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Biomedical subjects

K Tsukaguchi

Publications and source records attributed to K Tsukaguchi.

At least 37 records · Page 2Linked to original sources

[Two cases of generalized disseminated atypical mycobacterium showing multiple accumulations on bone scintigraphy].

For determining the spread of multiple bone lesions in generalized disseminated atypical mycobacteriosis a rare disease, bone scintigraphy was found useful in our two patients. They were both female, and the pathogenic microbe was M. avium intracellulare complex. The disease appeared to have been induced by defatigation. The depression of cellular immunocompetence was also suspected to be responsible. Bone scintigraphy disclosed multiple abnormal accumulations systematically. The Definitive diagnosis in these cases was established by biopsy. In differential diagnosis of this disease by bone scintigraphy, bone metastasis of a malignant tumor was considered of primary importance. Although antitubercular chemotherapy resulted in improvement of subjective symptoms and inflammation, abnormal accumulation persisted. There was necessity for taking notice that in the decision of the treatment effect of this disease, improvement of abnormal accumulations on bone scintigraphy was delayed that of inflammatory reaction.

Aged↗

[Interleukin-8 in sputum from patients with pulmonary emphysema].

We measured concentrations of interleukin-8 (IL-8) in sputum from 38 patients with pulmonary emphysema, from 30 patients with bronchial asthma, and in induced sputum from 10 healthy subjects. Concentrations of IL-8 were significantly higher in sputum from patients with emphysema than in sputum from patients with asthma (mean +/- SE: 22,961 +/- 1,412 pg/ml and 9,135 +/- 1,590 pg/ml, respectively, p<0.0001) and were also higher than in sputum from healthy subjects (3,253+/-687 pg/ml, p<0.0001). Concentrations of IL-8 in sputum from patients with emphysema were unrelated to whether the patient was a current smoker or an ex-smoker, and did not correlate with concentrations of IL-8 in serum. Concentrations of IL-8 in sputum from patients with emphysema correlated significantly with FEV1% (r=-0.78, p<0.0001) and with %RV/TLC (r=0.63, p<0.01). These data suggest that IL-8 is mainly involved in chronic airway inflammation and that concentrations of IL-8 in sputum are closely related to airflow obstruction in patients with pulmonary emphysema.

Female↗

[Investigation of soluble tumor necrosis factor receptor in patients with active tuberculosis].

It is assumed that soluble tumor necrosis factor receptor I and II (sTNF-RI, II) play important roles in the regulation of tumor necrosis factor alpha (TNF-alpha) activity. We measured the levels of circulating sTNF-R in patients with active pulmonary tuberculosis (n = 31) and the correlation between TNF-alpha and sTNF-R in serum level was investigated. We also compared sTNF-R levels before and after the treatment in 7 cases. Significant increase of circulating sTNF-R were found in patients with tuberculosis compared with the normal controls (n = 28) (p < 0.01). Moreover, significant positive correlations were found between TNF-alpha and sTNF-R I and II (r = 0.520, r = 0.553) in serum comparing sTNF-R levels before and after the treatment for patients with tuberculosis, significant fall was found in sTNF-R I, but not in sTNF-R II. As a result, it is suggested that sTNF-R regulates TNF-alpha activity in patients with tuberculosis, and that sTNF-R I levels could be used as one of the indices to evaluate the clinical activity of tuberculosis.

Adult↗

[Interaction between nutrition and production of IL-1 beta, TNF alpha, and IL-6 by peripheral blood monocytes in patients with lung cancer].

Altered nutrient intake and metabolism are responsible for the progressive loss of body weight observed in most patients with advanced cancer, but the precise mechanism is still controversial. Under stressful conditions, some inflammatory cytokines such as IL-1 beta, TNF alpha, and IL-6 have a hypermetabolic effect and cause proteolysis and lipolysis in muscle and in fat tissues. To elucidate the mechanism of malnutrition in patients with lung cancer and normal food intake, we focused on the relationship between abnormal metabolism and these inflammatory cytokines. Patients with lung cancer were confirmed to be malnourished, and this malnutrition was found to be caused by hypermetabolism as estimated with visceral proteins, plasma levels of amino acids, and anthropometric indices. The production of IL-1 beta, TNF alpha, and IL-6 by blood monocytes was significantly higher in these patients than in healthy controls, and it correlated significantly and inversely with indices of nutrition. The present results suggest that nutritional status and these cytokines are closely related in patients with lung cancer. IL-1 beta, TNF-alpha, and IL-6 may serve as anti-cancer bioactive molecules, but "overfunctioning" of these cytokines may induce a hypermetabolic status that causes malnutrition, i.e. cancer cachexia.

Adult↗

[Clinical benefit of nutritional assessment and support in patients with chronic obstructive pulmonary disease].

Weight loss is common in patients with chronic obstructive pulmonary disease (COPD). Comprehensive nutritional assessment was conducted in two large groups of patients with COPD who were enrolled in the Respiratory Failure Research Program sponsored by the Japanese Ministry of Health and Welfare and the Kinki COPD Research Group. The incidences of mild malnutrition (%IBW < 90%) were 74% and 62%, respectively. The incidences of hypoalbuminemia were low: 10.0% and 6.5%, respectively. The incidence of imbalance in plasma amino acids, which was defined as an abnormally low BCAA/AAA ratio, was as high as 93% in patients with COPD and chronic respiratory failure. The %IBW was significantly related to the FEV1 and to the DLco/VA. The moderately-malnourished subpopulation was characterized by a greater degree of hyperinflation and hypercapnea: the measured resting energy expenditure (REE) was significantly higher than the values in age-matched healthy controls. REE/REEpred was significantly and inversely related to BCAA/AAA and to Pimax. REE was inversely related to FEV1%. REE in the subgroup with severe hyperinflation was significantly higher than REE in those with milder hyperinflation. Among patients with an FEV1% of less than 50%, mortality tended to be higher in those with lower body weight, and this relationship was stronger in patients with an FEV1% of more than 50%. When patients were given a BCAA-enriched enteral formula in addition to their usual diet for 3 months, there was a significant increase in body weight, transferrin level, and Pimax.

Amino Acids, Branched-Chain↗

CD4+ alpha beta T cell and gamma delta T cell responses to Mycobacterium tuberculosis. Similarities and differences in Ag recognition, cytotoxic effector function, and cytokine production.

CD4+ and gamma delta T cells are activated readily by Mycobacterium tuberculosis. To examine their role in the human immune response to M. tuberculosis, CD4+ and gamma delta T cells from healthy tuberculin-positive donor were studied for patterns of Ag recognition, cytotoxicity, and cytokine production in response to M. tuberculosis-infected mononuclear phagocytes. Both T cell subsets responded to intact M. tuberculosis and its cytosolic Ags. However, CD4+ and gamma delta T cells differed in the range of cytosolic Ags recognized: reactivity to a wide m.w. range of Ags for CD4+ T cells, and a restricted pattern for gamma delta T cells, with dominance of Ags of 10 to 15 kDa. Both T cell subsets were equally cytotoxic for M. tuberculosis-infected monocytes. Furthermore, both CD4+ and gamma delta T cells produced large amounts of IFN-gamma: mean pg/ml of IFN-gamma in supernatants was 2458 +/- 213 for CD4+ and 2349 +/- 245 for gamma delta T cells. By filter-spot ELISA (ELISPOT), the frequency of IFN-gamma-secreting gamma delta T cells was one-half of that of CD4+ T cells in response to M. tuberculosis, suggesting that gamma delta T cells on a per cell basis were more efficient producers of IFN-gamma than CD4+ T cells. In contrast, CD4+ T cells produced more IL-2 than gamma delta T cells, which correlated with diminished T cell proliferation of gamma delta T cells compared with CD4+ T cells. These results indicate that CD4+ and gamma delta T cell subsets have similar effector functions (cytotoxicity, IFN-gamma production) in response to M. tuberculosis-infected macrophages, despite differences in the Ags recognized, IL-2 production, and efficiency of IFN-gamma production.

Antigens, Bacterial↗

[Studies on production of interleukin-1 beta (IL-1 beta) and granulocyte. Macrophage-colony stimulating factor (GM-CSF) by peripheral blood monocytes from patients with Mycobacterium avium-intracellulare complex (MAC) infection].

Production of Interleukin-1 beta (IL-1 beta) and granulocyte macrophage-colony stimulating factor (GM-CSF) by peripheral blood monocytes (PBMs) from patients with Mycobacterium avium-intracellulare complex (MAC) infection was assessed and the relationship with their clinical course was analyzed. PBMs were obtained from MAC-infected patients in their active stage as well as in the inactive stage and the healthy controls. Spontaneous release of IL-1 beta by PBMs from patients in the active stage was higher than those by the cells in the inactive stage or the healthy controls. On the other hand, spontaneous GM-CSF release by PBMs from patients in the active stage was higher than the healthy controls. When PBMs were stimulated with MAC-derived purified protein derivatives (PPD-B), increased production of both IL-1 beta and GM-CSF were obtained for PBMs in their active stage. While these enhanced production upon stimulation with PPD-B related to the persistent infection with MAC, the increased IL-1 beta production correlated with the exhausted nutritional state. Both IL-1 beta and GM-CSF produced by PBMs seemed to be closely related with the clinical course of human MAC infection.

Aged↗

[The evaluation of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) level in peripheral blood of patients with active pulmonary tuberculosis].

We investigated the serum level of IL-8 and TNF-alpha using ELISA in 16 patients with active pulmonary tuberculosis before administration of antituberculous drugs and in age-, smoking habit-matched 20 healthy controls. The mean level of serum IL-8 in patients with active pulmonary tuberculosis was significantly higher than that in healthy controls (P < 0.001). The mean level of serum TNF-alpha in tuberculosis patients was also high, while TNF-alpha was not detectable in the sera of healthy controls. We also examined the relationship between clinical pictures mainly defined by radiographic findings and the serum levels of IL-8 and TNF-alpha. The serum IL-8 level of 9 patients with tuberculous cavity is significantly higher than that of 7 patients without cavity. (P < 0.05) We classified the patients with cavities into two subgroups according to the radiographic classification of the Japanese Society of Tuberculosis. Four patients with advanced lesions on chest X-ray showed higher serum IL-8 level than 5 patients with moderate lesions (P < 0.05). On the other hand, there was no correlation between serum TNF-alpha level and radiographic findings. These results suggest that IL-8 appears to be involved in the formation of tuberculous cavitary lesion.

Adult↗

[Production of tumor necrosis factor alpha and interleukin-6 by peripheral monocytes from patients with atypical mycobacteriosis--relationship to clinical activity].

The production of tumor necrosis factor alpha (TNF alpha) and of interleukin-6 (IL-6) by peripheral blood monocytes (PBMs) from patients infected with Mycobacterium avium intracellular complex (MAC) were assessed. Spontaneous release of both TNF alpha and IL-6 were greater during the active stage than during the inactive stage and in healthy controls. When the cells were stimulated with MAC-derived purified protein derivative B (PPD-B). TNF alpha production by PBMs in the active stage increased and IL-6 production by cells in both the active and inactive stages decreased. Moreover, the in vitro increase in TNF alpha production after stimulation in the active stage seemed to be related to the persistent MAC infection, which resulted in an exhaustion of nutrition. These results suggest that the ability of PBMs to produce TNF alpha and IL-6 in vitro is closely related to the clinical stage of MAC infection.

Aged↗

[Studies on mucociliary transport in patients with pulmonary atypical mycobacteriosis--by aerosol inhalation cine-scintigraphy].

Mucociliary transport (MCT) was studied in 22 patients with atypical mycobacteriosis (Group I : 16 with M. avium-intracellulare complex (MAC), Group II : 6 with M. kansasii) by aerosol inhalation cine-scintigraphy. In most of the patients, the MCT was abnormally slow both in the main bronchus and in the trachea, while in healthy controls the transport of the inhaled aerosol in the bronchus and the trachea were rapid and smooth. In both groups, the tracheal MCT was impaired in two thirds of the patients, while the MCT in the main bronchus was impaired in all except one in Group I and in two-thirds in Group II. The results indicate that the grade of bronchial impairment was higher in MAC than in M. kansasii infections. In atypical mycobacteriosis, especially in MAC infections, such impairment of MCT could be closely related to the disruption of local defence mechanisms in the airways.

Adult↗

[Pulmonary infection due to Mycobacterium szulgai associated with multiple bullous disease of the lung].

A 46-years-old male was admitted to our hospital because of productive cough and infiltrates on the chest roentogenogram. The patient had a history of left upper bullectomy ten years prior to the admission. The CT scan of the chest on admission showed infiltrats with cavitation in the left apex and multiple bullae in almost whole lung. Microscopical examination of smears of sputum and bronchoalveolar lavage fluid revealed acid-fast bacilli. They were identified as Mycobacterium szulgai by DNA-DNA hybridization method. The patient was treated with isoniazid, streptomycin and rifampicin. After treatment for about a month, the culture of sputum converted to negative for M. szulgai. After about three months hospitalization, the infiltrates decreased and the cavity wall became thin, and no recurrence sign has been observed after the discharge. There are a few case reports of pulmonary infection due to M. szulgai associated with bullous disease of the lung in Japan.

Anti-Bacterial Agents↗

Characterization of a 10- to 14-kilodalton protease-sensitive Mycobacterium tuberculosis H37Ra antigen that stimulates human gamma delta T cells.

gamma delta T-cell receptor-bearing T cells (gamma delta T cells) are readily activated by intracellular bacterial pathogens such as Mycobacterium tuberculosis. The bacterial antigens responsible for gamma delta T-cell activation remain poorly characterized. We have found that heat treatment of live M. tuberculosis bacilli released into the supernatant an antigen which stimulated human gamma delta T cells. gamma delta T-cell activation was measured by determining the increase in percentage of gamma delta T cells by flow cytometry in peripheral blood mononuclear cells stimulated with antigen and by proliferation of gamma delta T-cell lines with monocytes as antigen-presenting cells. Supernatant from heat-treated M. tuberculosis was fractionated by fast-performance liquid chromatography (FPLC) on a Superose 12 column. Maximal gamma delta T-cell activation was measured for a fraction of 10 to 14 kDa. Separation of the supernatant by preparative isoelectric focusing demonstrated peak activity at a pI of < 4.0. On two-dimensional gel electrophoresis, the 10- to 14-kDa FPLC fraction contained at least seven distinct molecules, of which two had a pI of < 4.5. Protease treatment reduced the bioactivity of the 10- to 14-kDa FPLC fraction for both resting and activated gamma delta T cells. Murine antibodies raised to the 10- to 14-kDa fraction reacted by enzyme-linked immunosorbent assay with antigens of 10 to 14 kDa in lysate of M. tuberculosis. In addition, gamma delta T cells proliferated in response to an antigen of 10 to 14 kDa present in M. tuberculosis lysate. gamma delta T-cell-stimulating antigen was not found in culture filtrate of M. tuberculosis but was associated with the bacterial pellet and lysate of M. tuberculosis. These results provide a preliminary characterization of a 10- to 14-kDa, cell-associated, heat-stable, low-pI protein antigen of M. tuberculosis which is a major stimulus for human gamma delta T cells.

Antigens, Bacterial↗

[Responsiveness of lymphocytes from patients with M. avium-intracellulare complex (MAC) infection to PPDs as measured by IFN-gamma production].

We investigated the responsiveness of peripheral blood lymphocytes (PBLs) from patients with M. avium-intracellulare complex (MAC) infection to the stimulation with PPDs by measuring their IFN-gamma producing ability. PBLs were obtained from MAC patients at active stage (culture-positive after three-month chemotherapy), those at inactive stage (culture-negative for three months after or during chemotherapy), and healthy donors. PPDs used were PPD-S prepared from M. tuberculosis, PPD-B from M. intracellulare, and PPD-Y from M. kansasii. PBLs from active MAC patients did not produce IFN-gamma to a significant extent by stimulation with any of three PPDs, while PBLs from inactive MAC patients showed higher responses to each PPD compared to those from active patients. In inactive MAC patients, the maximal response was observed to PPD-B among three PPDs. On the other hand, PBLs from healthy controls produced different levels of IFN-gamma in response to three different PPDs, and their response was most remarkable to PPD-S. These results indicated that the responsiveness of patients' PBLs to PPDs was impaired during active stage of MAC infection and restored on recovery from the disease.

Adult↗

[Anorexia nervosa complicated with pulmonary tuberculosis].

A study was made on a patient with anorexia nervosa complicated with pulmonary tuberculosis treated with intravenous hyperalimentation (IVH). A 24-year-old female was admitted to our hospital because of progressive loss of body weight during medication for pulmonary tuberculosis at another hospital. She was diagnosed as having anorexia nervosa. After the nutritional assessment IVH was performed. As a result of IVH, her body weight increased and her nutritional deprivation, (i.e., low visceral proteins, low branched amino acids, etc.) recovered. Nutritional support was effective upon treating pulmonary tuberculosis.

Adult↗

[Tumor necrosis factor alpha in bronchoalveolar lavage fluid and its production by alveolar macrophages with asbestos exposure].

It is generally accepted that asbestos exposure causes pulmonary fibrosis and carcinogenesis. Several studies have suggested that TNF alpha is produced principally by mononuclear phagocytes and that it may play a role in inflammation, fibrosis and anti-tumor activity. We studied TNF alpha production by alveolar macrophages and the TNF alpha concentration in bronchoalveolar lavage fluid harvested from asbestos-exposed subjects and healthy controls. TNF alpha production by alveolar macrophages was significantly higher in the asbestos-exposed subjects than in healthy controls (3696 +/- 1606, 1938 +/- 753 pg/ml; p < 0.01). The period from first exposure correlated inversely with TNF alpha production (r = -0.6; p < 0.05). The TNF alpha concentration in bronchoalveolar lavage fluid was also significantly higher in the asbestos-exposed subjects than in healthy controls. These results suggest that abnormal TNF alpha production by alveolar macrophages may be related to fibrosis and carcinogenesis due to asbestos.

Adult↗

[Relationship between nutritional depletion and cell-mediated immune function in active pulmonary tuberculosis].

A survey on the nutritional status and cell-mediated immune function of 47 hospitalized patients with active pulmonary tuberculosis and healthy controls was conducted. In the patients group: 1) Anthropometric measurements, such as %ideal body weight (%IBW), %arm circumference (%AC), %arm muscle circumference (%AMC) and %triceps skin fold (%TSF), were significantly reduced. 2) Visceral proteins including serum albumin (Alb), transferrin (Tf), prealbumin (PA) and retinol binding protein (RBP) were significantly reduced. 3) The imbalance of plasma amino acids, which was characterized by the depression of Fischer ratio, a molar ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA), was observed. Fischer ratio was significantly correlated with anthropometric measurements (%IBW, %AC and %AMC). Delayed-type hypersensitivity to DNCB (2,4-dinitrochlorobenzene) and lymphocyte transformation to phytohemagglutinin (PHA) and concanavalin A (Con A) were significantly impaired in the patients group, whereas NK cell activity was higher than that of controls. Alb, PA, RBP and Fischer ratio were significantly lower in the patients with reduced DNCB reaction than in those with normal responses. Lymphocyte transformation was significantly correlated with Fischer ratio, and NK cell activity was significantly correlated with Alb, PA, RBP. These data may suggest that the imbalance of plasma amino acids represented by the reduction of Fischer ratio and the depletion of visceral proteins are closely related to the impairment of lymphocyte function in the patients with active pulmonary tuberculosis.

Adult↗

[Clinical features of primary and secondary atypical mycobacteriosis].

A clinical investigation was carried out in 39 patients with atypical mycobacteriosis (AM). The patients at our hospital diagnosed as having AM during an 11-year period from 1981 to 1991 were reviewed in this study. The incidence of AM among all of mycobacterial infections has been increasing since 1988. The atypical mycobacteria detected included M. avium complex (MAC) in 79%, M. kansasii in 26%, and other organisms in 5%. Patients who had primary infection without underlying respiratory disease were compared with those who had secondary infection. In secondary infection, MAC was detected in the sputum of a high percentage of patients and was positive for more than 6 months despite therapy. Gamma globulin levels were also increased in patients with secondary infection. Cell mediated immunity was examined by the DNCB reaction and the detection of CD4- and CD8- positive T lymphocytes. The DNCB skin reaction was positive in 6 out of 26 patients with secondary infection. The percentage of CD8- positive T lymphocytes was higher in patients with secondary disease. Fischer's ratio (indicating the balance of plasma amino acids) was also examined as an index of the nutritional status. It was significantly lower in secondary infection compared with primary infection. Moreover, secondary infection was associated with a lower positive rate for the DNCB skin reaction and a lower Fischer's ratio when compared with pulmonary tuberculosis. Thus impairment of cell-mediated immunity, malnutrition, and a poor prognosis were significantly more common in secondary infection compared with primary infection.

Adolescent↗

[An autopsy case of atypical mycobacteriosis accompanied with chest wall deformity].

An autopsy case of 63-year old male of atypical mycobacteriosis with severe scoliosis was reported. He was diagnosed as atypical mycobacteriosis in 1981 and controlled by antimycobacterial treatment. But since 1989, dyspnea and sputum have been increasing, new abnormal shadow in company with progression of curvature of the scoliosis was revealed on the chest roentgenogram. In spite of various treatments for mycobacteriosis, he died of respiratory failure. The aggravation of this mycobacteriosis brought on advancement of malnutrition and impairment of cell mediated immunity. Findings of autopsy showed the remarkable chest wall deformity and tuberculous change of the lung parenchyma. In this case, chest deformity was thought as the major risk factor of onset of mycobacterial mycobacteriosis.

Humans↗