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Biomedical subjects

N Ono

Publications and source records attributed to N Ono.

At least 199 records · Page 11Linked to original sources

[Indication and method for surgical treatment of metastatic spinal tumors].

We studied 38 patients with metastatic spinal tumors and discussed the indications and methods for surgical treatment. Metastatic spinal lesions were from carcinomas (31 cases) and sarcomas (7 cases). 20 patients underwent conventional decompressive laminectomy, 10 patients were treated by posterior decompressive laminectomy with stabilization, which included Harrington or Luque instrumentation. The remaining 8 patients were treated by anterior decompression and stabilization. Anterior decompression and stabilization (effective cases 87.5%) were better than the other procedures (effective cases of posterior decompressive laminectomy and stabilization: 70%: that of conventional laminectomy: 30%) to sustain relief of pain and reduction of paralysis. Our surgical procedures were palliative and directed at relief of pain and prevention of neurological deterioration. But our results suggested that the spinal column stabilization was worthwhile in treatment of metastatic spinal tumors.

Adult↗

Effects of proglumetacin maleate and its major metabolites on allergic air pouch inflammation in rats.

The mechanism of the anti-inflammatory effect of proglumetacin maleate, a novel indomethacin derivative, was examined in vivo in an allergic air pouch inflammation model in rats. Proglumetacin maleate did not affect the volume of pouch exudate 6 h after immunological challenge, irrespective of whether it was administered orally or locally, but it caused dose-dependent inhibition 24 h after challenge. It also caused dose-dependent reduction of leukocyte migration into the pouch exudate both 6 and 24 h after challenge. It markedly decreased the prostaglandin E2 content of the pouch exudate, but tended to increase the leukotriene B4 content. The main metabolites of proglumetacin maleate, desproglumideproglumetacin maleate and indomethacin, had effects similar to those of proglumetacin maleate on these four parameters on an equimolar dose basis. Unlike these three drugs, dexamethasone decreased the leukotriene B4 content of the pouch exudate. These results suggest that the action of proglumetacin maleate is qualitatively the same as that of indomethacin in vivo; that is, it inhibits cyclo-oxygenase in inflammatory sites.

Administration, Oral↗

Pathobiology of intracranial germ-cell tumors: immunochemical, immunohistochemical, and electron microscopic investigations.

In an attempt to clarify the pathobiology of intracranial germ-cell tumors, we studied 56 patients with these tumors, both clinically and pathologically. Our evaluations included immunochemical, immunohistochemical, and electron microscopic observations. Thirty tumors originated in the pineal region, ten in the suprasellar region, nine in the basal ganglia, and two in other regions. Five had double sites of origin. Histologically, there were 39 germinomas, six teratomas, four embryonal carcinomas, two choriocarcinomas and five mixed tumors. Among tumors tested immunochemically, serum carcinoembryonic antigen (CEA) was positive in 3.4%, serum alpha-fetoprotein (AFP) in 25.8%, and serum human chorionic gonadotropin (HCG) in 32.1%. In CSF, CEA was positive in 14.3%, AFP in 26.3%, and HCG in 75%. One third of germinomas were positive for serum HCG, and 88.9% for CSF HCG. One half of teratomas were positive for CEA of CSF. In immunohistochemical testing, the positive rates for CEA, AFP, HCG, and placental alkaline phosphatase (PLAP) were 26.9%, 11.5%, 24.1%, and 55.6%, respectively. Most teratomas were positive for CEA and the reactions were prominent in gland-like structures. HCG-positive syncytial cells were found in three germinomas and two embryonal carcinomas as well as in choriocarcinomas. The majority of germinomas were positive for PLAP and the reactive sites were tumor cell membranes and cytoplasm. On electron microscopy, germinomas were least differentiated, followed in order by embryonal carcinomas, choriocarcinomas, and teratomas. Further clinical and pathological studies will be necessary for a better understanding of the biology of these tumors.

Adolescent↗

The effect of neurotransmitters on cataleptic behavior induced by PG D2 in rats.

The effects of several neurotransmitters on prostaglandin (PG) D2-induced cataleptic behavior in rats were investigated by the high bar test. Intracerebroventricular administration of PG D2 elicited cataleptic behavior in a dose-dependent manner without producing a marked change in spontaneous motor activity. The incidences of cataleptic behavior were 20% and 100% at doses of 2 nmol and 50 nmol of PG D2, respectively. Intraperitoneal pretreatment with L-DOPA (100 mg/kg), apomorphine (1 mg/kg), amantadine (0.2 mg/kg), atropine (0.5 mg/kg) or p-chlorophenylalanine (300 mg/kg) significantly decreased the cataleptic behavior induced by 50 nmol of PG D2. Conversely, simultaneous treatment with 5-hydroxy-L-tryptophan (30 mg/kg), 5-methoxy-N,N-dimethyltryptamine (5 mg/kg), imipramine (20 mg/kg) or clomipramine (10 mg/kg) markedly increased the cataleptic behavior induced by 2 nmol of PG D2. Propranolol (10 mg/kg) and phenoxybenzamine (10 mg/kg) did not affect the induction of cataleptic behavior by either 2 nmol or 50 nmol of PG D2. These results suggest that PG D2 might be involved in inducing cataleptic behavior by modulating serotonergic, cholinergic and dopaminergic systems.

Acetylcholine↗

Analysis of hemangiopericytic meningiomas by immunohistochemistry, electron microscopy and cell culture.

Intracranial hemangiopericytic meningiomas (HM) from seven patients were examined by immunostaining, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and cell culture. Positive staining for Factor VIII-related antigen was restricted to capillary endothelial cells. There was no reaction with anti-glial fibrillary acidic protein (GFAP) serum or anti-S-100 protein serum. In these neoplasms TEM displayed extracellular basement membrane-like material (BMLM), cytoplasmic intermediate filaments (IF) associated with a dense body, dilated rough-surfaced endoplasmic reticulum containing BMLM, a small area of interdigitation of cell membranes, and a unique intercellular punctate or linear density. By SEM these tumors had intercellular shell-like or reticular structures and irregularly branched capillaries which were compressed by ellipsoidal- or carrot-shaped tumor cells. Short-term monolayer culture showed rapid and vigorous growth of tumor cells, and the formation of pseudolumens but not of whorls. The TEM of cultured cells also showed cytoplasmic IF associated with the dense body. By SEM the cultured cells were flat and had a discoid nucleus with conspicuous nucleolar hillocks. Our results show that HM are mainly poorly specialized mesenchyme-related tumors of the meninges; some possess a potential for aggressive growth and some for differentiation into smooth muscle cells. Further study is needed to determine their histogenesis.

Aged↗

The role of brain peptides in neuroimmunomodulation.

Since neuroimmunomodulation is brought about in part, at least, by secretion of pituitary hormones involved in stress and immune responses, we review briefly the hypothalamic control of the release of ACTH, growth hormone, and prolactin. The release of ACTH is controlled particularly by corticotropin-releasing factor (CRF), but vasopressin has intrinsic releasing activity and potentiates the action of CRF at both hypothalamic and pituitary levels. Oxytocin may even potentiate the action of CRF, but has little, if any, ACTH-releasing activity by itself. In addition, epinephrine may augment responses to the CRFs. In contrast, growth hormone is under dual control by growth-hormone-releasing factor (GRF) and somatostatin, and prolactin is under multifactorial control by a series of inhibitors and stimulators. Dopamine is accepted as a physiological prolactin-inhibiting factor (PIF), but probably GABA and possibly acetylcholine as well are PIFs. There is good evidence for a peptide PIF as well. There are a number of prolactin-releasing factors (PRFs) which include oxytocin, vasoactive intestinal polypeptide, PHI and TRH. Several other peptides can also release prolactin, including angiotensin II. In response to stress there is a complex interaction of peptides intrahypothalamically. CRF augments its own release by an ultra short-loop positive feedback, and there is negative ultra short-loop feedback of GRF and somatostatin. Vasopressin appears to augment CRF release as well as to act directly on the pituitary, and there are complex interactions of various peptides to influence prolactin and GH release.

Adjuvants, Immunologic↗

Clinical pathology of primitive gliomas in the cerebrum.

To clarify the biological features of primitive gliomas in the cerebrum and clearly distinguish them from malignant or anaplastic gliomas and glioblastomas, we studied eight cases clinically and pathologically. Our evaluations included immunohistochemical and electron microscopic observations. We divided the patients into two groups, children and young adults. Most tumours appeared as ring-like, enhanced masses on computed tomography and avascular or ring-like, vascular masses on angiography. Macroscopically, the tumours were well demarcated and contained cysts. Occassionally we found tumour dissemination. Microscopically, the tumours were composed of small, round cells without remarkable structural features. Ependymal, astroglial, and oligodendroglial differentiation was evident, in varying proportions; tumours in which the differentiated areas constituted more than half of the mass were classified as poorly differentiated gliomas. By these criteria, this series comprised four undifferentiated and four poorly differentiated gliomas. Cell anaplasia and polymorphism were rare in both undifferentiated and differentiated areas of the tumours. Immunohistochemical and electron microscopic examinations also revealed glial differentiation. These primitive gliomas appear to be biologically similar, but not identical, to cerebellar medulloblastomas. In this series, five patients died because of recurrence or dissemination. Whole brain and spinal irradiation should be considered after total or subtotal surgical removal.

Adolescent↗

Diagnosis of germinal neoplasm in the thalamus and basal ganglia.

Germinal neoplasms originating in the thalamus and basal ganglia were histologically verified by stereotactic biopsies in five cases and by other methods in three cases. Immunoperoxidase staining was performed on the tumors using antibodies against human chorionic gonadotropin and placental alkaline phosphatase. The presence of human chorionic gonadotropin was demonstrated in one germinoma and two mixed tumors, but not in three germinomas. Placental alkaline phosphatase was demonstrated to be present in four germinomas and one mixed tumor. Stereotactic biopsy specimens can be studied immunohistochemically, and the placental isoenzyme of alkaline phosphatase appears to be a new tumor marker for germinoma.

Adolescent↗

Germ cell tumor in the basal ganglia: immunohistochemical demonstration of alpha-fetoprotein, human chorionic gonadotropin, and carcinoembryonic antigen.

A case of germ cell tumor in the basal ganglia and its vicinity was successfully treated surgically and by radiation. alpha-Fetoprotein, human chorionic gonadotropin, and carcinoembryonic antigen were found in the tumor tissue, using the immunoperoxidase method. The presence of three immunohistochemically demonstrated tumor markers in a single germ cell tumor is extremely unusual. These results strongly suggest a cell differentiation or transformation in germ cell tumors.

Adolescent↗

Possible involvement of prostaglandins in cataleptic behavior in rats.

Involvement of prostaglandin (PG) in cataleptic behavior was investigated by a high bar test method in rats. PG F2 alpha (F2a) and E2 administered intracerebroventricularly (ICV) elicited cataleptic behavior in a dose-dependent manner. The cataleptic behaviors produced by PGs were markedly inhibited by ICV pretreatment with propranolol. The cataleptic behaviors induced by haloperidol were also inhibited by propranolol. The PG F2a- and haloperidol-induced cataleptic behaviors were almost abolished by the thermal coagulation of bilateral striatum where the dopaminergic and cholinergic link is found. The pilocarpine-induced cataleptic behavior was potentiated by ICV treatment with PG F2a. On the other hand, the cataleptic behavior elicited by haloperidol was reduced after oral treatment with aspirin, a PG synthesis inhibitor. These results suggest that PGs seem to be participated in incidence of cataleptic behavior, which might involve alteration of brain beta-adrenoceptor activity.

Animals↗

[Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug. (3) Damaging effects on the gastrointestinal tract].

Damaging effects on the gastrointestinal tract of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were examined in comparison with those of IND. Gastric and small intestinal lesions were maximum 4 and 24 hr after a single oral administration of PGM, respectively. Ulcerogenic effects of PGM on the gastric mucosa were approximately 1/7 and 1/10 times as potent as those of IND on a molar ratio 4 hr after single oral dosing to fasting and feeding rats, respectively. PGM was also less active on the small intestinal mucosa 24 hr after single oral dosing. After repeated dosing for 7 days, ulcerogenic effects of PGM were about 1/3 and 1/2 times more potent than those of IND on the gastric and the small intestinal mucosa, respectively. The weak ulcerogenicity of PGM appears to be due to the fact that it has little direct action on the gastrointestinal mucosa. On the other hand, protective effects of PGM on diarrhea induced by arachidonic acid in mice were about 1/2 times as potent as those of IND in both 1 and 4 hr pretreatments. So PGM must have less inhibitory effects on prostaglandin biosynthesis in the intestine than IND. PGM is a safer drug than IND because it has less damaging effect on the gastrointestinal mucosa. Therefore, it may be much more useful for the treatment of chronic inflammatory disorders like rheumatoid arthritis.

Administration, Oral↗

[Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug. (1). Anti-inflammatory effects].

Anti-inflammatory effects of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were compared with those of IND on an equimolar-dose basis. PGM produced a dose-dependent inhibition of vascular permeability and carrageenin edema. These inhibitory effects of PGM were greater when given 4 hr prior to phlogistic agents than when given 1 hr before. Moreover, these effects of PGM were long-acting. Inhibitory effects of PGM on kaolin edema and UV-erythema were slightly less active than those of IND. PGM markedly reduced the leukocyte migration in carrageenin pleurisy. Subacute anti-exudative and anti-granuloma effects of PGM were nearly equal to those of IND. Also, PGM showed strong prophylactic and therapeutic effects on adjuvant arthritis, the model of chronic (immuno-reactive) inflammation. These effects of PGM were superior or equal to those of IND. These pharmacological properties of PGM suggested its potential usefulness in rheumatic and other inflammatory disorders. It was considered that the mode of action of PGM mainly depended on its active metabolite, IND. However, PGM was also active in the case of local administration into the sites of inflammation on rat hind paw edema. Therefore, it seemed that PGM had a different behavior than a so called "prodrug".

Animals↗

[Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug. (2). Analgesic and antipyretic effects].

Analgesic and antipyretic effects of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were investigated in comparison with those of IND on an equimolar-dose basis. The suppression of phenylquinone-induced writhing in mice by PGM was about 0.8 and 2 times as potent as that by IND when given 1 and 4 hr before the phenylquinone injection, respectively. The analgesic activity of PGM in rat silver nitrate arthritis was about 1.5 times more potent than that of IND. PGM was slightly less active in rat adjuvant arthritic pain than IND. On the other hand, PGM provoked a dose-dependent antipyretic effect on the yeast-induced fever in rats within the dose range without affecting the normal body temperature. Furthermore, PGM showed a significant antipyretic effect on LPS-febrile rabbits. Generally, the antipyretic effect of PGM was moderate as compared with that of IND. These analgesic and antipyretic actions of orally administered PGM may be mainly due to its active metabolite, IND. The above results indicate that PGM may be useful for inflammatory diseases associated with pain and/or fever.

Animals↗

Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug (4). Mode of action on anti-inflammatory activity.

The possible mechanism of the anti-inflammatory activity of proglumetacin maleate (PGM), a new indomethacin (IND) derivative interacting with arachidonic acid (AA) metabolism, was investigated to elucidate the contributions of PGM itself and its two major metabolites, desproglumideproglumetacin maleate (DPP) and IND. PGM caused much less inhibition of PGE2 formation by sheep seminal vesicle microsomes (IC50 = 310 microM) and TXB2 formation by a washed rabbit platelet suspension (IC50 = 6.3 microM) than IND. DPP also caused less inhibition of cyclooxygenase than IND. Moreover, PGM had less effect on sodium arachidonate (SAA)-induced rat platelet aggregation ex vivo and AA-induced sudden death in rabbits than IND. These results show that PGM has anti-inflammatory activity after its conversion to the active metabolite IND. However, the inhibitory effects of PGM and DPP were as strong as that of IND on SAA- or collagen-induced rabbit platelet aggregation in vitro. These activities are considered to be associated with platelet membrane interaction. Moreover, unlike IND, PGM (IC50 = 1.5 microM) and DPP (IC50 = 16.3 microM) strongly inhibited 5-HETE formation by the cytosol of guinea pig polymorphonuclear leukocytes. This unique activity of PGM on 5-lipoxygenase may contribute to its anti-inflammatory activity.

Animals↗

Corticotropin-releasing factor (CRF) and vasopressin concentration in major brain regions after adrenalectomy and their involvement in adrenalectomy-induced ACTH elevation.

CRF and vasopressin concentrations in major brain regions after bilateral adrenalectomy and their involvement in adrenalectomy-induced ACTH secretion were investigated. At 5, 14 and 28 days after bilateral adrenalectomy, the plasma ACTH level was greatly elevated, whereas hypothalamic CRF content was reduced at 5 days and was not changed at 14 and 28 days after adrenalectomy. The CRF concentration in the medulla oblongata was reduced at 2-4 weeks after adrenalectomy. On the other hand, the arginine vasopressin (AVP) concentration was significantly elevated 2-4 weeks after adrenalectomy. An intrajugular administration of anti-ovine or anti-rat CRF serum significantly suppressed the elevated plasma ACTH level in adrenalectomized, freely moving rats, whereas anti-AVP serum or antipressor AVP antagonist, dpTyr(Me)AVP did not suppress the ACTH level. These results indicate that CRF played an important role in the adrenalectomy-induced ACTH elevation but that vasopressin was not involved.

Adrenalectomy↗

Role of arginine vasopressin in control of ACTH and LH release during stress.

To determine the role of arginine vasopressin (AVP) in stress-induced release of anterior pituitary hormones, AVP antiserum or normal rabbit serum (NRS) was micro-injected into the 3rd ventricle of freely-moving, ovariectomized (OVX) female rats. A single 3 microliter injection was given, and 24 hours later, the injection was repeated 30 min prior to application of ether stress for 1 min. Although AVP antiserum had no effect on basal plasma ACTH concentrations, the elevation of plasma ACTH induced by ether stress was lowered significantly. Plasma LH tended to increase following ether stress but not significantly so; however, plasma LH following stress was significantly lower in the AVP antiserum-treated group than in the group pre-treated with NRS. Ether stress lowered plasma growth hormone (GH) levels and this lowering was slightly but significantly antagonized by AVP antiserum. Ether stress also elevated plasma prolactin (Prl) levels but these changes were not significantly modified by the antiserum. To evaluate any direct action of AVP on pituitary hormone secretion, the peptide was incubated with dispersed anterior pituitary cells for 2 hours. A dose-related release of ACTH occurred in doses ranging from 10 ng (10 p mole)-10 micrograms/tube, but there was no effect of AVP on release of LH. The release of other anterior pituitary hormones was also not affected except for a significant stimulation of TSH release at a high dose of AVP. The results indicate that AVP is involved in induction of ACTH and LH release during stress. The inhibitory action of the AVP antiserum on ACTH release may be mediated intrahypothalamically by blocking the stimulatory action of AVP on corticotropin-releasing factor (CRF) neurons and/or also in part by direct blockade of the stimulatory action of vasopressin on the pituitary. The effects of vasopressin on LH release are presumably brought about by blockade of a stimulatory action of AVP on the LHRH neuronal terminals.

Adrenocorticotropic Hormone↗