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Biomedical subjects

K Shirato

Publications and source records attributed to K Shirato.

At least 181 records · Page 10Linked to original sources

The role of extracellular cations in the development of myogenic contraction in isolated rat small arteries.

The purpose of this study was to determine the roles of extracellular cations (Na+, Ca2+ and K+), membrane K+ channels and Na+/K+ ATPase in the development of myogenic contraction (transmural pressure-induced contraction) in isolated rat skeletal muscle and mesenteric small arteries. The vessels were pressurized under no-flow conditions in a tissue bath. Lumen diameter was measured with a videomicroscopic system. Myogenic contraction was evoked by increasing the lumen pressure from 40 to 100 mmHg. The vessels demonstrated myogenic contraction in low-Na+ (Na+ 1.18 mmol/L) physiological salt solution (PSS), and this was abolished by removing Ca2+ or by applying nifedipine or nisoldipine (10 mumol/L). Neither tetraethylammonium (TEA, 1 mmol/L), Ba2+ (10 mumol/L) nor glibenclamide (1 mumol/L) affected the magnitude of the myogenic contraction. K(+)-free PSS and ouabain (0.1 mmol/L) partially depressed myogenic contraction. In conclusion, myogenic contraction was triggered by a cellular process that requires extracellular Ca2+, but not Na+ or K+. This triggering process is not affected by TEA, Ba2+ or glibenclamide.

Animals↗

The incidence of respiratory tract pathogens and antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis isolated between 1990 and 1993.

Using a quantitative culture of sputum, the incidence of pathogenic bacteria in respiratory infection in our laboratory between 1990 and 1993 were investigated. While Haemophilus influenzae, Streptococcus pneumoniae and Moraxella (Branhamella) catarrhalis were isolated at high rates (67-78%) from the specimens of outpatients throughout the study period, the incidence of S pneumoniae has increased gradually. The antimicrobial susceptibilities of these three pathogens were examined with the agar dilution method. A marked increase of penicillin (PC) resistant S. pneumoniae (MIC > or = 0.1 microgram/ml) was observed with a resistance rate of 2.1% in 1990 and 25% in 1993. Resistance to erythromycin (EM, MIC > or = 1.56 micrograms/ml) was 8.5% in 1990 but then increased to 34% in 1992. Most of the PC resistant isolates were resistant to multidrugs such as EM, minocycline and clindamycin. The MICs of all beta-lactams examined for S. pneumoniae increased along with the MICs of PC, though the level varied between drugs. The rates of beta-lactamase positive H. influenzae gradually decreased, being 14.3% in 1990 and 7.4% in 1993, whereas those of M. (B) catarrhalis were consistently high (> 90%) every year. In addition to beta-lactamase production, the emergence of strains of H. influenzae and M. (B) catarrhalis resistant to new quinolone drugs should be noted.

Drug Resistance, Microbial↗

A new method for evaluating right ventricular dimensions and volume by cineangiography.

The aim of the present study was to establish a new method to evaluate the right ventricular dimensions and volume. Biplane right ventriculography of steep left anterior oblique view (LAO) and right anterior oblique view perpendicular to LAO were performed in 32 patients. The right ventricular volume and ejection fraction calculated from the three axial dimensions of the right ventricular cavity (the septum-free wall dimension, the anterior-posterior dimension, and either the long axis dimension or the tricuspid valve-apex dimension at end-diastole and end-systole) were well correlated to those from Simpson's method. In conclusion, we developed a new method for estimating right ventricular dimensions and volume.

Adolescent↗

Diffuse alveolar hemorrhage caused by lung metastasis of ovarian angiosarcoma.

A case of diffuse alveolar hemorrhage due to lung metastasis of ovarian angiosarcoma is described. A 33-year-old woman developed persistent cough and recurrent hemoptyses with resultant anemia. Chest radiograph and computerized tomography (CT) showed diffuse and patchy shadows in both lungs with nodules in the central area of the shadows. In spite of intensive care and administration of large amounts of glucocorticoids, she died of respiratory failure 5 months after the onset of her symptoms. Histological examination by both thoracoscopic biopsy and autopsy revealed diffuse tumor emboli of disseminated angiosarcoma which originated from the right ovary and diffuse alveolar hemorrhage which appeared to be caused by the tumor emboli with resultant invasion and destruction to vascular walls. This is the first description of diffuse alveolar hemorrhage probably caused by tumor emboli of metastatic angiosarcoma.

Adult↗

[A comparative study on the efficacies of ritipenem acoxil and cefotiam hexetil in bacterial pneumonia by the double-blind method].

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against bacterial pneumonia, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as the control drug. Both RIPM-AC and CTM-HE were orally administered at 200 mg t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 208, of which 152 cases (RIPM-AC group: 73, CTM-HE group: 79) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent + good) were 91.8% (67/73) in the RIPM-AC group and 94.9% (75/79) in the CMT-HE group. There was no significant difference between the two groups, and the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 84.6% (22/26) in the RIPM-AC group and 91.7% (22/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 9 cases (9.6%) of the RIPM-AC group and 5 cases (4.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 23 cases (26.7%) of the RIPM-AC group and 15 cases (15.6%) of the CTM-HE group. There was no significant differences between the two groups in the incidence of side effects nor of abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 64 cases (68.1%) and CTM-HE in 82 cases (80.4%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 86.5% (64/74) in the RIPM-AC group and 92.5% (74/80) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of bacterial pneumonia.

Adolescent↗

[Genotypes of cystic fibrosis (CF) reported in the world and polymorphisms of cystic fibrosis transmembrane conductance regulator (CFTR) gene in Japanese].

Cystic fibrosis (CF) is a common autosomal recessive genetic disorder in Caucasians. Since identification of the gene responsible for CF in 1989, over 400 sequential alterations of the CFTR gene have been tabulated by the CF Genetic Analysis Consortium. However, except for the delta F508 mutation, which occurs in approximately 70% of CF chromosomes, the worldwide frequency of most mutations in this gene is less than 1%. In Orientals and African blacks, CF is very rare. In Japanese only 100 cases have been reported. A few genotypes of these cases have been analyzed but no delta F508 or other mutations were found. We have analyzed mutations of the CFTR gene in Japanese with diffuse panbronchiolitis (DPB), which is found only in Orientals and shares pathologic and clinical characteristics with mild adult CF. However, no significant mutation of the CFTR gene was identified in this series. This suggests a different etiological background from that of CF.

Asian People↗

Tissue factor pathway inhibitor production by human mesangial cells in culture.

Fibrin formation within the glomeruli has been observed in various forms of human and experimental glomerulonephritis and it may play an important role in progressive glomerular injury. Furthermore it has been hypothesized that glomerular fibrin deposition may occur through activation of either the intrinsic or extrinsic coagulation pathway. It has been demonstrated that a procoagulant activity (PCA) which is compatible with tissue factor is present in the glomeruli and becomes increased in human proliferative glomerulonephritis and in animal models of nephritis. Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation through its ability to inhibit tissue factor activity. TFPI is present in plasma and in platelets, and it is now thought to be produced mainly by endothelial cells. We examined whether human mesangial cells (HMC) could produce TFPI and attempted to clarify regulatory factors which affect TFPI production. Cultured HMC were used and TFPI in the cell supernatants was measured by ELISA using a specific antibody. Cultured HMC showed the production of TFPI. Immunoblot analysis revealed 40 kD protein of TFPI. The concentration of TFPI was significantly increased following the incubation with thrombin and heparin, including low molecular weight heparin, in a dose- and time-dependent manner. However, fetal calf serum, phorbol myristate acetate, lipopolysaccharide, IL-1 beta and tissue factor did not stimulate TFPI synthesis. Our data show that cultured HMC have the ability to produce TFPI which inhibits fibrin formation. It is possible that thrombin-induced enhancement of TFPI synthesis may be caused by the autoregulatory system of blood coagulation and that with heparin it may represent another anticoagulatory effect of heparin.

Anticoagulants↗

[Comparative study on the efficacy of ritipenem acoxil and cefotiam hexetil in chronic lower respiratory tract infections by the double-blind method].

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against chronic lower respiratory tract infections, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as a control drug. RIPM-AC was orally administered at 200 mg, and CTM-HE at 400 mg, t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 202, of which 151 cases (RIPM-AC group: 75, CTM-HE group: 76) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent+good) were 85.3% (64/75) in the RIPM-AC group and 80.3% (61/76) in the CTM-HE group. There was no significant difference between the two groups, hence the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 50.0% (13/26) in the RIPM-AC group and 75.0% (18/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 10 cases (11.0%) of the RIPM-AC group and 10 cases (10.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 8 cases(9.5%) of the RIPM-AC group and in 14 cases (16.7%) of the CTM-HE group. There were no significant differences between the two groups in the incidence of side effects and abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 73 cases (80.2%) and CTM-HE in 71 cases (77.2%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 79.5% (62/78) in the RIPM-AC group and 76.9% (60/78) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of chronic lower respiratory tract infections.

Adult↗

Deterioration of urinary findings after tonsil stimulation in patients with IgA nephropathy.

We studied whether urinary findings are affected by stimulation of tonsils in patients with IgA nephropathy. In 62 patients with IgA nephropathy and 20 patients with other renal diseases tonsils were stimulated by an ultra short wave for 10 min. Changes in amount of urinary protein, urinary sediment, blood leucocyte count, concentrations of serum IgA and serum secretory IgA were evaluated after tonsil stimulation. Forty of 62 patients with IgA nephropathy (65%) showed deterioration of urinary findings after the stimulation compared with 6 of 20 patients with other renal diseases (30%). The deterioration was significantly more frequent in IgA nephropathy than in other renal diseases (p <0.005). Previous episodes of gross hematuria following upper respiratory tract infections had occurred in 17 of 40 patients who showed deterioration of urinary findings after tonsil stimulation (43%) as against in 4 of 22 without deterioration (18%). The level of serum secretory IgA was higher in patients who showed deterioration of urinary findings after tonsil stimulation than in those who did not show it. Though tonsil stimulation increased blood leucocyte count it did not affect the concentrations of serum IgA or secretory IgA. It is concluded that tonsil stimulation often deteriorates urinary findings in patients with IgA nephropathy; therefore chronic tonsillitis may play a part in the pathogenesis of IgA nephropathy.

Adolescent↗

[Relief of dyspnea after lung volume reduction in patients with pulmonary emphysema].

We studied dyspnea and pulmonary function during treadmill exercise in 10 patients with pulmonary emphysema before and at least 3 months after thoracoscopic volume reduction. Dyspnea was significantly less after surgery. Ventilatory function, gas exchange, respiratory muscle function, and exercise performance also improved significantly. The degree of volume reduction, estimated by the decrease in FRC as measured by body plethysmography correlated with the degree to which dyspnea was relieved. Volume reduction may be appropriate as a treatment for dyspnea in patients with pulmonary emphysema.

Dyspnea↗

Role of the parabrachial nucleus in ventilatory responses of awake rats.

1. The parabrachial nucleus (PBN) is thought to play an important role in cardiorespiratory control. However, the circumstances under which it affects ventilation are still not known. The purpose of the present study was to investigate how the PBN modulates the ventilatory responses to hypercapnia, hypoxia or a resistive load in awake rats with chemical lesions of the PBN. 2. In three groups of rats (with lateral PBN lesion, with Kölliker-Fuse nucleus lesion and control), ventilation was measured under various conditions. 3. There was no difference in the breathing of normal room air in any of the groups. However, the lesioned groups showed a reduced ventilatory response to hyperoxic hypercapnia (inspired CO2 fractions (FI,CO2) of 3, 5, 8 and 10%) and to graded hypoxia (inspired O2 fractions (FI,O2) of 16, 12, 10 and 8%) compared with the control group. The control group showed a biphasic response to sustained hypoxia (FI,O2 at 10% for 30 min), known as 'hypoxic depression', while the lesioned groups showed moderate ventilatory exaggeration throughout hypoxia. In response to a resistive load, the lateral PBN lesion group showed no change in ventilatory compensation. 4. The PBN appeared to have a considerable influence on ventilation stimulated in various ways during wakefulness.

Airway Resistance↗

Nitric oxide as a retrograde messenger in the nucleus tractus solitarii of rats during hypoxia.

1. We examined the role of nitric oxide (NO) in respiratory regulation in the nucleus tractus solitarii (NTS), where L-glutamate release associated with peripheral chemoreceptor activation modulates the hypoxic ventilatory response. 2. Experiments were performed in unanaesthetized freely moving rats. First, the effects on the hypoxic ventilatory response of sodium nitroprusside (SNP, a NO donor) or NG-monomethyl-L-arginine (L-NMMA, a NO synthase inhibitor), microinjected into the NTS, were investigated. Second, using in vivo microdialysis, changes in extracellular L-glutamate during hypoxia were examined in the presence of L-NMMA. Third, the effect of L-NMMA on ventilatory augmentation by exogenous L-glutamate was examined. Furthermore, we measured extracellular L-citrulline concentration changes during hypoxia in the NTS to assess NO formation indirectly and also examined the effect of MK-801 (an NMDA receptor antagonist) on L-citrulline levels during hypoxia. 3. SNP increased ventilation during both normoxia and hypoxia. L-NMMA did not alter ventilation or L-glutamate levels during normoxia but significantly attenuated the hypoxic ventilatory response and the increase in L-glutamate during hypoxia. The inhibition by L-NMMA was blocked by L-arginine. The ventilatory augmentation by exogenous L-glutamate was attenuated by L-NMMA. L-Citrulline increased during hypoxia, and this increase was inhibited by MK-801. 4. We provide the first in vivo evidence that, in the NTS, NO works as a retrograde messenger in an L-glutamate-releasing positive feedback system contributing to the augmentation of ventilation during hypoxia.

Animals↗

Gramicidin-perforated patch recording: GABA response in mammalian neurones with intact intracellular chloride.

1. By the development of a new perforated patch method using gramicidin, the effects of GABA on neurones dissociated from the rat substantia nigra pars reticulata (SNR) were examined without disturbing the intracellular chloride concentration. 2. Using the patch pipette solution containing gramicidin (100 micrograms ml-1), the access resistance dropped to less than 20 M omega within 40 min after making the gigaohm seal. 3. Under current-clamp conditions, GABA caused a hyperpolarization accompanied by a blockade of spontaneous firing. Under voltage clamp at a holding potential (Vh) of -50 mV, GABA evoked an outward current by way of bicuculline- and picrotoxin-sensitive GABAA receptors. 4. A 10-fold change of extracellular chloride concentration resulted in a 58 mV shift of the reversal potential of GABA-induced outward current (EGABA), indicating that the membrane behaves like a chloride electrode in the presence of GABA. 5. The intracellular chloride activities (aCli), calculated with the Nernst equation using both extracellular chloride activity and EGABA values, ranged from 2.8 to 19.7 mM with a mean value of 9.5 mM. The aCli was not affected either by different pipette solutions or by different holding potentials more hyperpolarized than -40 mV. 6. In the recording from SNR neurones in brain slice using the gramicidin-perforated patch-clamp technique, the inhibitory and excitatory postsynaptic currents were recorded in different current directions and the former was blocked by bicuculline. 7. In conclusion, the gramicidin-perforated patch method will disclose previously unknown aspects of biological responses involving Cl-.

Amphotericin B↗

Isoproterenol augments ATP-evoked Cl- secretion across canine tracheal epithelium.

Using an Ussing chamber, both the posterior epithelial membrane and cultured epithelial cell monolayers from canine trachea were used for measurements of potential difference (PD) and short circuit current (SCC). Conductance (G) was calculated as the ratio SCC/PD. Adenosine (10(-5) to 10(-3) M) failed to produce any significant increases in PD and SCC. ATP (10(-6) to 10(-4) M) produced a significant transient increase in SCC in a dose-dependent fashion, reaching a peak value within 3 min after stimulation. Isoproterenol (ISOP) at 10(-8) M itself did not significantly alter the SCC value. In both the epithelial membrane and cultured epithelial cells treated with amiloride, however, pretreatment with 10(-8) M ISOP significantly augmented the ATP-induced SCC rise, whereas G did not significantly change. These findings indicate that beta-adrenergic stimulation augments Cl- secretion induced by P2-receptor stimulation in airway epithelial cells.

Action Potentials↗

Effect of intramedullary procaine injection on tracheal tone and phrenic neurogram.

To map the superficial locations which are involved in the control of respiration and tracheal smooth muscle tone in ventrolateral medulla, we examined the effects of local anesthesia on phrenic activity and tracheal tone in twelve anesthetized, paralyzed, and artificially ventilated dogs. 0.5 microliter of 5% procaine was injected 0.3 to 0.5 mm below the surface unilaterally to the ventral superficial layer (from the rostral part of the trapezoid body to the caudal hypoglossal rootlets and lateral from the pyramids to 5.5 mm from the midline), which included rostral, intermediate and caudal areas, and the area lateral to the hypoglossal rootlets. The peak amplitude of the integrated phrenic neurogram was decreased by procaine injection to the intermediate area and the area lateral to the hypoglossal rootlets. Tracheal tone decreased only by procaine injection to the intermediate area. In the intermediate area, some injections decreased either phrenic output alone or tracheal tone alone. These results suggest that the two ventral medullary areas, i.e. the intermediate and caudolateral parts, contain neural structures which are involved in the shaping of phrenic output, but only the intermediate area is involved in the regulation of tracheal tone. It is also suggested that, in the intermediate area, the structures responsible for the maintenance of respiration and tracheal tone are, at least in part, separable.

Animals↗

Submental stimulation and supraglottic resistance during mouth breathing.

We studied submental stimulation on supraglottic resistance (Rsg) in 5 normals and 6 patients with obstructive sleep apnea. We then examined the most effective sites of stimulation in the submental regions, and the relationships between Rsg and stimulation frequency and voltage in the supine position. Inspiratory and expiratory Rsg's were obtained as the slope of the linear portion of the pressure-flow relation determined at zero flow. Before stimulation, inspiratory and expiratory Rsg's were 0.76 +/- 0.06 (means +/- SE) and 0.61 +/- 0.02 cmH2O.L-1.sec, respectively, in normals, and 1.04 +/- 0.20 and 0.92 +/- 0.29 cmH2O.L-1.sec, respectively, in patients. Stimulation in the proximal half submental region with surface electrodes 1 cm apart decreased inspiratory and expiratory Rsg's in patients, and inspiratory Rsg in normals. Inspiratory Rsg measured in this submental region showed a stimulation frequency-and voltage-dependency in both groups, but expiratory Rsg did not. These findings suggest that submental stimulation in the proximal half region widens the supraglottic airway during mouth breathing and probably involves the upper airway muscles.

Adult↗

Nitric oxide regulation of glycoconjugate secretion from feline and human airways in vitro.

To determine whether nitric oxide (NO) regulates mucus secretion from airway submucosal glands which are the main source of human airway secretion, we examined the effects of NO synthase inhibitors (L-NAME and L-NMMA) on mucus glycoprotein (MGP) secretion from feline and human airway explants (with epithelium) and isolated submucosal glands. MGP secretion was estimated by measuring trichloroacetic-acid (TCA) precipitable [H3]-glycoconjugates using secretory indices. NO synthase inhibitors alone did not alter significantly MGP secretion from explants or isolated glands. Pretreatment with NO synthase inhibitors significantly inhibited both methacholine (MCh) and bradykinin (BK)-induced secretion from isolated glands, but not significantly inhibit the secretion from explants. The inhibition by L-NAME was reversed by the addition of L-arginine in both MCh- and BK-induced secretions from isolated glands. Further, a NO generator isosorbide dinitrate induced a significant increase in the secretion. These findings suggest that endogenous NO has a stimulatory action in airway submucosal gland secretion and directly regulates the secretion from submucosal glands independently of superficial epithelial cells.

Animals↗