Biomedical subjects
M Yamaoka
Publications and source records attributed to M Yamaoka.
Airflow receptors in the lip and buccal mucosa.
Airflow receptor afferents in the oral mucosa responding to changes in intraoral air pressure during blowing were found to be innervated by the infraorbital nerve. They provided one response corresponding to the onset of blowing, a second related to an increase in air pressure, a third corresponding to the cessation of blowing, and a fourth that exhibited little change throughout sustained blowing. Intraoral air pressure in the cavity between the lips and the velopharyngeal portal may be monitored by these receptors, and the data they provide may contribute to the control of phonation.
Properties of the lingual and LVP branches of the glossopharyngeal nerve.
We investigated the effects of various stimuli on the afferent and efferent branches of the glossopharyngeal nerve in the rat soft palate. One of the sensory components, the lingual branch, responded to tactile stimulation, while the LVP branch responded to stretching of the levator veli palatini muscle. We also obtained physiological and morphological evidence of the existence of muscle spindles in the levator veli palatini muscle and showed that tactile stimulation of the contralateral soft palate and stretching of the contralateral LVP modulated discharges from the motor component of the ipsilateral levator veli palatini muscle. Our results suggest that these receptor units with both sensory and motor efferents may be the main determinants of modulation of respiratory movements in the upper airway by the IXth nerve.
Muscle spindles in the mylohyoid muscle of rats.
The mylohyoid muscle has several functions in relation to respiration, deglutition, and phonation, but these functions are not fully understood. The interaction of the mylohyoid nerve and muscle in 25 rats was studied by neurophysiologic and histologic methods. Stretching of the muscle elicited electrical responses from the branch of the mylohyoid nerve innervating the mylohyoid muscle, and stretch-sensitive receptors were demonstrated histologically in the mylohyoid muscle. This study indicates that the mylohyoid muscle plays an active role in functions such as swallowing, breathing, and phonation.
Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888.
1. In our search for compounds that inhibit the binding of [3H]-substance P (SP) to guinea-pig lung membranes, the dipeptide SP antagonist, FK888, was developed by chemical modification of the parent compound, (D-Pro4, D-Trp7,9,10, Phe11)SP4-11. 2. In a [3H]-SP binding assay using guinea-pig lung membranes and rat brain cortical synaptic membranes, FK888 displaced [3H]-SP binding with a Ki value of 0.69 +/- 0.13 nM and 0.45 +/- 0.17 microM, respectively, in a competitive manner. 3. FK888 inhibited the contraction of guinea-pig isolated ileum induced by SP in the presence of atropine and indomethacin (a NK1 receptor bioassay) with a pA2 value of 9.29 (8.60-9.98). 4. FK888 inhibited contractions of rat vas deferens by NKA (a NK2 receptor bioassay) and of rat portal vein by NKB (a NK3 receptor bioassay) at concentrations at least 10,000 times greater than that required to inhibit contractions of guinea-pig ileum. 5. FK888 also inhibited SP-induced airway oedema in guinea-pig after both intravenous and oral administration. 6. These data demonstrate that FK888 is a potent and selective NK1 antagonist which is active both in vitro and in vivo.
Muscle spindle distribution in the levator veli palatini muscle in the rat.
We previously reported that the levator veli palatini muscle (LVP) in the rat is innervated by the glossopharyngeal nerve. The LVP positioned between the mouth and nasopharynx, has important roles in respiration, swallowing, and speech. Muscle spindles, structures scattered through skeletal muscles, appear to function like miniature strain gauges, sensing the degree of tension in the muscle. Muscle spindles were demonstrated in the rat's LVP in our neurophysiologic and histologic studies. We think the stretch of LVP modulates the rapid movements of the LVP by the proprioceptive component of the muscle spindle. Our results infer it is important to protect the innervation and the muscle spindles of the LVP from damage during any surgical dissection of the soft palate musculature.
Studies on condensed-heterocyclic azolium cephalosporins. IV. Synthesis and antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)- alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl cephalosporins including SCE-2787.
The synthesis and in vitro antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetami do] cephalosporins bearing various condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus are described. The thiadiazolyl cephalosporins showed good antibacterial activity against both Gram-positive and Gram-negative bacteria and the MICs of the thiadiazolyl cephalosporins against Pseudomonas aeruginosa was more potent than that of the corresponding 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3- (condensed-heterocyclic azolium)methyl cephalosporins. Also, the thiadiazolyl cephalosporins bearing (imidazo[1,2-b]-pyridazinium-1-yl)methyl groups at the 3 position showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Among the cephalosporins tested, 7 beta-[2-(5- amino-1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido]-3-(imidaz o[1,2- b]pyridazinium-1-yl)methyl-3- cephem-4-carboxylate (4, SCE-2787) which exhibited the most potent antibacterial activity and the broadest antibacterial spectrum was selected as a parenteral cephalosporin candidate for further biological evaluation.
FK 224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor selectivity.
We have discovered a novel cyclopeptide substance P (SP) antagonist, FK 224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2-pentylphenyl )- propionyl]-L-threonyl]tyrosyl-L-leucynyl]-D-phenylalanyl]-L-allo- threonyl]-L-asparaginyl]-L-serine-nu-lactone), which inhibited [3H]SP binding to guinea pig lung membranes in a dose-dependent manner. According to Rosenthal analysis, the inhibitory effect of FK 224 on [3H]SP binding appears to be competitive. In order to clarify the receptor subtype selectivity of FK 224, we have studied the interaction of FK 224 with three tachykinin receptors (NK1, NK2 and NK3) by using receptor binding techniques and in vitro bioassays, and have also compared FK 224 with the novel nonpeptide antagonist, (+/-)-CP-96,345. In binding experiments, FK 224 dose-dependently inhibited [3H]SP binding to rat cerebral cortical membranes (NK1) and [3H]neurokinin (NK) A (NKA) binding to rat duodenum smooth muscle membranes (NK2), but did not affect [3H]eledoisin binding to rat cerebral cortical membranes (NK3). In bioassay experiments, FK 224 inhibited SP-induced contraction of guinea pig ileum (NK1) and NKA-induced contraction of rat vas deferens (NK2) in a dose-dependent manner, but did not affect NKB-induced contraction of rat portal vein (NK3). In contrast, (+/-)-CP-96,345 inhibited SP-induced contraction of guinea pig ileum, but not NKA-induced contraction of rat vas deferens or NKB-induced contraction of rat portal vein. In the presence of FK 224, SP dose-response curves and NKA dose-response curves were shifted to the right in parallel with no depression of the maximal contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
The innervation of the levator veli palatini muscle by the glossopharyngeal nerve.
We developed a novel method which enables bloodless exposure of the levator veli palatini muscle in rat in order to investigate the physiological properties of this muscle. The levator veli palatini muscle which is innervated by a branch of the glossopharyngeal nerve showed rhythmic spontaneous movement in rats. Cutting the branch supplying LVP of the glossopharyngeal nerve caused cessation of the spontaneous movement of the levator veli palatini muscle. The spontaneous discharges of the glossopharyngeal nerve were synchronized with those of the phrenic nerve. A mixture of 95% oxygen and 5% room air influenced the efferent discharges from the branch of the glossopharyngeal nerve supplying the levator veli palatini muscle. These findings indicate that the motor nerve supply to the levator veli palatini muscle is the glossopharyngeal nerve, and the levator veli palatini muscle is related to the respiratory system, in particular with inspiration in rats.
Intravenous bolus of prednisolone decreases 15-hydroxyeicosatetraenoic acid formation in the rat model of acid aspiration.
BACKGROUND AND METHODS: To test the hypothesis that the effect of steroids on hydrochloric acid aspiration may be involved in the metabolism of eicosanoids, we investigated the effects of an iv bolus of prednisolone on the metabolism of 15-hydroxyeicosatetraenoic acid and 11-dehydrothromboxane B2 (11-dehydro-TxB2) in the rat model of acid aspiration. Wistar rats were randomly selected for three groups and treated with either a) an iv bolus of saline after intratracheal injection of saline (control group), b) an iv bolus of saline after intratracheal injection of acid (acid-saline group), or c) an iv bolus of prednisolone after intratracheal injection of acid (acid-prednisolone group). The concentrations of 15-hydroxyeicosatetraenoic acid and 11-dehydro-TxB2 in bronchoalveolar lavage fluid were measured by radioimmunoassay. RESULTS: The concentration of 15-hydroxyeicosatetraenoic acid in bronchoalveolar lavage fluid of either acid-saline group (804 +/- 129 pg/mL) or acid-prednisolone group (748 +/- 112 pg/mL) was significantly greater than that of the control group (143 +/- 27 pg/mL, p less than .01) 1 hr after the administration. The iv bolus of prednisolone caused a significant decrease in 15-hydroxyeicosatetraenoic acid (acid-saline group 1027 +/- 43 pg/mL; acid-prednisolone group 514 +/- 62 pg/mL; p less than .01) and cell counts of bronchoalveolar lavage fluid 48 hrs after intratracheal injection of acid, while there was no significant change in 11-dehydro-TxB2. CONCLUSION: These findings suggest that corticosteroid administration may contribute to the inhibition of the inflammatory process of lungs after acid aspiration by decreasing the release of 15-hydroxyeicosatetraenoic acid in the distal lung unit.
Prevalence of antibody to influenza C virus among pigs in Hyogo Prefecture, Japan.
The prevalence of influenza C virus among pigs in Hyogo Prefecture, Japan, was investigated by serological techniques. Out of 240 sera tested, 45 (19%) showed haemagglutination inhibition (HI) to influenza C virus. Pig sera with high HI titres also scored high in neutralization tests and ELISAs. When fractionated by sucrose density gradient ultracentrifugation, the HI/ELISA reactivities corresponded to antibodies of the IgM and IgG classes. Radioimmunoprecipitation tests revealed that some, but not all, of the pig sera with high HI activities precipitated HEF glycoprotein of influenza C virus. These results suggested that the HI activities of pig sera in Hyogo Prefecture were due to the presence of antibody to influenza C virus. Sera with IgM class antibody to influenza C virus were found throughout the year. However, the question of whether or not pigs serve as a natural reservoir for human influenza C virus still remains to be solved.
Efficacy of oral administration of ofloxacin in lower respiratory tract infections in aged patients with chronic lung disease.
The efficacy of ofloxacin for the treatment of lower respiratory tract infection was evaluated in aged patients with chronic lung disease. Results are the following: improvement of leukocytosis and arterial oxygen tension was observed; peripheral blood cell analysis showed a decrease in natural killer cell counts and in helper/suppressor T cell ratio; superoxide production by peripheral blood white cells was decreased after treatment; interleukin-2 production was rather increased. We concluded that improvement in the immunological parameters indicated the efficacy of ofloxacin for lower respiratory tract infection in aged patients with chronic lung disease.
Studies on condensed-heterocyclic azolium cephalosporins. I. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- alkoxyiminoacetamido]-3-(imidazo[1,2-a]pyridinium-1-yl)methyl-3- cephem-4-carboxylates.
In our study of the structure-activity relationships of cephalosporins bearing quaternary ammonium groups at the 3 position, we postulated that delocalization of the azolium positive charge would lead to an expanded antibacterial spectrum and increased activity. Since quaternization of condensed-heterocyclic compounds such as imidazo[1,2-a]pyridine gives positive charge delocalization, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporin derivatives (1-53) bearing various (imidazo[1,2-a]pyridinium-1-yl)methyl moieties at the 3 position were prepared and their antibacterial activity was determined. As expected, these cephalosporins exhibited potent activity against both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. These results imply that imidazo[1,2-a]pyridine is a quite useful substituent for improving antibacterial activity and spectrum. The structure-activity studies revealed that a favorable substituent on the imidazo[1,2-a]pyridine is the cyano radical at the 6 position of the ring, and ethoxyimino or 1-carboxy-1-methylethoxyimino groups are suitable for the alkoxyimino substituent. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- ethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2-a]pyridinium -1-yl)methyl-3-cephem-4-carboxylate (45) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-(1- carboxy-1-methylethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2- a] pyridinium-1-yl)methyl-3-cephem-4-carboxylate (49) showed good antibacterial activity.
Studies on condensed-heterocyclic azolium cephalosporins. II. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3-(condensed- heterocyclic azolium)methyl-3-cephem-4-carboxylates.
From our series of studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]ceph alosporins containing imidazo[1,5-a]pyridinium, imidazo[1,2-b]pyridazinium, imidazo[1,2-a]pyrimidinium, imidazo[1,2-c]pyrimidinium, and pyrazolo[1,5-a]pyridinium methyl groups at the 3 position. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3- (imidazo[1,5-a]pyridinium-2-yl) (1), (imidazo[1,2-b]pyridazinium-1-yl) (2), and (pyrazolo[1,5-a]-pyridinium-1-yl) (3)methyl-3-cephem-4-carboxylates showed potent antibacterial activity and broad antibacterial spectrum. The antibacterial activity of these cephalosporins (1 approximately 3) was superior to that of ceftazidime (CAZ). These results imply that the delocalization of the positive charge of the imidazo[1,5-a]pyridinium, pyrazolo[1,5-a]pyridinium and imidazo[1,2-b]pyridazinium groups leads to an expanded antibacterial spectrum and increased activity and that these condensed-heterocyclic compounds as well as imidazo[1,2-a]pyridine are effective moieties for improving antibacterial activity and spectrum.
[The change in immunohistochemical localization of basic fibroblast growth factor (b-FGF) around the lens capsule after extracapsular extraction].
It has been reported that basic fibroblast growth factor (b-FGF) accelerates proliferation of mesenchymal cells and epithelial cells of cornea and crystalline lens in vitro. The immunohistochemical localization of b-FGF on guinea pig lens capsule after extracapsular extraction (ECE) of the lens was studied in order to investigate the role of b-FGF on posterior capsular opacification after ECE and neovascularization. On the 12th postoperative day, immunohistochemical staining of b-FGF was recognized along the posterior capsule on the cortical side, but not along the anterior capsule. On non-operated eyes, scanty immunoreactive materials were seen in cells at the germinative center of the equatorial region. More than two months after ECE, almost no immunoreactive staining could be recognized. In this study, immunoreactive staining of b-FGF was recognized along the posterior capsule on cortical side after operation. It has also been reported that b-FGF stimulates proliferation of the lens epithelial cells in vitro. Therefore, it is suggested that b-FGF plays an important role on posterior capsular opacification after cataract formation.
Inhibitory effects of mold oil including gamma-linolenate on platelet thrombus formation in mesenteric microvessels of the rat.
Diet including mold oil from a lipid accumulative fungus, containing gamma-linolenic acid, showed an inhibitory effect on thrombus formation in the microvessels of rats by the light/dye method of the authors. Male Wistar rats were fed for 3 to 4 weeks with two series of experimental diets and were examined for thrombus formation. The thrombus formation times to totally occlude, ts, were 347 sec for (mold + soybean)-oil and 236 sec for (palm + soybean)-oil in the first series of diets and 1288 sec for mold oil, 538 sec for olive oil and 575 sec for safflower oil in the second series of diets. Fatty acid composition of plasma, erythrocyte and liver lipids showed an increase in arachidonate content with the diet including the mold oil. Higher arachidonate content seem favorable in inhibiting thrombus formation with increasing PGI2 formation. In terms of the level of lipid hydroperoxides, indicated as a desaturation index of constituent fatty acids, the higher desaturation index with safflower oil gave shorter ts, which suggested some oxygen derived free radicals from polyunsaturated fatty acids were involved in the mechanism of thrombogenesis study by this method.
Necrotizing buccal and cervical fasciitis.
A bite wound led to necrotizing fasciitis in the temporal space, the lateral pharyngeal space and the carotid sheath, indicative of a Streptococcus and Bacteroides infection, and was successfully treated with repeated incisions, radical debridement and antibiotic therapy.
[An aged case of orthostatic hypotension possibly due to parasympathetic neurodysfunction].
94-year-old male patient, with orthostatic hypotension, possibly due to impairment of vasoconstriction and parasympathetic nervous system dysfunction was reported. This patient experienced faintness and lower muscle weakness on standing. The blood pressure was 180/90 mmHg in a supine position, while it significantly decreased to 100/58 mmHg in an upright position. There was no evidence indicating the presence of organic brain diseases, cardiovascular diseases, and endocrine diseases, plasma catecholamine, renin, aldosterone, and vasopressin levels at rest were within normal range. Thus, the cause of orthostatic hypotension of this patient was unknown. His systolic blood pressure decreased by 70 mmHg, and his diastolic blood pressure also decreased by 25 mmHg in response to a 70 degrees head-up tilting test (170/71-100/46 mmHg). Plasma vasopressin level significantly increased in response to this test (0.62-67.2 pg/ml). Plasma catecholamine levels also increased (Adr 0.01-0.10 ng/ml, Ndr 0.05-0.22 ng/ml). Other autonomic nervous system examinations revealed normal responses to mental arithmetic test, hyperventilation test, cold pressure test, and adrenalin test. However, the results of the carotid occlusion test, acetylcholine test, atropine test, phenylephrine test were considered to be abnormal. From these findings, we concluded that the functions of sympathetic nervous system were almost intact, while the parasympathetic functions were impared in this case. The orthostatic hypotension of the patient as effectively treated with fludrocortisone. This report suggests that impairment of vasoconstriction and parasympathetic neurodysfunction might be involved in the development of orthostatic hypotension in the elderly.