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Biomedical subjects

M Hayasaka

Publications and source records attributed to M Hayasaka.

At least 19 recordsLinked to original sources

Basal layer reactivity in hyperplastic and metaplastic lesions of the bronchi as studied by lectin histochemistry.

The relationship between squamous metaplasia and squamous cell carcinoma of the bronchi has been the subject of controversy. We investigated basal cell hyperplasia, stratification, squamous metaplasia, and squamous cell carcinoma by means of lectin histochemistry with peanut agglutinin (PNA), Ulex europeus agglutinin-I, soybean agglutinin, and Dolichos biflorus agglutinin for all normal basal cells that are reactive. A basal layer stained with PNA was observed in basal cell hyperplasia, stratification, and squamous metaplasia, but this layer was not exhibited by squamous cell carcinoma. In hyperplasia and metaplasia, PNA staining was biased toward the lowest (basal) layer, whereas staining for the other lectins was more uniformly distributed across the layers. A PNA-positive basal layer may be important for the morphologic reversibility of the bronchial mucosa in hyperplastic and metaplastic lesions, and destruction of this layer may be associated with a progression from metaplasia to squamous cell carcinoma.

Adenocarcinoma↗

Unilateral hilar lymphadenopathy of sarcoidosis or sarcoid reaction compressing the trunk of the right pulmonary artery.

A case of sarcoidosis or sarcoid reaction with a rare manifestation of unilateral lymphadenopathy compressing the trunk of the right pulmonary artery is presented. A 71-year-old woman was admitted for evaluation of a left hilar mass. Chest CT scans showed a mass invading the right pulmonary artery. A frozen section obtained following open lung biopsy showed lymph node tissue largely replaced by noncaseous granulomas indicating sarcoidosis or sarcoid reaction. Old uveitis was compatible with sarcoidosis, and no malignancy was evident. These findings suggested sarcoidosis, however, other evidence of sarcoidosis was not obtained.

Aged↗

Proliferation of type II pneumocytes and alteration in their apical surface membrane antigenicity in pulmonary sarcoidosis.

STUDY OBJECTIVE: To evaluate both the proliferation of type II pneumocytes in the alveolitis associated with pulmonary sarcoidosis and any alteration in their surface membrane antigenicity. MATERIALS AND METHODS: We investigated 20 transbronchial lung biopsy (TBLB) specimens from 20 patients with pulmonary sarcoidosis, 7 TBLB specimens from 7 sarcoidosis patients without pulmonary involvement, and 19 normal lung specimens, using colloidal iron stain and immunostaining with anti-Thomsen-Friedenreich (TF) antigen and anti-surfactant protein-A monoclonal antibodies. RESULTS: The density of type II pneumocytes was significantly higher in the pulmonary sarcoidosis specimens ([mean +/- SD] 11.1+/-3.7 per 1 mm alveolar septal length) than in the nonpulmonary sarcoidosis (7.8+/-1.3) or normal lung specimens (7.2+/-0.8). TF antigen was directly expressed on the apical surface of some type II pneumocytes in the pulmonary sarcoidosis specimens, but it was completely masked by sialic acids in the nonpulmonary sarcoidosis specimens and in the normal lung tissues. CONCLUSIONS: In pulmonary sarcoidosis, type II pneumocytes proliferated and the antigenicity of the surface membrane was altered. It is suggested that these type II pneumocytes may be vulnerable to injury by natural anti-TF antibodies that are cytotoxic when present with complement. This damage may decrease alveolar surfactant and cause focal alveolar collapse proceeding to pulmonary fibrosis in some cases of pulmonary sarcoidosis.

Antigens, Surface↗

[ADOC regimen for unresectable advanced thymic cancer].

Between 1996 and 1998, we treated 6 patients with unresectable and advanced thymic cancer (stages IVa and IVb). All received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (i.v.) on day 1,0.6 mg/m2 of vincristine i.v. on day 3, and 700 mg/m2 of cyclophosphamide i.v. on day 4; ADOC regimen, respectively at 3-4 week intervals. Four patients obtained a partial response (PR) after ADOC chemotherapy and the overall clinical response rate was 67%. No life-threatening side effects were noted. In 2 patients, cisplatin plus VP-16 chemotherapy failed to demonstrate any benefits prior to the ADOC regimen. Radiotherapy was initiated after the achievement of PR in the other 2 patients. ADOC chemotherapy appears to be an effective treatment for thymic cancer.

Aged↗

Mycobacterium avium-intracellulare pulmonary infection in patients without known predisposing lung disease.

We tried to characterize the clinical features and findings on chest high resolution computed tomography (HRCT) of patients with Mycobacterium avium-intracellulare (MAI) pulmonary infection without known predisposing lung disease and with no immunodeficiency. We also aimed to clarify the small airway and alveolar inflammation using bronchoalveolar lavage (BAL) from the affected regions. MAI infection was diagnosed in 53 patients from respiratory samples, including sputum and materials obtained using a fiberoptic bronchoscope. None had a predisposing lung disease or immunodeficiency, as assessed by medical history, routine laboratory data, and previously normal chest radiographs and/or CT scans. The mean age of the 53 patients was 60 +/- 11 years, and 48 were nonsmoking females. They had few respiratory symptoms, although 42% had chronic paranasal sinusitis. Chest HRCT findings showed centrilobular small nodules and ectasia of small bronchi and/or bronchioles located mainly in segment (S) 2, 3, 4, and 5. S1, which is usually affected by pulmonary tuberculosis, was completely free of these opacities. The BAL study revealed that the predominant cells were activated T lymphocytes and neutrophils. The CD4+/CD8+ ratio increased significantly. Bacteriology was negative for other bacteria and fungi. Although our patients did not present with distinct respiratory symptoms, the regions affected by MAI showed a chronic inflammation of mainly neutrophils and activated T lymphocytes. The presence of chronic sinusitis may be merely coincidental. However, its high prevalence and the finding of bronchiectasis in chest HRCT raise the question of whether silent bronchiectasis may be a predisposition.

Aged↗

Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude pulmonary edema.

To evaluate the pathogenesis of high-altitude pulmonary edema (HAPE), we performed bronchoalveolar lavage (BAL) and pulmonary hemodynamic studies in seven patients with HAPE at its early stage. We measured cell counts, biochemical contents, and concentrations of pro-inflammatory cytokines including interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha and of anti-inflammatory cytokines including IL-1 receptor antagonist (ra) and IL-10 in the BAL fluid (BALF). All patients showed increased counts for total cells, alveolar macrophages, neutrophils and lymphocytes, and markedly elevated concentrations of proteins, lactate dehydrogenase, IL-1beta, IL-6, IL-8, TNF-alpha and IL-1ra. The levels of IL-1alpha and IL-10 were not increased. Patients also showed pulmonary hypertension with normal wedge pressure. Both the driving pressure obtained as pulmonary arterial pressure minus wedge pressure and the PaO2 under room air were significantly correlated with the concentrations of IL-6 and TNF-alpha in the BALF. These findings suggest that the inflammatory cytokines play a role at the early stage of HAPE and might be related to pulmonary hypertension.

Adult↗

Protein kinase C mediates increase of Ca2+ sensitivity for contraction by cholinoceptor partial agonist in ileal longitudinal muscle of guinea pig.

1. Experiments were designed to study the roles of protein kinase C in carbachol- and pilocarpine-induced contraction and the increase in cytosolic Ca2+ concentration ([Ca2+]i) in guinea pig ileal longitudinal muscle. 2. The protein kinase C inhibitors, GF 109203X (10 microM), calphostin C (10 microM) and H-7 (10 microM), reduced the maximum of the concentration response curve produced by pilocarpine more effectively than that produced by carbachol. 3. The slopes of the regression lines between [Ca2+]i and tension development for pilocarpine and carbachol in tissues treated with GF 109203X were significantly gentler than those for untreated tissues. 4. The protein kinase C alpha- and beta 1 selective inhibitor Goe 6976 (1 microM) decreased both [Ca2+]i and contraction, but did not affect the slopes of the regression lines for pilocarpine and carbachol. 5. These results suggest that protein kinase C (both n- and/or a-type) plays an important role in the increase of Ca2+ sensitivity of the contractile element, and that pilocarpine mainly activates the protein kinase C-dependent pathways for contractile mechanisms in guinea pig ileal longitudinal muscle.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Spontaneous regression of primary mediastinal germ cell tumor.

A case of primary mediastinal germ cell tumor, which demonstrated spontaneous regression, is presented. The serum human chorionic gonadotropin level was elevated on admission and then decreased to the normal range with decrease in the size of the anterior mediastinal mass. Thoracotomy was performed with artificial replacement by grafts between the bilateral brachiocephalic veins and the right atrium. Histological diagnosis of combined teratoma with seminoma was made. After subsequent chemotherapy, the patient has remained alive without recurrence for over 10 years.

Adult↗

Cardiac sarcoidosis mimicking hypertrophic cardiomyopathy: clinical utility of radionuclide imaging for differential diagnosis.

A 62-year-old woman with skin sarcoidosis was admitted to our hospital to ascertain whether she had cardiac involvement. Although she displayed no cardiac signs or symptoms, the electrocardiogram showed first-degree atrioventricular block, right bundle branch block with left anterior fascicular block, and giant negative T waves in the V3 lead. Echocardiography revealed marked hypertrophy localized in the basal portion of the interventricular septum (IVS) without systolic dysfunction, mimicking hypertrophic cardiomyopathy (HCM). Exercise thallium-201 myocardial imaging revealed redistribution in the anteroseptal region. Both gallium-67 (67Ga) and technetium-99m pyrophosphate (99mTc-PYP) scintigraphy revealed abnormal uptake in the myocardium. These findings disappeared after 2 months of steroid treatment. Reports of cardiac sarcoidosis mimicking HCM are rare. However, hypertrophy in the basal portion of the IVS is an important sign of early cardiac involvement in sarcoidosis. 67Ga and 99mTc-PYP scintigraphy were useful and necessary to differentiate this type of cardiac sarcoidosis from HCM.

Cardiomyopathies↗

Laminin alpha2 chain-null mutant mice by targeted disruption of the Lama2 gene: a new model of merosin (laminin 2)-deficient congenital muscular dystrophy.

Using the gene targeting technique, we have generated a new mouse model of congenital muscular dystrophy (CMD), a null mutant for the laminin alpha2 chain. These homozygous mice, designated dy3Kldy3K, are characterized by growth retardation and severe muscular dystrophic symptoms and die by 5 weeks of age. Light microscopy revealed that muscle fiber degeneration in these mice begins no later than postnatal day 9. In degenerating muscles, considerable amounts of TUNEL positive nuclei were detected as well as DNA laddering, suggesting increased apoptotic cell death was involved in the process of muscle fiber degeneration.

Animals↗

Functional expression and germline transmission of a human chromosome fragment in chimaeric mice.

Human chromosomes or chromosome fragments derived from normal fibroblasts were introduced into mouse embryonic stem (ES) cells via microcell-mediated chromosome transfer (MMCT) and viable chimaeric mice were produced from them. Transferred chromosomes were stably retained, and human genes, including immunoglobulin (Ig) kappa, heavy, lambda genes, were expressed in proper tissue-specific manner in adult chimaeric tissues. In the case of a human chromosome (hChr.) 2-derived fragment, it was found to be transmitted to the offspring through the germline. Our study demonstrates that MMCT allows for introduction of very large amounts of foreign genetic material into mice. This novel procedure will facilitate the functional analyses of human genomes in vivo.

Animals↗

Diffuse pulmonary amyloidosis with monoclonal IgG-kappa gammopathy.

A 62-year-old female with diffuse pulmonary amyloidosis developed abnormal radiographic findings while under observation for hyperimmunoglobulinemia over a ten-year period. Serum immunoglobulin G (IgG) was elevated (4,620 mg/dl), and associated with monoclonal gammopathy (M protein) of the kappa type, but no evident abnormalities were apparent in bone marrow. Chest radiograph and computed tomography showed a diffuse reticulonodular shadow in the bilateral lung. Thoracoscopic lung biopsy specimen revealed depositions of amyloid in the bronchus and pulmonary vessel. We emphasize that diffuse pulmonary amyloidosis should be considered a possible diagnosis in the presence of monoclonal immunoglobulin.

Amyloidosis↗

Direct determination of serum glycyrrhetic acid by a monoclonal antibody-based inhibition ELISA using ibuprofen for releasing serum albumin-bound glycyrrhetic acid.

We found that ibuprofen (IBU) had a potential for releasing serum albumin-bound glycyrrhetic acid (GA). Based on this observation, IBU was used to pretreat samples for the determination of serum GA levels by an inhibition ELISA. This method, termed IBU method was evaluated by the recovery of GA from human serum albumin (HSA) or normal human serum (NHS) that contained the exogeneously added GA (37-1000 ng/ml). The mean recovery of GA from HSA and NHS samples treated with IBU were 104.7 and 105.2%, respectively, whereas those without IBU pretreatment were 2.8 and 10.7%, respectively. Comparison of IBU method and chloroform extraction method revealed that the GA content of serum samples pretreated by each method were almost the same. These results suggest that IBU method is useful as a serum processing procedure for the determination of serum GA levels by an inhibition ELISA.

Antibodies, Monoclonal↗

Bronchoalveolar lavage fluid findings in patients with chronic hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection has recently been incriminated as an aetiological agent in idiopathic pulmonary fibrosis. This study was performed to determine the cellularity and lymphocyte phenotypes of bronchoalveolar lavage (BAL) fluid in patients with chronic hepatitis C. METHODS: BAL fluid and lavage lymphocyte subsets from 13 patients (10 men) with active chronic hepatitis C, diagnosed by sustained elevated serum glutamic pyruvic transaminase and typical histological findings in the liver, were analysed. Lavage findings in these patients were compared with those from 13 healthy volunteers (eight men) as controls. RESULTS: There was no difference in total cell counts in lavage fluid between the two groups. Lavage lymphocyte and eosinophil numbers were increased in patients with chronic hepatitis C. Surface marker analysis of the lymphocyte populations showed increases in CD2, CD3, CD4, and HLA-DR. CD4/CD8 ratios were not different. CONCLUSIONS: The numbers of lymphocytes and eosinophils in BAL fluid are increased in patients with chronic hepatitis C. These findings suggest that HCV infection may trigger alveolitis.

Adult↗

Cytokines in bronchoalveolar lavage fluid in patients with high altitude pulmonary oedema at moderate altitude in Japan.

BACKGROUND: The precise mechanism of high altitude pulmonary oedema (HAPE) remains unclear. The purpose of this study was to evaluate the role of cytokines and P-selectin in the development of HAPE which occurred at moderate altitude in Japan. METHODS: The following cellular and biochemical markers and chemotactic cytokines were measured in the bronchoalveolar (BAL) fluid from four patients with HAPE at 2857-3180 m in the Japanese Alps: total proteins, albumin, lactate dehydrogenase (LDH), and interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor antagonist (ra), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, and the soluble form of P-selectin. RESULTS: At admission there were significant increases in the levels of total cells, especially macrophages and neutrophils, total protein, albumin and LDH when compared with 13 healthy individuals. Furthermore, the levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were also considerably increased but returned quickly to the normal ranges or were not detected after recovery. The levels of IL-1 alpha, IL-10, and P-selectin did not change. CONCLUSIONS: These results suggest that an inflammatory process almost identical with acute respiratory distress syndrome (ARDS) may occur in HAPE, but that these changes are transient and are not associated with any increase in P-selectin levels in the BAL fluid.

Adult↗

Two cases of severe bronchiectasis successfully treated with a prolonged course of trimethoprim/sulfamethoxazole.

Two patients with severe bronchiectasis, one patient without other disease and the other with hyper IgE syndrome, were successfully treated with long-term therapy with low doses of trimethoprim and sulfamethoxazole (TMP-SMZ). Recurrent respiratory infections with productive cough and high fever were resistant to various antibiotics and often disturbed the patients' activities in daily life. However, they showed marked improvement following TMP-SMZ therapy, which was started for methicillin-resistant Staphylococcus aureus (MRSA) infection. MRSA disappeared some months later, but Pseudomonas aeruginosa appeared again in the sputum. Both patients, however, have remained free from symptoms for over one year.

Adult↗

[Two cases of primary Sjögren's syndrome with pulmonary involvement histopathological study of open-lung biopsy specimens].

We report two cases of primary Sjögren's syndrome with pulmonary involvement, in which open lung biopsies were done. The patient in the first case was a 58-year-old woman and the patient in the second case was a 54-year-old woman. Both patients were admitted to our hospital because of dry coughing and exertional dyspnea. Chest X-ray films and CT scans showed interstitial shadows in both cases and multiple bullae in the first case. Pulmonary-function tests showed decreased diffusing capacity, and examination of bronchoalveolar lavage fluid revealed increased percentages of lymphocytes. Open-lung biopsy specimens showed thickening of the alveolar septa and interstitial mononuclear cell infiltration, composed predominantly of lymphocytes, with lymphoid follicles in both cases, and peribronchiolar mononuclear cell infiltration in the first case. Therefore, the histopathological diagnosis was cellular interstitial pneumonia with lymphoid follicles. Both patients were treated with oral corticosteroids. Symptoms were relieved and laboratory findings improved.

Biopsy↗

[Analysis of cells and proteins in bronchoalveolar lavage fluid].

We studied cells and proteins in bronchoalveolar lavage fluid examined at the First Department of Internal Medicine of Shinshu University Hospital between 1990 and 1994. The samples came from 21 healthy subjects and from 216 patients with various diseases. Lymphocyte counts were abnormally high in patients with bronchiolitis obliterans organizing pneumonia. Sjögren's syndrome, sarcoidosis and hypersensitivity pneumonitis. Neutrophil counts were very high in the patients with diffuse panbronchiolitis and in those with high-altitude pulmonary edema, and eosinophil counts were high in those with eosinophilic pneumonia. The CD4:CD8 ratio was significantly higher in the patients with stage I sarcoidosis than in the healthy subjects. The total protein concentration and the albumin concentration were significantly higher in the patients with eosinophilic pneumonia and in those with high-altitude pulmonary edema than in the healthy subjects, and these findings suggest that in those two conditions the permeability of the pulmonary microvasculature was abnormally high.

Adolescent↗