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Biomedical subjects

H Segawa

Publications and source records attributed to H Segawa.

At least 19 recordsLinked to original sources

Regulation of interleukin-1 receptors on AtT-20 mouse pituitary tumour cells.

To study the cellular mechanisms of interleukin-1 (IL-1) in the pituitary corticotroph, we studied the properties of IL-1 receptors on a mouse pituitary ACTH-producing cell line, AtT-20. Scatchard plot analysis revealed a single type of receptor with a Kd (dissociation constant) of 93 pM, and 482 binding sites/cell. [125I]IL-1 alpha binding competed with IL-1 alpha and IL-1 beta in an equimolar fashion. A 24 h pre-incubation with either CRH, epinephrine or nor-epinephrine increased the [125I]IL-1 alpha binding sites in the AtT-20 cells and conversely, a similar pre-incubation with either dexamethasone or tumour necrosis factor-alpha (TNF alpha) decreased them without affecting the affinity of the receptors in either case.

Adrenocorticotropic Hormone

Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery.

There is currently accumulating evidence for bidirectional communication between the neuroendocrine and immune systems. Various cytokines have been suggested to be involved in the stimulation of stress hormone secretion during the times of infection and inflammation. To assess the possible involvement and pathophysiologic significance of cytokines in the mechanisms responsible for the perioperative stress response of the hypothalamo-pituitary-adrenal axis, we observed the changes of plasma adrenocorticotropic hormone and cortisol levels together with those of plasma endotoxin and cytokine levels. In patients undergoing pancreatoduodenectomy, perioperative stimulation of adrenocorticotropic hormone and cortisol secretion was accompanied by a significant elevation of plasma cytokine levels. Application of epidural block up to the upper thoracic levels failed to suppress this stress response effectively. In patients undergoing unilateral total hip replacement, the response of plasma hormone levels was smaller and briefer with no significant increase of plasma cytokine levels. Application of epidural block up to the lower thoracic levels suppressed this hormonal response almost completely. In patients undergoing pancreatoduodenectomy, a significant elevation of plasma endotoxin level was followed by a gradual but significant elevation of plasma tumor necrosis factor alpha and interleukin-6 levels. It seems likely that the stimulatory effects of these cytokines on the secretion of adrenocorticotropic hormone and cortisol might be involved in the development of the greater and more prolonged stress response of hypothalamo-pituitary-adrenal axis. Our present study suggests that not only neural input from the surgical wound but also stimulation of cytokine production were responsible for the development of the stress response of the hypothalamo-pituitary-adrenal axis during and after upper abdominal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone

Distribution and characterization of immunoreactive corticostatin in the hypothalamic-pituitary-adrenal axis.

Using an antiserum against synthetic rabbit corticostatin-1 (CS-1), we established a specific RIA for CS-1 and examined its distribution in various tissues, including the hypothalamic-pituitary-adrenal axis. Among the tissues examined, the highest levels of CS-1-like immunoreactivity (-LI) were found in the lung and spleen. CS-1-LI was also detected at relatively high levels in the pituitary, adrenal medulla, and small intestine, while it was barely detectable in the hypothalamus. Immunocytochemical studies revealed the widespread distribution of CS-1 in these tissues. Plasma CS-1 levels averaged 7.8 ng/ml and increased to 185.4 ng/ml in the presence of infection. CS-1-LI in the adrenal gland, small intestine, and hypothalamus also increased in rabbits with active inflammation. These data suggest that CS-1 may modify the hypothalamic-pituitary-adrenal axis in an endocrine or paracrine manner in response to infection.

Animals

Roles of interleukin-1 alpha and -1 beta in endotoxin-induced suppression of plasma gonadotropin levels in rats.

Using specific antagonists to rat interleukin (IL)-1 alpha and IL-1 beta, the roles of these IL-1s in endotoxin-induced suppression of plasma gonadotropin levels in freely-moving rats were studied. In orchiectomized rats, recombinant rat IL-1 alpha and IL-1 beta administered into the lateral ventricles almost equipotently suppressed plasma LH levels. Twenty five micrograms of bacterial endotoxin or lipopolysaccharide (LPS) administered similarly showed a comparable effect as that of 1 microgram IL-1 alpha or IL-1 beta, and completely lowered plasma LH levels by 60 min after the injection. To examine the roles of endogenous IL-1 alpha and IL-1 beta, anti-rat IL-1 alpha antiserum (anti-IL-1 alpha) and a recombinant human IL-1 receptor antagonist (IL-1ra) were used as specific blockers for IL-1 alpha and IL-1 beta, respectively. Anti-IL-1 alpha (10 microliters) or IL-1ra (10 micrograms) administered intracerebroventricularly (icv) with 25 micrograms LPS, significantly attenuated the LPS-induced effect on plasma LH levels during the first 60 min after LPS infusion, but not during the second 60 min. LPS at a dose of 5 micrograms induced smaller but still significant changes in plasma LH levels compared with 25 micrograms LPS or 1 microgram IL-1 beta. IL-1ra (10 micrograms) completely blocked LH suppression induced by 1 microgram IL-1 beta, but did not completely reverse the changes of LH induced by 5 micrograms LPS. IL-1ra injected iv also significantly attenuated the early suppressive effect of iv administered LPS, but not its late effect on plasma LH levels. However, iv administered IL-1ra had no influence on the effects of icv administered LPS. These data indicate that at least a part of plasma LH suppression caused by icv administered LPS is mediated via IL-1 alpha and IL-1 beta synthesized within the brain, while factor(s) other than IL-1 also participate in the LPS-induced change, particularly during the later period. A similar mechanism may also work peripherally in the case of iv administered LPS-induced plasma LH suppression.

Animals

Syntheses of oligonucleotide derivatives with P(V) porphyrin and their properties.

Two types of oligonucleotide derivatives which are substituted by P(V) porphyrin at the phosphorus atom of an internucleotidic linkage and at the 5'-terminal internucleotidic linkage via a spacer were synthesized (Fig. 1), and hybridization capabilities of them with complementary oligonucleotides were evaluated. A novel method for a sensing of oligonucleotide by the fluorescence quenching via photo-induced electron transfer between the P(V) porphyrin labeled oligonucleotide and pyrene-labeled one on the oligonucleotide template is reported.

Base Sequence

Correlation between bromodeoxyuridine-labeling indices and patient prognosis in cerebral astrocytic tumors of adults.

Bromodeoxyuridine (BUdR), a nonradioactive thymidine analogue, is taken up by cells in S-phase, and the ratio of BUdR-positive nuclei to the total number of cells counted is defined as the labeling index (LI). In this study, BUdR LI and the clinical course of 50 cerebral astrocytic tumors in adults were analyzed. The obtained LI distributed continuously in a broad range from 0% to 19%. The mean LI of 28 glioblastomas, 12 anaplastic astrocytomas, and ten astrocytomas were 8.5%, 4.2%, and 1.2%, respectively, and these differences were statistically significant (P = 0.05). In the analysis of LI and the recurrence-free period (RFP), regardless of the histologic findings, 23 patients with LI more than 5% had a median RFP of 9.0 months; the median RFP of nine patients with LI of 3% to 5% was 14.7 months. Nine of 13 patients with LI less than 3% have not yet recurred after a median follow-up of 36 months. These differences were also statistically significant by the generalized Wilcoxon test (P = 0.05). The proliferative potential reflected by the BUdR LI is a good clinical indicator for predicting the rate of tumor growth in cerebral astrocytic tumors. In combination with histologic diagnosis, BUdR LI could help in determining a patient's prognosis more precisely.

Adult

Synthesis and properties of oligonucleotide derivative with P(V) porphyrin.

Oligonucleotide derivatives with a P(V)tetraphenylporphyrin at the internucleotidic phosphodiester linkage were synthesized. Their interactions with the complementary oligonucleotide and pyrene-labeled oligonucleotide were investigated. Fluorescence from the porphyrin moiety was strongly quenched by the addition of the pyrene-labeled oligonucleotide and the template oligonucleotide.

Base Sequence

[Clinical effects of theophylline in the therapy of intractable asthmatic children. II. Theophylline therapy and behavior problems in children with asthma].

This study examined the relationship between long-term theophylline therapy and behavior problems in 14 asthmatic children that includes 5 intractable cases and 24 non-asthmatic children. Asthmatic children have received theophylline therapy and cromolyn inhalation for 3.6 +/- 3.8 years. Subjects were tested on neuropsychologic batteries; behavior problems and personality of children questionnaire, child behavior checklist, caffeine-like side effects questionnaire, manifest anxiety scale, visual attention test, Uchida-Kraepelin test and soft neurological signs. These tests were repeated with an interval of 1 to 12 weeks. Parents noted caffeine-like side effects, stomach ache and difficulty in sleeping, in their child during the theophylline therapy. The caffeine-like side effects decreased after stopping theophylline therapy. The rate of mistake in Uchida-Kraepelin test for the asthmatic group and for the intractable cases was significantly higher than that of the control group. Time of the sequential finger thumb opposition of the soft neurological signs was significantly prolonged in asthmatic group. There was no significant change in the other tests between asthmatic and non-asthmatic children and before and after stopping theophylline therapy. It seems that behavior problems and learning disability observed in the asthmatic children are due to the pathogenesis or symptoms of asthma rather than the effect of long-term theophylline therapy.

Administration, Inhalation

[Fundamental study of alveolar bone measurements in the hamster using an apparatus for intraoral radiography].

Morphometry of bone resorption in experimental periodontitis is performed primarily by radiography after sacrificing the animal or by microscopy of histopathologic specimens prepared from resected jaw bones. Both techniques are recognized as effective examinations. However, these are cross-sectional procedures involving resection of specimens, and for evaluation of changes in symptoms from reversible to irreversible, which are characteristic of periodontal diseases, or for follow-up of the aging process, application of standard radiography and a method to properly interpret the images obtained are needed. The author designed an apparatus that allows in site radiographic evaluation of individual animals, which has not been considered in conventional morphometric analyses of periodontal bone resorption. With this apparatus, radiograms are obtained by placing a soft X-ray film in the oral cavity and exposing it with a soft X-ray projector. As a fundamental study of the usefulness of this apparatus, author evaluated the optimal conditions of radiography for imaging of soft tissues, the accuracy of the measurements, and the method for bone measurement. Experimental bone resorption was induced in the mandibular alveolar bone of the hamster, the changing lesion was radiographed daily with this apparatus by the standard procedure, and measurements were attempted by the length measuring method and densitometry method. The following results were obtained: 1) The intraoral apparatus was designed to allow radiography of both sides of the mandibular molar regions of the hamster. The apparatus consisted basically of a film cartridge, an opening, and a fixing portion. The projection angle can be adjusted by the fixing portion so that soft X-ray is always projected orthoradially on the surface of the film, and the soft X-ray film can be kept attached to the hamster mandibular molar region by microadjustment of the opening and the calibrations for angle adjustment. With this apparatus, the percent enlargement was minute at 0.43%, and the reproduced image showed a correlation of 0.998 with the standard. (2) The radiographic conditions of a focus-film distance of 30 cm. acceleration potential of 40 kV, current of 2.5 mA, and projection time of 20 sec. were considered to be optimal in hamsters with regard to the quality of the image and stress to the animals. 3) Palladium used as a reference for densitometry was highly manipulatable with a maximum thickness of 0.1 mm and was appropriate for estimation of the mineral content of the hamster mandibular bone. 4) According to morphometry of the hamster lower jaw alveolar region by the length measuring method and the densitometry method in serial standard soft X-ray images, bone absorption was greater in the order of the diet + inoculation group, diet group and control group in a decreasing order. In the control group, the growth of the bilateral alveolar region reached a peak 23 weeks (about 165 days) after birth, and bone resorption probably due to aging was thereafter observed at the apex of the alveolar bone.

Alveolar Bone Loss

[A case of surgical excision of intracerebral cavernous angioma in a patient with thrombasthenia].

A case of thrombasthenia (Glanzmann) associated with an intracerebral cavernous angioma in a 32-year-old woman is reported. Since her childhood, the patient had experienced a tendency to develop purpura following minor trauma. But she had not had major bleeding even during pregnancy and delivery. On April 4, 1987, she presented generalized convulsion. A high density mass in the right temporal lobe was demonstrated with CT scan. Carotid angiogram was normal except that the right anterior choroidal artery was stretched. Inhomogeneous signal intensities in T1- and T2-weighted MRI images were seen in the tumor locus. The clinical diagnosis was cavernous angioma which was complicated with intracerebral hemorrhage. The patient had a disorder of platelet function without thrombocytopenia. Her bleeding time was markedly prolonged. Because of this, we did not try surgical excision at first. During the 13-month observation period, however, intracerebral bleeding occurred 5 times. We decided to operate on the patient using fresh blood and platelet transfusion. The postoperative course was uneventful and pathological diagnosis confirmed cavernous angioma. We would like to emphasize possible pitfalls in treating cases of intracerebral angioma with thrombasthenia.

Adult

[A case of acute spinal epidural hematoma in a patient with antiplatelet therapy].

The authors report a case of acute spinal epidural hematoma occurring in a patient receiving antiplatelet drugs. A 76-year-old man with a history of cerebral infarction had been taking antiplatelet agents for one year. He suddenly developed severe back pain which woke him from sleep, and numbness of his lower extremities was then noted. He was hospitalized 15 hours later. Neurological examination revealed flaccid paralysis of both lower extremities with negative Babinski's reflex, and sensory disturbance below the level of L1. The bleeding time and prothrombin time were prolonged. Computed tomographic (CT) scan revealed a biconvex, relatively hyperdense mass in the posterior spinal canal at the level of T12. Metrizamide myelography disclosed an incomplete blockage caused by an epidural mass at the level of T11. Post-myelographic CT scan demonstrated a sharply demarcated extradural filling defect at the level of T11. Seventeen hours after the onset of symptoms, an emergency laminectomy was performed extending from T12 to L3, and the epidural clot was totally evacuated. Histological examination of the capsule of the hematoma revealed no vascular anomalies. The patient made a good postoperative recovery. To the authors' knowledge, this is the first reported case of spontaneous intraspinal hemorrhage in a patient taking antiplatelet drugs. Acute onset of persistent pain anywhere along the spinal axis and the development of spinal neurological deficits in a patient on antiplatelet therapy should raise the suspicion of a spinal epidural hematoma. It should be stressed that prompt neuroradiological diagnosis and rapid surgical decompression are essential to allow good recovery. The present case illustrates that neurological emergencies can occur in patients receiving antiplatelet therapy.

Acute Disease

rCBF in brain tumours as measured by xenon enhanced CT.

Heretofore, the rCBF of brain tumours has been measured by the 133Xe clearance method, but the resolving power of this method is limited and flow values measured by this method correlate poorly with the anatomical structure. On the other hand, our xenon-enhanced method has several advantages over the conventional isotope method and enables us to evaluate rCBF with a resolving power of 4 mm. With this method, we evaluated rCBF in 15 brain tumour cases and obtained the following results: Mean rCBF value of the tumour is a little lower than that of grey matter and higher than that of white matter with oedematous change. The xenon-enhanced method enables us to distinguish the demarcation between the tumour area and the surrounding oedematous area and offers useful information for determining the extent of resection in surgery. Mean lambda value of the tumour which is not obtainable in vivo by radionuclide scanning, was 1.02 +/- 0.06 for gliomas and 0.72 +/- 0.09 for metastatic tumours.

Adult

[Surgical indication for extracranial-intracranial arterial bypass determined by cerebral blood flow study and neurological function--a retrospective study].

In order to establish more strict and objective indication for EC-IC bypass, a retrospective study on the surgical effect on cerebral blood flow (CBF) and neurological function was carried out in 37 cases. STA-MCA bypass was carried out on 20 cases with IC occlusion and 17 cases with MCA occlusion. Twenty-two cases with completed stroke, 9 cases with TIA and 6 cases with RIND. All patients were able to ambulate before surgery, and none of them were hemiplegic. CBF study by 133Xe inhalation method was carried out before and 2 to 4 weeks after surgery. Bypass was patent in all cases. Thirty percent of all cases showed more than 16% increase in CBF (++ group) on the side of bypass surgery and another 30% demonstrated 6 to 15% increase (+). On the other hand 30% of cases appeared to be unchanged (+/-), and 10% showed more than 6% decrease (-). The less the pre-operative CBF value was, the more the post-operative CBF was expected to be increased. Patients with pre-operative CBF less than 60% of normal value (ISI = 63 +/- 4) showed remarkable increase (++), and those with 60 to 70% showed moderate increase (+). Contrarily, cases with more than 70% of normal value showed either no change or decrease. Neurological change was evaluated as to disappearance of TIA attack and improvement of hemiparesis or mental dysfunction. Seventy-seven percent of patients in groups with (++) and (+) effect on CBF showed improvement in neurological function, whereas only 27% of patients in groups with (+/-) and (-) effect demonstrated improvement, which was statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain