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Biomedical subjects

H Segawa

Publications and source records attributed to H Segawa.

At least 91 records · Page 5Linked to original sources

Bacterial lipopolysaccharide-induced expression of interleukin-6 messenger ribonucleic acid in the rat hypothalamus, pituitary, adrenal gland, and spleen.

Whereas the stimulatory effect of interleukin-6 (IL-6) on the hypothalamic-pituitary-adrenal (HPA) axis is well established, its mode of action in this axis has yet to be fully elucidated. To further study the role of IL-6 in the HPA axis, we compared the expression of IL-6 messenger RNA (mRNA) in the rat hypothalamus, pituitary, and adrenal gland with that in the spleen after ip or intracerebroventricular (icv) administration of bacterial lipopolysaccharide (LPS). After either ip or icv administration, LPS induced the expression of IL-6 mRNA, which consists of 1.2 kilobases (kb) and 2.4 kb subclasses, in all these tissues of the HPA axis as well as in the spleen. Although we used 100 times less amount of LPS for the icv administration than that used for ip LPS, plasma ACTH levels in both the conditions rapidly reached comparable levels. This icv dose induced IL-6 mRNA expression in the hypothalamus faster than ip dose but also stimulated IL-6 mRNA expression in the hypothalamus, pituitary, and adrenal gland more effectively and smoothly than the ip LPS dose did. Northern blot analysis revealed that in the hypothalamus, pituitary, and adrenals, the predominant subclass of IL-6 mRNA was not 1.2 kb but 2.4 kb. In contrast, this subclass was the minor component in the spleen induced under the same circumstances. These findings indicate that IL-6-synthesizing cells in the HPA axis differ in character from those in the spleen, and that LPS applied in vivo may modulate IL-6 expression in these cells directly and/or indirectly through secondarily activated functions in the neuronal or endocrine systems.

Animals↗

Granulomatous angiitis of the central nervous system--case report.

A 22-year-old male presented with granulomatous angiitis manifesting as headache. Computed tomography (CT) demonstrated a low-density area and ring-like enhancement in the right frontoparietal region. Steroid therapy caused rapid improvement in the signs and symptoms. Withdrawal of steroid was followed by recurrence of the headache and low-density area. The steroid treatment was resumed until he became asymptomatic 3 months after admission. He was followed up as an outpatient once every 2 weeks. One month after discharge, he complained of mild headache, and CT again demonstrated a mild increase in the low-density area. He was followed up continuously without steroid treatment. Two months after discharge, he suddenly lost consciousness, and CT demonstrated multiple intracerebral hematomas in the bilateral parietal regions. Removal of an intracerebral hematoma in the right parietal region and external decompression were carried out, but he died 3 days later. Histological examination of tissues from the right parietal cortex and leptomeninges demonstrated granulomatous inflammation with several giant cells in the vessels of the cerebral cortex and leptomeninges.

Adult↗

Photochemical cleavage of DNA by phosphorus(V) porphyrin derivatives.

Photocleavages of double-stranded circular DNA and oligonucleotide were investigated by the use of phosphorus(V)tetraphenylporphyrin (P(V)TPP) derivatives. The P(V)TPP derivatives cleaved the DNA and the oligonucleotide under the visible light irradiation, in air and in argon, respectively. It is suggested that the photocleavage reactions include an electron transfer mechanism as well as a singlet oxygen (1O2) one.

Bacteriophage phi X 174↗

Lowered insulin-sensitive Ca2+ transport in cultured glomerular mesangial cells from spontaneously hypertensive rats.

Insulin-resistant state has been postulated in the pathogenesis of hypertension. To investigate the role of insulin in Ca2+ regulation of the glomerular mesangial cell (MC) in hypertension, the effect of insulin on Ca2+ transport and intracellular-free calcium concentration ([Ca2+]i) was measured in serially passaged cultured MC obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Insulin produced a substantial increase in 45Ca uptake as well as [Ca2+]i in quiescent cultured MC from both strains. These stimulatory effects of insulin were completely inhibited by diltiazem, and partially inhibited by H-7, TMB-8 and 5-N,N (hexamethylene) amiloride (HMA), but were not inhibited by W-7 or trifluoroperazine. Although basal ([Ca2+]i) values were not different, insulin-sensitive 45Ca uptake of SHR MC was significantly less than that of WKY MC. Insulin-sensitive increase in ([Ca2+]i) of SHR MC was also less than that of WKY MC. We concluded that insulin increased 45Ca uptake, leading to an increase in ([Ca2+]i), presumably through the voltage-dependent Ca2+ channel, intracellular Ca2+ release and/or proteinkinase C-mediated mechanisms in cultured MC. Blunted response of insulin-sensitive Ca2+ uptake and ([Ca2+]i) in SHR MC suggested differential regulation of Ca2+ transport in response to insulin in the kidney with primary hypertension.

Animals↗

[Cerebral hemorrhage in a case of antiphospholipid antibody syndrome].

We describe a 36-year-old man with antiphospholipid antibody syndrome complicated by cerebral hemorrhage. In December 1991 he was brought to another hospital with sudden onset of left hemiparesis and status epilepticus. He had been well previously. A CT scan and MRI showed a cerebral hematoma located in the right frontoparietal region. Twelve days later he was transferred to our hospital. Although a CT scan, MRI, and cerebral angiography were repeated, they did not reveal any abnormality regarding an etiology. Only persistently abnormal finding in laboratory studies was positive for lupus anticoagulant and anticardiolipin antibody, i.e. antiphospholipid antibodies. There was no serological evidence of SLE or other autoimmune diseases. Stereotactic biopsy of the hematoma wall and scalp artery showed no abnormality. Based on above findings we conclude that antiphospholipid antibodies have played an important role for the hemorrhage. Antiphospholipid antibody syndrome should be considered in a case of an unexplained cerebral hemorrhage especially in a young and normotensive patient.

Adult↗

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↗