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Biomedical subjects

Y Fujisawa

Publications and source records attributed to Y Fujisawa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Distinct roles of cathepsin K and cathepsin L in osteoclastic bone resorption.

The role of cathepsin K (CAK), cloned as a novel collagenolytic cysteine protease (CCP), cathepsin L (CAL) and cathepsin B (CAB) in bone resorption was investigated. In mouse calvarial organ culture medium, CAL, detected in trace amounts in control conditions, and CCP activity were increased by stimulants of bone resorption: 1alpha,25-(OH)2D3 parathyroid hormone (PTH), IL-1alpha, IL-6 or TNF-alpha. CAK was the most abundantly detected CCP and was not increased by these stimulants. In the absence of the stimulants, only antisense oligodeoxynucleotide (AS-ODN) for CAK suppressed collagenolysis and CCP activity. On the other hand, in the presence of the stimulants, AS-ODN for both CAK and CAL suppressed collagenolysis and CCP activity, and these activities were additive. AS-ODN for CAB did not suppress collagenolysis. These results suggested CAK was constitutively synthesized as the main CCP, and CAL was synthesized as an inducible CCP in osteoclasts to degrade type-I collagen in combination with CAK.

Animals↗
PubMed2000

[Chemotherapy for unresectable recurrent or metastatic squamous cell carcinomas of the head and neck].

The efficacy of chemotherapy for unresectable recurrent or metastatic squamous cell carcinomas of the head and neck can not be proved by survival periods. However, the efficacy of chemotherapy has been observed in some select patients. We investigated the effect of chemotherapy for unresectable recurrent squamous cell carcinomas of the head and neck. Four patients with a good performance status (PS) were treated with high-doses of leucovorin (LV), cisplatin (CDDP), and 5-fluorouracil (5-FU). The regimen consisted of 25 mg/m2 of CDDP on days 1-5; 600 mg/m2 of 5-FU of days 2-6; and 200 mg/m2 of LV on days 1-6. Patients received 3 cycles of this regimen at 28-day intervals. Ten patients with a poor PS were treated with low-doses of CDDP and tegafur.uracil upon admission. The regimen of seven poor PS patients consisted of 8 mg/m2 of CDDP on days 1-5 and 8-12, and 400 mg/body of tegafur.uracil administered orally on days 1-14. The other three patients received chemotherapy on an outpatient basis for ten weeks. The weekly regimen consisted of 7.5 mg/m2 of CDDP on days 3 and 6 and 400 mg/body of tegafur.uracil administered orally on days 1-7. With respect to the LV + CDDP and 5-FU treatment, complete remission was obtained in one patient. Two patients showed no change (NC), while one patient developed a progressive disease (PD). This regimen is highly toxic, has severe side effects including myelosuppression, oral mucositis, and diarrhea, and has a survival period of between 16 and 32 weeks. The low-dose CDDP + tegafur.uracil treatment produced a partial response in three patients, NC in three patients, and four patients developed a PD. This regimen doses not have any severe side effects and has a survival period of between 4 and 67 weeks.

Aged↗
PubMed2000

[A novel instrument for off-pump coronary artery bypass grafting: traction-type coronary artery stabilizer].

A new instrument for heart stabilization during beating coronary bypass grafting without cardiopulmonary bypass and a clinical experience of off-pump LITA-to-LAD bypass using this mechanical stabilizer are described. This device provide optimal motionless field by traction mechanism in which traction sutures placed proximal and distal to the target coronary artery are tied to the U-shaped foot plate with multiple small holes. The advantages of this stabilizer are as follows; no need of heart compression, ability to displace the target lesion to facilitate anastomosis, reusable, compact size and easy handling. We believe this novel instrument will improve the anastomosis quality in patient undergoing coronary artery bypass without cardiopulmonary bypass.

Aged↗
PubMed2000

Comparative aspects of invertebrate neuropeptides.

1. We searched for bioactive peptides, most of which were considered to be neuropeptides, in various animals of several phyla. These peptides were compared with each other and with peptides identified by many other investigators. Consequently, we found that structures of neuropeptides are generally conserved in each phylum. 2. We also found some exceptional interesting aspects. First, there are a number of peptide groups whose members are distributed among several phyla. Second, there are many structural similarities between molluscan and annelidan peptides as if molluscs and annelids were the animals in a phylum. Third, certain toxic peptides of invertebrates are closely related to vertebrate neuropeptides. 3. In addition to the above phylogenetic aspects, we found some other interesting aspects. A wide structural variety of members of a peptide group is generally found in invertebrate species. Invertebrate muscles seem to be generally regulated not only by some or several classical non-peptidic neuromediators but also by various peptidic neuromediators. Peptides containing a D-amino acid residue are not rare.

Amino Acid Sequence↗
PubMed2000

Mytilus inhibitory peptide (MIP) induces a Na+-activated K+-current in snail neurons.

Two microelectrode voltage-clamp and single-channel recordings were performed on D-cluster neurons of snail right parietal ganglion in order to study the properties of MIP-activated potassium current. It was found that the octapeptide member of the MIP-family, ASHIPRFVa elicits an outward current, which possesses all the properties characteristic for the hexapeptide(s) inward membrane response. The main component of the peptide elicited response is highly [K+]o dependent, however the response was attenuated in Na-free extracellular saline. The peptide elicited response was mimicked by raising the [Na+]i by pressure injection of Na+ into the cell. Single channel recordings indicated that MIP-induced outward K-current is Na-dependent. The probability to find a channel in open state increases with increasing intracellular Na+-concentration. Excised inside-out patches obtained from D-neurons contained I(K(Na)) channels could be activated by exposure of the cytoplasmic face of the patch membrane to 40 mM Na+, and 40 mM Li+, as well. The single channel current amplitude at -60 mV is 15 pA and the single channel conductance is 212 pS between -80 and 0 mV. It was concluded that MIP's activate a novel type of K+-current in the snail neurons. This current is the Na-activated K+-current. The single channel properties of the MIP activated channel is in concert with I(K(Na)) data obtained on different vertebrate and invertebrate preparations.

Amino Acid Sequence↗
PubMed2000

Preventive effect of local plasmid DNA vaccine encoding gD or gD-IL-2 on herpetic keratitis.

PURPOSE: The goal of this study was to evaluate the effectiveness of a local plasmid DNA vaccine encoding herpes simplex virus (HSV) type 1 glycoprotein D (gD) or gD-interleukin (IL)-2 (chimeric gene of gD and human IL-2) in preventing murine herpetic keratitis. METHODS: Plasmids containing gD (pHSDneo1), gD-IL-2 (pHDLneo1), or vaccine vector (pHSGneo) were injected subconjunctivally with BALB/c mice on days 0 and 7 (90 microgram x 2). Immunization was indicated by positive virus-neutralizing antibody titer, swollen pinna (due to delayed-type hypersensitivity [DTH] reaction), and release of (51)Cr from splenic and/or local cytotoxic effector cells on day 28. In another group of the immunized mice, corneas were challenged with HSV-1 (CHR3 strain, 10 microliter of 3 x 10(6) plaque-forming units [PFU]/ml). Mice were evaluated for clinical signs of epithelial or stromal keratitis on days 1 through 8 and days 10 and 14 or measured on days 2, 4, or 6 for viral titers in the eyes, trigeminal ganglia, and brain. RESULTS: All gD-DNA-injected mice obtained specific immunity. Furthermore, gD-IL-2-DNA elicited a higher DTH reaction and more vigorous cytotoxic effector cell activity. Stromal keratitis scores were lower for all immunized mice compared with control mice, although the difference in epithelial keratitis scores was not statistically significant. Viral titers in eyes, trigeminal ganglia, and brains were suppressed in all immunized mice. CONCLUSIONS: Local immunization with plasmid DNA encoding gD or gD-IL-2 induces humoral and cellular immunity against HSV-1 and inhibits development of stromal keratitis. gD-IL-2 DNA induces greater cell-mediated immunity than gD DNA alone. A plasmid encoding gD-IL-2 is therefore a promising candidate for a vaccine against HSV-1.

Animals↗
PubMed1999

Renal interstitial concentration of adenosine during endotoxin shock.

The present experiments were designed to measure the renal interstitial concentration of adenosine in an attempt to determine whether adenosine participates in the regulation of renal hemodynamics during endotoxin shock. The renal concentration of adenosine in response to lipopolysaccharide (LPS) administration was measured in anesthetized dogs using a microdialysis method. Renal hemodynamic responses to LPS were also determined with and without the adenosine A(1) receptor antagonist, (E)-(R)-1-[3-(2-phenylpyrazolo[1, 5-a]pyridin-3-yl)acryloyl]pyperidin-2-ylacetic acid (FK352). Intravenous administration of LPS (0.5 mg/kg) significantly decreased renal blood flow and mean arterial pressure. These parameters reached the minimum level at 5-10 min after the LPS administration and then returned to their respective preinjection levels. The renal interstitial concentration of adenosine increased from 118+/-18 to 381+/-46 nM. During treatment with FK352, LPS decreased renal blood flow and mean arterial pressure, however, these reductions were significantly attenuated. LPS also increased adenosine concentration, but its rise was reduced along with the attenuation of LPS-induced renal blood flow reduction. These results suggest that adenosine was involved in LPS-induced renal hemodynamic changes and that FK352 has a protective effect against renal dysfunction during endotoxin shock. Since the adenosine concentration was inversely proportional to renal blood flow levels, it can be assumed that adenosine plays an important role as a mediator, but not as an initiator of renal hemodynamic changes during endotoxin shock.

Adenosine↗
PubMed1999

The Aplysia mytilus inhibitory peptide-related peptides: identification, cloning, processing, distribution, and action.

Neuropeptides are a ubiquitous class of signaling molecules. In our attempt to understand the generation of feeding behavior in Aplysia, we have sought to identify and fully characterize the neuropeptides operating in this system. Preliminary evidence indicated that Mytilus inhibitory peptide (MIP)-like peptides are present and operating in the circuitry that generates feeding in Aplysia. MIPs were originally isolated from the bivalve mollusc Mytilus edulis, and related peptides have been identified in other invertebrate species, but no precursor has been identified. In this study, we describe the isolation and characterization of novel Aplysia MIP-related peptides (AMRPs) and their precursor. Several AMRPs appear to have some structural and functional features similar to vertebrate opioid peptides. We use matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to confirm that all 14 AMRPs predicted by the precursor are processed in isolated neurons. Northern analysis, whole-mount in situ hybridization, and immunohistochemistry are used to map the abundant expression of these peptides in the CNS and peripheral tissues such as the digestive tract, vasculature, and the reproductive organs. Physiological studies demonstrate that the rank order of the inhibitory actions of these peptides is different for three target muscles. These results underscore the importance of using a multidisciplinary approach to identifying and characterizing the actions of neuropeptides in an effort to gain understanding of their role in systems of interest. The widespread distribution of the AMRPs indicates that they may be operating in many different systems of Aplysia.

Amino Acid Sequence↗
PubMed1999

Suppression of the heterotrimeric G protein causes abnormal morphology, including dwarfism, in rice.

Transgenic rice containing an antisense cDNA for the alpha subunit of rice heterotrimeric G protein produced little or no mRNA for the subunit and exhibited abnormal morphology, including dwarf traits and the setting of small seeds. In normal rice, the mRNA for the alpha subunit was abundant in the internodes and florets, the tissues closely related to abnormality in the dwarf transformants. The position of the alpha-subunit gene was mapped on rice chromosome 5 by mapping with the restriction fragment length polymorphism. The position was closely linked to the locus of a rice dwarf mutant, Daikoku dwarf (d-1), which is known to exhibit abnormal phenotypes similar to those of the transformants that suppressed the endogenous mRNA for the alpha subunit by antisense technology. Analysis of the cDNAs for the alpha subunits of five alleles of Daikoku dwarf (d-1), ID-1, DK22, DKT-1, DKT-2, and CM1361-1, showed that these dwarf mutants had mutated in the coding region of the alpha-subunit gene. These results show that the G protein functions in the formation of normal internodes and seeds in rice.

Base Sequence↗
PubMed1999

Ionic mechanism mediating Mytilus inhibitory peptides elicited membrane currents in identified Helix neurons.

Effects of seven, pressure applied MIP (Mytilus inhibitory peptides) had been studied on D-neurons of the CNS of Helix pomatia in voltage-clamp experiments. In physiological saline, the peptides produced a hyperpolarization usually coupled with the cessation of any spontaneous spiking activity. Clamped at the resting potential ( approximately -60 mV), peptide applications elicited an outward current, which increased its amplitude by shifting the holding potential towards depolarisation. The response was concentration-dependent and accompanied by an increased membrane conductance. Reversal potentials obtained at different [K+]o were plotted with a slope of 52 mV per ten-fold change in [K+]o showing that the peptide-elicited current was mainly due to the increased K+-conductance(s). The peptide-induced outward current could partially be blocked by Ba2+ (5 mM), CdCl2 (1 mM), TEACl (10 mM) or apamin (2.5x10(-5) M) or furosemide (10 mg/ml) and decreased either in Na+-free or Cl--free solutions. 4-Aminopyridine at 5 mM concentration completely blocked the peptide-induced current. In the presence of high [K+]o, the peptide(s) was still found to induce an outward current at membrane potentials beyond K+-reversal potential. This component was not present in Cl--free saline, suggesting that the current was due to the inward flow of Cl- ions. Our results show that the MIPs have at least two (three) independent actions, each associated with different voltage-, concentration-dependence and ionic mechanisms. It is suggested, that the peptide-induced currents are carried by K+, and Cl- ions. According to our present finding, the observed effects are mediated by the same receptor, activating different second messenger systems, inducing multiple conductance changes in the membrane of neurons of the snail ganglia.

Animals↗
PubMed1999

Synthesis of novel 2-benzothiopyran and 3-benzothiepin derivatives and their stimulatory effect on bone formation.

In a search for therapeutic agents for the treatment of osteoporosis and bone fracture, we found that 2-benzothiopyran-1-carboxamide derivatives 1, derived from ipriflavone as a lead compound, increase cellular alkaline phosphatase activity in cultures of rat bone marrow stromal cells. Further modification of 1 has led to the discovery of more potent 3-benzothiepin-2-carboxamide derivatives 2. Of these, 3-benzothiepin derivatives bearing a 4-(dialkoxyphosphorylmethyl)phenyl group on the 2-carboxamide moiety such as 2h and 2q exhibited significant improvement of activity compared to ipriflavone. Asymmetric synthesis of 2h and 2q revealed that the (-)-isomers possessed activities superior to those of the (+)-isomers. Further evaluation of these compounds using the mouse osteoblastic cell line MC3T3-E1 revealed that (-)-2q enhanced the effect of bone morphogenetic protein. In addition, application of a sustained-release agent containing 2q increased the area of newly formed bone in a rat skull defect model. Based on these findings, (-)-2q was selected for further investigation as a new drug stimulating bone formation. Synthesis and structure-activity relationships for this novel series of 2-benzothiopyran and 3-benzothiepin derivatives are detailed.

3T3 Cells↗
PubMed1999

Polyarthritis nodosa with mesenteric aneurysms demonstrated by angiography: report of a case and successful treatment of the patient with prednisolone and cyclophosphamide.

Polyarteritis nodosa is a necrotizing angitis that predominantly affects small and medium-sized arteries. The prognosis of untreated polyarteritis nodosa is very poor. Since symptoms are diverse and no serologic test is specific for polyarteritis nodosa, the diagnosis is difficult and often delayed. We describe a patient with polyarteritis nodosa who had gastrointestinal involvement with multiple aneurysms of the inferior mesenteric artery; only abdominal angiography provided a conclusive diagnosis. Alleviation of symptoms and regression of aneurysms were observed after combination therapy of an immunosuppressive agent, cyclophosphamide, and prednisolone. We emphasize the importance of early diagnosis by angiography and aggressive therapy in patients in whom physical signs indicating definite polyarteritis nodosa are not present.

Aneurysm↗
PubMed1999

Role of nitric oxide in regulation of renal sympathetic nerve activity during hemorrhage in conscious rats.

The effect of inhibition of nitric oxide (NO) synthesis on the responses of blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) during hemorrhaging was examined with the use of an NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), in conscious rats. In the 0.9% saline group, hemorrhage (10 ml/kg body wt) did not alter BP but significantly increased HR and RSNA by 88 +/- 12 beats/min and 67 +/- 12%, respectively. Intravenous infusion of L-NAME (50 microg. kg(-1). min(-1)) significantly attenuated these tachycardic and sympathoexcitatory responses to hemorrhage (14 +/- 7 beats/min and 26 +/- 12%, respectively). Pretreatment of L-arginine (87 mg/kg) recovered the attenuation of HR and RSNA responses induced by L-NAME (92 +/- 6 beats/min and 64 +/- 10%, respectively). L-NAME by itself did not alter the baroreceptor reflex control of HR and RSNA. Hemorrhage increased the plasma vasopressin concentration, and its increment in the L-NAME-treated group was significantly higher than that in the 0.9% saline group. Pretreatment with the vascular arginine vasopressin V(1)-receptor antagonist OPC-21268 (5 mg/kg) recovered the attenuation of RSNA response induced by L-NAME (54 +/- 7%). These results indicate that NO modulated HR and RSNA responses to hemorrhage but did not directly affect the baroreceptor reflex arch. It can be assumed that NO modulated the baroreflex function by altering the secretion of vasopressin induced by hemorrhage.

Animals↗
PubMed1999

A new insulin-mimetic vanadyl complex, (N-pyridylmethylaspartate)oxovanadium(IV) with VO(N2O2) coordination mode, and evaluation of its effect on uptake of D-glucose by Ehrlich ascites tumour cells.

Because it has been confirmed that the vanadyl(IV) ion and its complexes act as insulin mimetics, a new organic vanadyl complex, (N-pyridylmethylaspartate)oxovanadium (VOPASP) with VO(N2O2) coordination mode, was prepared. Development of a simple and rapid in-vitro assay is needed for recognition of potent insulin-mimetic complexes. Treatment of Ehrlich ascites tumour cells with 2-deoxyglucose in the presence of vanadyl sulphate, or other vanadyl complexes with the same coordination mode (VOPASP, bis(picolinate)oxovanadium (VOPA) and bis(6-methyl picolinate)oxovanadium (VOMPA)), in the presence of 2-deoxy-D-[1-3H]glucose ([3H]deoxyglucose), resulted in concentration-dependent uptake of 2-deoxyglucose by the cells. The responses of the cells to the vanadyl complexes were reflected, in part, by results obtained from the free fatty acid-releasing assay using rat adipocytes. These results show that the in-vitro assay with Ehrlich ascites tumour cells provides an accurate and rapid assessment of glucose uptake by the cells. The assay is proposed as a means of predicting the insulin-mimetic activity of the vanadyl complexes and for studying the mechanism of action of the complexes.

Animals↗
PubMed1999

Depression in the early stages of Pick's disease.

To better understand the nature of the symptoms of depression in the early stages of Pick's disease, we performed a retrospective study of the medical records of eight patients who were originally treated for major depressive disorders before being clinically diagnosed with Pick's disease. Six of the eight manifested psychomotor retardation and social withdrawal, seven of the eight were agitated and five of the eight showed hyperbulia too. However, only two of the eight showed melancholia or physical symptoms such as insomnia or loss of appetite. All patients were treated with antidepressants but these were not effective in relieving the symptoms of depression. The data we gathered in this study will be useful in the future for distinguishing between Pick's disease-related depression (in the early stages of the disease) and major depression.

Affect↗
PubMed1999

Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin.

Excess of body fat, or obesity, is a major health problem and confers a higher risk of cardiovascular and metabolic disorders such as diabetes, hypertension, and coronary heart disease. Leptin is an adipocyte-derived satiety factor that plays an important role in the regulation of energy homeostasis, and its synthesis and secretion are markedly increased in obese subjects. To explore the metabolic consequences of an increased amount of leptin on a long-term basis in vivo, we generated transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. Overexpression of leptin in the liver has resulted in complete disappearance of white and brown adipose tissue for a long period of time in mice. Transgenic skinny mice exhibit increased glucose metabolism accompanied by the activation of insulin signaling in the skeletal muscle and liver. They also show small-sized livers with a marked decrease in glycogen and lipid storage. The phenotypes are in striking contrast to those of recently reported animal models of lipoatrophic diabetes and patients with lipoatrophic diabetes with reduced amount of leptin. The present study provides evidence that leptin is an adipocyte-derived antidiabetic hormone in vivo and suggests its pathophysiologic and therapeutic implications in diabetes.

Animals↗