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Biomedical subjects

K Tokuyama

Publications and source records attributed to K Tokuyama.

At least 127 records · Page 7Linked to original sources
PubMed1992

Effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage in guinea pig airways.

To study the effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage, we measured concomitant changes in lung resistance (RL) and in extravasation of Evans Blue dye in the airways of anesthetized immature (aged 14 +/- 2 days) and adult guinea pigs (aged 60 +/- 12 days). RL was measured for 6 min after iv. histamine (0, 5, 15, 30 and 50 micrograms/kg). For comparison, responses after 1 microgram/kg substance P were also examined. After measurement of RL, microvascular leakage in trachea, main bronchi, and proximal and distal intrapulmonary airways was also examined in the same animal. Immature animals required a larger dose of histamine than adults to achieve a similar degree of maximal bronchoconstriction after histamine. In contrast, equal doses of histamine (15 and 30 micrograms/kg) induced a significantly greater extravasation of dye in immature airways in both proximal and distal intrapulmonary airways, although not in trachea or main bronchi. Substance P did not cause any age-related differences in dye extravasation at any airway level. These results suggest that i.v. histamine specifically causes a greater degree of airway microvascular leakage in peripheral airways but induces less smooth muscle contraction in the airways of immature guinea pigs than in the airways of adult animals.

Aging↗
PubMed1992

Insulin sensitivity during very-low-calorie diets assessed by minimal modeling.

The time course of plasma glucose, insulin, and C-peptide after intravenous glucose (300 mg/kg body wt) injection was analyzed with minimal model approach in nine normal females and seven obese females. Glucose tolerance, estimated by glucose assimilation coefficient (KG), was positively correlated with glucose effectiveness (SG), but not correlated with peripheral insulin sensitivity (SI) in obese females as well as normal females. These factors were estimated before and after weight loss with 1.8-MJ (420-kcal) very-low-calorie diets (VLCDs) or with 2.5-3.3-MJ (600-800-kcal) low-calorie diets in two obese subjects. KG and glucose effectiveness decreased after acute weight loss with VLCD, although insulin sensitivity increased. Weight loss with low calorie diets resulted in improvement of KG and glucose effectiveness. These results suggest that a significant amount of glucose is taken up through insulin-independent mechanisms during the intravenous glucose tolerance test (ivGTT) in these subjects. This insulin-independent glucose uptake may be an important determinant of the fate of glucose in obese females as well as normal females.

Blood Glucose↗
PubMed1992

Neutrophil influx into guinea-pig airway lumen during cholinergic and non-cholinergic bronchoconstriction.

Sensory nerve activation will produce adherence of neutrophils to tracheobronchial microvessels. The aim of the present study was to investigate whether this adherence would lead to an influx of neutrophils into the airway lumen. To do this, we studied the effects of 20 minutes of vagal stimulation (1 Hz, 5 ms, 5 V) in anaesthetized and tracheostomized guinea-pigs on both lung resistance, and the cell picture in bronchoalveolar lavage. Any changes were compared to those of intravenous methacholine infusion, producing similar changes in lung resistance. Since high pressure ventilation could produce lung damage, we also studied the effects of ventilation through an extracorporeal resistor, producing a similar change in transpulmonary pressure (45 +/- 2 cmH2O) as vagal stimulation (42 +/- 4 cmH2O). The total number of cells recovered in the lavage was not increased by vagal stimulation, methacholine infusion or the extracorporeal resistor. However, both vagal stimulation and methacholine infusion significantly increased the relative number of neutrophils in the lavage compared to sham stimulated animals (21 +/- 11%, 13 +/- 4% and 4 +/- 1% respectively), but the extracorporeal resistor had no effect (4 +/- 2%). Our data suggests that prolonged bronchoconstriction per se may induce an influx of neutrophils into the airway lumen of the guinea-pig.

Animals↗
PubMed1992

A thromboxane mimetic, U-46619, produces plasma exudation in airways of the guinea pig.

Thromboxane A2 (TxA2) has been implicated in airway responses to allergen and in the bronchial hyperresponsiveness observed in asthma. Furthermore a TxA2 receptor antagonist and a TxA2 synthase inhibitor inhibit plasma exudation in airways induced by inhaled platelet-activating factor. To evaluate whether TxA2 has any direct effect on plasma exudation in the airways, we studied the effect of a stable TxA2 mimetic (U-46619; 2, 20, and 200 nmol/kg iv) on lung resistance (RL) and Evans blue dye extravasation (marker of plasma albumin; 20 mg/kg iv) at the airway levels of trachea, main bronchi, and proximal and distal intrapulmonary airways in anesthetized, tracheostomized, and mechanically ventilated guinea pigs. Injection of U-46619 produced an immediate and marked dose-dependent increase in RL, which peaked at approximately 30 s. At the highest dose of U-46619, we also observed a later increase in RL, starting at approximately 3 min and reaching a second peak at approximately 8 min. Mean systemic blood pressure increased in a dose-dependent manner [maximum 82 +/- 8 (SE) mmHg]. U-46619 also produces dose-dependent plasma exudation, measured as Evans blue dye extravasation, at all airway levels as well as into the tracheal lumen. Airway responses to U-46619 (200 nmol/kg iv) were abolished in animals pretreated with the TxA2 receptor antagonist ICI-192605 (0.5 mg/kg iv). We conclude that U-46619, despite being a vasoconstrictor, is potent in inducing plasma exudation in airways and that this effect is mediated via a TxA2 receptor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Pathogenic factors responsible for glucose intolerance in patients with NIDDM.

To define the pathogenic factors responsible for glucose intolerance in NIDDM, we estimated insulin secretory capacity, SI, and SG in 11 healthy, nondiabetic subjects and 9 NIDDM patients who had no SI impairment. All subjects studied were nonobese and normotensive. Each underwent a 75-g OGTT and a modified FSIGT: glucose was administered (300 mg/kg body weight), and insulin was infused (20 mU/kg over 5 min) from 20 to 25 min after the administration of glucose. SI and SG were estimated by Bergman's minimal-model method. The insulin response to oral glucose was significantly lower in NIDDM patients than in normal control subjects. First-phase insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 20 min was much smaller in NIDDM subjects (214 +/- 112 pM.min) than in control subjects (4643 +/- 885 pM.min, P < 0.01). SI was not statistically different in normal control subjects (1.27 +/- 0.18 x 10(-4) min-1.pM-1) versus diabetic patients (1.62 +/- 0.33 x 10(-4) min-1.pM-1). However, SG was significantly lower in diabetic subjects (1.11 +/- 0.17 x 10(-2) min-1) than in control subjects (2.35 +/- 0.26 x 10(-2) min-1, P < 0.01). These results suggest that impaired insulin secretion and decreased SG are the factors responsible for glucose intolerance of Japanese NIDDM patients with normal insulin sensitivity. Because SI and SG are the factors responsible for glucose intolerance of NIDDM patients with insulin resistance, it is conceivable that decreased SG is common in NIDDM patients regardless of their SI index.

Adult↗
PubMed1992

[Solitary infected renal cyst: a case report].

A 48-year-old man was admitted to our hospital because of high fever and left flank pain. Laboratory findings revealed a high white blood cell count, high C-reactive protein level, and severe pyuria. Sonographic examination revealed an enlargement of the cyst at the upper pole of the left kidney that had already been detected. Percutaneous drainage was performed for the cyst and 60 ml of purulent fluid was obtained. Bacterial culture of the fluid was positive for Propionibacterium acnes and gamma-Streptococcus. The drainage and administration of povidone-iodine was continued for 7 days. The size of the cyst was reduced with disappearance of symptoms.

C-Reactive Protein↗
PubMed1991

Bradykinin-induced airway microvascular leakage is potentiated by captopril and phosphoramidon.

Bradykinin can be inactivated by the peptidases angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), both of which are present in the airways. We evaluated the role of these enzymes in bradykinin-induced airway microvascular leakage and lung resistance in anesthetized and mechanically ventilated guinea pigs. We studied the effects of captopril (inhaled; 350 nmol), a specific ACE inhibitor, and phosphoramidon (inhaled; 7.5 nmol), a specific NEP inhibitor. Airway microvascular leakage was measured with the albumin marker Evans Blue dye (20 mg/kg i.v.), and airflow obstruction was measured as lung resistance (RL). Bradykinin was given by inhalation (0.1, 0.3 and 1 mM; 45 breaths), and caused a dose-dependent increase in both RL and airway microvascular leakage. Inhibition of NEP or ACE potentiated the bradykinin-induced microvascular leakage in main bronchi and proximal and distal intrapulmonary airways. However, only NEP inhibition significantly potentiated the extravasation of Evans Blue dye into the tracheal wall and lumen. The combined inhibition of NEP and ACE significantly potentiated plasma leakage at all airway levels, as well as the increase in RL induced by inhaled bradykinin. Recovery RL after one lung inflation significantly correlated with the extravasation of Evans Blue dye in the tissue at all airway levels, indicating that airway edema may have contributed to airway narrowing. We conclude that in the guinea pig, both NEP and ACE modulate bradykinin-induced airway microvascular leakage.

Acetylcholine↗
PubMed1991

Inhaled formoterol inhibits histamine-induced airflow obstruction and airway microvascular leakage.

We studied the effects of inhaled formoterol (0.75 mg/ml, 60 breaths = 26 micrograms), a long-acting beta 2-adrenoceptor agonist, or of the more short-acting drug, salbutamol (25 mg/ml, 60 breaths = 875 micrograms), on acute airflow obstruction and airway microvascular leakage (MVL) induced by inhaled histamine in anesthetized guinea pigs. Lung resistance (RL) and its recovery following hyperinflation (recovery RL) were measured for 6 min after histamine (1 or 2 mg/ml, 30 breaths) in animals pretreated with either inhaled beta 2-adrenoceptor agonist or inhaled saline (0.9%, 60 breaths). MVL was measured by determining the amount of extravasated Evans blue dye at various airway levels. Histamine increased RL dose dependently with a mean peak RL (+/- S.E.M.) of 13.1 +/- 2.41 cmH2O/ml per s after 2 mg/ml of histamine. Both formoterol and salbutamol significantly inhibited both peak and recovery RL and MVL to a similar degree. There was a significant correlation between the degree of extravasated dye and both peak and recovery RL, suggesting that MVL partly contributes to histamine-induced airflow obstruction. Formoterol is approximately 35 times more potent than salbutamol to inhibit both MVL and airflow obstruction induced by histamine aerosol.

Administration, Inhalation↗
PubMed1991

Seasonal glucose uptake in marmots (Marmota flaviventris): the role of pancreatic hormones.

1. Glucose uptake was measured throughout the year in marmots (Marmota flaviventris) by the hyperglycemic clamp technique. During each 2 hr experiment, the plasma glucose level was maintained at 215 mg/dl while blood samples were collected and analysed for glucose, insulin, glucagon, cortisol and catecholamines. 2. Glucose uptake was calculated from the glucose infusion rate, changes in the glucose pool (using a correction factor), and urinary glucose excretion. 3. In autumn, animals peaked in body weight (greater than 4.0 kg) and ceased to feed. Basal plasma insulin levels in autumn were significantly elevated over all other seasons (P less than 0.01) and glucose uptake in autumn was 9.7 +/- 2.4 mg/min which was significantly lower (P less than 0.05) than summer (21.7 +/- 2.4 mg/min) during the steady state phase of the glucose clamp (90-120 min). 4. Plasma glucagon levels declined during the clamp in all seasons but there was no significant difference between seasons. Plasma cortisol and catecholamine (norepinephrine and epinephrine) levels remained unchanged under basal and experimental conditions throughout the seasons. 5. During glucose infusion, beta-hydroxybutyrate levels were suppressed suggesting that lipolysis was reduced during the experiment. 6. These results suggest that the marmot exhibits seasonal changes in glucose uptake; the lowest rate of glucose uptake occurring in the autumn after the animals peak in body weight and cease to feed.

3-Hydroxybutyric Acid↗
PubMed1991

Plasma exudation into airways induced by inhaled platelet-activating factor: effect of peptidase inhibition.

1. To evaluate whether endogenous peptide release is involved in the airway responses to inhaled platelet-activating factor, we measured lung resistance and airway microvascular leakage in anaesthetized guinea pigs pretreated with inhalation of either saline or a combination of the peptidase inhibitors phosphoramidon (0.1 mmol/l: 60 breaths; 7.5 nmol), to inhibit neutral endopeptidase, and captopril (4.6 mmmol/l: 60 breaths; 350 nmol), to inhibit angiotensin-converting enzyme. 2. Airway microvascular leakage was determined by the albumin marker Evans Blue dye injected intravenously (20 mg/kg) before platelet-activating factor or sham challenge. 3. Inhaled platelet-activating factor induced a maximum increase in lung resistance (1.43 +/- 0.33 cmH2O s-1 ml-1) which was not significantly different after pretreatment with phosphoramidon and captopril (1.44 +/- 0.21 cmH2O s-1 ml-1). 4. Inhalation of platelet-activating factor caused a significant increase in extravasated Evans Blue dye at all airway levels, an effect which was not potentiated by peptidase inhibition. Similar results were obtained with dye extravasated into the airway lumen and absorbed by a filter paper placed on the tracheal mucosa. Approximately 11% of the total tracheal dye was found in the lumen. There was a high correlation between tracheal tissue and tracheal lumen Evans Blue dye (r = 0.91; P less than 0.001). 5. We found a significantly lower dry to wet weight ratio in proximal intrapulmonary airways of animals exposed to platelet-activating factor, suggesting that platelet-activating factor caused airway oedema at this airway level.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Differential effects of phosphoramidon on neurokinin A- and substance P-induced airflow obstruction and airway microvascular leakage in guinea-pig.

1. The effects of the inhaled neuropeptides, neurokinin A (NKA) and substance P (SP) on lung resistance (RL) and airway microvascular permeability were studied in anaesthetized guinea-pigs. 2. Single doses of inhaled NKA (3 x 10(-5), 1 x 10(-4), 3 x 10(-4) M; 45 breaths) and SP (1 x 10(-4), 3 x 10(-4), 1 x 10(-3); 45 breaths) caused a dose-dependent increase in both RL and airway microvascular leakage, assessed as extravasation of the albumin marker, Evans blue dye. 3. NKA at 1 x 10(-4) and 3 x 10(-4) M resulted in a significantly higher increase in RL than SP at the same doses. 4. Inhaled SP (3 x 10(-4) M; 45 breaths) caused significantly higher Evans blue dye extravasation in main bronchi and proximal intrapulmonary airways compared to the same dose of NKA. 5. Pretreatment with the specific inhibitor of neural endopeptidase (NEP24.11), phosphoramidon, caused an approximately 100 fold leftward shift of the RL responses to inhaled NKA and SP. 6. Phosphoramidon significantly potentiated both NKA- and SP-induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level. 7. Inhibition of NEP24.11 potentiate both the SP- or NKA-induced airflow obstruction to a larger extent than the induced airway microvascular leakage, suggesting that NEP24.11 is more important in the modulation of the airflow obstruction observed after these mediators.

Administration, Inhalation↗
PubMed1991

Peptidase modulation of noncholinergic vagal bronchoconstriction and airway microvascular leakage.

We investigated whether inhibition of neutral endopeptidase 24.11 (NEP) and/or angiotensin-converting enzyme (ACE) modifies vagally induced nonadrenergic noncholinergic (NANC) airflow obstruction and airway microvascular leakage as measured by extravasation of Evans blue dye (intravenous) in anesthetized guinea pigs. We gave phosphoramidon to inhibit NEP and enalapril maleate or captopril to inhibit ACE. Animals pretreated with inhaled phosphoramidon (7.5 or 75 nmol), enalapril maleate (87 or 870 nmol), or captopril (350 nmol) reached higher peak lung resistance (RL) values (14.3 +/- 2.7, 15.7 +/- 3.8, 16.7 +/- 3.8, 11.4 +/- 1.6, and 24.6 +/- 3.5 cmH2O.ml-1.s, respectively) than saline-treated animals (5.9 +/- 1.1; P less than 0.05) after bilateral vagus nerve stimulation (5 Hz, 10 V, 10 ms, 150 s). Intravenous phosphoramidon (1 mg/kg), but not intravenous captopril (6 mg/kg), potentiated peak RL (22.9 +/- 6.9 and 7.1 +/- 1.5 cmH2O.ml-1.s, respectively). Vagal nerve stimulation (1 and 5 Hz) increased the extravasation of Evans blue dye in tracheobronchial tissues compared with sham-stimulated animals, but this was not potentiated by inhaled enzyme inhibitors or intravenous captopril. However, intravenous phosphoramidon significantly augmented the extravasation of Evans blue dye in main bronchi and intrapulmonary airways. We conclude that degradative enzymes regulate both NANC-induced airflow obstruction and airway microvascular leakage.

Acetylcholinesterase↗
PubMed1991

Role of thromboxane A2 in airway microvascular leakage induced by inhaled platelet-activating factor.

We studied the effects of OKY-046 (1, 10, and 30 mg/kg iv), a selective thromboxane synthase inhibitor, and of ICI 192605 (0.5 mg/kg), a selective thromboxane A2 receptor antagonist, on airflow obstruction and airway microvascular leakage induced by inhaled platelet-activating factor (PAF). Extravasated Evans blue dye content was measured as a reflection of airway microvascular leakage. In control animals, PAF caused a significantly higher increase in extravasation of dye and significantly less increase in lung resistance (RL) than histamine. OKY-046 significantly inhibited both changes in RL and airway microvascular leakage after PAF in a dose-dependent manner, whereas it inhibited histamine-induced airway microvascular leakage only at main bronchi, without any significant effect on RL. ICI 192605 significantly inhibited both RL and airway microvascular leakage induced by PAF, but not after histamine. After both PAF and histamine, changes in RL correlated significantly with the degree of microvascular leakage. Airway microvascular leakage and airflow obstruction after PAF, but not after histamine, may be dependent on thromboxane A2 generation.

Administration, Inhalation↗
PubMed1991

Mechanism of airway narrowing caused by inhaled platelet-activating factor. Role of airway microvascular leakage.

In order to study the mechanism of airway narrowing after inhaled platelet-activating factor (PAF) we measured concomitant changes in lung resistance (RL) and in airway microvascular leakage in anesthetized guinea pigs. RL and its recovery after hyperinflation at 5 min were measured until 6 min after PAF aerosol (0.1, 0.3, 1, and 3 mM), and in the case of 3 mM PAF also until 10 min. Microvascular leakage in trachea, main bronchi, and proximal and distal intrapulmonary airways was determined by measurement of extravasated Evans blue dye content. For comparison, the responses to inhaled histamine (3 mM) and 5-hydroxytryptamine (5HT) (3 mM), which act directly on airway smooth muscle, were also examined. Inhaled PAF increased RL dose-dependently, with a maximal response (peak RL) at 4 min after the inhalation, whereas the response to histamine or 5HT was maximal within a few seconds after the inhalation. Peak RL (cm H2O/ml/s) was significantly less after PAF (1.03 +/- 0.09) than after histamine (8.39 +/- 1.07) or 5HT (18.3 +/- 6.48), although there was no significant difference in RL after hyperinflation (recovery RL). No additional increase in RL was seen between 5 and 10 min after exposure. PAF caused a dose-dependent increase in Evans blue dye extravasation; 3 mM PAF induced significantly higher leakage than did histamine or 5HT at all airway levels at 6 min. PAF did not cause any additional extravasation of Evans blue dye at 10 min compared with that at 6 min after exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

[Clinical study of urinary fungal infection: survey of patient background and fungal strains from the urine].

Clinical features of urinary fungal infections were analyzed in 152 patients in whom fungi were cultured from urine and mycologically identified between February, 1989 and June, 1990. The average age was 66 years old, and approximately 70% of the patients were 60 years old or older. Systemic and urinary tract underlying diseases were observed in 145 patients (95.4%) and 70 patients (46.1%) had urinary indwelling catheters. Previous use of antimicrobial agents before isolation of urinary fungi was recorded in 103 patients (67.8%), the 2nd and 3rd generation cephems and new quinolones being most frequent. A mixture of fungi and bacteria was observed in 68 patients (44.7%). Gram-positive cocci were isolated from 50% of them. Of 173 strains of fungi, C. glabrata was the most frequent (31.2%), followed by C. albicans (27.8%), C. tropicalis (17.3%) and T. beigelii (15.0%). All strains of C. glabrata, C. albicans, C. tropicalis and T. beigelii were highly sensitive to flucytosine (5-FC), miconazole (MCZ) and amphotericin B (AMPH), except for 3 strains which were resistant to 5-FC. The consecutiveness was confirmed by repeated culture in 59.4% of the patients. Fungi in the urine, however, spontaneously disappeared in the other patients.

Aged↗
PubMed1991

[11 cases of anaphylaxis caused by grand keyhole limpet (abalone like shellfish)].

We reported 11 cases of patients who developed moderate to severe anaphylactic reactions induced by the ingestion of grand keyhole limpet (GKL) and abalone. Specific IgE-mediated hypersensitivity to these shellfish was demonstrated by history, skin prick test, RAST and immunoblotting. The RAST inhibition technique revealed cross antigenicity between GKL, abalone and keyhole limpet hemocyanin. By immunoblotting analysis, the major antigens of GKL are shown in the MW range of about 38 Kd and 80 Kd.

Adolescent↗
PubMed1990

Capsaicin and sensory neuropeptide stimulation of goblet cell secretion in guinea-pig trachea.

1. We studied the effect of capsaicin and sensory neuropeptides on tracheal goblet cell secretion in anaesthetized guinea-pigs using a semi-quantitative morphometric technique whereby the magnitude of discharge of stained intracellular mucus, expressed as a mucus score (MS), was related inversely to discharge. 2. Capsaicin (i.v.) induced goblet cell secretion: a decrease of 50% in MS below control (indicative of increased secretion) was maximal at 3.3 x 10(-9) mol/kg. 3. Capsaicin-induced secretion was unaffected either by prior vagus nerve section or by pre-treatment with atropine, propranolol and phentolamine which suggests that local axon reflexes with release of sensory neuropeptides are involved in the response. 4. Intravenous substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and calcitonin gene-related peptide (CGRP) produced dose-related increases in goblet cell secretion, with SP the most potent. Doses (mol/kg) causing a 50% decrease in MS from control were 3.5 x 10(-12) for SP; 72 x 10(-10) for NKA; 1.6 x 10(-9) for NKB; and 1.2 x 10(-8) for CGRP. The maximal increase in goblet cell secretion was 75% of control and occurred with SP at 10(-10) mol/kg. 5. SP-induced mucus discharge was not inhibited by atropine or the histamine receptor antagonists mepyramine or cimetidine. 6. We conclude that in guinea-pig trachea, goblet cell secretion is under the control of capsaicin-sensitive sensory nerves and release of neuropeptides from these nerves may induce mucus discharge via tachykinin receptors of the NK-1 subtype (indicated by an order of potency of SP greater than NKA greater than NKB).

Anesthesia, General↗