Biomedical subjects

H Okamura

Publications and source records attributed to H Okamura.

At least 307 records · Page 17Linked to original sources

PubMed1997

Peptide expression in GABAergic neurons in rat suprachiasmatic nucleus in comparison with other forebrain structures: a double labeling in situ hybridization study.

We investigated the characteristics of GABAergic neurons in the rat suprachiasmatic nucleus (SCN) in normal untreated rats by examination of co-expressed peptides. We adopted double labeling in situ hybridization using a digoxigenin-labeled glutamic acid decarboxylase (GAD) riboprobe and 35S-labeled peptide riboprobes. GAD mRNA-positive neurons were distributed throughout the SCN from the rostal to the caudal pole. In the dorsomedial part of the SCN, most GAD mRNA-positive neurons co-expressed arginine vasopressin mRNA. In the ventrolateral part of the SCN, about two thirds of GAD mRNA-positive neurons co-expressed vasoactive intestinal peptide (VIP) mRNA. Co-expression of GAD and somatostatin mRNA was observed in virtually all neurons of the intermediate part of the SCN. In contrast, these peptidergic traits were poorly expressed in hypothalamic GABAergic neurons outside the SCN. Vasopressin mRNA-positive cells in the supraoptic nucleus did not express GAD mRNA, and co-expression of somatostatin mRNA and GAD mRNA was rare in the periventricular hypothalamic nucleus. Similarly, the VIP mRNA co-expression ratio of GABAergic neurons in the cerebral cortex was far lower than that in the SCN.

Animals↗

PubMed1997

Mitogenic activity of Clostridium perfringens enterotoxin in human peripheral lymphocytes.

Clostridium perfringens enterotoxin (CPE) was found to possess interferon (IFN)-producing and mitogenic activities to human peripheral blood mononuclear cells. Both activities were demonstrated only in the T lymphocyte-rich fraction from healthy volunteers. The IFN produced appeared to be gamma-type since the activity of the IFN was neutralized by antiserum against human IFN-gamma. With formalin-treated CPE, the IFN-producing and mitogenic activities were weakly found. Similar findings were also obtained in the mouse lethality and cytotoxicity to Vero (African green monkey) cells, suggesting that the biological activities of the CPE molecule may be existing on the similar (or the same) sites. From these findings, human peripheral T cells may be one of useful reagents to study the mode of action of CPE since CPE was found to be a T cell mitogen which is supposed to be a superantigen.

Adult↗

PubMed1997

Distribution and fine structure of macrophages in the human ovary during the menstrual cycle, pregnancy and menopause.

We evaluated the distribution and ultrastructural characteristics of macrophages in the ovaries of women of reproductive ages, during pregnancy, and after menopause, by immunohistochemistry and transmission electron microscopy. Macrophages appeared around the ovarian follicle with its development. Their organelles were poorly developed, and no vacuoles or granules were observed in the cytoplasm. Macrophages were also present in the cavity of the atretic follicle, being larger in size than those in the developing follicle and characterized by cytoplasmic vacuoles and granules of a lysosomal nature. With the luteinization of the follicle, macrophages were seen to be distributed inside and outside the corpus luteum, but constituted only a minor population as compared with other kinds of leukocytes. The intracellular organelles were well-developed, including the lysosomal granules. In early pregnancy, the number of macrophages was noticeably increased in the corpus luteum. They were observed mainly outside the corpus luteum, and stained strongly with hCG immunohistochemically. Macrophages were present in the regressing corpus luteum and in the corpus albicans. Numerous lipid droplets and elongated cholesterol crystals were seen in the cytoplasm. Macrophages therefore appeared to be present throughout the ovarian cycle and may be involved in the development and atresia of the follicles and the progression and the regression of luteal tissues.

Adult↗

PubMed1997

MR imaging of the fetus by a HASTE sequence.

OBJECTIVE: The value of a half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence, in which high-resolution heavily T2-weighted images can be obtained within 2 sec, was evaluated in the imaging of the fetus during the second or third trimester. MATERIALS AND METHODS: Eighteen women with complicated pregnancies as revealed on a sonogram during the second and third trimesters (16-36 weeks' gestation) were studied with a 1.5-T superconductive MR imaging unit that used a body phased-array coil. After informed consent, T1-weighted fast low-angle shot images, T2-weighted turbo spin-echo images, and HASTE images were obtained without any premedication. Images were analyzed with regard to image quality, degree of blurring, visualization of the normal fetal organs, and visualization of fetal and maternal abnormalities. RESULTS: On HASTE sequences, visualization of the fetal brain, visceral organs (lung, heart, liver, kidney, and bladder), extremities, and umbilical cord were significantly better than on fast low-angle shot or turbo spin-echo sequences (p < .01). In the brain, the white matter-gray matter distinction, gyrus formation, and myelination of the brain were clearly revealed by the HASTE sequence. Pathologic processes including fetal abnormalities (anomalies of the central nervous systems [n = 5], placenta previa [n = 1], and transverse lie in the third trimester [n = 1]) and maternal abnormalities (leiomyoma [n = 5], ovarian tumors [n = 3], and hydronephrosis [n = 1]) were clearly seen on HASTE imaging. The peak specific absorption rate for RF exposure in these studies was less than 1.5 W/kg. CONCLUSION: In situations when sonography is suggestive but not definitive, MR imaging with a HASTE sequence allows clear fetal imaging with high T2-weighted contrast.

Adult↗

PubMed1997

Virtual reality support system in palliative medicine.

We have been examining the potential value of a VR system for the palliative care of cancer. We recently developed palliative care system which consists of a 100-inch-wide screen, HMD (Head-mounted display) and 8-mm video or a PC. Our goal is to use VR techniques to help alleviate a patient's stress and concern regarding their cancer during hospitalization. We can use this system to present (1) personal video movies, (2) video letters from friends and family, (3) personal video instruction about medical examinations, and (4) interactive information about their cancer using a PC-based VR system. Our preliminary results indicate that interesting VR presentations are useful for reducing stress.

Computer-Assisted Instruction↗

PubMed1997

Self-injurious behavior and dopaminergic neuron system in neonatal 6-hydroxydopamine-lesioned rat: 1. Dopaminergic neurons and receptors.

Dopaminergic neuronal circuits underlying self-injurious behavior (SIB) were investigated in neonatal 6-hydroxydopamine (6-OHDA)-induced dopamine-depleted rats. The extent of damaged dopamine neuronal areas was investigated by quantitative analysis of tyrosine hydroxylase (TH) immunocytochemistry and the biochemical quantification of dopamine levels in three groups; neonatal 6-OHDA-treated rats showing SIB (the SIB(+) group), neonatal 6-OHDA-treated rats not showing SIB (SIB(-) group) and neonatal saline-treated controls (control group). In the SIB(+) group, both dorsal and ventral mesostriatal dopaminergic neuron systems were severely destroyed, but the mesocortical dopaminergic neuron system and intrahypothalamic dopaminergic neuron system remained intact. In SIB(-) group, the dorsal mesostriatal dopaminergic neuron system was severely destroyed, but the ventral mesostriatal dopaminergic neuron system was only partially impaired. The effect of neonatal 6-OHDA treatment on dopaminergic receptors was analyzed by quantitative in vitro receptor autoradiography using [3H]SCH-23390 for the D1 site and [3H]YM-09151-2 for the D2 site. Although D1 and D2 binding was not altered in the dorsal and ventral striatum, cerebral cortex and hypothalamus, the D1 binding in the substantia nigra pars reticulata was increased in the SIB(+) group compared with the SIB(-) or control groups. The D1 binding assay using the membrane preparation of the nigral homogenates, revealed that the KD did not change, but the Bmax in the SIB(+) group was higher than that in the SIB(-) or control groups (P < .05). These results suggest that the region-specific change of dopaminergic neurons and receptors underlies the manifestation of SIB.

Animals↗

PubMed1997

Self-injurious behavior and dopaminergic neuron system in neonatal 6-hydroxydopamine-lesioned rat: 2. Intracerebral microinjection of dopamine agonists and antagonists.

Intracisternal 6-hydroxydopamine treatment to newborn rats caused massive and permanent damage of brain dopaminergic neurons, and many of these animals show self-injurious behavior (SIB) when loaded by systemic injection of L-dihydroxyphenuylalanine (L-DOPA) or D1 agonist, SKF-38393. SIB occurred at life-long time in neonatal 6-hydroxydopamine-lesioned rats, because SIB confirmed rats at 4 to 6 wk all showed SIB at 3 to 5 mo and at 12 to 13 mo after L-DOPA loading. To elucidate the brain locus important for the induction and cessation of SIB, in our study, we microinjected dopamine agonists and antagonists into various dopamine neuron innervating areas. L-DOPA-induced SIB was inhibited by the injection of a D1 antagonist, SCH-23390 (5 microg), into the bilateral substantia nigra, but not into the bilateral caudate-putamen or nucleus accumbens. The microinjection of YM-09151-2 (10 microg), a D2 antagonist, into these regions could not stop SIB. For examining the important area for the induction of SIB, we microinjected SKF-38393, D1 agonist, and/or LY-141865, D2 agonist (each 1 microg) into bilateral (or ipsilateral) caudate-putamen and substantia nigra. SIB was induced only in the case of D1 and D2 receptors in both the bilateral caudate putamen and bilateral substantia nigra being stimulated simultaneously by the mixed application of SKF-38393 and LY-141865. SIB was not induced by the sole injection of SKF-38393 into bilateral caudate-putamen or bilateral substantia nigra. These observations suggest that both caudate-putamen and nigral D1- and D2-like receptors are important for the induction of SIB, but, for cessation of SIB, up-regulated nigral D1 receptor is crucial.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1997

Cytokine gene expression in the foot pad and spleen of BALB/cAJcl mice infected with M. leprae.

The cytokine mRNAs expressed in the foot pads and spleens of BALB/cAJcl mice infected with Mycobacterium leprae were studied by the reverse transcriptase-polymerase chain reaction (RT-PCR) method using cytokine-specific primers for interleukin-1 alpha (IL-1 alpha), -2, -4, -6, -10, -12-(p40), gamma interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and TNF-beta, and then for CD4 and CD8 markers. The pattern of cytokine gene expression in the foot pad which supports M. leprae growth was different from the expression in the spleen which does not permit M. leprae multiplication in mice. Before BALB/cAjcl mice were infected with M. leprae, IL-1 alpha and TNF-beta mRNAs were expressed physiologically in the foot pad while all of the cytokine genes examined were expressed in the spleen. In the foot pads of mice inoculated with M. leprae, in addition to the physiological appearance of IL-1 alpha and TNF-beta mRNAs, these signals were intensified. TNF-alpha expression was induced by the infection. On the other hand, in the spleens of mice inoculated with M. leprae, CD4 mRNA expression disappeared on day 1 of the infection, which was accompanied by the reduced expression of IL-2, -4, -6, and -12 mRNAs. The recovery of CD4 mRNA expression at a latter stage was accompanied by a corresponding increase of the cytokine mRNA expression. It was suspected that these results might permit restricted growth of M. leprae in the foot pads of normal mice. Furthermore, our study suggests that tissue-specific, local, immunologic characteristics are important in M. leprae growth.

Animals↗

PubMed1997

Effects of highly purified eicosapentaenoic acid on vascular reactivity to angiotensin II and norepinephrine in pregnant rabbits.

OBJECTIVE: We sought to determine whether the pressor response to an infusion of angiotensin II during pregnancy would be reduced by the oral administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E). METHODS: We administered EPA-E orally to nine pregnant rabbits (200 mg/kg/day) from day 5 of gestation to day 5 postpartum. Pressor responses to graded doses of intravenously infused angiotensin II and norepinephrine were examined serially during pregnancy and the postpartum period. RESULTS: The EPA-E-treated, as well as the control pregnant rabbits (n = 6), were significantly less responsive to the vasoconstrictor effects of angiotensin II throughout pregnancy than the nonpregnant rabbits (n = 8). The vascular reactivity to infused angiotensin II in EPA-E-treated pregnant rabbits, as compared with that of control pregnant rabbits was unchanged, but reactivity to angiotensin II was lower only on the fifth postpartum day. The pressor responses to infused norepinephrine were unchanged during pregnancy and in the postpartum period, and EPA-E did not alter the response. The litters of four of the nine rabbits were partially or completely macerated. CONCLUSION: EPA-E did not reduce the already blunted pressor responsiveness to angiotensin II during pregnancy in rabbits. The effect of EPA-E in a state of increased pressor responsiveness during pregnancy due to a deficiency of vasodilatory prostaglandins needs to be determined.

Angiotensin II↗

PubMed1997

[Cytokine producing ability of peripheral blood mononuclear cells in the clinical course of pulmonary tuberculosis].

Interferon-gamma (IFN-gamma) and interleukin-10 (IL-10)-producing ability of peripheral blood plastic-dish adherent cells and non-adherent cells obtained from patients with active pulmonary tuberculosis (N = 17) and healthy controls (N = 14) upon stimulation with purified protein derivatives (PPD) were assessed. Adherent cells and non-adherent cells were obtained two times from each patient with active pulmonary tuberculosis without any underlying diseases, on admission before the initiation of administering anti-tuberculous drugs and 2 months later from the negative conversion of Mycobacterium tuberculosis in sputum culture. ELISA was performed to measure IFN-gamma and IL-10 levels in culture media of adherent cells and non-adherent cells stimulated with PPD. IFN-gamma levels produced by non-adherent cells on admission were significantly higher than that of healthy controls (p < 0.001). Elevated IFN-gamma levels on admission was reduced after treatment for tuberculosis (p < 0.03), but still remained higher than that in healthy controls. IL-10 levels of non-adherent cells of patients were lower than those of healthy controls, although the difference was not significant. IL-10 levels produced by non-adherent cells on admission correlated with the time needed for negative conversion of bacilli in sputum culture (p < 0.05). IL-10 level produced by adherent cells from nutritionally normal patients were significantly higher than that of healthy controls (p < 0.05), and elevated IL-10 level was significantly reduced after therapy (p < 0.05). In the normonourished patients, the time needed for negative conversion of the bacilli in sputum culture of patients kept higher level of IL-10 of non-adherent cells (N = 5) was significantly longer than that of patients reduced IL-10 level after therapy. These results suggest that IL-10 produced by monocytes may diminish the TH1 responses of patients with pulmonary tuberculosis.

Acute Disease↗

PubMed1997

[A case of Mycobacterium intracellulare infection associated with sinobronchial syndrome].

The patient was 71-year-old male with a history of sinobronchial syndrome since 8 years ago. He has been suffering from cough, sputum and upper abdominal discomfort since January 1994. He was diagnosed as an early gastric cancer by endoscopy, and his chest X-ray film showed an infiltrative shadow in the right upper lung field. A smear of the sputum specimen was positive for acid fast bacilli, which were later identified as Mycobacterium intracellulare. In this case, before the Mycobacterium intracellulare infection, it was confirmed that his mucociliary transport was severely impaired by using aerosol inhalation cine-scintigraphy. This case suggests that an impairment of the local defence mechanisms may play an important role in the pathogenesis of Mycobacterium intracellulare infection.

Aged↗

PubMed1997

[The relation between diabetes mellitus and IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and monocytes in patients with pulmonary tuberculosis].

Diabetics are prone to bacterial infection in part, due to polymorphonuclear neutrophil dysfunction, but the precise mechanism is not yet fully explained. Of many complications, diabetes mellitus (DM) is one of the most common diseases, which causes pulmonary tuberculosis. To elucidate the mechanism of susceptibility to tuberculosis infection in patients with diabetes mellitus, we measured IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and autologous monocytes stimulated with live BCG in patients with pulmonary tuberculosis complicated with DM (TB + DM) or without DM (TB) and healthy controls. The levels of IFN-gamma and IL-12 production in TB patients were significantly lower than those in the control. These cytokine productions were also lower in TB + DM patients than in TB patients significantly. The level of IL-10 production in TB patients were highest among these three groups. The production of this cytokine in TB + DM patients was lowest. The level of IFN-gamma production was significantly lower in TB + DM patients under poor DM control than in those patients under good DM control and showed a significant negative correlation to HbA1c, an indicator of diabetic control. The period for negative conversion of culture finding in TB + DM patients under poor control was prolonged when compared with those in TB patients. These results demonstrated the difference in cytokines secretion profile between TB patients and TB + DM patients, and suggest that the immunological mechanism underlying pathogenesis of tuberculosis might work differently between these two patients groups.

Adult↗

PubMed1997

The termination of optic nerve fibers in the albino mouse.

To establish the terminal sites of the optic nerve fibers in the albino mouse, the immunohistochemical method using cholera toxin, subunit B (CTB), as well as three kinds of selective silver impregnation methods for degenerating nerve fibers were used. Termination was confirmed in the following nuclei: bilateral dorsal nuclei of the lateral geniculate body (LGB), ventral nuclei of LGB, preoptic areas, posterolateral nuclei, superior colliculi, suprachiasmatic nuclei, medial terminal nuclei of the accessory optic tract (AOT), and dorsal terminal nuclei of AOT. The percentage of the optic nerve fibers crossing at the optic chiasm was estimated at 90 to 95. Fibers from the unilateral retina were observed to terminate more in the contralateral nucleus. With regard to the suprachiasmatic nucleus, however, the terminations were observed to be distributed evenly and bilaterally.

Animals↗

PubMed1997

[CD4+ alpha beta T cell and gamma delta T cell responses to BCG in patients with pulmonary tuberculosis--comparison with healthy controls].

We demonstrated that CD4+ alpha beta (CD4+) and gamma delta T cell subsets from healthy donors had similar effector functions (cytotoxicity and cytokine production) in response to mycobacterial antigens, despite differences in the antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis, this study was undertaken to compare T cell functions between patients with pulmonary tuberculosis with no complications and healthy controls. Both resting and activated CD4+ and gamma delta T cells from the patient group proliferated in response to live BCG at a significantly lower rate than those from the control group. The cytotoxicity of BCG-pulsed monocytes and IFN-gamma production in both the CD4+ and gamma delta T cells from patients was significantly lower than those of controls. In contrast to IFN-gamma, significantly higher IL-10 production by both CD4+ and gamma delta T cells from patients was detected. The proliferative responses to BCG by CD4+ and gamma delta T cells from patients after antituberculous therapy were partially restored, but remained at lower levels compared with controls. These results suggest that not only a general deterioration in CD4+ and gamma delta T cells effector functions, but also suppressive factors (such as IL-10) might be responsible for the pathogenesis of pulmonary tuberculosis, and that the low response to BCG by both CD4+ and gamma delta T cells in patients with tuberculosis is in part attributable to patient predisposition.

Aged↗

PubMed1996

Antidiuretic action of tachykinin NK-3 receptor in the rat paraventricular nucleus.

Studies were performed on the central antidiuretic actions via the tachykinin NK-3 receptor in the rat hypothalamic paraventricular nucleus (PVN). Microinjections of the selective tachykinin NK-3 receptor agonist senktide (2-200 pmol) into the PVN resulted in prolonged inhibition of urine output in water-loaded rats, its effect being dose-dependent. The antidiuretic action of senktide was blocked by pretreatment with the vasopressin V2 receptor antagonist OPC-31260 (1 mg/kg, i.v.), but not by microinjection of the angiotensin II AT-1 receptor antagonist losartan (1 nmol) into the PVN. NK-3 receptor mRNA was strongly detected in the magnocellular part of the PVN and the supraoptic nucleus (SON) of the hypothalamus as detected by in situ hybridization histochemistry. Moreover, [3H]senktide binding sites were also detected in the PVN and the SON by receptor autoradiography. These findings suggest that NK-3 receptors in the PVN may be involved in water regulation by stimulation of vasopressin secretion from the posterior pituitary gland, and that vasopressin caused water reabsorbtion via the kidney V2 receptor.

Angiotensin Receptor Antagonists↗

PubMed1996

Interferon-gamma-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells.

Fas ligand (FasL), expressed on activated T cells, plays a central role in regulating the immune response by inducing apoptosis in activated lymphocytes through binding to its receptor, Fas. We report here that a newly discovered cytokine, interferon-gamma-inducing factor (IGIF) (H. Okamura et al., Nature 378, 88, 1995), selectively enhances the FasL-mediated cytotoxicity of cloned murine Th1 cells, but not Th0 or Th2 cells. Anti-IFN-gamma antibody (Ab) did not block the IGIF-induced cytotoxicity of Th1 cells, nor did IFN-alpha, IFN-gamma, or TNF-alpha augment the cytotoxic activity of Th1, thus indicating that this enhanced cytotoxicity of Th1 cells was mediated by IGIF. In addition, IL-12 was also found to enhance the FasL-mediated cytotoxicity of Th1 cells, suggesting that Th1 cells possesses receptors for both cytokines although these cytokines can act via different pathways. The results thus show that IGIF, recently proposed as IL-18, might play a potential role in immunoregulation or in inflammation by augmenting the functional activity of FasL on Th1 cells.

Animals↗

PubMed1996

IFN-gamma-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones.

NK cells, non-T non-B immune effector lymphocytes, are localized in many organs, including liver, as well as in the circulation. To investigate the regulatory mechanism of killing apparatus in hepatic NK cells, we established IL-2-dependent NK cell clones from liver lymphocytes of BALB/c nude mice. To generate the NK cell clones, we incubated liver lymphocytes with a high dose of IL-2 in the presence of irradiated Kupffer cells, as feeder cells and as the source of IL-12, originally identified as NK cell stimulatory factor. Unless liver lymphocytes were incubated with both IL-2 and Kupffer cells, no cell growth was observed. Hepatic NK cell clones were established from this cell line by limiting dilution. The surface phenotypes of cloned NK cells were IL-2R beta-chain+ CD16+ CD3- IgM-. The clones did not express NK2.1, which is expressed by a half of NK-enriched spleen cells of BALB/c mice. Although the cells contained dense granules reactive to mAb against perforin, they exerted no conventional cytolytic activity against YAC-1. They constitutively expressed Fas ligand (FasL) and specifically killed Fas-positive target cells by fragmenting DNA. This Fas-FasL-mediated killing activity was enhanced by IFN-gamma-inducing factor, a recently identified novel cytokine produced by activated Kupffer cells, but was not affected by other Kupffer cell-produced cytokines, such as IL-12, IL-1beta, and TNF-alpha. Taken together, these findings suggest that hepatic NK cells participate in the immune response as effector cells through the Fas-FasL system in collaboration with cytokines from Kupffer cells.

Animals↗

PubMed1996

Relationship of neuropeptides to nitrergic innervation of the canine laryngeal glands.

The participation of vasoactive intestinal polypeptide (VIP) or calcitonin gene-related peptide (CGRP) in the nitrergic innervation of the canine laryngeal glands was investigated using a double-staining technique of NADPH-diaphorase (NADPHd) histochemistry and VIP or CGRP immunohistochemistry. NADPHd-positive nerve fibers with varicosities appeared to terminate in some acinar cells. Double staining revealed that NADPHd reactivity and VIP- or CGRP-like immunoreactivity were colocalized in some nerve fibers distributed around the acini. A cluster of NADPHd-positive cells were occasionally found in the larynx. Many NADPHd-positive cells had VIP-like immunoreactivity and no NADPHd-positive cells were CGRP-like immunoreactive. These findings suggest that nitric oxide participates in the neural control of the laryngeal exocrine secretion in cooperation with intrinsic VIP and/or extrinsic CGRP.

Animals↗