappropriate luteinizing hormone secretion by bromocriptine in polycystic ovary syndrome with elevated serum dehydroepiandrosterone sulfate.

Ten clomiphene-resistant, normoprolactinemic women with polycystic ovary syndrome (PCOS) were treated by continuous and increasing administration of bromocriptine (Brc), and changes in hormonal profiles as well as therapeutic efficacy were examined. Ovulation was restored in four patients (responders), and two of them became pregnant, whereas the other six patients did not ovulate with Brc alone (non-responders). Endocrine analyses revealed distinct differences between responders and non-responders: 1) pretreatment serum levels of dehydroepiandrosterone sulfate (DHAS) in non-responders were significantly higher than those in responders: 2) exaggerated LH secretion was definitely aggravated with Brc therapy in non-responders, but unchanged or slightly reduced in responders: 3) basal PRL secretions showed a marked reduction in both groups, whereas this response to TRH in responders decreased more markedly than in non-responders with the therapy. It is concluded that low DHAS group patients of PCOS are likely to respond to Brc, whereas high DHAS group patients appear contraindicated for this treatment due to its aggravating effect on LH secretion.

Adult↗

Role of prolactin in age-related change in serum dehydroepiandrosterone sulphate concentrations.

Serum dehydroepiandrosterone sulphate concentrations were measured in 70 patients with prolactinoma and in 54 patients with acromegaly with normal adrenocortical function. Compared with values in normal subjects of corresponding age, serum dehydroepiandrosterone sulphate levels were increased in 22 patients with prolactinoma (31%) and in 5 patients with acromegaly (9%). The four acromegalic patients who had elevated serum dehydroepiandrosterone sulphate levels had hyperprolactinemia. The mean serum dehydroepiandrosterone sulphate concentrations in patients with prolactinoma in each decade decreased with advancing age. There was a significant negative correlation between serum dehydroepiandrosterone sulphate concentrations and ages of the patients with prolactinoma. In all 8 women with prolactinoma as in 6 normal women, serum dehydroepiandrosterone sulphate levels declined definitely during the 9 years of follow-up despite persistent hyperprolactinemia. These results indicate that serum dehydroepiandrosterone sulphate levels are increased in a substantial number of patients with hyperprolactinemia, however, PRL per se may not play a significant role in the age-related change in serum dehydroepiandrosterone sulphate levels.

Acromegaly↗

Multiple saccular cerebral aneurysms associated with systemic lupus erythematosus--case report.

A rare case of multiple saccular cerebral aneurysms in a patient with systemic lupus erythematosus (SLE) is presented. The aneurysms were located at the junction of the left internal carotid artery (ICA) and the posterior communicating artery (PComA), at the anterior communicating artery, at the middle cerebral artery, at the junction of the right ICA and the PComA, and at the top of the basilar artery. All the aneurysms, except for the one on the basilar artery, which was unruptured, were successfully clipped. Histopathological examination of one resected aneurysmal dome confirmed the diagnosis of transmural arteritis secondary to SLE. Postoperatively, she died of a massive hemorrhage from a rectal ulcer. The etiology and prognosis of cerebral aneurysms in SLE are discussed.

Arteritis↗

Pharmacological effect of endothelin, an endothelium-derived vasoconstrictive peptide, on canine basilar arteries.

The purpose of this study was to evaluate the constrictive effect of endothelin, a peptide vasoconstrictor derived from endothelium, on canine basilar artery. Constriction was measured by an isometric tension recording method. Endothelin induced prolonged contraction of canine basilar artery in a dose-dependent fashion, the estimated concentration at 50% contraction being (2.1 +/- 0.5) X 10(-9) M (mean +/- SEM). Removal of endothelium significantly augmented the arterial response to endothelin. In Ca(++)-free medium no contractile response was elicited at 10(-8) M endothelin. Papaverine (10(-4) M) and nicardipine (10(-8) M), a calcium channel blocker, almost completely inhibited the contraction induced by 10(-8) M endothelin. Pretreatment with nicardipine (10(-8) - 10(-6) M) also significantly suppressed the response to endothelin. Acetylcholine (10(-7) - 10(-4) M), adenosine triphosphate (10(-7) - 10(-5) M), and thrombin (0.1 and 1.0 U/ml) dose-dependently inhibited contraction of canine basilar artery in response to 3 X 10(-9) M endothelin. These results show that endothelin has a potent constrictive effect on canine basilar artery and suggest that this substance may play an important role in the pathogenesis of vasospasm following subarachnoid hemorrhage.

Adenosine Triphosphate↗

Measurement of serum alkaline phosphatase isozyme I in brain-damaged patients.

The authors measured alkaline phosphatase isozyme I (ALP-I) in sera of 24 brain-damaged patients and four with disorders other than brain damage. The study population comprised three patients with postresuscitation encephalopathy, four with ruptured cerebral aneurysms, 14 with acute subdural hematoma and cerebral contusion, and three with nontraumatic intracerebral hemorrhage. ALP-I detected in brain damage is physicochemically different from the other known ALP-Is that appear in patients with obstructive jaundice or hepatoma. In the brain-damaged patients, ALP-I became elevated about 7 days after admission and markedly increased as secondary brain damage developed. Excluding patients who died within 9 days of admission, the maximum serum ALP-I concentration was well correlated with the functional outcome. In cases in which barbiturate therapy was effective, the appearance of ALP-I was delayed and its elevation was suppressed. The results of this study suggest that measurement of serum ALP-I is useful not only in the management but also in predicting the prognosis of brain damage.

Adolescent↗

Postradiation astrocytoma. Report of two cases.

The authors describe two cases of malignant astrocytomas associated with previous radiation therapy in childhood for intracranial germinoma and craniopharyngioma. In both patients, there was no recurrence at the primary tumor site. Because of a geometric coincidence between the tumor location and the radiation field, radiotherapy was strongly implicated as a cause of these two astrocytomas.

Adolescent↗

[A clinicopathological study of central neurocytoma].

In 1982, Hassoun et al. reported two cases of differentiated neuroblastoma with the clinical and light microscopic appearance of intraventricular oligodendroglioma and gave a name of "central neurocytoma" to this tumor. Jerdan et al. (1983) called the similar tumor as "differentiated cerebral neuroblastoma in adults". As the tumor can be diagnosed only by ultrastructural study, the established cases so far reported are very rare. In this paper we present five cases identical to those presented by Hassoun et al. and clarify the essential nature of this new category of brain tumors. All of our cases of central neurocytoma occurred in the lateral ventricles of young adults. Clinically there was no evidence of leptomeningeal or ventricular dissemination of tumor cells. After subtotal resection of the tumor and 6000 rads of whole brain irradiation, the tumor mass disappeared and no evidence for recurrence of the tumor was noted on CT scan. All cases showed almost the same histology. The tumor cells contained a small round and/or oval nucleus, and had eosinophilic thin delicate cytoplasmic processes. There were no Homer Wright rosette, but were anuclear spaces consisting of fine fibrillar structures, like so called "broad rosettes" or "large rosettes". Capillary mesh was found among the tumor cells, but there was no endothelial proliferation. The tumor cells were monotonous, lacking pleomorphism, mitotic figures, and necrotic foci. Calcifications were observed in two cases. In the areas where the tumor cells arranged loosely, cytoplasms became clear, showing perinuclear halo, like those of oligodendrogliomas. Immunohistochemical examination showed GFAP and vimentin positive cells were all reactive astrocytes around capillaries and near calcifications. No tumor cells contained GFAP and vimentin. The tumor cells were also negative for neurofilament both of 70 KD and 200 KD. NSE was more or less positive for tumor cell cytoplasm as well as fine fibrils. Anti-Leu7 antibodies stained only fine cytoplasmic processes, but not cytoplasm. Some reactive astrocytes were stained with anti-Leu7 antibodies. Electron microscopic examination showed nuclei of the tumor cells were roughly round or oval without nuclear indentations and contained finely dispersed nuclear chromatin. In the cytoplasm, there were numerous free ribosomes, mitochondria, Golgi apparatus and electron dense various-shaped granules. Microtubules were found in the periphery of the cells, but filamentous structures were not identified.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

International neurosurgery: neurosurgical training and practice in India, Korea, Japan, and Australasia.

During the 1985 annual meeting of the Congress of Neurological Surgeons in Honolulu, neurosurgical training and practice in India, Korea, Japan, and Australasia were discussed at the International Committee symposium. This article summarizes the information presented. India has about 300 neurosurgeons for a population of 650 million, while Japan has about 4,000 neurosurgeons and trainees for a population of 120 million. Korea has 424 neurosurgeons for a population of 41.5 million, and Australasia has 92 neurosurgeons and 19 trainees for 17.5 million people. Various other demographic, institutional, organizational, and economic aspects of neurological health care and delivery, education, and quality control are described. While financing and availability of adequate neurosurgical care remains a major problem in India, it appears that reducing the number of neurosurgical trainees remains, as it is in North America, a major issue in Japan and, to a lesser extent, in Korea. This problem, as well as certification of the quality of training, is being managed effectively in Australasia.

Asia↗

Intramedullary cavernous angioma with trigeminal neuralgia: a case report and review of the literature.

A case of intramedullary cavernous angioma of the upper cervical spinal cord, initially associated with trigeminal neuralgia, is reported. Magnetic resonance imaging precisely depicted the entire extent of the lesion. The angioma was totally removed and the operation was successful in relieving the patient of neuralgia. The previously reported 23 cases of intramedullary cavernous angiomas are reviewed, and the clinical symptoms, diagnosis, and treatment of this rare condition are discussed.

Adult↗

[Chemical modifiers in radiotherapy].

The halogenated pyrimidine analogue bromodeoxyuridine (BrdU), which is incorporated into nuclei during DNA synthesis, has long been known to be a radiation sensitizer. Since 1965, BAR therapy (BrdU-antimetabolite-radiation therapy), in which BrdU was administered intraarterially as a radiosensitizer, has been applied to patients with malignant gliomas and the improvement in survival rate within two years has been reported. Recently, intravenous infusion of BrdU has prove to be sufficiently effective as a radiosensitizer and BrdU is still being utilized as a chemical modifier for patients with malignant gliomas. Misonidazole was developed as a hypoxic cell sensitizer and was expected to enhance the radiation response of malignant tumors. However, the clinical trial of misonidazole in patients with brain tumors showed little clinical benefit of this agent as a radiosensitizer, and therefore it is no longer used in the treatment of malignant gliomas. Synchronized chemoradiotherapy, in which alkaloid and alkyl agents are used to accumulate cells into the radiosensitive G2 and M phases, was developed for the treatment of malignant gliomas in 1976 and significant improvement in survival has been reported. However, phase II studies demonstrated that radiotherapy with alkyl agents such as BCNU and ACNU did not prolong the survival of patients with malignant gliomas as compared with radiotherapy alone, although they did increase the response rate. Since 1985, the Brain Tumor Interferon Study Group has clinically applied one of the biological response modifiers (BRM), interferon-beta (INF-beta) as a chemical modifier in patient with malignant gliomas. They have reported that the response rates in patients treated with ACNU + radiation and INF-beta + ACNU + radiation were 19.6% and 41.2%, respectively. Their results suggested that IFN-beta with ACNU was a promising regimen as a chemical modifier in radiotherapy for patients with malignant gliomas. In order to improve the rate of local control of malignant gliomas and to prolong the survival of patients, it is necessary to continue to seek effective chemical modifiers including BRMs, as well as to develop irradiation techniques.

Brain Neoplasms↗