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Biomedical subjects

H Okamura

Publications and source records attributed to H Okamura.

At least 163 records · Page 9Linked to original sources
PubMed2000

IL-18 and IL-12 induce intestinal inflammation and fatty liver in mice in an IFN-gamma dependent manner.

BACKGROUND: In murine models of inflammatory bowel disease, colonic inflammation is considered to be caused by an aberrant Th1-type immune response. AIM: To investigate if systemic administration of interleukin (IL)-12 and IL-18 to wild-type BALB/c mice induces liver injury and intestinal inflammation, and if pathological changes are observed, what cytokines are involved. METHODS: Mice (BALB/c-wild-type (wt), MRL-lpr/lpr, BALB/c-interferon gamma knock out (IFN-gamma KO), C57BL/6-inducible nitric oxide synthase (iNOS) KO, and BALB/c tumour necrosis factor alpha (TNF-alpha) KO) were injected intraperitoneally each day with IL-12 (20 ng/g/mouse) and/or IL-18 (200 ng/g/mouse). RESULTS: Administration of IL-12 and IL-18 to BALB/c-wt mice induced prominent intestinal mucosal inflammation and fatty liver, leading to piloerection, bloody diarrhoea, and weight loss. IL-12 and IL-18 induced striking elevations in serum levels of IFN-gamma that caused NO production, although increased NO had no exacerbating effect on mice. Moreover, iNOS KO mice, or MRL lpr/lpr mice lacking functional Fas were equally susceptible to IL-12 and IL-18. Administration of IL-12 and IL-18 did not induce TNF-alpha production in wild-type mice, and the same treatment to TNF-alpha KO mice induced intestinal mucosal inflammation. Furthermore, they had diffuse and dense infiltration of small fat droplets in their hepatocytes associated with an increase in serum levels of liver enzymes. In contrast, the same treatment in IFN-gamma KO BALB/c mice and iNOS KO mice did not induce these changes. CONCLUSIONS: Our study strongly indicates that IL-18 together with IL-12 induces intestinal mucosal inflammation in an IFN-gamma dependent but TNF-alpha, NO, and Fas ligand independent manner, and fatty liver is dependent on IFN-gamma and NO.

Animals↗
PubMed2000

Normal fetal brain development: MR imaging with a half-Fourier rapid acquisition with relaxation enhancement sequence.

PURPOSE: To analyze normal maturation of the fetal brain with half-Fourier rapid acquisition with relaxation enhancement (RARE) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The normal brains of 25 fetuses of 12-38 weeks gestational age were examined in utero with half-Fourier RARE imaging. Gyrus maturation, gray and white matter differentiation, ventricle-to-brain diameter ratio, and subarachnoid space size were evaluated with respect to gestational age. RESULTS: At 12-23 weeks, the brain had a smooth surface, and two or three layers were differentiated in the cerebral cortex. At 24-26 weeks, only a few shallow grooves were seen in the central sulcus, and three layers, including the immature cortex, intermediate zone, and germinal matrix, were differentiated in all fetuses. At 27-29 weeks, sulcus formation was observed in various regions of the brain parenchyma, and the germinal matrix became invisible. Sulcation was seen in the whole cerebral cortex from 30 weeks on. However, the cortex did not undergo infolding, and opercular formation was not seen before 33 weeks. At 23 weeks and earlier, the cerebral ventricles were large; thereafter, they gradually became smaller. The subarachnoid space overlying the cortical convexities was slightly dilated at all gestational ages, most markedly at 21-26 weeks. CONCLUSION: Changes in brain maturation proceed through stages in an orderly and predictable fashion and can be evaluated reliably with half-Fourier RARE MR imaging.

Brain↗
PubMed2000

Dynamic contrast-enhanced MR imaging of uterine cervical cancer: pharmacokinetic analysis with histopathologic correlation and its importance in predicting the outcome of radiation therapy.

PURPOSE: To investigate the histopathologic bases of different enhancement patterns on dynamic contrast material-enhanced magnetic resonance (MR) images of cervical cancer and to assess their importance in predicting the outcome of patients after radiation therapy. MATERIALS AND METHODS: Dynamic enhanced MR imaging and pharmacokinetic analyses were performed in 26 patients with cervical cancer who subsequently underwent hysterectomy and in 36 patients with cervical cancer who received radiation therapy. Histopathologic findings and clinical outcomes were correlated with results of dynamic MR imaging and pharmacokinetic analysis. RESULTS: On dynamic MR images of the surgical patients, areas with intense homogeneous enhancement showed increased permeability (k = 27.4 x 10(-3)) compared with areas with poor enhancement (k = 19.0 x 10(-3)). Well-enhanced areas were predominantly composed of cancer cell fascicles, whereas poorly enhanced areas were composed of fibrous tissue with scattered cancer cells. Radiation therapy was more effective in tumors with higher tissue permeability (k = 31.3 x 10(-3)) on dynamic MR images than in those with lower tissue permeability (k = 18.3 x 10(-3)). CONCLUSION: Areas of increased contrast enhancement are mainly composed of abundant cancer cell fascicles, whereas poorly perfused areas are composed of fibrous tissue with scattered cancer cells. Radiation therapy is more effective in well-enhanced tumors, resulting in improved local control.

Adenocarcinoma↗
PubMed2000

Nitric oxide affects angiotensin II pressor response: possible mechanism of attenuated pressor response during pregnancy and etiology of pregnancy-induced hypertension.

OBJECTIVE: To investigate the mechanism of attenuated pressor responses to several vasoconstrictors during gestation, we sought to characterize the effects of N(G)-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) on the pressor response to the infusion of angiotensin II in rats. METHODS: L-NMMA and L-Arg were infused intraperitoneally into rats at a constant rate by means of an osmotic minipump. The L-NMMA group received an infusion of L-NMMA (3 mg/day) daily for 13 days, whereas the L-NMMA plus L-Arg group received L-NMMA (3 mg/day) daily for 4 days, followed by L-NMMA plus L-Arg (12 mg/day) daily for 9 days. Sham-operated rats served as controls. The animals were anesthetized on day 13, and catheters were placed into the femoral artery and vein. After the animals had recovered from anesthesia, the pressor response to intravenous bolus doses of angiotensin II (50, 100, 200, and 400 ng/kg) were determined after recovery from anesthesia. RESULTS: While the baseline mean arterial blood pressure was not affected by L-NMMA, with or without L-Arg, the pressor response to angiotensin II in the L-NMMA group was significantly increased as compared with that in the control group, at doses of 50, 100, and 200 ng/kg. The response of the L-NMMA plus L-Arg group did not differ significantly from that of the control group. CONCLUSION: Results indicate that the infusion of a nitric oxide synthase inhibitor, at a dose insufficient to produce hypertension, increases the pressor response to angiotensin II.

Angiotensin II↗
PubMed2000

Primary vaginal stone in an 11-year-old recumbent girl.

Primary vaginal stones are extremely rare, particularly in young women. We describe the occurrence of a primary vaginal calculus in a severely retarded 11-year-old girl who was not diagnosed until she was examined using computerized tomography. We postulate that the calculus was formed as a consequence of urinary contamination of the vagina in association with incontinence and prolonged maintenance in a recumbent posture.

Calculi↗
PubMed2000

Increased levels of circulating interleukin-18 in patients with advanced tuberculosis.

Interleukin-18 (IL-18) has recently been identified as an interferon- gamma-inducing factor and it plays an important role in the Th1 response. We measured serum levels of IL-18 and interferon-gamma (IFN-gamma) in 43 patients with pulmonary tuberculosis and 25 healthy control subjects. Significantly increased levels of circulating IL-18 and IFN-gamma were found in pulmonary tuberculosis as compared with those in healthy control subjects. Circulating IL-18 and IFN-gamma correlated with the extent of disease in pulmonary tuberculosis. We found significantly increased levels of circulating IL-18 and IFN-gamma in the patients with high-grade fever. Circulating IL-18 significantly correlated with circulating IFN-gamma. IL-18 may play an important role in immune response to human infection with Mycobacterium tuberculosis.

Adolescent↗
PubMed2000

Increased levels of interleukin-18 in patients with pulmonary sarcoidosis.

Interleukin-18 (IL-18) has recently been identified as an interferon-gamma (IFN-gamma)-inducing factor, and it plays an important role in T helper 1 (Th1) response. We measured the serum levels of IL-18 and IFN- gamma in 37 patients with pulmonary sarcoidosis and 25 healthy control subjects. We also measured the levels of IL-18 and IFN-gamma in 10-fold concentrated bronchoalveolar lavage (BAL) fluids of 19 patients with pulmonary sarcoidosis and 9 healthy control subjects (all lifelong nonsmokers). The levels of serum IL-18 and IFN-gamma were significantly increased in patients with sarcoidosis. The levels of BAL fluid IL-18 were significantly elevated in patients with sarcoidosis, however, the IFN-gamma levels of the patients and control subjects were all below sensitivity. Serum IL-18 levels significantly correlated with serum IFN-gamma levels and lysozyme activity. The patients positive for gallium-67 ((67)Ga) scan had significantly elevated serum IL-18 levels as compared with those of the negative patients. BAL fluid IL-18 levels significantly correlated with serum IL-18 levels in patients with sarcoidosis, and there was a significant correlation between IL-18 levels and lymphocyte proportions in sarcoid BAL fluids. In patients with sarcoidosis, IL-18 seems to induce IFN-gamma production and IL-18 levels in sera may reflect disease activity of sarcoidosis.

Adult↗
PubMed2000

Orally administered lactoferrin exerts an antimetastatic effect and enhances production of IL-18 in the intestinal epithelium.

The effects of oral administration of bovine lactoferrin (bLF) and its hydrolysate on the lung colonization by colon 26 carcinoma were investigated. At doses of 100 or 300 mg/kg/day for seven successive days, bLFs demonstrated a significant inhibitory effect on experimental metastasis, which indicated effectiveness before and after tumor implantation. Oral administration of bLFs augmented CD4+, CD8+, and asialoGM1+ cells in the spleen and peripheral blood. Their cytotoxic activities against Yac-1 and colon 26 carcinoma were enhanced by bLF. In the small intestinal epithelium, CD4+ and CD8+ cells were markedly increased, and, simultaneously, enhanced production of interleukin-18 (IL-18) was confirmed in the intestinal epithelial cells. In this model, intravenous injection of murine IL-18 showed significant inhibition of the lung colonization by colon 26 carcinoma. These results suggested that inhibition of experimental metastasis by oral administration of bLF and pepsin hydrolysate of bLF might be due to enhanced cellular immunity, presumably mediated by enhanced IL-18 production in the intestinal epithelium.

Administration, Oral↗
PubMed2000

Induction of early growth response protein-1 gene expression in the rat ovary in response to an ovulatory dose of human chorionic gonadotropin.

Granulosa cells in a mature ovarian follicle have an abundance of LH/hCG receptors that respond rapidly to an ovulatory surge in gonadotropins. Within minutes, membrane signal transduction sets in motion metabolic changes that lead to follicular rupture. This study provides evidence that the initial ovarian response to such an ovulatory stimulus includes induction of the immediate-early transcription factor gene for early growth response protein-1 (Egr-1). Immature Wistar rats were primed with 10 IU equine CG (eCG), sc, and 48 h later the 12-h ovulatory process was initiated by 10 IU hCG, sc. Ovarian RNA was extracted at 0, 0.5, 1, 2, 4, 8, 12, and 24 h after the primed animals were injected with hCG. The RNA extracts were used for RT-PCR differential display for random detection of gene expression in the stimulated ovarian tissue. Northern analysis of one of the differentially amplified complementary DNAs confirmed that it was part of a gene that was significantly up-regulated within 1 h after the ovaries had been stimulated by hCG. Maximum transcription was at 4 h after hCG, and expression declined to 0 h control levels by 24 h after hCG. Subcloning and sequence analysis revealed that the complementary DNA matched the gene for Egr-1. In situ hybridization indicated that the Egr-1 messenger RNA was in the granulosa layer of mature follicles. Western blotting confirmed the temporal pattern of Egr-1 expression detected by differential display, Northern analysis and in situ hybridization. The Egr-1 protein is approximately 84 kDa. In conclusion, the data show that expression of the zinc finger transcription factor Egr-1 is an early event in the cascade of inflammatory-like changes that occur in an ovulatory follicle in response to a trophic hormone.

Androstenols↗
PubMed2000

Effects of chronic administration of sibutramine on body weight, food intake and motor activity in neonatally monosodium glutamate-treated obese female rats: relationship of antiobesity effect with monoamines.

When the hypothalamic ventromedial nucleus and arcuate nucleus were destroyed in rats by treatment with monosodium glutamate in the neonatal stage, increase in the Lee index (body weight 1/3/body length) and in retroperitoneal fat as well as decreases in spontaneous motor activity, food consumption and growth hormone secretion function associated with hypothalamic low body length obesity (monosodium glutamate-treated obesity; MSG-OB) were observed as these rats grew. Treatment with sibutramine at 3 and 10 mg/kg p.o. once a day continuously for 14 days improved these parameters, and the degree of improvement was dose related. The plasma lipid values in MSG-OB rats, which were the same as those in normal rats, were decreased by consecutive administration of sibutramine. Levels of hypothalamic monoamines (MAs) such as norepinephrine, 5-HT (serotonin) and dopamine and their metabolites DOPAC, HVA and 5-HIAA were decreased in MSG-OB rats, and further decrease in them, though slight, was observed with consecutive daily administration of sibutramine, probably as a result of the feedback attributable to an increase in MA in synapses caused by inhibition of MA uptake by sibutramine. These results suggest that sibutramine can activate the MA nervous system by MA uptake inhibition in regions of the brain such as the lateral hypothalamic area and the paraventricular nucleus, which control food intake and sympathetic nerve activity, and the nigrostriatal area related to the extrapyramidal motor system, and thereby exhibit anti-obesity effects in the MSG-OB rat.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Recurrent Wegener's granulomatosis with subglottic granulation.

While following the course of patients with Wegener's granulomatosis (WG) in which it had been possible to achieve a remission, we encountered a patient in whom we observed granuloma formation in the subglottis. A tracheotomy was performed because of the risk of respiratory distress, and after that there was a recrudescence of the patient's WG. During the course of the above, the patient remained cANCA (anti-neutrophil cytoplasmis antibody with cytoplasmic pattern)-negative. When these facts were considered, it appeared that when the lesions are localized and progressing gradually, cANCA positivity does not develop. While cANCA test has gradually become a powerful tool for the diagnosis of WG, a comprehensive physical examination to identify localized lesions, together with biopsy and histopathological examination, should allow the diagnosis of WG.

Adult↗
PubMed2000

[A case report: Carpentier-Edwards porcine bioprosthesis malfunction due to the stent dehiscence at 17 years after the implantation in the mitral position].

A 53-year-old female had undergone mitral valve replacement with Carpentier-Edwards (C-E) porcine bioprosthesis for mitral valve regurgitation at the other hospital in November, 1981. Postoperative clinical course was uneventful, since she was referred from the other hospital in 1990. In December, 1997, she had sudden complaint of shortness of breath on effort, and the chest X-ray showed pulmonary congestion and increase of cardio-thoracic ratio. Echocardiography and catheterization revealed severe mitral regurgitation due to bioprosthesis malfunction and aortic valve regurgitation. Combined mitral and aortic valve replacement was successfully performed with mechanical valves in February, 1998. The explanted C-E porcine bioprosthesis showed the commissural dehiscence from only one of the three stents without any leaflet perforation, commissural tear, pannus overgrowth, impaired leaflet mobility and leaflet deterioration or calcification. This case suggested the variety of malfunction of C-E porcine bioprosthesis and the limitation of its long-term durability.

Aortic Valve↗
PubMed2000

Ultrastructural and functional studies of cryopreserved rat lungs for transplantation using a new hyperosmolal solution.

One of the most promising approaches for extending the period of tissue or organ preservation is to induce a state of cryopreservation. In this report, to achieve successful lung cryopreservation, we created a new hyperosmolal solution (HOS) containing 10% glycerol and 5% dimethyl sulfoxide (Me2SO). We compared the efficacy of HOS with that of Euro-Collins solution (ECS) in rat lung cryopreservation from an ultrastructural and functional point of view. Using ECS, widespread damage to the air-blood barrier was observed even in the lungs cryopreserved at -10 degrees C. At -196 degrees C, the capillary lumen was obstructed with a mesh-like formation derived from deteriorated endothelial cells. In contrast, using HOS, the cryopreserved lungs at -10 degrees C were characterized by well preserved endothelial cells and basal laminae, despite the existence of focal cytoplasmic swelling of epithelial cells. The endothelial cells and basal laminae were successfully preserved up to -196 degrees C. Considering the survival rates at day 7 after cryopreserved lung transplantation, the grafted left lungs functioned normally only when perfused by and preserved in HOS at -10 degrees C. These findings demonstrate that HOS was effective not only for endothelial cells and basal laminae up to -196 degrees C, but also lung cryopreservation at least up to -10 degrees C.

Animals↗
PubMed2000

Effect of dopaminergic drugs on the reserpine-induced lowering of hippocampal theta wave frequency in rats.

The effects of dopaminergic drugs on the lowering of hippocampal theta wave frequency induced by reserpine 1 mg/kg s.c. were examined. Sibutramine (monoamine reuptake inhibitor) 10 mg/kg p.o., methamphetamine (monoamine releaser) 1 mg/kg, quinpirole (dopamine D2 receptor agonist) 10 mg/kg i.p., and SKF 38393 (dopamine D1 receptor agonist) 10 mg/kg i.p. each antagonized the reserpine-induced lowering of hippocampal theta wave frequency in rats. Moreover, the combined administration of SKF 38393 1 mg/kg i.p. and quinpirole 1 mg/kg i.p. synergistically antagonized a reserpine-induced lowering of this frequency. Dosulepin, amitriptyline, and desipramine, which are weak inhibitors of dopamine reuptake, each had little effect on the reserpine-induced lowering of theta wave frequency at a dose of 40 mg/kg p.o. Furthermore, atropine (muscarinic anticholinergic drug) 20 mg/kg p.o. decreased theta wave power in the low-frequency range following a shift to the lower range by reserpine. A positive correlation was observed for each of the above drugs between a reversal of reserpine-induced lowering of theta wave frequency and a reversal of impairment of reserpine-induced conditioned avoidance responses (ACAR) in rats. These results suggest that the reserpine-induced lowering of hippocampal theta wave frequency plays a role in the impairment of reserpine-induced ACAR, and that dopamine D1 and D2 receptors play important roles in antagonizing this lowering of frequency.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock.

Mice lacking mCry1 and mCry2 are behaviorally arrhythmic. As shown here, cyclic expression of the clock genes mPer1 and mPer2 (mammalian Period genes 1 and 2) in the suprachiasmatic nucleus and peripheral tissues is abolished and mPer1 and mPer2 mRNA levels are constitutively high. These findings indicate that the biological clock is eliminated in the absence of both mCRY1 and mCRY2 (mammalian cryptochromes 1 and 2) and support the idea that mammalian CRY proteins act in the negative limb of the circadian feedback loop. The mCry double-mutant mice retain the ability to have mPer1 and mPer2 expression induced by a brief light stimulus known to phase-shift the biological clock in wild-type animals. Thus, mCRY1 and mCRY2 are dispensable for light-induced phase shifting of the biological clock.

Animals↗
PubMed1999

IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils.

IL-18 is a proinflammatory cytokine that plays an important role in natural killer cell activation and T helper 1 (Th1) cell responses. Mast cells and basophils are major inducers and effectors of allergic inflammation. Here we show that basophils and mast cells derived by culture of bone marrow cells with IL-3 for 10 days express IL-18Ralpha chain and that basophils produce large amounts of IL-4 and IL-13 in response to stimulation with IL-3 and IL-18. Injection of IL-12 and IL-18 inhibits IgE production in helminth-infected wild-type mice and abolishes the capacity of their basophils to produce IL-4 and IL-13 in response to stimulation either with IL-3 and IL-18 or with FcepsilonR cross-linkage. By contrast, this combination of cytokines actually increases IgE levels in helminth-infected IFN-gamma(-/-) mice and enhances IL-4 and IL-13 production by their basophils. Furthermore, injection of IL-18 alone enhances basophil production of IL-4 and histamine both in wild-type and IFN-gamma(-/-) mice. Thus, IL-18 has the potential to stimulate basophils but, when given with IL-12, exhibits an antiallergic action in vivo.

Animals↗
PubMed1999

A putative transcription factor with seven zinc-finger motifs identified in the developing suprachiasmatic nucleus by the differential display PCR method.

The suprachiasmatic nucleus (SCN) is a mammalian central circadian pacemaker. This nucleus develops in the last stage of fetal life and matures to make strong synaptic connections within 2 weeks of postnatal life to establish strong oscillation characteristics. To identify factors that initiate the circadian oscillation, we applied a differential display PCR method to developing SCN, and isolated a gene with seven zinc-finger motifs, Lot1, which encodes a gene that appeared at a very high level in the SCN during the early postnatal days. Lot1 mRNA first appeared at postnatal day 1 (P1) at a very high level, and the signal in the SCN continued to be very high until P10 and thereafter rapidly decreased until P20 and was expressed at a very faint level during adulthood. Lot1 mRNA expression was observed only in neurons of the dorsomedial SCN throughout the course of development. During the developmental stage, Lot1 mRNA expression shows a circadian rhythm with a peak in the day time and a trough at night time in both light-dark and constant dark conditions. These observations imply that Lot1 is the first identified putative transcription factor expressed only in the period of active synaptogenesis in the SCN, where Lot1 might play a role in establishing autonomous oscillation.

Aging↗