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Biomedical subjects

S Shimura

Publications and source records attributed to S Shimura.

At least 91 records · Page 5Linked to original sources

Pulmonary emphysema followed by pulmonary fibrosis of undetermined cause.

Idiopathic pulmonary fibrosis (IPF) and pulmonary emphysema (PE) have distinct clinical and pathological characteristics, and have been considered to be separate disorders. However, recent animal experiments have suggested that, with regard to their pathogenesis, the diseases have some features in common. However, there are no clinical data supporting this hypothesis. We report here 9 patients (all male, 67 +/- 2 years, mean +/- SE) who had PE followed by IPF. They were found among 152 PE patients who came to Tohoku University Hospital during the past 15 years (1976-1991). All patients were male and heavy smokers and 2 patients also had prostate cancer and gastric cancer, respectively. Three patients were alive during this study and had been diagnosed as having IPF and PE by the combination of transbronchial biopsy, selective alveolobronchogram, CT examination and lung function tests. The diagnosis of IPF and PE in the other patients was based on the pathological findings of autopsied lungs in addition to clinical findings. All patients showed PE mainly in the upper lobes and IPF in the lower lobes. In all patients, in addition to all known causes of pulmonary fibrosis, the possibilities that chronic or recurrent infections in PE induced pulmonary fibrosis and that IPF produced emphysematous changes were carefully excluded by medical records and pathological findings. It is not clear whether the occurrence of emphysema and pulmonary fibrosis in these cases is coincidental, or whether the two diseases are linked by a common pathogenetic pathway.

Aged↗

Morphometric analysis of airways in Sjögren's syndrome.

Sjögren's syndrome is characterized by a decrease in exocrine gland secretion and the destruction of secretory tissue and cells, that is, salivary and lacrimal glands. Although patients with Sjögren's syndrome have chronic cough and sometimes sputum, we have little knowledge concerning the morphology of their airways. We performed morphometric analysis of goblet cells and bronchial glands and compared them with intraluminal mucus volume by measuring the mucus-occupying ratio (MOR) in the airways of patients with Sjögren's syndrome. A total of 6 nonsmoking patients with Sjögren's syndrome who had no significant prolonged airway infections (Group SG) (6 women, 55 +/- 2 yr) were compared with four control patients with no pulmonary diseases (Group NL) (1 woman and 3 men, 64 +/- 2 yr) and five patients with chronic bronchitis (Group CB) (1 woman and 4 men, 52 +/- 5 yr). Autopsied lungs from 15 patients were used for morphometry by a digitalizing computer. Area proportion of bronchial glands (gland %) to bronchial wall, goblet cell-occupying ratio to total epithelial layer (goblet %), and MOR were measured in central (3-8 mm in diameter) and peripheral airways (2 mm or less in diameter). Gland % and goblet % in central and MOR in peripheral airways from Group SG were significantly larger than those from Group NL: 15 +/- 2 versus 6 +/- 1% (p < 0.01), 6 +/- 1 versus 2 +/- 1% (p < 0.05), and 9 +/- 2 versus 0.6 +/- 0.3% (p < 0.05), respectively. Further, these values from Group SG did not significantly differ from those from Group CB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Changes of lipid concentrations in liver and serum by administration of carnitine added diets in rats.

Carnitine [4,-(N,N,N-trimethyl-ammonio)-3-hydroxybutanoate] was added to the diet to study its effect on lipid concentrations in liver and serum of rats. In rats administered with a high-fat diet containing 30% corn oil, simultaneous administration of carnitine reduced the concentrations of triglycerides and total cholesterol in both liver and serum. The addition of carnitine to a high-cholesterol diet decreased the levels of cholesterol and lipids in serum, but the cholesterol level to remain higher than control level. The present findings suggested that addition of carnitine may improve the lipid metabolism in obesity.

Animals↗

[Immunohistochemical study of the prostatic tissues with monoclonal antibody against gamma-seminoprotein. Analyses of benign prostatic hyperplasia, metastatic foci from adenocarcinoma of the prostate and malignant neoplasms other than adenocarcinoma of the prostate].

The immunohistochemical specificity of the monoclonal antibody (43-21-1-1) against gamma-seminoprotein (gamma-Sm) in the prostatic tissues was evaluated by avidin-biotin peroxidase complex method. The normal tissues of various organs, other than male genitourinary organs already examined in the previous study, the brain, skin, spinal cord, tongue, esophagus, stomach, small intestine, rectum, trachea, lung, pleura, diaphragm, liver, spleen, pancreas, mesentery, kidney, lymph node, bone, bone marrow and striated muscle were examined for control study. The prostatic tissues obtained by surgery or biopsy, benign prostatic hyperplasia (BPH; 72) urethral polyp with prostatic-type epithelium (1), bone (3) or testicular (2) metastases from adenocarcinoma of the prostate and malignant neoplasms other than adenocarcinoma of the prostate, including primary small-cell carcinoma (1), secondary embryonal carcinoma (1) and secondary mucinous adenocarcinoma (1) of the prostate were then examined. Since all but 2 (97%) specimens of BPH were obtained by transurethral resection (TUR), which might cause non-specific staining due to electro-mechanical effects, the tissue of BPH obtained by suprapubic prostatectomy were examined simultaneously, serving as a control for immunostaining. The normal tissues of various organs were never stained positively for gamma-Sm. Positive reactions of gamma Sm with this monoclonal antibody were recognized in the cytoplasms of urethral polyp with prostatic-type epithelium, bone or testicular metastases from adenocarcinoma of the prostate. The malignant neoplasms other than adenocarcinoma of the prostate examined in this study, were never stained positively. There was obviously evidence of non-specific staining in the TUR tissues of BPH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Kidney-conservative surgery followed by bacillus Calmette-Guerin instillation therapy for transitional cell carcinoma of solitary renal pelvis: a case report].

We report a case (62-year-old male) of transitional cell carcinoma (grade 2) of solitary right renal pelvis which was successfully treated with tumor excision followed by bacillus Calmette-Guerin instillation therapy. He had a past history of left radical nephroureterectomy for renal pelvic tumor 11 years earlier. Kidney-preserved surgery with BCG instillation therapy is expected to be an alternative for radical forms of therapy, especially in the patients with a solitary kidney.

BCG Vaccine↗

Urea kinetics and clinical features of long-term continuous ambulatory peritoneal dialysis patients.

The purpose of this study was to assess urea kinetic modeling (UKM) as a marker for adequate dialysis in continuous ambulatory peritoneal dialysis (CAPD) patients. UKM was conducted on 19 anuric patients on CAPD for more than 2 years. Serum beta 2-microglobulin (beta 2M) was also measured as a marker of large molecular weight substances. Patient clinical conditions were evaluated by the doctors and patients as well. The patients were thus asked to complete a questionnaire on uremic symptoms and daily activities. A comparison was made in urea kinetics and biochemical parameters based on clinical assessment scores. Patient and doctor scores showed a close correlation (r = 0.69) and were correlated to days of hospitalization. The peritonitis rate was significantly higher in the "not doing well" group. No correlation could be found between indexes of UKM or beta 2M plasma level and clinical assessment scores. A significant correlation was noted between serum albumin concentration and doctor scores (r = 0.52). It was thus concluded that UKM was not a good indicator of the adequacy of dialysis for CAPD, but serum albumin was. However, clinical symptoms and signs are more important than biochemical parameters for assessing adequacy.

Adult↗

Autonomic innervation to feline tracheal submucosal glands for mucus glycoprotein secretion.

We examined the effect of electrical field stimulation (FS) on radiolabeled glycoconjugate released from feline tracheal isolated glands. Trichloroacetic acid precipitable [3H]-glycoconjugates released into the culture medium were counted, divided by the dry weight of sample, and data were expressed as percent of the release from the same animal that was unstimulated but otherwise received identical treatment. FS produced an increase in the glycoconjugate release that was dependent on the duration of stimulation, reaching a maximum response of 215% of nonstimulated sample for 30 min stimulation (10 Hz, 10 V). FS-evoked secretion was abolished by 10(-7) M tetrodotoxin but not altered by 10(-5) M hexamethonium. Atropine (10(-6) M) alone abolished the response to FS for 3 min or less. By contrast, a mixture of 10(-6) M atropine, 10(-5) M propranolol, and 10(-5) M phentolamine blocked only part of the response to FS for 15 min or more. The mixture of three antagonists reduced the response to FS for 30 min to 159% of control, which was significantly higher than control. Furthermore, 10(-6) M atropine, 10(-5) M propranolol, or 10(-5) M phentolamine significantly reduced the response to FS for 30 min to 162, 193, and 195%, respectively, from 215% of sample in the absence of blockers. Serotonin (10(-5) M) augmented FS-evoked response, which was abolished by 10(-6) M atropine or by 10(-5) M methysergide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endothelin regulation of mucus glycoprotein secretion from feline tracheal submucosal glands.

We examined the effects of endothelin on both the trichloroacetic acid precipitable 3H-labeled glycoconjugate release and intracellular Ca2+ concentration ([Ca2+]i]) measured by the usage of fura-2 in submucosal glands isolated from feline trachea. Endothelin-1 produced a significant increase in glycoconjugate release from the isolated glands in a dose-dependent fashion, reaching a response of 161% of the control at 10(-6) M. Atropine, propranolol, phentolamine, or indomethacin did not produce any significant alterations in the ET-1-evoked glycoconjugate secretion from the isolated glands. In contrast, in tracheal explants which contained epithelium, ET-1 produced a significant reduction in the glycoconjugate secretion in a dose-dependent fashion, reaching a response of 59% of the control at 10(-6) M. In the presence of cultured epithelial cells, ET-1 also produced a significant reduction in the glycoconjugate secretion from isolated glands. In isolated glands, ET-1 produced a sustained increase in the [Ca2+]i which was abolished by the removal of Ca2+ from the medium or by the presence of cultured epithelial cells. Pretreatment with indomethacin failed to alter the epithelial inhibitory action evoked by ET-1 in both the glycoconjugate secretion and the [Ca2+]i in isolated glands. ET-2 and ET-3 failed to produce significant alterations in the glycoconjugate secretion or [Ca2+]i. These findings indicate 1) that ET-1 induces mucus glycoprotein secretion via a Ca2+ influx and 2) that it possibly augments the an epithelial action inhibitory to the mucus glycoprotein secretion from airway submucosal glands.

Animals↗

Muscarinic receptor subtypes in feline tracheal submucosal gland secretion.

To determine what muscarinic receptor subtype regulates [Ca2+]i mediating airway submucosal gland secretion, we examined the effects of atropine (Atr), pirenzepine (PZ), 11([2-(diethylamino)methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzo-diazepin-6-one (AF-DX116) and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, and compared this with mucus glycoprotein (MGP) and electrolyte secretion evoked by MCh from submucosal glands isolated from feline trachea. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura 2. We determined MGP secretion by measuring TCA-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half-maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. IC50 of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M Atr (P less than 0.01, each) but not by 10(-7) M PZ. Receptor binding assays with [3H]quinuclidinyl benzilate showed that the Ki values for PZ, AF-D x 116, 4-DAMP and Atr were 2.2 x 10(-8) M, 6.6 x 10(-7) M, 6.2 x 10(-10) M, and 2.9 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endothelin-1 stimulates chloride secretion across canine tracheal epithelium.

Although much attention has been paid to the effect of endothelin on the bronchopulmonary system, there are few reports concerning the effect of endothelin on Cl- secretion across airway epithelium. We examined the effects of endothelin-1, -2 and -3 on bioelectric parameters of canine tracheal epithelium, a tissue in which Cl- is actively secreted and Na+ is absorbed. Potential difference (PD) and short-circuit current (SCC) were measured using an Ussing chamber with 0.5 cm2 of exposed area, and conductance (G) was calculated by dividing SCC by PD. Luminal endothelin-1 produced transient increases in PD and SCC, returning to baseline values within 5 min after stimulation in a dose-dependent fashion and reached mean responses of 123 and 126% of baseline PD and SCC, respectively, at 10(-6) M of endothelin-1, whereas submucosal endothelin-1 did not alter PD and SCC. G remained unchanged when stimulated by endothelin-1. Endothelin-2 and -3 did not produce any significant alterations in PD and SCC. Endothelin-1 evoked increases in PD and SCC, which were not altered by pretreatment with luminal amiloride (10(-4) M), or by treatment with submucosal propranolol (10(-5) M). Ionic substitution of Cl- with nontransported anions, iodide and gluconate, inhibited endothelin-1-induced increases in PD and SCC. Pretreatment with 10(-5) M indomethacin partially inhibited Endothelin-1-evoked increases in PD and SCC. These findings indicate that endothelin-1 stimulates Cl- secretion partially through the generation of cyclooxygenase products of arachidonic acid.

Amiloride↗

Airway epithelial cells enhance eosinophil survival.

Guinea pig and human eosinophils were co-cultured with or without epithelial cells (controls). Eosinophil survival was enhanced in the presence of the cultured epithelial cells in a number-dependent fashion. Further, supernatants from cultured epithelial cells also enhanced eosinophil survival. Both a monoclonal antibody to GM-CSF and indomethacin inhibited these epithelial-cell-mediated effects, and GM-CSF and PGE2 were shown to prolong eosinophil survival. These findings indicate that airway epithelial cells can enhance eosinophil survival. It is suggested that the mechanism may involve GM-CSF and PGE2 generation.

Animals↗

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↗

Delta F508 mutation of cystic fibrosis gene is not found in chronic bronchitis with severe obstruction in Japan.

Diffuse panbronchiolitis (DPB) in Japan is a chronic bronchitis observed in nonsmoking adults, with severe obstruction and poor prognosis. DPB shares pathologic and clinical characteristics with mild adult cystic fibrosis (CF), except that CF is frequent in whites (Europeans and Americans of European descent) but not in Japanese. Recently, the cystic fibrosis transmembrane conductance regulator (CFTR) gene was identified, and a 3-base pair deletion (delta F508) was confirmed as a major mutation responsible for CF. We extracted genomic DNA from white blood cells of 17 DPB patients and from paraffin-embedded tissues of 4 DPB patients at autopsy. Two polymerase chain reaction (PCR) primers were made in exon 10 of the CFTR gene so that a three-base shorter segment of 78 base pairs was amplified from the CFTR gene with the delta F508 mutation; the DNA segment amplified from the normal gene contains an F508 area with 81 base pairs. Every DNA segment amplified from DPB patients showed a normal 81-base pair length, indicating no DNA sample contained the delta F508 mutation. These results based on delta F508 mutation analysis in the CF gene indicate that DPB may represent a disease different from CF.

Adult↗

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↗

Role of chronic Pseudomonas aeruginosa infection in the development of bronchiectasis.

To understand the role of Pseudomonas aeruginosa infection in the development of bronchiectasis, we investigated by CT the presence of bronchiectasis in two groups of chronic bronchitis patients and in a control group. There were no differences in clinical or laboratory findings between groups A and B. Three observers without any knowledge of these patients reported bronchiectasis on a scale of 0 to 3 and bronchial wall thickness on a scale of 0 to 3 in each lobe of both lungs. Bronchiectasis and wall thickness scores in group A (chronic bronchitis with P aeruginosa infection) were significantly higher than bronchiectasis scores and wall thickness in group B (chronic bronchitis without P aeruginosa infection). Both scores in group B were higher than those in group C (control group). These findings support the idea that chronic P aeruginosa infection plays a role in the development of bronchiectasis.

Adult↗

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↗

[The role of muscarinic receptor subtypes in feline tracheal submucosal gland secretion].

To determine what muscarinic receptor subtype regulates the rise of intracellular calcium concentration ([Ca2+]i) and resultant airway submucosal gland secretion on muscarinic receptor stimulation, we examined the effects of atropine (ART), pirenzepine (PZ), 11([2-(diethylamino) methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pirido (2,3-b)(1,4)-benzodiazepine-6-one (AF-DX116) and 4-diphenylacetoxy-N-methylpiperidine methiodode (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, mucus glycoprotein (MGP) secretion and electrolyte secretion from submucosal glands isolated from feline tracheae. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura2. We determined MGP secretion by measuring trichloroacetic acid (TCA)-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP and ATR against MCh (10(-5) M)-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M and 6 x 10(-9) M, respectively. IC50 values of these antagonists against MCh (10(-5) M)-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na-efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M ATR (p < 0.01, respectively), but the inhibitory effect of PZ (10(-7) M) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗