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Biomedical subjects

M Oikawa

Publications and source records attributed to M Oikawa.

At least 73 records · Page 4Linked to original sources
PubMed1994

Tissue-specific increase in norepinephrine turnover by central interleukin-1, but not by interleukin-6, in rats.

To examine the effects of brain cytokines on the sympathetic nervous system, norepinephrine (NE) turnover in peripheral organs (spleen, lung, diaphragm, pancreas, heart, liver, kidney, and interscapular brown adipose tissue) was assessed after intraperitoneal or intracerbroventricular administrations of human recombinant interleukin (IL)-1 beta and IL-6 in rats. An intraperitoneal injection of IL-1 (1 microgram/rat) accelerated NE turnover in the spleen, lung, diaphragm, and pancreas without appreciable effects in other organs examined. When IL-1 was injected intracerebroventricularly at much lower doses (1-100 ng/rat), a dose-dependent increase in NE turnover was observed in the spleen, lung, diaphragm, and pancreas. IL-6 did not affect NE turnover in every organ examined, even when it was given at much higher doses, 100 micrograms/rat and 100 ng/rat for intraperitoneal and intracerebroventricular injections, respectively. In contrast to tissue NE turnover, plasma corticosterone level was increased after the administration of IL-6 as well as IL-1, regardless of the site of administration. These results suggest that central IL-1, but not IL-6, increases sympathetic nerve activity in some specific organs, whereas both cytokines are effective for adrenocortical activation. A possible role of the sympathetic nervous system in physiological and immune responses to central IL-1 was discussed.

Animals↗
PubMed1993

Cytokine-induced change in hypothalamic norepinephrine turnover: involvement of corticotropin-releasing hormone and prostaglandins.

Changes in norepinephrine (NE) turnover in restricted brain regions were examined in rats after administration of the major mediators of the acute phase response, interleukin-1 beta (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF). An increase in NE turnover was observed after intraperitoneal injection of IL-1 (1 microgram/rat) in the whole hypothalamus and several specific hypothalamic nuclei, but not in the medulla oblongata and cerebral cortex. The stimulatory effect of IL-1 was mimicked by an intracerebroventricular injection of much lower doses of IL-1 (10-100 ng/rat). This IL-1-induced increase in hypothalamic NE turnover was blocked by the pretreatment with either indomethacin (cyclooxygenase inhibitor) or anti-corticotropin releasing hormone (CRH) antibody but not by naloxone. Intracerebroventricular injection of CRH increased NE turnover not only in the hypothalamus but also in the medulla oblongata and cerebral cortex. However, prostaglandin (PG) E2 and PGF2 alpha did not show such effect. It was therefore suggested that IL-1 activates noradrenergic neurons projecting to the hypothalamus by its direct action to the brain, and that CRH and eicosanoid-cyclooxygenase product(s) within the brain are involved in this process. In contrast, neither IL-6 nor TNF influenced brain NE turnover regardless of whether they were given intraperitoneally or intracerebroventricularly. Thus, although IL-6 and TNF, as well as IL-1, show common central effects such as fever and pituitary-adrenal activation, these effects may be independent of the activation of NE metabolism in the hypothalamus.

Animals↗
PubMed1993

Microscopical characteristics of uterine wall arteries in barren aged mares.

The morphology of the arteries in the uterine wall was studied in three multiparous aged mares that had suffered repeated pregnancy failure. The uterine wall arteries exhibited elastosis of the intima or adventitia, or both, resembling "physiological pregnancy sclerosis". In areas affected by elastosis, degeneration of the pre-existing elastic fibres and increased glycosaminoglycans were frequently observed. Newly formed elastic fibres were not evident. Delayed resorption due to disordered metabolic turnover of the elastin was thought to be an important factor in the pathogenesis of the arterial elastosis in the uterine wall.

Aging↗
PubMed1993

Pathological analysis of bone fractures in race horses.

Pathomorphological analysis was performed on fractured bones of 470 race horses. The most common fracture site was the limb (98% of cases), and the majority of fractures were intra-articular. Focal osteochondral lesions consisting of osteochondrosis, osteonecrosis and osteosclerosis were observed frequently in fractured and non-fractured bones. In the fractured bones, the lesions frequently appeared in the vicinity of the fractured site. Under the influence of antecedent osteochondrosis from the young stage, osteosclerotic and osteonecrotic lesions may have been induced by immoderate exercise and localized ischemia. These morbid conditions may be important as local predisposing factors for bone fracture because the osteosclerotic and osteonecrotic lesions may contribute to diminished resistance to torsion and shearing forces.

Age Factors↗
PubMed1992

Villous hypoplasia of the small intestine in neonatal foals.

To elucidate the pathomorphogenesis of extremely shortened small-intestinal villi, occurring spontaneously in neonatal foals, the morphology of the small intestine with stunted villi was studied in eight cases. All intestinal wall elements and the villi were poorly developed. Most villi were found to be extremely short throughout the entire length of the small intestine. The villous core consisted of undifferentiated, fibroblast-like cells held loosely together by ground substance which was rich in glycosaminoglycan. Development of the villous lamina propria was poor with respect to capillaries, lymphatic vessels, connective tissues and smooth muscle cells. When compared with the structure of small-intestinal villi in age-matched foals as controls, it appeared that the histological structure of the stunted villous interstitium had remained at the immature state observable during the intrauterine period. Hypoplasia of the intestinal villi was assumed to reduce the functional surface area available for absorption of colostrum, causing malabsorption in newborn foals.

Animals↗
PubMed1992

Histologic features of the carotid artery trifurcation in thoroughbreds.

The common, external, and internal carotid and occipital arteries were examined histologically at the trifurcation of the common carotid arteries in 13 Thoroughbred foals (0 to 30 days old) and 64 Thoroughbred adults (2 to 4 years old). Calcification in the media of the common carotid and external carotid arteries was observed in 3 of the 13 foals and in 30 of the 64 adult horses. Calcification resembled that seen in Mönckeberg's arteriosclerosis in human beings, the cause of which is unknown.

Animals↗
PubMed1991

2.5S nerve growth factor enhances survival, phagocytosis, and superoxide production of murine neutrophils.

The effect of 2.5S nerve growth factor (NGF) on survival, phagocytosis, and superoxide production of murine neutrophils was examined and compared with the effects of interleukin-3 (IL-3) and recombinant GM colony-stimulating factor (rGM-CSF). NGF enhanced the viability of neutrophils isolated from peripheral blood and peritoneal cavity in a dose-dependent way. IL-3 50 U/mL had no effect. rGM-CSF 50 U/mL had an effect similar to that of 50 ng/mL NGF. NGF also enhanced the phagocytosis of hydrophilic microspheres by peritoneal neutrophils, and the activity of NGF was greater than that of IL-3 or rGM-CSF. NGF enhanced the superoxide production induced by phorbol 12-myristate 13-acetate (PMA), which acts at postreceptor sites, and that induced by opsonized zymosan, a receptor-mediated ligand. The stimulating activity of NGF was largely comparable to that of rGM-CSF. The present data show that NGF bound to neutrophils enhances their survival, phagocytosis, and superoxide production. Thus, we postulate that NGF plays an important role in the inflammatory processes.

Animals↗
PubMed1991

Nerve growth factor-like activity detected in equine peripheral blood after running exercise.

Addition of sera, collected from Thoroughbred horses after sprint exercise, induced significant neurite outgrowth from chick embryo dorsal root ganglia after a 24-hour culture. The nerve growth factor (NGF)-like activity was detected in sera collected immediately, or 1 hour or more, after the exercise. These findings suggest a possible role of serum NGF-like activity under stress conditions (running exercise) of horses.

Animals↗
PubMed1991

Regulation of luteinizing hormone receptor messenger ribonucleic acid levels by gonadotropins, growth factors, and gonadotropin-releasing hormone in cultured rat granulosa cells.

The induction of LH receptors in granulosa cells is prerequisite for ovarian follicles to ovulate and form corpora lutea. Earlier studies have demonstrated the modulatory role of gonadotropins, growth factors, and GnRH on ovarian LH receptor content. We have now analyzed the influences of gonadotropins (FSH, LH, and PRL), several growth factors, and GnRH on LH receptor mRNA levels in cultured granulosa cells. Cells were obtained from immature estrogen-treated rats and cultured in medium containing FSH with or without growth factors or GnRH for 48 h. Some cells were also treated with FSH for 48 h, followed by treatment with FSH, LH, or PRL for another 2 days. Cellular total RNA was extracted, and blot hybridization with 32P-labeled LH receptor cRNA or 28S ribosomal RNA cDNA probes was performed. Treatment of granulosa cells with FSH increased the levels of five species of LH receptor mRNAs in a dose- and time-dependent manner. In FSH-primed cells, LH receptor mRNA levels were maintained by FSH, LH, and PRL. In contrast, treatment of cells with basic fibroblast growth factor or epidermal growth factor suppressed FSH induction of LH receptor mRNA in a dose-dependent manner, whereas treatment with insulin-like growth factor-I had no effect. In addition, GnRH suppressed FSH-stimulated LH receptor mRNA levels in a dose-dependent manner; the effects of GnRH could be counteracted by coincubation with a GnRH antagonist, suggesting mediation by specific GnRH-binding sites. These studies demonstrated that the observed stimulatory effects of gonadotropins (FSH, LH, and PRL) and the inhibitory effects of growth factors (epidermal growth factor and basic fibroblast growth factor) and GnRH on LH receptor content are correlated to their regulation of LH receptor mRNA levels. The granulosa cell culture system should provide a useful model for studying LH receptor gene regulation.

Animals↗
PubMed1991

Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species.

Studies on human LH receptors are difficult due to the limited availability of clinical samples. Recent cloning of rat and porcine LH receptor cDNAs indicated that these binding sites are single polypeptides of the G-protein-coupled receptor family with seven transmembrane domains. Based on the conserved sequences of rat and porcine receptors, we performed reverse transcription polymerase chain reaction, using human ovarian mRNA as template and obtained partial human LH receptor cDNA clones. Further screening of a human ovary cDNA library and subsequent ligation of individual cDNA clones generated a human LH receptor cDNA containing the entire amino acid-coding region. Sequence analysis indicated that the human receptor cDNA displays 89% and 82% homology at the nucleotide level with its porcine and rat counterparts, respectively. A region spanning the second extracellular and third transmembrane domains is highly conserved among the human LH, FSH, and TSH receptors. The ovarian LH receptor clone is, however, significantly different from an incompletely spliced LH receptor cDNA recently obtained from a human thyroid library. Unlike the thyroid clone, the ovarian LH receptor cDNA could be expressed in the human fetal kidney cell line (293), and radioligand receptor assay identified high affinity (Kd, 1.2 x 10(-10) M) LH/hCG-binding sites on the plasma membrane. Binding specificity of the human LH receptor was studied using recombinant human CG, LH, and FSH secreted by CHO cells transfected with the respective genes. Human CG and LH displaced [125I]hCG binding with an ED50 of 4.3 and 4.8 ng/ml, respectively. In contrast, recombinant FSH was not effective. Treatment of transfected cells with recombinant gonadotropins also induced dose-dependent increases in extracellular cAMP production (hCG = LH much greater than FSH; ED50 25, 10, and greater than 3000 ng/ml). Although equine, rat, and ovine LH as well as equine CG competed effectively for rat testicular LH receptor binding, these hormones were unable to displace [125I]hCG binding to the human receptor, suggesting evolutionary changes in receptor binding specificity and the importance of using human receptors for clinical studies. Thus, the cloning and expression of the human LH receptor cDNA allowed analysis of interactions between human LH receptor and gonadotropins from diverse species. The present work should provide the basis for future design of therapeutic agents capable of interacting with the human receptor and for understanding the structural basis for LH receptor binding to different gonadotropins.

Amino Acid Sequence↗
PubMed1991

[A case of adult type of anomalous origin of left coronary artery from pulmonary artery--with a referential consideration to the disease in Japan].

A case of a 33-year-old man with anomalous origin of the left coronary artery from the pulmonary artery (ALCP) was reported with a referential consideration to the adult type of ALCP previously reported in Japan. The patient visited our hospital for further examination of cardiac murmur detected on a mass physical checkup. He was found to have a continuous murmur, the loudest in the left sternal border of 3rd intercostal space, and developed evidence of ischemia during the exercise stress test in the ECG leads of L2, L3, aVF, and V2 through V6. In addition, studies using echocardiography and color Doppler-echocardiography detected a hypertrophied intraventricular septum and a pattern of turbulent blood flow in the proximal pulmonary artery. Cardiac catheterization and aortography proved the existence of ALCP with a markedly developed collateral circulation from the right coronary artery to the left coronary artery. After surgical restoration by ligating the anomalous opening of the left coronary artery, and by bypass grafting to the left coronary artery, it was clear that dilation and kinking of the right coronary artery was lessened and hypoperfusion in the anterior left ventricular wall was improved. As far as we know, this case is the 35th of adult type ALCP reported in our country. Results from this case and others suggest that early detection and therapy for adult type ALCP is important from the point of view preventing ischemic progression, and indicate that restoration by ligation and bypass grafting may be one of the effective surgical procedures for ALCP.

Adult↗
PubMed1991

[Detection of gonadotropin releasing hormone (GnRH) messenger RNA in the ovary and cloning of LH, chorionic gonadotropin (CG) receptor].

Detection of gonadotropin releasing hormone (GnRH) mRNA in rat ovary was carried out, and cloning of LH, chorionic gonadotropin (CG) receptor in human ovary was attempted by use of polymerase chain reaction (PCR). Firstly, in an attempt to detect the expression of GnRH or related gene in rat ovaries at the RNA level, GnRH message was amplified. Total RNA from rat ovaries was converted to cDNA using reverse transcriptase and amplified in PCR using a pair of specific primers complementary to the rat GnRH cDNA. The DNA products were subcloned into plasmid vectors and their sequence determined. 1. In the rat ovary, a prominent PCR product of 462 bp was identified as a fragment of prothymosin alpha cDNA previously found in the spleen. 2. In contrast, RT-PCR amplification of hypothalamus and granulosa cell messages indicated the presence of a 244 bp product with identical sequence to GnRH. To confirm the presence of GnRH message, a second set of GnRH primers was used. PCR amplification of cDNA from hypothalamus, granulosa cells and whole ovary yielded a product identical with the authentic GnRH cDNA sequence. These data demonstrated the presence of mRNA for GmRH and prothymosin alpha in the rat ovary. Secondly, a part of the human LH, CG receptor was obtained from human granulosa cells by selective amplification with PCR of DNA segments presenting possible sequence similarity with genes for the porcine or rat LH, CG receptor. Total RNA from human granulosa cells was converted to cDNA and amplified in PCR using degenerate oligonucleotide primers corresponding to possible conserved regions in extracellular segments of the porcine or rat LH, CG receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

[Coronary venous oxygen saturation dynamics during intracoronary infusion of ergonovine or acetylcholine in vasospastic angina].

We investigated changes in coronary venous oxygen saturation (CSO2-Sat) dynamics during intracoronary infusion of ergonovine (ERG) or acetylcholine (ACh) in patients with vasospastic angina. In 16 patients with suspected vasospasm in the left coronary artery, intracoronary ERG injection provoked vasospasm in 4 out of 6 patients, and intracoronary ACh in 6 out of 11 patients. A gradual decrease in CSO2-Sat, anteceding angina and ischemic ECG evidence, was characteristic in ERG-induced vasospastic patients, while no significant change of CSO2-Sat was observed in non ERG-induced patients. Intracoronary infusion of ACh was followed in all 11 patients by a transient increase in CSO2-Sat, suggesting decreased myocardial oxygen extraction due to increased coronary blood flow with ACh. However, earlier and sudden decreases in CSO2-Sat below the control levels were characteristic in 6 patients with ACh-induced vasospastic angina. These findings suggest that effects of ERG and ACh on coronary flow dynamics are essentially different although both drugs can provoke vasospasm.

Acetylcholine↗
PubMed1990

Morphology of equine allantochorion at the tip of the pregnant horn.

The morphology of the equine allantochorion at the tip of the pregnant horn was studied in the membranes of 14 mares. The findings in the allantochorion at the tip of the pregnant horn were of two types; one was growth retardation (hypoplastic villi, tunica adventitia of the vessels resembling embryonal connective tissue and the extended spaces of remnants of the extraembryonic coelom), the other was placental hypoxia or ischaemia (parakeratosis, stratified squamous metaplasia, necrosis of the trophoblasts, thickening of the basement membrane and fibrous hyperplasia of villous stroma). It seems likely that hypoplastic villi are caused by disordered formation of the microcotyledon accompanying the progression of pregnancy.

Animals↗
PubMed1990

Gonadotropin-induced up- and down-regulation of rat ovarian LH receptor message levels during follicular growth, ovulation and luteinization.

Induction of follicular growth by PMSG is associated with increased ovarian LH receptor content, whereas the preovulatory surge of LH decreases LH binding sites, followed by a secondary increase in receptor numbers coincident with corpora lutea formation. Based on the recently reported LH receptor cDNA sequence, we have performed a reverse transcription-polymerase chain reaction to obtain LH receptor cDNA clones and generated a 32P-labeled cRNA probe to examine the dynamic changes in ovarian LH receptor mRNA levels during gonadotropin induction of follicular growth, ovulation and luteinization. Northern blot analysis of ovary RNA revealed hybridization signals of about 7.0, 4.2, 2.5 and 1.8 kb, with no hybridization to nongonadal tissues. PMSG increased the intensity of all four LH receptor messages at 24 h, preceding an increase in LH receptor number, with peak LH receptor mRNA and receptor content observed at 52 h. Treatment with hCG resulted in decreased LH receptor binding and mRNA levels by 6 h after injection, with maximal inhibition (greater than 85%) of message at 12 to 24 h after hCG treatment. Subsequently, LH receptor message levels increased again at 3 days after hCG, concomitant with increased [125I]hCG binding. A further increase in LH receptor content, but not message levels, was observed 5 days after hCG. These results demonstrate that the induction of LH receptors by PMSG is preceded by increased LH receptor mRNA levels. Furthermore, ligand-induced down-regulation of the LH receptor following an ovulatory dose of hCG is associated with decreased LH receptor message content, followed by increases in LH receptor message levels and binding sites during subsequent luteinization. Thus, the up- and down-regulation of ovarian LH receptors during follicle growth, ovulation and luteinization is probably due, at least in part, to changes in receptor message modulation.

Animals↗
PubMed1990

Expression of gonadotropin-releasing hormone and prothymosin-alpha messenger ribonucleic acid in the ovary.

GnRH exerts paradoxical effects on ovarian cells through specific receptors. Based on observed direct effects of GnRH and its antagonists on ovarian functions, the presence of endogenous ovarian GnRH-like peptide(s) has been postulated. In an attempt to detect the ovarian expression of GnRH or related genes at the RNA level, we used the reverse transcription-polymerase chain reaction (RT-PCR) to amplify GnRH mRNA levels. Total RNA from rat ovaries was converted to first strand cDNA using reverse transcriptase and amplified in PCR using a pair of primers complementary to the rat GnRH cDNA. The DNA products obtained were subcloned into plasmid vectors, and their sequences were determined. The most prominent PCR product of 462 basepairs (bp) was unexpectedly identified as a fragment of prothymosin-alpha cDNA previously found in the spleen. This cDNA was obtained because of an identical 10 bp match with the 3' end of one of the GnRH primers. Northern blot analyses using the cloned prothymosin-alpha cDNA as probe revealed the presence of mRNA for this factor in ovary, thymus, testis, placenta, and hypothalamus. RT-PCR amplification of hypothalamus and granulosa cell messages indicated the presence of a 244-bp product with a sequence identical to that of GnRH. To further confirm the presence of GnRH messages in the ovary, a second set of GnRH primers was used. PCR amplification of cDNA from hypothalamus, granulosa cells, and whole ovary yielded a 241-bp product identical to the authentic GnRH sequence based on analysis on both strands. In contrast, no PCR product was evident after amplification of thyroid cDNA. Our data demonstrated the expression of mRNA for GnRH and prothymosin-alpha in the ovary. Although the exact ovarian role of the immune hormone awaits further study, the detection of GnRH transcript in the ovary suggests potential intragonadal roles of this decapeptide.

Amino Acid Sequence↗