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Biomedical subjects

A Fu

Publications and source records attributed to A Fu.

At least 37 records · Page 2Linked to original sources

[Photomicrographs of a pleural biopsy specimen, showing malignant mesothelioma and necrosis--malignant pleural mesothelioma in a patient with sarcoidosis].

A 45-year-old woman was admitted to Nara Medical University Hospital because of right-sided chest pain. Both a chest X-ray film and a chest CT scan revealed bilateral hilar and mediastinal lymphadenopathy and right pleurisy. She underwent fiberoptic bronchoscopy and mediastinoscopy. Biopsy specimens of the lung and mediastinal lymph nodes showed non-caseous epithelioid cell granulomas. After on ophthalmologic examination, she was given a diagnosis of sarcoidosis with a pleural lesion and uveal involvement. The pleurisy become less severe and the lymph nodes shrank without any treatment. About one year later, she complained of right-sided chest pain again and a chest X-ray film revealed diffuse thickening of the pleural on the right side. Examination of pleural biopsy specimens revealed malignant mesothelioma. We know of no previous report from Japan of malignant pleural mesothelioma in a patient with sarcoidosis.

Biopsy↗

[The relation between diabetes mellitus and IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and monocytes in patients with pulmonary tuberculosis].

Diabetics are prone to bacterial infection in part, due to polymorphonuclear neutrophil dysfunction, but the precise mechanism is not yet fully explained. Of many complications, diabetes mellitus (DM) is one of the most common diseases, which causes pulmonary tuberculosis. To elucidate the mechanism of susceptibility to tuberculosis infection in patients with diabetes mellitus, we measured IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and autologous monocytes stimulated with live BCG in patients with pulmonary tuberculosis complicated with DM (TB + DM) or without DM (TB) and healthy controls. The levels of IFN-gamma and IL-12 production in TB patients were significantly lower than those in the control. These cytokine productions were also lower in TB + DM patients than in TB patients significantly. The level of IL-10 production in TB patients were highest among these three groups. The production of this cytokine in TB + DM patients was lowest. The level of IFN-gamma production was significantly lower in TB + DM patients under poor DM control than in those patients under good DM control and showed a significant negative correlation to HbA1c, an indicator of diabetic control. The period for negative conversion of culture finding in TB + DM patients under poor control was prolonged when compared with those in TB patients. These results demonstrated the difference in cytokines secretion profile between TB patients and TB + DM patients, and suggest that the immunological mechanism underlying pathogenesis of tuberculosis might work differently between these two patients groups.

Adult↗

[The relationship between a decrease in fat mass and serum levels of TNF-alpha in patients with chronic obstructive pulmonary disease].

To investigate the relationship between malnutrition and TNF-alpha levels in patients with chronic obstructive pulmonary disease (COPD), we measured concentrations of TNF-alpha in serum from fifty four patients with stable COPD. The patients were divided into three groups, according to ideal body weight (IBW): group A, %IBW > or = 90; group B, 90 > %IBW > or = 80; group C, %IBW < 80. Serum TNF-alpha levels in group C were significantly higher than in group A (mean +/- SD; 3.00 +/- 0.43 pg/ml and 2.25 +/- 0.29 pg/ml, respectively, p < 0.0001), group B (2.41 +/- 0.47 pg/ml, p < 0.001), and healthy controls (2.33 +/- 0.30 pg/ml, p < 0.001) who were age- and %IBW-matched with patients in group C. Sixteen patients with COPD underwent body composition analysis by dual energy X-ray absorptiometry. Serum TNF-alpha levels in patients with COPD significantly correlated with fat mass (r = -0.67, p < 0.001). No association was observed between lean mass and serum TNF-alpha levels. These data suggest that TNF-alpha is involved with malnutrition in patients with COPD, and that TNF-alpha may cause a decrease in fat mass in patients with COPD.

Absorptiometry, Photon↗

[CD4+ alpha beta T cell and gamma delta T cell responses to BCG in patients with pulmonary tuberculosis--comparison with healthy controls].

We demonstrated that CD4+ alpha beta (CD4+) and gamma delta T cell subsets from healthy donors had similar effector functions (cytotoxicity and cytokine production) in response to mycobacterial antigens, despite differences in the antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis, this study was undertaken to compare T cell functions between patients with pulmonary tuberculosis with no complications and healthy controls. Both resting and activated CD4+ and gamma delta T cells from the patient group proliferated in response to live BCG at a significantly lower rate than those from the control group. The cytotoxicity of BCG-pulsed monocytes and IFN-gamma production in both the CD4+ and gamma delta T cells from patients was significantly lower than those of controls. In contrast to IFN-gamma, significantly higher IL-10 production by both CD4+ and gamma delta T cells from patients was detected. The proliferative responses to BCG by CD4+ and gamma delta T cells from patients after antituberculous therapy were partially restored, but remained at lower levels compared with controls. These results suggest that not only a general deterioration in CD4+ and gamma delta T cells effector functions, but also suppressive factors (such as IL-10) might be responsible for the pathogenesis of pulmonary tuberculosis, and that the low response to BCG by both CD4+ and gamma delta T cells in patients with tuberculosis is in part attributable to patient predisposition.

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↗

[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↗

[Analysis of body composition by dual energy X-ray absorptiometry and its relation to pulmonary function in patients with pulmonary emphysema].

The purpose of this study was to investigate body composition in patients with chronic obstructive pulmonary disease, and its relation to pulmonary function. Seventeen men with pulmonary emphysema who were being treated as outpatients were divided into three groups, according to ideal body weight (IBW): group A, %IBW > or = 90%; group B, 90 > %IBM > or = 80; and group C, %IBW < 80. All underwent body composition analysis by dual energy X-ray absorptiometry. Fat mass and bone mineral content were significantly lower in groups B and C than in control subjects. Lean mass was significantly lower in group C than in control subjects. By contrast, group A did not differ significantly from control subjects. Lean mass correlated significantly with %VC, FEV1, RV/TLC, and MVV. These data suggest that lean mass is low in moderately and severely malnourished patients, that bone mineral content and fat mass are low in mildly malnourished patients, and that abnormal body composition is associated with ventilatory impairment in patients with chronic obstructive pulmonary disease.

Absorptiometry, Photon↗

[Allergic granulomatous angiitis in a patient with positive reactions on serological tests for parasite antigens].

A 68-year-old woman with bronchial asthma complained of fever, right thigh pain, sensory disturbance at the tips of the upper and lower limbs, and abdominal pain. She had severe eosinophilia and radiologic examination showed a mass-like shadow in the left lower lobe of the lung. Allergic granulomatous angiitis was diagnosed on the basis of findings from a muscle biopsy (gangrenous vasculitis with eosinophilia). This patient also had positive results of serological tests (Ouchterlony method) for various parasite antigens, despite the fact that no eggs of parasites were found in her feces. After steroid administration, the serological reactivity to parasite antigens had decreased. The positive reactions to parasite antigens was probably related to the cause of the vasculitis.

Aged↗

[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↗

[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↗

Isolation and characterization of two herpes simplex virus type 1 variants containing duplication of sequences within the unique long component of their genomes.

This paper reports the first spontaneous isolation of two DNA duplication variants in the unique long (UL) component of herpes simplex virus type 1 (HSV-1) strain 17+ genome, one (1719) with a duplication of 7.5 kb DNA sequences centered around OriL and the other (1740In) with a 356 bp DNA duplication between the UL19 (MCP) and UL20 open reading frames (ORFs). The variant 1719 is stable with the rare isolation of a wild type (strain 17+) genome presumably generated by the excision of the duplicated sequences during homologous recombination. Because of the 7.5 kb duplication, UL29 (DBP) is diploid and UL30 (DNA pol) is present as one complete and one partial copy. Although duplication in the variant 1740In involved sequences from the UL20 ORF, the virus produces an intact UL20 gene product. Both variants show normal growth characteristics when compared with the parental viruses. DNA duplications in these variants suggest a link between replication and recombination in HSV-1.

Amino Acid Sequence↗

[Diagnostic value of tissue polypeptide antigen in pleural effusions with malignant pleural mesothelioma].

There are no known tumor makers of malignant pleural mesothelioma. We measured the concentration of TPA in the pleural effusions from patients with malignant pleural mesothelioma and from patients with other pleural diseases, evaluate its clinical usefulness. The concentration of TPA was more than 7,000 U/l (mean: 18,600 +/- 9,867 U/l, n = 5) in all patients with malignant pleural mesothelioma, but it was less than 4,000 U/l in those with benign asbestos pleurisy and other benign pleural effusion (benign asbestos pleurisy 1,598 +/- 570, n = 5: p < 0.01, tuberculous pleurisy 1.37 +/- 759, n = 11: p < 0.01, others 2,497 +/- 2,152 n = 3: p < 0.05). The concentration of TPA in the pleural effusions was not significantly different between malignant pleural mesothelioma and lung cancer (12,287 +/- 17,070 U/l). However, in all patients with lung cancer and high TPA concentrations, cytologically malignant cells were detected in the pleural effusions. TPA was high in all five patients with malignant pleural mesothelioma, but cytologically malignant cells were detected in only one patient. Only in malignant pleural mesothelioma (not in other benign disease or in lung cancer) was the concentration of TPA more than 4,000 U/l, and no evidence of malignancy was obtained by cytological methods. These findings suggest that assessing TPA in the pleural effusion might contribute to the diagnosis of malignant pleural mesothelioma.

Adult↗

[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 granule-independent lytic mechanism used by CTL hybridomas.

The mechanism(s) by which CTL induce target cell lysis have not been clearly elucidated. Perforin and the cytotoxic cell proteinases (granzymes) contained within the granules of CTL and NK, have been implicated, but abundant evidence for the existence of alternate lytic pathways has accumulated. In this report we characterize the mechanism of killing used by two cytolytic hybridomas (PMM-1 and MD90) that express neither perforin nor the granzymes. These characteristics are compared with results obtained by using a representative Ag-dependent, granule-containing T cell clone in cytolysis assays. The major differences were that the granule-negative hybridomas could lyse a variety of target cells in the presence of cyclosporin and the absence of calcium. All the effectors could kill in the presence of protein synthesis inhibitors (cycloheximide and emetine) and induced DNA fragmentation in the target cells. The cytolytic hybridomas had to be stimulated to be cytolytic and this activation required the presence of calcium, was dependent on protein synthesis, and inhibited by the addition of cyclosporin. Although TNF was shown not be involved, the sensitivity of the target cells to lysis by the granule-negative killers correlated with the level of expression of Fas Ag. With the use of L1210 and an L1210 cell line transfected with Fas cDNA we demonstrated that these MD90 and PMM-1 kill the latter much more effectively and that this increase was effectively inhibited with anti-Fas Ab. Furthermore the lack of sensitivity to cyclosporin, cycloheximide, emetine, and EGTA was confirmed with these targets. We conclude that these two cytolytic hybridomas use the Fas lytic pathway to induce lysis in target cells.

Animals↗

Hyperzincuria in individuals with insulin-dependent diabetes mellitus: concurrent zinc status and the effect of high-dose zinc supplementation.

The urinary excretion of zinc in individuals with insulin-dependent diabetes mellitus (IDDM) is approximately doubled. In the absence of a compensatory mechanism, this hyperzincuria should induce a deficient or marginal Zn status. We examined parameters of Zn status in plasma and in blood cells with respect to urinary Zn losses and Zn supplementation. We measured Zn levels in the urine, plasma, and erythrocytes of 14 IDDM subjects and 15 nondiabetics who kept dietary records for 3 consecutive days. Subsequently, six IDDM subjects and seven nondiabetics were supplemented with 50 mg Zn daily for 28 days. We measured the above parameters, as well as mononuclear leukocyte Zn (MNL-Zn) and the plasma subfraction of albumin-bound Zn (alb-Zn). The total plasma Zn-binding capacity was also assessed. Plasma copper and erythrocyte Cu were monitored as indicators of potential Zn toxicity. Individuals with IDDM displayed the expected hyperzincuria, but had normal blood Zn parameters. Zincuria increased by a similar amount in both groups during supplementation, as did the MNL-Zn content. However, erythrocyte Zn (e-Zn) was refractory, so a trend toward lower e-Zn among IDDM subjects persisted during Zn supplementation. Hemoglobin A1c (HbA1c) increased markedly in the Zn-supplemented IDDM group. Despite their chronic hyperzincuria, individuals with IDDM appear not to be Zn-deficient. Large-dose Zn supplementation increases MNL-Zn and induces an undesirable elevation of HbA1c in all individuals. This is especially disconcerting for those with IDDM, and may reflect an exacerbation of a chronic "Zn diabetes." These data suggest a potential for toxicity from large-dose Zn supplementation.

Adult↗