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Biomedical subjects

H Mukae

Publications and source records attributed to H Mukae.

At least 73 records · Page 4Linked to original sources

Increase in activated CD8+ cells in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis.

To study the role of T cells in diffuse panbronchiolitis (DPB), we investigated T-cell subsets in bronchoalveolar lavage fluid (BALF) or 33 patients with DPB, nine patients with bronchiectasis, and 20 healthy volunteers. BALF from DPB patients contained a higher percentage of neutrophils than that from patients with bronchiectasis or healthy volunteers, whereas the percentage of lymphocytes was similar in the three groups. DPB patients, however, had a higher number of lymphocytes and a reduced CD4/CD8 ratio compared with the other subjects. A two-color analysis of T-cell subsets in peripheral blood and BALF revealed a significant increase in the percentage and number of CD8+HLA-DR+ cells and in the number of CD4+HLA-DR+ cells in BALF of DPB patients. The expression of the adhesion molecules CD 11a and CD18 on lung CD3+ cells was enhanced over that on blood CD3+ cells in DPB patients. However, there was no significant difference in the expression of these antigens in peripheral blood or BALF among the groups. There was no significant relationship between BALF interleukin (IL)-8 and lymphocyte accumulation in the lungs of the DPB patients, whereas a significant correlation between the percentage of neutrophils and IL-8 levels in BALF of DPB patients was observed. After treatment with macrolide antibiotics, a significant reduction in the number of lymphocytes and activated CD8+ cells and an elevation in the CD4/CD8 ratio in BALF of DPB patients was observed. Our findings suggest an activation of CD8+ cells in the airway lumen of DPB patients, supporting the hypothesis that lymphocytes are important cellular components of bronchial inflammation in DPB.

Anti-Bacterial Agents↗

Increase of activated T-cells in BAL fluid of Japanese patients with bronchiolitis obliterans organizing pneumonia and chronic eosinophilic pneumonia.

To study the role of T cells in bronchiolitis obliterans organizing pneumonia (BOOP) and chronic eosinophilic pneumonia (CEP) and to examine the influence of differing racial background, T-cell subsets in bronchoalveolar lavage (BAL) fluid (BALF) and in peripheral blood of 8 Japanese patients with idiopathic BOOP and 5 with CEP were compared with those of 15 normal subjects. The BALF pattern in BOOP was characterized by a significantly high number and percentage of lymphocyte and by a low CD4 to CD8 ratio compared with patients with CEP and healthy volunteers. Patients with CEP showed a significantly higher percentage of BALF eosinophils compared with other groups. There was no significant difference in BALF CD4 to CD8 ratio between patients with CEP and volunteers. Two-color analysis of T-cell subsets revealed that CD3+HLA-DR+ cells (activated T cell) in BALF of patients with BOOP and CEP increased significantly compared with volunteers, while BALF CD3+CD25+ cells (interleukin 2 receptor+ T-cell) did not. In addition, BALF CD8+HLA-DR+ cells (activated suppressor/cytotoxic T cell) in patients with BOOP and CD4+HLA-DR+ cells (activated helper T cell) in patients with CEP were significantly higher than levels detected in healthy subjects. The percentage of CD8+CD57+ cells and the number of CD8+CD11b- cells (cytotoxic T cell) in BALF were significantly higher in patients with BOOP compared with patients with CEP and healthy volunteers. There were no significant differences in the expression of peripheral blood T-lymphocyte surface antigens among the groups. These findings indicate that cytotoxic T cells in Japanese patients with idiopathic BOOP and helper T cells in CEP appear in the lungs is consistent with a previous report in Caucasians, supporting the hypothesis that T cells may play an important role in the pathogenesis of these diseases.

Aged↗

[Pulmonary endometriosis with recurrent catamenial hemoptysis].

A 32-year-old woman with a history of dilation and curettage for missed abortion at 31 years old had sudden hemoptysis during menstruation on May 25, 1993. She had catamenial hemoptysis again, and was admitted to our hospital on July 21, 1993. After admission, catamenial hemoptysis occurred, and a nodular shadow was noted in the right S4 area on chest roentgenogram and computed tomogram. A few days after menstruation, hemoptysis and the abnormal shadow on chest roentgenogram disappeared. Pulmonary endometriosis was diagnosed by clinical course, past history, and chest roentgenographic findings. During the next menstruation, hemoptysis and a nodular shadow in the right S4 area on chest roentgenogram recurred, so transbronchial lung biopsy and laparoscopy were done. TBLB specimens revealed macrophages with phagocytosed hemosiderin, and laparoscopy revealed pelvic endometriosis. She was treated with buserelin acetate. Catamenial hemoptysis and the nodular shadow on the chest roentgenogram disappeared after treatment.

Adult↗

[Simultaneous production of parathyroid hormone-related protein (PTHrP) and granulocyte colony-stimulating factor (G-CSF) in lung cancer patients with hypercalcemia and leukocytosis].

Hypercalcemia and leukocytosis are often associated with primary lung cancer as a paraneoplastic syndrome. Recently, parathyroid hormone-related protein (PTHrP) and granulocyte colony stimulating factor (G-CSF) have been identified as major causative peptides for hypercalcemia and leukocytosis, respectively. We studied four men with advanced primary lung cancer (stages from IIIA to IV) who presented with hypercalcemia (corrected serum calcium levels: 10.5 mg/dl) and leukocytosis (WBC > 10,000 per mm3). The age of the patients ranged from 59 to 79 years old. The pathological subtypes were squamous cell carcinoma in three and adenocarcinoma in one. The mean serum calcium levels and leukocyte counts were 15.8 +/- 1.4 mg/dl (mean +/- SE) and 24,800 +/- 3,253 cells/mm3 (mean +/- SE), respectively. Abnormally high serum levels of PTHrP and G-CSF were found in three patients (mean +/- SE: 137 +/- 68 pg/ml; normal range in human serum, < 16 pg/ml), and in all four (mean +/- SE: 72 +/- 7.7 pg/ml; normal range in human serum, < 20 pg/ml), respectively. Immuno-histochemical examination of cancerous tissue obtained from these patients showed positive staining for both PTHrP and G-CSF within the cytoplasm of all the cancerous tissue. These results suggest that the association of hypercalcemia and leukocytosis in patients with advanced primary lung cancer is caused by production of both PTHrP and G-CSF by cancerous tissue.

Aged↗

Increase in T-cells bearing CD25 in bronchoalveolar lavage fluid from HAM/TSP patients and HTLV-I carriers.

To determine the immunologic characteristics of T-cells in local pulmonary lesions of human T-cell lymphotropic virus type I (HTLV-I) carriers, we investigated lymphocyte surface markers in peripheral blood and bronchoalveolar lavage fluid (BALF) of 38 HTLV-I carriers, 8 HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, 44 HTLV-I seronegative patients with pulmonary diseases and 7 healthy volunteers using two-color flow cytometric analysis. In peripheral blood, activated T-cells, CD4+HLA-DR+, CD8+HLA-DR+ and CD3+CD25+, and CD4+CD29+ cells increased significantly in carriers and HAM/TSP patients compared with healthy volunteers and seronegative patients. In BALF, T-cells, especially CD25+ cells, increased significantly in carriers and HAM/TSP patients, compared with healthy volunteers and seronegative patients. These findings indicated that T-cells in the lungs, as well as in peripheral blood, are activated in carriers and HAM/TSP patients. Interestingly, there was dissociation between expression of CD3+CD25+ cells in BALF and peripheral blood from these patients. These results suggest that T-cells activated probably by HTLV-I accumulate in the lungs in some carriers and HAM/TSP patients, and HTLV-I may be involved in the immunologic dysfunction in the lungs of these patients. However, we did not find any correlation between the degree of clinical features and the elevation of CD3+CD25+ cells in BALF, or its characteristic features on chest roentgenograms.

Aged↗

Expression of human T lymphotropic virus type 1 (HTLV-1) tax/rex gene in fresh bronchoalveolar lavage cells of HTLV-1-infected individuals.

Accumulating evidence has suggested the involvement of HTLV-1 in the inflammatory lesions of various organs, including the lung. However, the causal relationship between HTLV-1 and inflammatory responses in the organs remains to be elucidated. In order to evaluate the expression of HTLV-1 and its effects in the lung, we examined the expression of mRNA for the HTLV-1 tax/rex gene in fresh bronchoalveolar lavage cells (BALC) and peripheral blood mononuclear cells (PBMC) of 23 seropositive individuals, including six patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), by use of an improved method of reverse transcription-polymerase chain reaction (RT-PCR). The tax/rex mRNA was more frequently detected in BALC than in PBMC. All the HAM/TSP patients and eight of 17 carriers without neurological symptoms showed the expression of tax/rex mRNA in the BALC. IgM class antibodies to HTLV-1 were preferentially detected in sera of the tax/rex mRNA-positive individuals. The detection of tax/rex mRNA correlated closely with the presence of lymphocytosis accompanied by an elevated proportion of IL-2 receptor-bearing T cells in the BALC. Our findings indicate the crucial role of viral expression in the inflammatory response in the lung in HTLV-1-infected individuals.

Adolescent↗

[Coexisting respiratory tract infection and bacteremia or sepsis caused by the same bacterium].

We experienced 12 patients who were suffering from bacteremia or sepsis and pneumonia or lung abscess coincidently caused by the same bacterium, during the 8 years from 1985 to 1992 a Hokusyo Central Hospital. All of them has some underlying diseases, and the average age was 73.6 years old. In ten out of 12 patients bacteremia or sepsis preceded the respiratory tract infection, and in 7 cases indwelling intravenous catheter was thought to be the port of entry of the bacteria. Respiratory tract infections were composed of pneumonia in 8 cases and lung abscess in 4 cases. Methicillin resistant Staphylococcus aureus (MRSA) was detected in 4 cases, Methicillin sensitive Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Pseudomonas aeruginosa were in 2 cases respectively, Citrobacter freundii and Methicillin resistant Staphylococcus spp. were in one cases respectively. Eight out of 12 cases died in spite of current antibiotics therapy, suggesting poor prognosis.

Aged↗

Two-color analysis of lymphocyte subsets of bronchoalveolar lavage fluid and peripheral blood in Japanese patients with sarcoidosis.

Analysis of T-cell surface markers was carried out in peripheral blood and bronchoalveolar lavage (BAL) fluid of Japanese patients with sarcoidosis to examine the influence of differing racial background. The subjects were 26 untreated patients in whom a diagnosis of active sarcoidosis had recently been established and 9 healthy volunteers, and two-color immunofluorescence analysis was performed. CD3+HLA-DR+ cells, CD4+HLA-DR+ cells, and CD4+CD29+ cells in peripheral blood and BAL fluid were significantly increased in the patients compared with the healthy volunteers, and the mean percentages increased in parallel with the extent of the radiologic stage. The percentage of CD3+HLF-DR+ cells in peripheral blood and lavage fluid also significantly correlated with serum activity of angiotensin-converting enzyme (r = 0.69, p < 0.001; r = 0.61, p < 0.001, respectively). Thus, the evaluation of these antigens' expression is an important clinical approach for the staging of the disease. However, no significant differences were found in CD3+CD25+, CD4+CD45RA+, or CD8+CD11+ cells in either peripheral blood or BAL fluid between the patients and volunteers. Our results indicated that in Japanese patients with sarcoidosis, circulating T cells are activated but CD25+ cells are not increased in peripheral blood and BAL fluid, but there is not a significant association with racial background.

Adult↗

[A case of eosinophilic pneumonia with elevated levels of carcino-embryonic antigen (CEA)].

A 70-year-old woman was admitted for productive cough and infiltrative shadows in the right lower lung field on chest X-ray film. Eosinophilia (17%) in blood, an abnormally high percentage of eosinophiles (7%) in bronchoalveolar lavage fluid and eosinophilic infiltration with proliferated goblet cells in transbronchial lung biopsy specimens led to the diagnosis of eosinophilic pneumonia. Laboratory data on admission also revealed a high level of CEA (17.1 ng/ml) in serum. After administration of prednisolone (30 mg/day), the symptoms ameliorated and the CEA levels were normalized. The proliferated goblet cells were immunohistochemically positive for CEA, which suggests that the high levels of CEA were caused by excessive CEA secretion from the goblet cells associated with eosinophilic pneumonia. These studies showed that serum CEA also may be a marker for disease activity in eosinophilic pneumonia.

Aged↗

[Association between diffuse panbronchiolitis and HTLV-I infection].

To determine whether HTLV-I infection is associated with diffuse panbronchiolitis (DPB), we investigated T-cell surface markers of peripheral blood and bronchoalveolar lavage fluid (BALF) in 9 healthy volunteers, 6 HTLV-I seronegative DPB patients (HTLV-I(-)DPB) and 8 HTLV-I seropositive DPB patients (HTLV-I(+)DPB). In peripheral blood, no significant difference was observed between HTLV-I(-)DBP and healthy volunteers. However, in BALF, HTLV-I(-)DPB showed a significant decrease of the CD4/CD8 ratio and an increase of CD8+HLA-DR+ cells compared with healthy volunteers. CD3+CD25+ and CD4+HLA-DR+ cells in peripheral blood were significantly increased in HTLV-I(+)DPB compared with those in HTLV-I(-)DPB. No significant difference was observed in BALF cells between HTLV-I(-) and HTLV-I(+)DPB with the exception of CD3+CD25+ cells. The most striking result was a marked elevation of CD3+CD25+ cells in 2 of 8 HTLV-I seropositive patients. Microscopic findings of open lung biopsy specimens obtained from the 2 patients differed from the typical microscopic findings in DPB. From these findings, we consider that HTLV-I infection may be associated with pulmonary lesions like DPB, but of a different, pathologically distinct, type.

Adult↗

[A case of idiopathic chylothorax--successful pleurodesis with OK-432].

A 73-year-old woman was referred to our hospital because of left pleural effusion. Chyle was obtained by thoracocentesis. Because there was no organic lesion to cause chylothorax, idiopathic chylothorax was diagnosed. Her condition improved by chest-tube drainage and pleurodesis with intrapleural injection of OK-432. We report a rare case of idiopathic chylothorax and conclude that pleurodesis with intrapleural injection of OK432 is very useful for the treatment of idiopathic chylothorax.

Aged↗

[A study of respiratory infection and sepsis caused by MRSA at Hokusho Central Hospital].

At Hokusho Central Hospital, we studied the isolation rate of methicillin-resistant Staphylococcus aureus (MRSA) from 1985 to 1989; respiratory infection with MRSA, in 1989; and sepsis of MRSA, from 1988 to 1989. The isolation rate of MRSA from sputum increased from 0% in 1985 to 65.4% in 1989. MRSA was isolated mainly from elderly patients in a geriatric ward, with 55 of 67 strains (82%) being isolated from these patients in 1989. MIC80 of isolated MRSA strains was 0.01 microgram/ml to rifampicin, 0.02 microgram/ml to mynomycine, 3.13 micrograms/ml to vancomycin, 12.5 micrograms/ml to ofloxacin and 100 micrograms/ml to imipenem in 1989. One-third of the 60 isolated cases showed respiratory infections including 10 cases of pneumonia and 10 sepsis patients and 11 blood samples in 1988 and 1989, especially 92.9% of S. aureus isolated in 1989 was MRSA. Four of the 6 patients with respiratory infections of MRSA and 1 of the 3 patients with MRSA sepsis were treated successfully by a combination therapy of imipenem/cilastatin and cefazolin.

Aged↗

[Effect of erythromycin on neutrophil adhesion molecules].

The mechanisms of erythromycin (EM) in chronic lower respiratory tract diseases including diffuse panbronchiolitis (DPB) has been reported. In this study we investigated the effect of EM on peripheral neutrophil adhesion molecules such as LFA-1 and Mac-1 obtained from six healthy subjects. Pretreatment of neutrophils with each concentration (10 ng/ml approximately 100 micrograms/ml) of EM resulted in no significant reduction in the expression of LFA-1 alpha, beta and Mac-1. Moreover, EM had no capability of reducing these expressions even when neutrophils were pretreated with 1 microgram/ml of EM at time from 0 to 60 min. These findings indicate that EM does not directly reduce the expression of LFA-1 alpha, beta and Mac-1 on peripheral neutrophil obtained from healthy subjects.

Adult↗

A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis.

Recently, "low-dose and long-term" erythromycin treatment has been reported as effective on diffuse panbronchiolitis (DPB), but its mechanism is still obscure. Patients with DPB were found to have significantly higher percentages of neutrophils in the pre-erythromycin treatment bronchoalveolar lavage fluid (BALF) than healthy nonsmoking volunteers (p < 0.001). They showed a significant reduction in BALF neutrophil percentages after erythromycin treatment (p < 0.01). The neutrophil chemotactic activity (NCA) was significantly elevated in BALF obtained from 19 patients with DPB compared with that from healthy volunteers (p < 0.001). A significant reduction in the NCA was observed in post-erythromycin treatment BALF of 11 patients with DPB (p < 0.001). Additionally, there was a significant correlation between the reduction of NCA and neutrophil percentage in pre- and post-erythromycin treatment BALF (r = 0.726, p < 0.05). Finally, we investigated the effect of erythromycin on the intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide (LPS) and interleukin-8 (IL-8) in mice. The intrapulmonary influx of neutrophils was significantly suppressed (p < 0.001) in mice intraperitoneally injected with erythromycin at 5 mg per animal 2 h before intratracheal injection of LPS (control group: 6.5 +/- 1.6 x 10(5) versus erythromycin-treated group: 1.7 +/- 0.5 x 10(5)), but not 10 h before lung challenge. This inhibition was observed at 6 h after lung challenge and became maximal with 84% suppression at 24 h. Week-long administration of erythromycin did not alter the intrapulmonary influx of neutrophils. The number of neutrophils in the peripheral blood was not affected by erythromycin, indicating that the drug was not toxic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Elevation of tumor-associated carbohydrate antigens in patients with diffuse panbronchiolitis.

We investigated the serum levels of the tumor-associated carbohydrate antigens sialyl SSEA-1 (SLX) and sialyl Lewis(a) (CA19-9) in patients with diffuse panbronchiolitis (DPB) and other nonmalignant lung diseases. Both antigens were high in the serum and bronchoalveolar lavage fluid (BALF) of patients with DPB, bronchiectasis (BE), idiopathic pulmonary fibrosis (IPF), and interstitial pneumonia associated with collagen vascular disease (CVD). Markedly high levels of the antigens were demonstrated in the serum and BALF from patients with DPB. An immunohistochemical study of open-lung biopsy specimens from patients with DPB indicated that these antigens were selectively expressed on the bronchiolar epithelial cells and mucinous exudates in airspaces. Low-dose, long-term erythromycin (EM) treatment was recently reported to be effective for DPB, and we investigated its influence on serum and BALF antigen levels in DPB patients. Antigen levels in both serum and BALF decreased after EM treatment, with improvement of symptoms and laboratory data, and there was a significant correlation between the reduction in the SLX level in serum and neutrophil percentage in BALF pre- and post-EM treatment. Our result suggests that secreted carbohydrate antigens from the bronchiolar epithelium in DPB may appear in the serum as a result of airway damage in the lower respiratory tract, and serum levels of the antigens may be decreased by a reduction in neutrophils in BALF after EM treatment.

Adult↗

[Studies of lymphocyte subpopulations of bronchoalveolar lavage fluid in HTLV-I seropositive patients with uveitis].

To determine whether HTLV-I infection is associated with uveitis, we investigated the bronchoalveolar lavage fluid (BALF) cells in 23 patients with uveitis. Of these, sarcoidosis was diagnosed in 13 patients, but could not be confirmed in the remaining 10 patients (non-sarcoidosis). Three of 13 patients (23.1%) with sarcoidosis and 7 of 10 non-sarcoidosis patients (70.0%) were HTLV-I seropositive. In BALF, no significant differences were observed between the HTLV-I seropositive and seronegative patients. However, in non-sarcoidosis patients, total cell counts, CD3+ and CD+ HLA-DR+ cells in BALF were significantly higher in seropositive patients than in seronegative patients. CD3+ CD25+ cells in BALF were markedly increased in 3 of 7 non-sarcoidosis seronegative patients. These findings indicated that BALF lymphocytes in HTLV-I seropositive non-sarcoidosis patients were more activated than those in seronegative non-sarcoidosis patients, supporting the hypothesis that HTLV-I infection may be associated with uveitis.

Adult↗

[Effect of erythromycin on intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide].

Recently, "low dose and long term" erythromycin (EM) treatment has been reported as effective on chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB). However the effective mechanism of EM is still obscure. In this study, we investigated the effect of EM on intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide (LPS), and the following results were obtained. 1) The intrapulmonary influx of neutrophils was significantly suppressed (p less than 0.001) in mice intraperitoneally injected with EM at 5 mg per animal 2 hr before intratracheal injection of LPS (control group: 6.5 +/- 0.8 x 10(5) vs EM-treated group: 1.7 +/- 0.3 x 10(5)), but not 10 hr before lung challenge. This inhibition was observed at 6 hr after lung challenge, and became maximum with 84% suppression at 24 hr. 2) The intrapulmonary influx of neutrophils was not affected when EM was injected intraperitoneally daily for 3, 7, or 14 days, and lung challenge was performed 24 hr after the final administration of EM. 3) The number of neutrophils in the peripheral blood was not affected by EM. These results suggest that EM treatment impairs the capacity for pulmonary inflammation by reducing, at least in part, the migration of neutrophils to inflammatory sites.

Animals↗

[Determination of the neutrophil chemotactic factor in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis].

It is well known that erythromycin (EM) therapy is effective on chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB). In this study we investigated the relationship between clinical findings and neutrophil chemotactic activity (NCA) in bronchoalveolar lavage fluid (BALF) in patients with DPB receiving orally EM therapy. The NCA in post-EM therapy BALF was significantly reduced (p less than 0.001) compared with that in BALF before EM therapy (30.17 +/- 7.84% vs 53.05 +/- 10.65%). On the respiratory function before and after EM therapy, DPB patients (20 cases) showed significant improvement of %VC, FEV1.0, RV/TLC (p less than 0.001, each) and V25 (p less than 0.05). And on the post-EM therapy blood gas, PaO2 and AaDO2 level were confirmed to be significantly improved (p less than 0.001). In addition, we examined the correlation between the improvement ratio of clinical finding and the reduction of NCA in BALF after EM therapy in 10 patients with DPB. We found the significant correlation between the improvement ratio of PaO2 and the reduction NCA in BALF of those patients (p less than 0.05). There were no significant relationships between the improvement ratio in other parameters as stated above and the reduction of NCA in BALF. These findings indicate that EM restrains the NCA in BALF of patients with DPB and impairs the accumulation of neutrophils in respiratory tract, ultimately contributes to the improvement of clinical symptoms such as sputum and clinical findings such as PaO2 in patients with DPB.

Adult↗