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Biomedical subjects

Y Fujisawa

Publications and source records attributed to Y Fujisawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin.

Leptin is an adipocyte-derived circulating satiety factor with a variety of biological effects. Evidence has accumulated suggesting that leptin may modulate glucose and lipid metabolism. In the present study, we examined lipid metabolism in transgenic skinny mice with elevated plasma leptin concentrations. The plasma concentrations of triglycerides and free fatty acids in transgenic skinny mice were 71.5 (P < 0.01) and 89.1% (P < 0.05) of those in their nontransgenic littermates, respectively. Separation of plasma into lipoprotein classes by ultracentrifugation revealed that very low density lipoprotein-triglyceride concentrations were markedly reduced in transgenic skinny mice relative to the controls. The clearance of triglycerides estimated by a fat-loading test was enhanced in transgenic skinny mice; the triglyceride concentration in transgenic skinny mice 3 h after fat loading was 39.7% (P < 0.05) of that of their nontransgenic littermates. Postheparin plasma lipoprotein lipase activity increased 1.4-fold (P < 0.05) in transgenic skinny mice. Our data demonstrated a significant reduction in plasma triglyceride concentrations, accompanied by increased lipoprotein lipase activity in transgenic skinny mice overexpressing leptin, suggesting that leptin plays a role in long-term triglyceride metabolism.

Animals↗
PubMed2001

Renal interstitial adenosine metabolism during ischemia in dogs.

The present study was conducted to determine the metabolism of renal interstitial adenosine under resting conditions and during ischemia. By using a microdialysis method with HPLC-fluorometric analysis, renal interstitial concentrations of adenosine, inosine, and hypoxanthine were assessed in pentobarbital-anesthetized dogs. Average basal renal interstitial concentrations of adenosine, inosine, and hypoxanthine were 0.18 +/- 0.04, 0.31 +/- 0.05, and 0.35 +/- 0.05 micromol/l, respectively. Local inhibition of adenosine kinase with iodotubercidin (10 micromol/l in perfusate) or inhibition of adenosine deaminase with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 100 micromol/l in perfusate) did not change adenosine concentrations in the nonischemic kidneys (0.18 +/- 0.04 and 0.24 +/- 0.05 micromol/l, respectively). On the other hand, treatment with iodotubercidin+EHNA significantly increased adenosine concentration (0.52 +/- 0.07 micromol/l) with significant decreases in inosine and hypoxanthine levels (0.13 +/- 0.03 and 0.19 +/- 0.04 micromol/l, respectively). During 30 min of ischemia, adenosine, inosine, and hypoxanthine were significantly increased to 0.76 +/- 0.29, 2.14 +/- 0.45, and 21.8 +/- 4.7 micromol/l, respectively. The treatment with iodotubercidin did not alter ischemia-induced increase in adenosine (0.84 +/- 0.18 micromol/l); however, EHNA alone markedly enhanced adenosine accumulation (13.54 +/- 2.16 micromol/l), the value of which was not augmented by an addition of iodotubercidin (15.80 +/- 1.24 micromol/l). In contrast, ischemia-induced increases in inosine and hypoxanthine were inversely diminished by the treatment with iodotubercidin+EHNA (0.90 +/- 0.20 and 9.86 +/- 1.96 micromol/l, respectively). These results suggest that both adenosine kinase and adenosine deaminase contribute to the metabolism of renal interstitial adenosine under resting conditions, whereas adenosine produced during ischemia is mainly metabolized by adenosine deaminase and the rephosphorylation of adenosine by adenosine kinase is small.sent

Adenine↗
PubMed2001

Role of nitric oxide in regional blood flow in angiotensin II-induced hypertensive rats.

The present study was designed to evaluate the contribution of nitric oxide (NO) to regional hemodynamics during the early phase of angiotensin II (Ang II)-induced hypertension. The responses of regional blood flow to chronic NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) were assessed using radioactive microspheres in conscious Ang II-infused hypertensive rats. Ang II-infused rats (270 ng/kg/min, subcutaneously for 12 days: n=11) showed higher mean arterial pressure (MAP: 153+/-4 mmHg) and total peripheral resistance (TPR: 1.61+/-0.06 mmHg/min/ml), and lower cardiac output (CO: 102+/-3 ml/min) than vehicle-infused normotensive rats (115+/-2 mmHg, 0.96+/-0.05 mmHg/min/ml and 130+/-7 ml/min, n=11, respectively). The blood flow rates in the brain, spleen, large intestine and skin were significantly reduced in Ang III-infused rats compared with vehicle-infused rats, while those in the lung, heart, liver, kidney, adrenal gland, small intestine, and skeletal muscle were similar. Treating Ang II-infused rats with L-NAME (75 mg/l in drinking water for 10 days, n=11) resulted in higher MAP (166+/-6 mmHg) and TPR (1.89+/-0.18 mmHg/min/ml) and lower CO (87+/-7 m/min) than untreated Ang II-infused rats. L-NAME-treated Ang II-infused rats showed widespread increases in regional vascular resistance and reduced blood flow rates in the kidney (3.81+/-0.27 ml/min/g) and skeletal muscle (0.20+/-0.03 ml/min/g) compared with untreated Ang II-infused rats (6.88+/-0.27 and 0.33+/-0.04 ml/min/g, respectively). However, there were no significant differences in the flow rates of other organs investigated between these animals. An NO donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409: 30 microg/kg/min, i.v.), significantly decreased MAP (110+/-6 mmHg) and TPR (1.23+/-0.18 mmHg/min/ml) without significant changes in CO (89+/-9 ml/min) in L-NAME-treated Ang II-infused rats. Furthermore, FK409 partially reversed blood flow rates in the kidney (4.72+/-0.40 ml/min/g) and skeletal muscle (0.25+/-0.02 ml/min/g)in these animals. These results suggest that NO counteracts, at least in part, the vasoconstrictor effects of elevated Ang II levels in renal and skeletal muscle vascular beds, and is an important modulator in the regulation of blood flow to these organs during the development of Ang II-induced hypertension.

Angiotensin II↗
PubMed2001

Benidipine dilates both pre- and post-glomerular arteriole in the canine kidney.

The aim of the present study was to determine the effects of benidipine on renal function and whether benidipine may dilate the efferent arteriole as well as the afferent arteriole of the canine kidney. The effects of benidipine on the renal segmental vascular resistance were estimated using Gomez's formula with some modification. The renal hemodynamic action of benidipine was also compared with that of amlodipine. Intrarenal arterial injection of benidipine at a dose of 3 microg/kg resulted in a significant increase in renal blood flow (RBF), urine flow and urinary excretion of sodium, but not in glomerular filtration rate (GFR). Amlodipine at a dose of 300 microg/kg also increased RBF, urine flow and urinary excretion of sodium to a significant degree equivalent to that by benidipine. However, in contrast to benidipine, amlodipine significantly increased GFR. After the administration of benidipine, autoregulation of RBF and GFR was relatively maintained and the renal perfusion pressure (RPP)-RBF relation shifted upward; that is, RBFs at 75 and 50 mmHg were maintained at a higher level than those of the control. In contrast to benidipine, amlodipine diminished the autoregulation of RBF and GFR. RBFs at 75 and 50 mmHg were not different from those of the control. The afferent and efferent arteriolar resistance (Ra and Re) were calculated based on the RPP-RBF and RPP-GFR relations. Benidipine reduced both Ra and Re, but amlodipine selectively reduced Ra. Benidipine increased RBF but not GFR via the dilation of both afferent and efferent arterioles. Thus, benidipine has unique renal hemodynamic actions which differ from those by most calcium antagonists.

Animals↗
PubMed2001

Relationship between meniscal degeneration and element contents.

The purpose of this study is to investigate the relationship between meniscal degeneration and element contents. The contents of elements (calcium, phosphorus, sulfur, and magnesium) in the menisci from 17 patients with osteoarthritis (OA) of the knee, 6 with rheumatoid arthritis (RA), and 2 who underwent the surgical operation for malignant tumors (control) were analyzed by inductively coupled plasma-atomic emission spectrometry, and the menisci were divided into four stages (Stage 0-3) of histological degeneration. The calcium contents of the menisci were 0.26 +/- 0.16 in Stage 0, 0.50 +/- 0.37 in Stage 1, and 0.69 +/- 0.66 in Stage 2, respectively (the values represent mg elements/g dry tissue). They increased with the progression of the stage. This tendency was found in the menisci with OA, but was not clear in those with RA. The calcium content in the control group was 0.17 +/- 0.09 mg/g. There was no significant relationship between the stage of degeneration and the contents of phosphorus, sulfur, or magnesium. The calcium content of the meniscus might indicate the degree of meniscal degeneration.

Adolescent↗
PubMed2001

[The effect of immunization with herpes simplex virus glycoprotein D fused with interluekin-2 against murine herpetic keratitis].

PURPOSE: To evaluate the effect of vaccination with fusion protein(gD-IL-2) consisting of herpes simplex type1(HSV-1) glycoprotein D(gD) and human interleukin-2(IL-2), and the effect of plasmid DNA vaccine encoding gD-IL-2 against murine herpetic keratitis. METHODS: Plasmid containing gD-IL-2(pHDL-neol) was constructed, and gD-IL-2 peptide was purified. BALB/c mice were injected twice hypodermally or subconjunctivally with 1 microgram/0.1 ml of gD-IL-2 peptide, or twice subconjunctivally with 90 micrograms/0.05 ml of gD-IL-2 plasmid DNA. Neutralizing antibody titer and delayed-type hypersensitivity (DTH) against HSV-1 were measured. Immunized mice were challenged with CHR3 strain of HSV-1 via the cornea. The clinical picture of epithelial and stromal keratitis was scored. RESULTS: Stromal keratitis was inhibited in gD-IL-2 peptide- or gD-IL-2 DNA-immunized mice, but epithelial keratitis was not. It was confirmed that plasmid gD-IL-2 elicited significant serum virus neutralizing titer and DTH response. CONCLUSION: Vaccination with gD-IL-2 was effective against herpetic keratitis.

Animals↗
PubMed2000

Rice dwarf mutant d1, which is defective in the alpha subunit of the heterotrimeric G protein, affects gibberellin signal transduction.

Previously, we reported that the rice dwarf mutant, d1, is defective in the alpha subunit of the heterotrimeric G protein (Galpha). In the present study, gibberellin (GA) signaling in d1 and the role of the Galpha protein in the GA-signaling pathway were investigated. Compared with the wild type, GA induction of alpha-amylase activity in aleurone cells of d1 was greatly reduced. Relative to the wild type, the GA(3)-treated aleurone layer of d1 had lower expression of Ramy1A, which encodes alpha-amylase, and OsGAMYB, which encodes a GA-inducible transcriptional factor, and no increase in expression of Ca(2 +)-ATPase. However, in the presence of high GA concentrations, alpha-amylase induction occurred even in d1. The GA sensitivity of second leaf sheath elongation in d1 was similar to that of the wild type in terms of dose responsiveness, but the response of internode elongation to GA was much lower in d1. Furthermore, Os20ox expression was up-regulated, and the GA content was elevated in the stunted internodes of d1. All these results suggest that d1 affects a part of the GA-signaling pathway, namely the induction of alpha-amylase in the aleurone layer and internode elongation. In addition, a double mutant between d1 and another GA-signaling mutant, slr, revealed that SLR is epistatic to the D1, supporting that the Galpha protein is involved in GA signaling. However, the data also provide evidence for the presence of an alternative GA-signaling pathway that does not involve the Galpha protein. It is proposed that GA signaling via the Galpha protein may be more sensitive than that of the alternative pathway, as indicated by the low GA responsiveness of this Galpha-independent pathway.

Epistasis, Genetic↗
PubMed2000

A novel avian hypothalamic peptide inhibiting gonadotropin release.

The neuropeptide control of gonadotropin secretion at the level of the anterior pituitary gland is primarily through the stimulatory action of the hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH), which was originally isolated from mammals and subsequently from non-mammals. To date, however, an inhibitory peptide of gonadotropin release is unknown in vertebrates. Here we show, in a bird, that the hypothalamus also contains a novel peptide which inhibits gonadotropin release. Acetic acid extracts of quail brains were passed through C-18 reversed-phase cartridges, and then the retained material was subjected to the reversed-phase and cation-exchange high-performance liquid chromatography (HPLC). The peptide was isolated from avian brain and shown to have the sequence Ser-Ile-Lys-Pro-Ser-Ala-Tyr-Leu-Pro-Leu-Arg-Phe-NH(2). Cell bodies and terminals containing this peptide were localized immunohistochemically in the paraventricular nucleus and median eminence, respectively. This peptide inhibited, in a dose-related way, gonadotropin release from cultured quail anterior pituitaries. This is the first hypothalamic peptide inhibiting gonadotropin release reported in a vertebrate. We therefore term it gonadotropin-inhibitory hormone (GnIH).

Amino Acid Sequence↗
PubMed2000

Regulation of collagenolytic protease secretion through c-Src in osteoclasts.

The role of pp60c-src activity in the synthesis and secretion of the collagenolytic cysteine proteases (CCPs), cathepsin K (CAK), cathepsin L (CAL), and cathepsin B (CAB), by osteoclasts was investigated. Synthesis and secretion of CAL were up-regulated by 1alpha,25-(OH)2D3, but neither those of CAK, dominant relative to CAL, nor CAB, barely detectable, levels changed in the experiments. Though PP1, a pp60c-src inhibitor, had no effect on CCPs synthesis, suppressed the CAK and CAL secretion. Wortmannin, a phosphatidylinositol 3-kinase (PI3-kinase) inhibitor that works as a second messenger for pp60c-src, and cytochalasin B, an inhibitor of actin polymerization, suppressed the secretion of both CAK and CAL without suppressing synthesis. Hydroxyproline release, an indicator of degradation of type-I collagen, and F-actin ring formation, a structure linked to osteoclastic bone resorption, were suppressed by PP1, cytochalasin B or wortmannin. These results suggested inhibition of pp60c-src activity affected the osteoclastic cytoskeleton, which in turn reflected the suppression of bone resorption.

Actins↗
PubMed2000

Cloning and function of rabbit peroxisome proliferator-activated receptor delta/beta in mature osteoclasts.

Osteoclasts modulate bone resorption under physiological and pathological conditions. Previously, we showed that both estrogens and retinoids regulated osteoclastic bone resorption and postulated that such regulation was directly mediated through their cognate receptors expressed in mature osteoclasts. In this study, we searched for expression of other members of the nuclear hormone receptor superfamily in osteoclasts. Using the low stringency homologous hybridization method, we isolated the peroxisome proliferator-activated receptor delta/beta (PPARdelta/beta) cDNA from mature rabbit osteoclasts. Northern blot analysis showed that PPARdelta/beta mRNA was highly expressed in highly enriched rabbit osteoclasts. Carbaprostacyclin, a prostacyclin analogue known to be a ligand for PPARdelta/beta, significantly induced both bone-resorbing activities of isolated mature rabbit osteoclasts and mRNA expression of the cathepsin K, carbonic anhydrase type II, and tartrate-resistant acid phosphatase genes in these cells. Moreover, the carbaprostacyclin-induced bone resorption was completely blocked by an antisense phosphothiorate oligodeoxynucleotide of PPARdelta/beta but not by the sense phosphothiorate oligodeoxynucleotide of the same DNA sequence. Our results suggest that PPARdelta/beta may be involved in direct modulation of osteoclastic bone resorption.

Acid Phosphatase↗
PubMed2000

Primary leiomyosarcoma of the heart subsequent to double carcinomas of the thyroid and lung.

A 63-year-old woman underwent surgical operations for left lower lung cancer and for thyroid cancer. Nine months later, a third cancer developed in her heart and this tumor was removed by open heart surgery. A pathologic study revealed that the tumor was primary leiomyosarcoma of the heart and thus independent from the previous lung and thyroid carcinomas. This case was regarded as a triple carcinoma including a primary leiomyosarcoma arising from the left atrium. Reports in the literature on primary malignant tumors of the heart are reviewed briefly.

Female↗
PubMed2000

Mytilus inhibitory peptides (MIP) in the central and peripheral nervous system of the pulmonate gastropods, Lymnaea stagnalis and Helix pomatia: distribution and physiological actions.

The distribution and neuroanatomy of Mytilus inhibitory peptides (MIP)-containing neurons in the central nervous system and their innervation pattern in the peripheral nervous system of the pulmonate snail species, Lymnaea stagnalis and Helix pomatia, have been investigated immunocytochemically, by applying an antibody raised to GSPMFVamide. A significant number of immunoreactive neurons occurs in the central nervous system of both species (Lymnaea: ca 600-700, Helix: ca 400-500), but their distribution is different. In Lymnaea, labeled neurons are found in all central ganglia where a number of large and giant neurons, previously identified physiologically, reveal MIP immunoreactivity. In Helix, most of the immunolabeled neurons are small (12-30 microm) and concentrated in the buccal and cerebral ganglia; the parietal ganglia are free of labeled cells. In both species, the ganglionic neuropils, peripheral nerves, connectives, and commissures are richly supplied with immunolabeled fibers. The MIP-immunoreactive innervation pattern in the heart, intestine, buccal mass and radula, and foot is similar in both species, with labeled axonal bundles and terminal-like arborizations (buccal mass, foot) or a network of varicose fibers (heart, intestine). Intrinsic neurons are not present in these tissues. The application of GSPYFVamide inhibits the spontaneous contractions of the esophageal longitudinal musculature in Helix, indicating the bioactivity of the peptide. An outside-out patch-clamp technique has demonstrated that GSPYFVamide opens the K+ channels in central nerve cells of Helix. Injection of GSPYFVamide into the body cavity inhibits the feeding of starved Helix. A wide modulatory role of MIP at central and peripheral levels is suggested in Lymnaea and Helix, including the participation in intercellular signalling processes and remote neurohormonal-like control effects.

Animals↗
PubMed2000

High prevalence of anticardiolipin antibodies in hepatitis C virus infection: lack of effects on thrombocytopenia and thrombotic complications.

Hepatitis C virus (HCV) causes various extrahepatic immunologic abnormalities. Recently, an association between HCV infection and antiphospholipid syndrome, including thrombocytopenia, has been reported. However, the precise relationship between thrombocytopenia and anticardiolipin antibodies in patients with chronic HCV infection is not fully understood; likewise, the association of antiphospholipid syndrome and various liver diseases is not well understood. To evaluate the prevalence and importance of antiphospholipid antibodies in various chronic liver diseases, we determined the levels of anticardiolipin antibodies, platelet numbers, and levels of platelet-associated immunoglobulin G (PA-IgG) and thrombin-antithrombin III complex (TAT) in patients with chronic HCV infection, chronic hepatitis B virus (HBV) infection, and primary biliary cirrhosis (PBC). The prevalence of anticardiolipin antibodies in patients with HCV infection was significantly higher than that in control subjects or individuals with the other liver diseases examined. However, there was no significant correlation between anticardiolipin antibodies and platelet counts or TAT. The frequency of thrombotic complications was similar in anticardiolipin antibody-positive and -negative patients with chronic HCV infection. Further, sera from all but one anticardiolipin antibody-positive HCV patient were negative for phospholipid-dependent anti-beta2 glycoprotein I antibodies. Our results suggest that anticardiolipin antibodies are frequently found in patients with chronic HCV infection, but they do not appear to be of clinical importance. Immunologic disturbances induced by HCV or prolonged tissue damage in systemic organs as a result of the extrahepatic manifestations of HCV infection may induce the production of antibodies to various cardiolipin-binding proteins or phospholipids.

Antibodies, Anticardiolipin↗
PubMed2000

Regulation of collagenolytic cysteine protease synthesis by estrogen in osteoclasts.

In ovariectomized (Ovx) mice, collagenolytic cysteine protease (CCP) activity in calvaria significantly increased 7 days after ovariectomy and was about 50% of that observed in sham-operated (Sham) mice 3 weeks later. In Ovx mice, subcutaneously (s.c.) administered estradiol-17beta (E2) (10 microg/kg) for 2 weeks led to a decrease in CCP activity in calvaria to the level observed in Sham mice. In Ovx mice, though the amount of cathepsin L increased more than that of cathepsin K, cathepsin K and cathepsin L content increased by 200-400% compared with the Sham mice; cathepsin K was detected in larger amounts than cathepsin L in calvaria from both Sham and Ovx mice. The amounts of cathepsin K and cathepsin L in Ovx mice were reduced to the values seen with Sham mice after administration (s.c.) of E2 (10 microg/kg) for 2 weeks. In mouse calvarial organ culture, the increase of CCP activity and release of hydroxyproline, an indicator of degradation of type-I collagen, in the presence of 1alpha,25-(OH)(2)D(3), parathyroid hormone, interleukin (IL)-1alpha, IL-6, or tumor necrosis factor-alpha was suppressed by E2 (10(-9)-10(-7) M). In all cases, secretion of both cathepsin K and cathepsin L were suppressed by E2. In osteoclasts, expression of cathepsin K and cathepsin L was suppressed by E2 at the mRNA level. Cathepsin B was detected faintly or not at all. These results suggest that synthesis of cathepsin K and cathepsin L was negatively regulated by E2 at the mRNA level. In Ovx mice, deficiency of E2 resulted in an augmentation of cathepsin K and cathepsin L synthesis, and the cathepsins might share roles in bone resorption in vivo.

Animals↗
PubMed2000

Fulicin regulates the female reproductive organs of the snail, Achatina fulica.

Fulicin is a D-amino acid-containing neuropeptide that has been thought to control male copulatory behavior in the land snail, Achatina fulica. In the present study, we demonstrated that the vagina and the oviduct of Achatina were densely innervated by fulicin-like immunoreactive neuronal fibers. We confirmed that fulicin was actually present in the vagina by mass spectrometry. Furthermore, fulicin showed a profound excitatory effect on contractions of the vagina and the oviduct. These results suggest that fulicin controls female egg-laying behavior as an excitatory neuropeptide regulating the female reproductive organs of the snail.

Animals↗
PubMed2000

Glycyrrhizin inhibits the lytic pathway of complement--possible mechanism of its anti-inflammatory effect on liver cells in viral hepatitis.

Glycyrrhizin, an aqueous extract of licorice root, has anti-inflammatory activity and has been used for the treatment of chronic viral hepatitis. In the present study we describe the mechanism by which glycyrrhizin inhibits complement. Glycyrrhizin inhibited the cytolytic activity of complement via the activation of both the classical and alternative pathways, while it had no effect on immune adherence, suggesting that it blocks C5 or a later stage of the complement cascade. Further analysis revealed that glycyrrhizin inhibits the lytic pathway in which the membrane attack complex (MAC) is formed. This mechanism suggests that glycyrrhizin may prevent tissue injury caused by MAC not only in chronic hepatitis but in many autoimmune and inflammatory diseases.

Animals↗
PubMed2000

Eccrine syringofibroadenoma in a patient with a burn scar ulcer.

A 72-year-old woman with a burn scar on the calves of both legs developed an ulcer on her right heel, surrounded by multiple verrucous nodules and plaques. She had experienced similar verrucous lesions on both legs in the burn scar areas. Although the clinical diagnosis was Marjolin's ulcer, histologically the ulcer region showed thick fibrous tissue without any atypical epithelial cells. The verrucous lesions were consistent with the diagnosis of eccrine syringofibroadenoma (ESFA). Moreover, an ESFA-like growth pattern was seen in the elevated margin of the ulcer. Our findings suggest that these lesions developed as a result of reactive eccrine duct hyperplasia followed by skin tissue remodelling.

Adenoma, Sweat Gland↗