PubMed Health⌕ Search

Biomedical subjects

T Aikawa

Publications and source records attributed to T Aikawa.

At least 19 recordsLinked to original sources
PubMed1992

Evidence that an atypical beta-adrenoceptor mediates the prejunctional inhibition of non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

We investigated the effect of the putative beta 3 agonist BRL 35135 on non-adrenergic non-cholinergic (NANC) contractions in guinea-pig bronchial strips. BRL 35135 (10(-9) to 10(-6) M) did not alter the baseline tension but reduced NANC contractions induced by electrical field stimulation (EFS) in a concentration-dependent fashion without having a significant effect on the contraction induced by substance P (10(-6) M). BRL 35135 (10(-6) M) also reduced the contraction induced by capsaicin (10(-7) M). Likewise, BRL 37344 (10(-9) to 10(-6) M) reduced NANC contractions induced by EFS in a concentration-dependent fashion. While BRL 37344 up to concentrations of 10(-8) M did not alter the contraction induced by SP (10(-6) M), BRL 37344 (10(-8) M) significantly inhibited NANC contractions induced by EFS and capsaicin (10(-7) M), (P less than 0.01). The inhibitory effect of BRL 35135 (10(-6) M) on NANC contractions induced by EFS was not significantly altered by the non-selective beta-adrenoceptor antagonists, propranolol and pindolol (P greater than 0.10), by the beta 1-selective antagonists, atenolol and metoprolol (P greater than 0.20) (10(-8) to 10(-6) M), or by the alpha-adrenoceptor antagonist, phentolamine (10(-7) to 10(-5) M) (P greater than 0.50). These results suggest that beta 3 agonists exert a prejunctional inhibitory action on NANC contractions.

Animals↗
PubMed1992

Inhibitory actions of prostaglandin E1 on neurogenic plasma extravasation in rat airways.

To determine whether neurogenic inflammation can be inhibited by prostaglandin E1 (PGE1), that is suggested to have an inhibitory effect on neuropeptide release from airway sensory nerves, we examined plasma extravasation in the airways of anesthetized rats in vivo with Evans blue due as a marker. Neurogenic inflammation was produced by an i.v. injection of capsaicin (100 micrograms/kg) or by antidromic electrical stimulation of the right vagus nerve (4 Hz, 1 ms, 4 V for 1 min). Capsaicin injection significantly increased leakage of dye in the trachea and main bronchi. Similar increases in leakage were seen in the trachea and right bronchus on electrical stimulation of the right vagus nerve. PGE1 (1-1000 micrograms/kg) inhibited the leakage induced by capsaicin in the trachea and bronchi concentration dependently with complete inhibition at a concentration of 1000 micrograms/kg. Likewise, PGE1 (1000 micrograms/kg) significantly inhibited electrical stimulation-induced leakage in the trachea and right bronchus (P less than 0.01). I.v. substance P (SP; 1 microgram/kg) increased Evans blue dye extravasation in the same way as the leakage induced by capsaicin and electrical stimulation but PGE1 (1000 micrograms/kg) failed to inhibit SP-induced leakage in the trachea and main bronchi (P greater than 0.20). These results suggest that PGE1 inhibits neurogenic plasma leakage by presynaptic inhibition of the release of neuropeptides from sensory nerves.

Alprostadil↗
PubMed1992

Vascular permeability and airway narrowing during late asthmatic response in dogs treated with Metopirone.

Recently, we have developed an animal model of late asthmatic response (LAR) by treating naturally sensitized dogs to Ascaris suum antigen with the cortisol-synthesizing inhibitor, Metopirone. By using this animal model, we examined the contribution of edema in the airway wall to the development of LAR. To study whether airway microvascular leakage is increased in association with LAR, we performed antigen challenge in dogs treated with Metopirone. We measured the amount of extravasated Evans blue (EB) dye from the esophagus, trachea, and large and small bronchi 8 hours after the antigen challenge in dogs demonstrating immediate asthmatic response alone (IAR) and in dogs demonstrating both IAR and LAR. Airway responses to A. suum antigen were assessed by changes in respiratory resistance measured with the force oscillation technique at 3 Hz. EB dye extravasation did not increase significantly from that of control in any tissues in IAR (P greater than 0.10), but in LAR, it increased significantly from that of control (p less than 0.01) and IAR (p less than 0.05) in large and small bronchi. Histologic assessment of vascular permeability revealed that Monastral blue-labeled leaking vessels were only in sections from LAR, and leaking vessels were limited to small vessels (10 to 25 microns) in the trachea, large (diameter, greater than 5 mm) and small bronchi (2 to 4 mm in diameter), and bronchiole. The permeability index defined as the ratio of area of small vessels labeled with Monastral blue to that of the total small vessels in the walls was highest in the small bronchi. LAR significantly increased submucosal thickness of the small bronchi (p less than 0.05) compared with that in IAR. Both EB dye extravasation and permeability index in large and small bronchi also significantly increased during IAR within 3 minutes after the antigen challenge (p less than 0.05), but IAR did not alter the submucosal thickness of the small bronchi. These results imply that the increase in vascular permeability and submucosal thickness, especially in small bronchi, may be an important factor in the pathogenesis of LAR.

Airway Obstruction↗
PubMed1992

The role of cyclic AMP in non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

1. We investigated the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in non-adrenergic non-cholinergic (NANC) contraction in guinea-pig bronchial strips. 2. Forskolin (3 nM to 1 microM) reduced NANC contraction induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC50 was 7.22 +/- 0.12 M and maximum inhibition was 100 +/- 0.01%). However, forskolin (less than 1 microM) did not alter the contraction induced by substance P (SP, 1 microM). 3. Dibutyryl cyclic AMP (1 mM) also reduced NANC contractions induced by EFS (100 +/- 0.01%) without significant effect on SP (1 microM)-induced contractions. In contrast, dibutyryl cyclic GMP (1 mM) was without effect against either NANC or SP-induced contractions. 4. Both the beta 2-adrenoceptor agonist, procaterol (0.1 nM to 3 nM) and theophylline (100 nM to 1 mM) concentration-dependently reduced EFS-induced NANC contractions without significant effect on SP (1 microM)-induced contractions. 5. In contrast to forskolin, procaterol and theophylline, both sodium nitroprusside and cromakalim inhibited the EFS-induced contractions only at those concentrations that similarly reduced the contractions induced by SP (1 microM). 6. These results suggest that cyclic AMP may mediate pre-junctional inhibition of NANC contractions in guinea-pig bronchi.

Animals↗
PubMed1992

Morphometric analysis of airways in idiopathic pulmonary fibrosis patients with mucous hypersecretion.

Five idiopathic pulmonary fibrosis (IPF) patients with sputum since the initial period of the disease (IPF SP+, more than 15 ml/day) were compared with five IPF patients without sputum throughout the course of the disease (IPF SP-) and four control subjects without pulmonary disease matched for age and sex. No significant differences in the duration of symptoms, pulmonary functions, or glucocorticoid therapy were observed between the two IPF groups. Autopsied lungs fixed by immersion into formaldehyde were used for morphometry by digitizing computer. The volume proportion of glands to bronchial wall thickness (gland%), volume proportion of goblet cells to total epithelial layer (goblet%), and luminal mucous volume were measured in central and peripheral airways. The gland percentage in the central airways of the IPF SP+ group was 18 +/- 1% (mean +/- SE), which was significantly greater than 7 +/- 0.6% of the IPF SP- group (p less than 0.001), similar to the 6 +/- 1% of control subjects. Luminal mucous volume in the peripheral airways of the IPF SP+ group was 11 +/- 2%, which was significantly greater than 3 +/- 1% of the IPF SP- group (p less than 0.05) or 0.6 +/- 0.3% of the control subjects (p less than 0.01). Furthermore, luminal mucous volume in both the central and peripheral airways significantly correlated with gland% (p less than 0.01, each). No significant difference in other parameters such as goblet% and cell infiltration between the IPF SP+ group and IPF SP- group was observed. These findings suggest that IPF with hypersecretion is associated with mucous glandular hypertrophy and the accumulation of mucus in the airways.

Aged↗
PubMed1992

Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack.

To examine the changes in airways in bronchial asthma (BA) during an asthma attack causing death, we performed morphometric analysis of autopsied lungs from three outpatients who died of severe acute asthma attacks (group A) and compared these to five patients who died of non-status asthmaticus (group B). Controls (group NL) were four patients who died of diseases other than respiratory disorders. Area proportions of bronchial glands to bronchial wall (gland [percent]) and of goblet cells to total epithelial layer (goblet [percent]) and the intraluminal amount of mucus in the airways (MOR) were measured in a paraffin section. There were no significant differences in age, sex, smoking history, duration of BA history, and dosage of glucocorticoids received between groups A and B. Although both groups A and B showed significantly larger values of gland (percent) in the central airways and of inflammatory cell numbers in the airway walls than did group NL, no significant differences were observed between groups A and B. In contrast, markedly significant increases in goblet (percent) and in MOR were observed in group A compared to groups B and NL. These increases in group A were more dominant in the peripheral airway: 30-fold and threefold increases of group B in goblet (percent) and MOR, respectively. Furthermore, MOR significantly correlated with goblet (percent) in the peripheral airways (p less than 0.05). These findings suggest that a marked increase in goblet cells of the airways is a feature characteristic of patients with BA who die of a severe acute attack.

Epithelium↗
PubMed1992

Perivascular fibrosis of muscular pulmonary arteries in chronic obstructive pulmonary disease.

We performed a morphometric analysis of peribronchiolar and perivascular fibrosis in lungs obtained at autopsy from six patients with chronic bronchitis, six with pulmonary emphysema, and four normal control subjects. The areas of fibrosis outside the smooth muscle layer of bronchioles and outside the external elastic lamina of muscular pulmonary arteries were measured and their thickness was then calculated by assuming a round airway or artery. Patients with chronic bronchitis had significantly thicker peribronchiolar fibrosis in bronchioles of 1 mm or less in diameter and also thicker perivascular fibrosis of the adjacent muscular pulmonary arteries than the other two groups. The extent of perivascular fibrosis was significantly correlated with peribronchiolar fibrosis only in the muscular pulmonary arteries adjacent to the bronchioles but not in those away from the bronchioles. These findings suggest direct extension of chronic inflammation from bronchioles to the adjacent muscular pulmonary arteries in chronic bronchitis but not in pulmonary emphysema. Such perivascular fibrosis might lead to sustained pulmonary hypertension.

Aged↗
PubMed1992

[A 52-week dermal toxicity study of prednisolone farnesylate (PNF) gel in rats with a recovery period of 8 weeks].

The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.125, 0.5 and 2.0 mg/kg/day for 52 weeks, then the drug was withdrawn for 8 weeks to evaluate the reversibility. The results are summarized as follows: 1. In the PNF gel 2.0 mg/kg/day group, thinning of the skin at the application site, slightly retarded body weight gains, a tendency toward a decrease in the white blood cell count, an elevation of serum GOT and GPT activity, free fatty acid level, and a decrease in alpha 1-globulin fraction were observed. In the pathological examinations, decreased organ weights of the thymus, spleen and adrenal glands, and thinning of the skin were observed. Histopathological examination revealed atrophy of the thymus and zona fasciculata of the adrenal glands, thinning of the skin with atrophied skin appendages, and hepatocellular hypertrophy with hypertrophied uncleus in the perilobular zone. 2. In the PNF gel 0.5 mg/kg/day group, thinning of the skin at the application site and a decrease in alpha 1-globulin fraction were observed. Histopathologically, thinning of the skin atrophied skin appendages was observed. 3. In the PNF gel 0.125 mg/kg/day group, there were no toxic signs induced by the drug. 4. After the 8-week recovery period, the changes in the skin were observed in the 2.0 mg/kg/day group, but the severity was lowered. The other changes disappeared and so it was demonstrated that the changes were reversible. 5. Based on these results, it was concluded that the overt toxic dose of PNF gel was 0.5 mg/kg/day and the non-toxic dose was 0.125 mg/kg/day in the present study.

Administration, Cutaneous↗
PubMed1992

[A 52-week oral chronic toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) in rats with a recovery period of 5 weeks.

The chronic toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 0.4, 2, 10, 50 and 250 mg/kg/day for 52 weeks. The drug was then withdrawn for 5 weeks. The results are summarized as follows: There were no deaths or toxic signs caused by the drug throughout the experimental period. There were no drug-related changes in food consumption, ophthalmological examination, hematology or blood chemistry. Slight suppression of growth was observed in males in the 250 mg/kg group. This change was reversed on withdrawal of the drug. Drug crystals were observed in the urinary sediments of both sexes in the 250 mg/kg group, but this change disappeared on withdrawal of the drug. Gross pathological examination revealed the following changes: enlargement and nodule formation in the pancreas in both sexes given more than 10 mg/kg of the drug; dark red spots in the glandular stomach in males in the 250 mg/kg group; thickening of the small intestinal walls in both sexes given more than 50 mg/kg. Of these organs, no changes were observed in the stomach and small intestine at the end of the recovery period. Increased pancreas weight was observed in both sexes given more than 50 mg/kg of the drug. Examination at the end of the recovery period suggested reversibility, showing a lesser degree of change. Histopathological examination revealed the following changes in the pancreatic acinar cells: acidophilic foci and nodules in both sexes given more than 10 mg/kg of the drug; adenoma in one male in the 250 mg/kg group; increased zymogen granules in both sexes given more than 50 mg/kg of drug; fine vacuolization in females in the 250 mg/kg group. At the end of the recovery period, increased zymogen granules and fine vacuolization of the acinar cells were not found. Furthermore, erosion or healed erosion in the glandular stomach, duodenum and jejunum was observed in a few males or females in the 250 mg/kg group, but those changes disappeared after the recovery period. In the liver, altered cell foci was observed more frequently in males in the 250 mg/kg group than the other groups, but this change also disappeared after the recovery period. In addition, brown pigmentation in the proximal renal tubules of the kidney was observed in both sexes in the 250 mg/kg group, but lesions observed in the examination after the recovery period were less noticeable than in the examination at the end of the administration period.

Administration, Oral↗
PubMed1992

Surgical treatment using porous hydroxylapatite blocks for severe habitual dislocation of the bilateral temporomandibular joint in a patient with epilepsy.

A patient with severe habitual dislocation of the bilateral temporomandibular joint involving epilepsy was operated using porous hydroxylapatite blocks as intervention material. The patient was followed up for 4 years. He has been well without recurrence of dislocation or any complication. In this paper, we report the procedure and the relevant literature is discussed.

Dental Care for Chronically Ill↗
PubMed1992

[A prospective randomized study of intra-arterial infusion chemotherapy in the treatment of advanced breast cancer].

A prospective randomized study among 3 preoperative modalities, which consisted of intra-arterial infusion chemotherapy (I.A.), systemic chemotherapy (I.V.) and nontreated group, was carried out on 70 patients with advanced breast cancer. The results were as follows. (1) The response rate of primary lesions to I.A. (68.2%) was significantly higher than that of I.V. (37.5%). (2) The post-operative survival of responders (CR, PR) was better than those of non-responders (NC). (3) The frequency of side effects was similar in both I.A. and I.V. groups. (4) There was no difference among survival rates of 3 groups. We confirmed that I.A. was an efficacious neoadjuvant therapy in terms of down staging of advanced breast cancer.

Alopecia↗
PubMed1992

[Intra-arterial infusion chemotherapy in the treatment of advanced breast cancer--doxorubicin versus epirubicin].

Doxorubicin (ADM) and epirubicin (epi-ADM) were tested at a dose of 150mg given intraarterially to 31 patients (ADM 14, epi-ADM 17) with advanced breast cancer. The clinical response rate was 78.6% in ADM (1 CR and 10 PR) and 76.5% in epi-ADM (1 CR and 12 PR). The histological response rate of 57.1% was also obtained in ADM and 56.3% in epi-ADM. No significant differences were evident between the two drugs. As for side effects, hair loss and gastrointestinal disorders were frequently documented low grade and less following administration of epi-ADM as compared to ADM. A more favorable prognosis seems possible with epi-ADM compared with ADM. Intra-arterial infusion chemotherapy with epi-ADM appears to be effective for the treatment of advanced breast cancer and is less toxic that ADM.

Alopecia↗
PubMed1992

[A comparative study with 5'-DFUR alone or in combination with tamoxifen (TAM) or medroxyprogesterone acetate (MPA) for advanced or recurrent breast cancer].

A comparative study of 5'-DFUR 600 mg/day alone (C-arm) or in combination with TAM 30 mg/day (A-arm) or MPA 600 mg/day (B-arm) was carried out. Thirty-four patients (aged 80 or less) with no prior treatment were evaluable, and the following results were obtained. 1) Patient characteristics were similar in each treatment group and the compliance in all groups was excellent. 2) The group B response rate (70.0%) was considerably higher than that of group A (23.1%) and C (27.3%). 3) In B, the response rates in soft tissues (80.0%) and bone (71.4%) were still good. 4) Mild side effects were encountered in about 15% of each group. We confirmed that combination chemotherapy with a low dose of 5'-DFUR and MPA was effective for first line treatment of metastatic breast cancer.

Adult↗
PubMed1991

Pre- and postjunctional muscarinic receptor subtypes in dog airways.

To examine muscarinic receptor subtypes involved in cholinergically mediated contractions of the airway, we studied the effects of the M1-selective antagonist, pirenzepine, the M2-selective antagonist, AF-DX 116, the M3-selective antagonist, 4-diphenyl-acetoxy-N-methylpiperidine (4-DAMP) methiodide, and the non-selective antagonist, atropine, on acetylcholine (ACh)- and electrically induced contractions in dog bronchi and bronchioles. The relative potencies of the antagonists based on IC50 values of each antagonist for contractions induced by the two concentrations of ACh that produced 50% of the maximum (ED50) and the maximum (EDmax) contractions and the pA2 values were atropine greater than or equal to 4-DAMP methiodide greater than pirenzepine = AF-DX 116 in both the bronchi and bronchioles. The IC50 and pA2 values of each antagonist did not differ significantly between the bronchi and bronchioles. 4-DAMP methiodide significantly inhibited the contractile response to electrical field stimulation (EFS) at 5 Hz at concentrations that did not alter the contractile responses to exogenous ACh in both the bronchi and bronchioles, whereas pirenzepine, AF-DX 116 and atropine inhibited the EFS-induced contraction only at the concentrations that reduced the contraction induced by exogenous ACh. The present results suggest that the cholinergic contraction is mediated via the postsynaptic receptor M3, based on functional potencies of muscarinic antagonists and presynaptic receptor auto-facilitatory M3, based on the suppression of the contractile response to EFS by 4-DAMP methiodide in central and peripheral airways.

Acetylcholine↗
PubMed1991

Effect of platelet-activating factor on cortisol and corticosterone secretion by perfused dog adrenal.

Administration of platelet-activating factor (PAF) to perfused adrenal increased cortisol and corticosterone secretion. With hexadecyl PAF (C16PAF; 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine), the increase was significant at 1 nM and maximal at 10 nM. The responses to 10 nM octadecyl PAF (C18PAF; 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) were one fourth of those to 10 nM C16PAF. The addition of C16PAF to dispersed adrenal cells significantly increased cortisol and corticosterone production at 0.1 nM and 10 nM, respectively. C16PAF was about 1000 times more potent than histamine on a molar basis in respect to cortisol response in both perfused adrenal and dispersed adrenal cells. The results suggest that PAF induces cortisol release from dog adrenal.

Adrenal Cortex↗
PubMed1991

Apolipoprotein E deficiency with a depressed mRNA of normal size.

We studied a 39-year-old man who had palmar xanthomas complicated with marked hyperlipidemia. His serum cholesterol and triglyceride were 2000 and 6300 mg/dl, respectively. Serum apolipoprotein E (apo E) was undetectable in the patient by the methods of single radial immunodiffusion, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and radioimmunoassay. Serum apo E concentrations of his father and sister were low. This evidence is consistent with a diagnosis of familial apo E deficiency. We studied the synthesis of apo E in cultures of peripheral blood monocyte macrophages (M-M cultures) obtained from the patient, and detected no secretion of apo E in the culture medium and no newly synthesized apo E in the cell lysate. There were only trace amounts of apo E mRNA of the M-M cultures and the size of the mRNA appeared the same as normal apo E mRNA, indicating a different mutation of the gene from that of the case reported by Zannis et al. (J. Biol. Chem., 260 (1985) 12891).

Adult↗
PubMed1991

Adenosine deaminase in the adductor muscle of the scallop, Patinopecten yessoensis.

1. The scallop enzyme was separated by DE52 ion-exchange chromatography into two forms with the same mol. wt of 38,000 and similar characteristics. 2. The enzyme was inactivated in the absence of dithiothreitol and complete reactivation was achieved by adding the agent within a critical storage period. 3. The apparent values of pKm and Vmax sensitively increased as ionic strength was raised to 250 mM and phosphate and sodium ions elevated the former value with a further increase of the ionic strength. 4. The apparent activation energies for the alpha (Vmax/Km) and beta (Vmax) parameters of both the forms were approximately 5 and 8 kcal/mol, respectively. 5. The enzyme deaminated 2'-, 3'-deoxyadenosine and 2',3'-isopropylidene adenosine but did not deaminate 5'-deoxyadenosine, alpha-adenosine and adenine nucleotides. 6. The affinity for inosine was much lowered with a high Ki value. Adenine and purine riboside inhibited the enzyme completely, and coformycin was a tight, slow binding inhibitor.

Adenosine Deaminase↗