Search PubMed⌕ Search

Biomedical subjects

M Yoshikawa

Publications and source records attributed to M Yoshikawa.

At least 37 records · Page 2Linked to original sources

Design and production of genetically modified soybean protein with anti-hypertensive activity by incorporating potent analogue of ovokinin(2-7).

The potent anti-hypertensive peptide, RPLKPW, has been designed based on the structure of ovokinin(2-7). The sequence encoding this peptide was introduced into three homologous sites in the gene for soybean beta-conglycinin alpha' subunit. The native alpha' subunit as well as the modified, RPLKPW-containing alpha' subunit were expressed in Escherichia coli, recovered from the soluble fraction and then purified by ion-exchange chromatography. The RPLKPW peptide was released from recombinant RPLKPW-containing alpha' subunit after in vitro digestion by trypsin and chymotrypsin. Moreover, the undigested RPLKPW-containing alpha' subunit given orally at a dose of 10 mg/kg exerted an anti-hypertensive effect in spontaneously hypertensive rats, unlike the native alpha' subunit. These results provide evidence for the first time that a physiologically active peptide introduced into a food protein by site-directed mutagenesis could practically function in vivo even at a low dose.

Administration, Oral↗

Generalized scaling laws of the formation and effects of plasma-confining potentials for tandem-mirror operations in GAMMA 10.

The main operations from 1979 to 2000 in the GAMMA 10 tandem-mirror, characterized in terms of the high-potential mode having kV-order plasma-confining potentials and the hot-ion mode yielding fusion neutrons with 10-20 keV bulk-ion temperatures, are summarized and generalized as a result of scalings of the formation and the effects of the potentials. The wide validity of potential-formation physics from Cohen's theory and the validity of the generalized Pastukhov's theory for the effects of thermal-barrier potentials on electron confinement are verified and consolidated through electron-energy balance.

Journal Article↗

New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice.

Myrrhanol A, a new triterpene isolated from guggul (Balsamodendron or Commiphora mukul Hook.)-gum resin, displays a potent anti-inflammatory effect on exudative pouch fluid, angiogenesis, and granuloma weights in adjuvant-induced air-pouch granuloma of mice. Its effects were more marked than those of hydrocortisone and the 50% aqueous methanolic extract of the crude drug. Myrrhanol A is a plausible candidate for a potent anti-inflammatory agent.

Animals↗

Effects of antisense oligodeoxynucleotides against opioid receptors on the receptor mRNA contents.

It was demonstrated in the previous study that the microinjection of antisense oligodeoxynucleotide (AS ODN) against mu-opioid receptor (MOR) into periaqueductal gray (PAG) of rat brain selectively decreased the MOR mRNA content in PAG, and the decrease in MOR mRNA content was enhanced by pretreatment of the PAG with MOR AS ODN. In the present investigation, effects of the pretreatment of PAG with AS ODN against kappa- or delta-opioid receptor (KOR or DOR) on the decrease in the MOR mRNA content induced by MOR AS ODN were examined. Both KOR and DOR AS ODNs significantly decreased the target mRNA contents, while they did not significantly change MOR mRNA content. The decrease in MOR mRNA content induced by MOR AS ODN, however, was significantly enhanced by the pretreatment of PAG with either KOR or DOR AS ODNs. Results show that the AS ODN has both the specific target mRNA decreasing action and the nonspecific enhancing action on the AS-induced decrease in the mRNA content.

Animals↗

Evidence that phenylalanine 69 in Escherichia coli RuvC resolvase forms a stacking interaction during binding and destabilization of a Holliday junction DNA substrate.

Escherichia coli RuvC resolvase is a specific endonuclease that recognizes and cleaves Holliday junctions formed during homologous recombination and recombinational repair. This study examines the phenotype of RuvC mutants with amino acid substitutions at phenylalanine 69 (F69L, F69Y, F69W, and F69A), a catalytically important residue that faces the catalytic center of the enzyme. F69Y, but not the other three mutants, almost fully complements the UV sensitivity of a DeltaruvC strain and substantially resolves synthetic Holliday junctions in vitro. In the presence of 100 mm NaCl, RuvC F69A and F69L are defective in junction binding, but F69Y and F69W retain near wild-type binding activity during a gel shift binding assay. KMnO(4) was used to probe synthetic Holliday junction DNA in a complex with wild-type and mutant RuvC; F69A and F69L did not induce disruption of base pairing at the crossover to the same extent as wild-type RuvC. Thus, the aromatic ring of Phe-69 is involved in DNA binding, probably via a stacking interaction with a nucleotide base, and this interaction may induce a structural change in junction DNA that is required to form a catalytically competent complex.

Bacterial Proteins↗

Total gastrectomy with distal pancreatectomy and splenectomy for advanced gastric cancer.

BACKGROUND: Pancreaticosplenectomy (PS) is often performed simultaneously with total gastrectomy (TG) to facilitate dissection of the lymph nodes around the splenic artery and splenic hilus. To evaluate the effects of PS on survival, a retrospective study was performed. METHODS: Various clinicopathological factors influencing lymph node metastasis around the splenic hilus (No. 10) and the splenic artery (No. 11) were studied retrospectively in the upper or middle third of advanced gastric cancer patients who underwent TG with PS. The postoperative morbidity, mortality, and survival rate of patients who underwent TG with PS (the TG with PS group) were compared with those of patients who underwent TG alone (the TG-alone group). RESULTS: Tumor size larger than 41 mm and lymph node No. 2 metastasis were independently correlated with lymph node No. 10 and No. 11 metastasis. The mortality rate was similar, but the morbidity rate was significantly higher in the TG with PS group. In the patients with stage I and III, there was no significant difference between the two groups, but in the patients with stage II, the TG-alone group was significantly better than the TG with PS group (P = 0.0400). CONCLUSIONS: Combined PS with TG should never be performed as the standard surgical procedure for every stage of gastric cancer, especially stage II.

Adult↗

Postsynaptic modulation of AMPA receptor-mediated synaptic responses and LTP by the type 3 ryanodine receptor.

The precise function of ryanodine receptors (RyRs) in synaptic transmission is unknown, but three of their subtypes are expressed in the brain. We examined the roleof RyRs in excitatory synaptic transmission in hippocampal slices, using type 3 RyR (RyR3)-deficient mice. The alpha-amino-3-hydroxy-5-methyl-4-isoxozolepropionic acid (AMPA) receptor-mediated basal synaptic responses in the CA1 region of mutant mice were smaller than those of wild-type mice, while there was no difference in N-methyl-d-aspartate receptor-mediated responses, suggesting selective postsynaptic modification of AMPA receptors by RyR3. The expression of synaptic AMPA receptor subunits examined by Western blotting or immunohistochemistry was indistinguishable, suggesting that the smaller AMPA synaptic responses in mutant mice were not due to the reduced number of synaptic AMPA receptors. Although the initial potentiation following tetanic stimulation of afferent fibers was similar, long-term potentiation (LTP) was smaller in mutant mice. There were no differences in presynaptic electrophysiological properties. We thus conclude that RyR3 postsynaptically regulates the properties of AMPA receptors and LTP.

2-Amino-5-phosphonovalerate↗

Lung volume reduction surgery and nutritional status in patients with severe emphysema.

OBJECTIVE: We studied the short-term effect of lung volume reduction surgery on nutritional status including body composition and the relationship between preoperative nutritional status and postoperative morbidity. METHODS: Subjects were 28 patients with emphysema who underwent bilateral thoracoscopic lung volume reduction surgery (23 simultaneously, 5 staged). Functional tests, body weight, and body composition were measured before and 6 months after surgery. Fat-free mass and fat mass were assessed by bioelectrical impedance analysis. RESULTS: FEV1.0 improved 35.2% following surgery and maximal oxygen uptake 23.8%. Body weight and fat-free mass increased significantly after surgery, while fat mass was unchanged. Of the 23 undergoing simultaneous bilateral lung volume reduction surgery, 8 had major complications-3 required additional surgery to close air leaks, 3 required mechanical ventilation (> 72 hrs), and 2 developed postoperative infection. The preoperative percentage of ideal body weight and fat-free mass was significantly higher among patients without major complications. CONCLUSIONS: Bilateral lung volume reduction surgery increases fat-free mass and provides functional improvement for underweight patients with severe emphysema. We found fat-free mass and body weight to be good predictors of unacceptable postoperative complications following bilateral lung volume reduction surgery.

Aged↗

Chronic rejection in H-2 matched cardiac allografts: early emergence of vasculopathy, alloantibody, and accumulation of IFN-gamma and IL-10 mRNA.

Cardiac allograft vasculopathy (CAV) is one of the crucial problems of clinical heart transplantation. We have developed a novel model of murine cardiac allograft rejection, in which chronic rejection associated with CAV occurs in its natural course. In this study we analyzed the pathogenesis of chronic cardiac allograft rejection using an H-2 matched multiple minor histocompatibility antigen-mismatched combination, AKR (H-2k) to C3H (H-2k) recipient mice. All the cardiac allografts survived for more than 100 days but were rejected within 260 days post-transplant (n = 13; mean survival times +/- standard deviation = 189.0+/-72.0; median = 210). The heartbeats of the graft became gradually weaker throughout the duration of the rejection process. Serial histological analyses with hematoxylin and eosin, elastica van Gieson or Masson trichrome staining revealed mononuclear cell infiltration and intimal thickening (i.e. CAV) which started in most grafts at 2 weeks post-transplant. These pathological changes eventually developed to severe graft fibrosis, and the severity of these changes correlated with the deterioration of the heartbeats. Production of anti-donor antibodies in most recipients was detectable by 2 weeks post-transplant, it peaked before day 100, and subsided before rejection was complete in most grafts. Intragraft expression of IFN-gamma and IL-10 mRNA was demonstrated by reverse transcriptase-polymerase chain reaction during early periods post-transplant. In this study, we demonstrate a novel model feasible for analysis of chronic cardiac allograft rejection, in which the vascular rejection processes, including fibrosis and alloantibody production, can be tested from an early stage on, after transplantation.

Animals↗

Microscopic polyangiitis complicated with massive intestinal bleeding.

Microscopic polyangiitis (MPA) is associated with renal dysfunction, in most cases, and occasionally with pulmonary hemorrhage. However, massive intestinal bleeding is a rare manifestation. We report a case of MPA in a man who developed arterial bleeding in the small intestine. A 74-year-old man was admitted after enduring a fever for 4 weeks. Laboratory examination revealed leucocytosis with neutrophil predominance, and renal dysfunction was noted. He did not respond to treatment with antibiotics, and the worsened renal function soon required hemodialysis. On the seventh hospital day, he suddenly developed massive melena. A colonoscopic examination suggested bleeding in the small intestine, and abdominal angiography demonstrated that the bleeding originated in a branch of the ileal artery. Hemostasis was achieved by transarterial embolization (TAE), but the patient suffered a massive pulmonary hemorrhage 2 days after the TAE. Although he responded well to a combination treatment with corticosteroid and cyclophosphamide, recurrence of pulmonary hemorrhage led to death, on the 87th hospital day. MPA in this patient was associated with three serious complications; deteriorating renal function, massive melena, and pulmonary hemorrhage. Of the various manifestations associated with MPA, arterial bleeding in the gastrointestinal tract, although rare, should be considered as one of the serious complications in MPA.

Aged↗

Hepatic adenomas treated with percutaneous ethanol injection in a patient with glycogen storage disease type Ia.

We report a 20-year-old man with glycogen storage disease type Ia (GSD Ia) who presented multiple hepatocellular adenomas (HCAs) in 1993 and in whom percutaneous ethanol injection (PEI) was conducted as treatment for some enlarging tumors beneath the liver surface. In a 6-year follow-up period, we observed gradual enlargement of some of the HCAs, and the rapid growth of a newly developed tumor. In August 1996, one slow-growth HCA was 52 mm in diameter and was located beneath the surface of the liver. We conducted PEI therapy to prevent its spontaneous rupture. During the following year, another tumor developed beneath the liver surface, but showed extremely rapid growth, reaching 51 mm in diameter, from being undetectable, within 12 months. PEI therapy was again conducted for this newly developed tumor. Although additional PEI therapy was required for each tumor, because of suspected recurrence, no findings of discrete recurrence have been detected by computed tomography and magnetic resonance imaging for more than 2 years, up to the time of this study. We consider PEI to be a useful and effective therapeutic modality for individual HCAs in patients with GSD Ia.

Adenoma↗

Congenital bronchoesophageal fistula with Crohn's disease in an adult: report of a case.

A 65-year-old man was diagnosed to have Crohn's disease in 1989. In 1991, frequent bronchitis developed, and bronchoesophageal fistula was diagnosed by esophagography. On esophagography and aortography, the disease was diagnosed to be Type IV based on Braimbridge's classification accompanied by pulmonary sequestration. A thoracoscope-assisted fistelectomy was performed. This paper reports the findings of a fistelectomy assisted by thoracoscopy for the treatment of a Type IV bronchoesophageal fistula according to Braimbridge's classification accompanied by Crohn's disease.

Aged↗

Predictive value of interleukin-8 and granulocyte elastase in pulmonary complication after esophagectomy.

BACKGROUND: We investigated whether or not interleukin-8 (IL-8) and granulocyte elastase (GE) can be associated with pulmonary complication after esophagectomy (the most common cause of postoperative death). METHODS: We measured serial changes in the IL-8 concentration and GE activity in the plasma and bronchoalveolar lavage fluid (BALF) of 17 patients who had undergone esophagectomy, and examined the relationship between these mediators and postoperative pulmonary complication. RESULTS: Pulmonary complication occurred in 6 patients (35%, Pneum+ group). Plasma IL-8 increased at the end of the surgery then decreased, but there was no significant difference between the Pneum+ group and the group without pulmonary complication (11[65%], Pneum- group). IL-8 and GE in BALF were significantly higher in the Pneum+ group than in the Pneum- group on days 1 and 3 after the operation. There was a significant and positive correlation between IL-8 and GE in BALF. CONCLUSIONS: Our results indicate that IL-8 and GE in BALF may be useful for the prediction of postoperative pulmonary complication.

Aged↗

Designing of an orally active complement C3a agonist peptide with anti-analgesic and anti-amnesic activity.

Complement C3a is an anti-opioid peptide, having anti-analgesic and anti-amnesic effects after intracerebroventricular administration. However, the peptide is inactive after oral administration. Orally active C3a agonist peptide was designed based on the structure of oryzatensin, a C3a agonist peptide derived from rice albumin. Tyr-Pro-Leu-Pro-Arg, a pentapeptide at the carboxyl terminus of oryzatensin is the minimally essential structure for exerting C3a activity. Due to the affinity for mu-opioid receptor, both oryzatensin and Tyr-Pro-Leu-Pro-Arg showed analgesia after intracerebroventricular administration in mice which was blocked by the opioid antagonist naloxone. Tyr-Pro-Leu-Pro-Arg lost opioid activity by substitution the amino terminus tyrosine with other hydrophobic residues. Among the newly designed peptides, Trp-Pro-Leu-Pro-Arg was found to possess the strongest C3a activity. The peptide antagonized morphine-induced analgesia at 300 mg/kg after oral administration and also improved scopolamine- and ischemia-induced amnesia in a step-through passive avoidance test.

Administration, Oral↗

Proadrenomedullin N-terminal 20 peptide (PAMP) inhibits food intake and gastric emptying in mice.

We found that proadrenomedullin N-terminal 20 peptide (PAMP) decreased dose-dependently (3-30 nmol/mouse) food intake after intra-third cerebroventricular administration in fasted ddY mice. Gastric emptying also was delayed after central injection of PAMP. In our previous study, PAMP was demonstrated to elicit hyperglycemia via bombesin (BN) receptor. Then, we examined whether the effects of PAMP on feeding and gastric emptying were induced through BN receptor. Surprisingly, PAMP-induced reductions in feeding and gastric emptying rate were not blocked by a BN antagonist, [D-Phe(6), Leu-NHEt(13), des-Met(14)]-BN (6-14). PAMP suppressed feeding in mice lacking gastrin-releasing peptide receptor or BN receptor subtype-3. These results indicate that centrally administered PAMP inhibits food intake, involving the delayed gastric emptying, not through BN receptors but through selective PAMP receptor.

Adrenomedullin↗

Novel actions of proadrenomedullin N-terminal 20 peptide (PAMP).

Poadrenomedullin N-terminal 20 peptide (PAMP) is a hypotensive peptide derived from the precursor of adrenomedullin. We identified novel actions of proadrenomedullin N-terminal 20 peptide (PAMP) on blood glucose, food intake and gastric emptying after exogenous administration. PAMP elevated blood glucose levels after central injection in fasted mice. PAMP had affinity for bombesin (BN) receptor and the hyperglycemic effect of PAMP was blocked by a BN antagonist, indicating that the elevation of blood glucose after central administration of PAMP was mediated by BN receptor. Centrally administered PAMP inhibited food intake and gastric emptying in fasted conscious mice. However, studies using a BN antagonist and BN receptor knockout mice suggested that the inhibitory effects of PAMP on feeding and gastric emptying were mediated not via BN receptor but via another receptor specific for PAMP. In the present review, we summarize these effects of PAMP and report other novel actions of PAMP on body temperature and oxygen consumption. In addition, the mechanism underlying the cardiovascular functions of PAMP is discussed.

Adrenomedullin↗

Plasma levels of amino acids and hypermetabolism in patients with chronic obstructive pulmonary disease.

Plasma levels of amino acids were measured by ion-exchange, high-pressure liquid chromatography in 30 ambulatory patients with chronic obstructive pulmonary disease (COPD; mean +/- SD: age 64 +/- 13 y and forced expiratory volume in 1 s [FEV1] 0.85 +/- 0.25 L) and 30 age- and sex-matched healthy control subjects with regard to nutritional status, resting energy expenditure (REE), and pulmonary function. The ratio of branched-chain amino acids to aromatic amino acids was significantly (P < 0.001) decreased in COPD patients and was significantly correlated with percentage of ideal body weight (r = 0.403, P < 0.05), percentage of arm-muscle circumference (r = 0.492, P < 0.01), and %FEV1 (r = 0.467, P < 0.05). Plasma levels of alanine and cysteine were decreased, whereas levels of glutamine, aspartic acid, serine, and ornithine were elevated in COPD patients as opposed to control subjects. The ratio of resting energy expenditure to predicted resting energy expenditure was negatively correlated with the ratio of branched-chain to aromatic amino acids (r = -0.716, P < 0.01), percentage of arm-muscle circumference (r = -0.770, P < 0.05), %FEV1 (r = -0.839, P < 0.01), and the maximal inspiratory pressure (r = -0.803, P < 0.001). Underweight COPD patients also exhibited a greater degree of hyperinflation (percentage of residual volume = 205 +/- 15 for underweight patients and 156 +/- 8 for normal-weight patients). In conclusion, a decrease in plasma levels of branched-chain amino acids in relation to hypermetabolism, possibly resulting from the severity of COPD and respiratory muscle weakness, and various disturbances in plasma amino-acid levels were found in underweight COPD patients.

Aged↗

Antioxidant constituents from rhubarb: structural requirements of stilbenes for the activity and structures of two new anthraquinone glucosides.

The methanolic extracts from five kinds of rhubarb were found to show scavenging activity for DPPH radical and .O2-. Two new anthraquinone glucosides were isolated from the rhizome of Rheum undulatum L. together with two anthraquinone glucosides, a naphthalene glucoside, and 10 stilbenes. In the screening test for radical scavenging activity of rhubarb constituents, stilbenes and a naphthalene glucoside showed activity, but anthraquinones and sennosides did not. In addition, most stilbenes inhibited lipid peroxidation of erythrocyte membrane by tert-butyl hydroperoxide. Detailed examination of the scavenging effect on various related compounds suggested the following structural requirements; 1) phenolic hydroxyl groups are essential to show the activity; 2) galloyl moiety enhances the activity; 3) glucoside moiety reduces the activity; 4) dihydrostilbene derivatives maintain the scavenging activity for the DPPH radical, but they show weak activity for .O2-. In addition, several stilbenes with both the 3-hydroxyl and 4'-methoxyl groups inhibited xanthine oxidase.

Animals↗