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Biomedical subjects

A Fu

Publications and source records attributed to A Fu.

At least 19 recordsLinked to original sources
PubMed2001

Functional cloning of Src-like adapter protein-2 (SLAP-2), a novel inhibitor of antigen receptor signaling.

In an effort to identify novel therapeutic targets for autoimmunity and transplant rejection, we developed and performed a large-scale retroviral-based functional screen to select for proteins that inhibit antigen receptor-mediated activation of lymphocytes. In addition to known regulators of antigen receptor signaling, we identified a novel adaptor protein, SLAP-2 which shares 36% sequence similarity with the known Src-like adaptor protein, SLAP. Similar to SLAP, SLAP-2 is predominantly expressed in hematopoietic cells. Overexpression of SLAP-2 in B and T cell lines specifically impaired antigen receptor-mediated signaling events, including CD69 surface marker upregulation, nuclear factor of activated T cells (NFAT) promoter activation and calcium influx. Signaling induced by phorbol myristate acetate (PMA) and ionomycin was not significantly reduced, suggesting SLAP-2 functions proximally in the antigen receptor signaling cascade. The SLAP-2 protein contains an NH2-terminal myristoylation consensus sequence and SH3 and SH2 Src homology domains, but lacks a tyrosine kinase domain. In antigen receptor-stimulated cells, SLAP-2 associated with several tyrosine phosphorylated proteins, including the ubiquitin ligase Cbl. Deletion of the COOH terminus of SLAP-2 blocked function and abrogated its association with Cbl. Mutation of the putative myristoylation site of SLAP-2 compromised its inhibitory activity and impaired its localization to the membrane compartment. Our identification of the negative regulator SLAP-2 demonstrates that a retroviral-based screening strategy may be an efficient way to identify and characterize the function of key components of many signal transduction systems.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Plasma levels of amino acids and hypermetabolism in patients with chronic obstructive pulmonary disease.

Plasma levels of amino acids were measured by ion-exchange, high-pressure liquid chromatography in 30 ambulatory patients with chronic obstructive pulmonary disease (COPD; mean +/- SD: age 64 +/- 13 y and forced expiratory volume in 1 s [FEV1] 0.85 +/- 0.25 L) and 30 age- and sex-matched healthy control subjects with regard to nutritional status, resting energy expenditure (REE), and pulmonary function. The ratio of branched-chain amino acids to aromatic amino acids was significantly (P < 0.001) decreased in COPD patients and was significantly correlated with percentage of ideal body weight (r = 0.403, P < 0.05), percentage of arm-muscle circumference (r = 0.492, P < 0.01), and %FEV1 (r = 0.467, P < 0.05). Plasma levels of alanine and cysteine were decreased, whereas levels of glutamine, aspartic acid, serine, and ornithine were elevated in COPD patients as opposed to control subjects. The ratio of resting energy expenditure to predicted resting energy expenditure was negatively correlated with the ratio of branched-chain to aromatic amino acids (r = -0.716, P < 0.01), percentage of arm-muscle circumference (r = -0.770, P < 0.05), %FEV1 (r = -0.839, P < 0.01), and the maximal inspiratory pressure (r = -0.803, P < 0.001). Underweight COPD patients also exhibited a greater degree of hyperinflation (percentage of residual volume = 205 +/- 15 for underweight patients and 156 +/- 8 for normal-weight patients). In conclusion, a decrease in plasma levels of branched-chain amino acids in relation to hypermetabolism, possibly resulting from the severity of COPD and respiratory muscle weakness, and various disturbances in plasma amino-acid levels were found in underweight COPD patients.

Aged↗
PubMed2001

Improvement in quality of life outcomes 2 weeks after left ventricular assist device implantation.

BACKGROUND: The successful use of left ventricular assist devices (LVADs) as a bridge to heart transplantation has prompted our examination of quality of life (QOL) outcomes. The purposes of this study are to describe QOL in patients 1 to 2 weeks after LVAD implantation and to compare QOL in a smaller cohort of patients from before to 1 to 2 weeks after surgery. METHODS: Data were collected from a convenience sample of 81 patients who completed booklets of questionnaires that measure domains of QOL 1 to 2 weeks after LVAD insertion and from 30 of 81 patients who completed booklets at both the pre-implantation and post-implantation periods. Patients completed booklets of 6 to 8 self-reporting instruments, with acceptable reliability and validity. Data were analyzed using descriptive and comparative statistics (chi-square, Mann-Whitney U and Wilcoxon signed ranks tests) with p = 0.01 considered statistically significant. RESULTS: One to 2 weeks after LVAD implantation, patients were quite satisfied with their lives, experienced moderately low amounts of stress, coped well, and perceived themselves as having good health and QOL, low symptom distress, and moderately low functional disability. Patients reported significantly better QOL, more satisfaction with health and functioning, and were significantly less distressed by symptoms from immediately pre-operatively to post-operatively. However, patients reported significantly more self-care disability and more dissatisfaction with socioeconomic areas of life from before to immediately after surgery. Psychological distress was low and did not change with time. CONCLUSION: Given that QOL improved from before to after LVAD implantation, our findings provide a springboard for investigation of the impact of LVADs on long-term QOL outcomes.

Adult↗
PubMed2001

Insulin's effect on synthesis rates of liver proteins. A swine model comparing various precursors of protein synthesis.

Insulin's effect on the synthesis of liver proteins remains to be fully defined. Previous studies using various surrogate measures of amino acyl-tRNA have reported variable results of insulin's effect on liver protein synthesis. We determined the effect of insulin with or without amino acid supplementation on the synthesis rates of liver proteins (tissue, albumin, and fibrinogen) using L-[1-13C]Leu as a tracer in 24 male miniature swine. In addition, we compared the isotopic enrichment of different precursors of liver proteins with that of amino acyl-tRNA using L-[1-13C]Leu and L-[15N]Phe as tracers. Although liver tissue fluid enrichment of [13C]Leu and [15N]Phe and that of plasma [13C]ketoisocaproatic acid (KIC) were very similar to that of tRNA, plasma isotopic enrichment of both Leu and Phe were substantially higher (P < 0.01) and VLDL apolipoprotein-B100 enrichment was lower (P < 0.01) than the respective amino acyl-tRNA enrichment. Plasma KIC enrichment most accurately predicted leucyl-tRNA enrichment, whereas plasma Leu enrichment was best correlated with that of tRNA. Neither insulin alone nor insulin plus amino acid infusion had an effect on liver tissue protein synthesis. In contrast, insulin alone decreased the albumin synthesis rate, and insulin with amino acids maintained the albumin synthesis rate. Insulin with or without amino acids inhibited the fibrinogen synthesis rate. These results, based on synthetic rates using amino acyl-tRNA, were consistent with those obtained using KIC or tissue fluid Leu or Phe as precursor pools. These studies demonstrated that plasma KIC enrichment is a convenient and reliable surrogate measure of leucyl-tRNA in liver. We also concluded that insulin has differential effects on the synthesis rates of liver proteins. Whereas insulin with or without amino acid supplement has no acute effect on the synthesis of liver tissue protein, insulin has a substantial inhibitory effect on fibrinogen synthesis. In contrast, insulin administration along with amino supplement is necessary to maintain albumin synthesis rate.

Amino Acids↗
PubMed1999

Body composition analysis by dual energy X-ray absorptiometry and exercise performance in underweight patients with COPD.

STUDY OBJECTIVES: The aim of this study was to examine the effect of body composition on maximal exercise performance in patients with COPD. METHODS: The study was carried out on 27 patients with COPD and was confirmed by pulmonary function testing. Body composition was measured by dual energy x-ray absorptiometry (DXA). Exercise performance was conducted on a cycle ergometer and was measured as maximal work rate (WRmax) and maximal oxygen uptake (VO2max). Bone mineral content (BMC), lean mass (LEAN), and fat mass (FAT) were assessed by DXA and were expressed as a percentage of ideal body weight, BMC, LEAN, and FAT. RESULTS: LEAN% correlated significantly with VO2max (r = 0.66, p = 0.0002) and WRmax (r = 0.70, p < 0.0001). No significant correlation was found between FAT% and exercise performance. By stepwise regression analysis, variables significantly contributing to WRmax and VO2max were LEAN% and the maximal voluntary ventilation. Total variance explained in these models was 81% for WRmax aid 82% for VO2max. CONCLUSION: Lean mass was an important determinant of maximal exercise performance in patients with COPD.

Absorptiometry, Photon↗
PubMed1999

[A study of factors relating to aggravation of patients with pulmonary Mycobacterium avium complex disease--with special reference to malnutrition].

We examined physical and blood statuses of 24 patients with pulmonary M. avium complex disease who entered our hospital from April 1993 to March 1997. Ten patients (41.7%) were diagnosed as primary infection type and 14 patients (58.3%) as secondary infection type. Twenty-four patients were classified to the following two groups: Group A was 14 patients who converted to MAC negative within six months after the admission and group B was 10 patients who continued to excrete MAC for more than six months after the admission. We made a comparison between group A and group B as to the results of physical and blood examinations on admission. Mean value of %IBW in group B was significantly lower (group B:74.4 +/- 8.9%, group A:82.9 +/- 12.7%, p < 0.05) than that of group A. The level of serum albumin in group B was significantly lower (group B: 3.39 +/- 0.53 g/dl, group A: 3.99 +/- 0.45 g/dl, p < 0.01) than that of group A. ChE in group B was significantly lower (group B: 321.2 +/- 94.5 IU/l, group A: 442.9 +/- 148.4 IU/l, p < 0.05) than that of group A. Group B was nutritionally depleted than group A. In conclusion, these findings suggested that nutritional support should be taken into consideration in combination with conventional chemotherapy in treating chronic, intractable MAC disease.

Aged↗
PubMed1999

Heliox in upper airway obstruction.

The use of a helium-oxygen (heliox) mixture in patients with airway obstruction was used as early as the 1930s. Although heliox does not resolve airway obstruction, it decreases airway resistance providing time to allow other treatments to become therapeutic, and thus, possibly preventing the need for intubation and mechanical ventilation. Despite new and advanced treatment options in airway obstruction, heliox continues to be a choice for treatment. It is important for critical care nurses to understand the rationale for the use of heliox, the mechanism of action and administration of heliox. Through a case study, the authors discuss the physical properties of helium and its use in airway obstruction. Nursing management of patients receiving heliox is also reviewed.

Acute Disease↗
PubMed1998

Age effect on fibrinogen and albumin synthesis in humans.

A strong association has been reported between atherosclerotic diseases and fibrinogen levels, and a decreased whole body protein synthesis has also been reported with aging. We investigated the effect of age on fractional synthesis rates (FSR) of fibrinogen and albumin in 12 human subjects of young (20-30 yr), middle (45-60 yr), and old (65-79 yr) age by use of L-[1-13C]leucine and L-[15N]phenylalanine as tracers. An age-related decline in FSR of fibrinogen (P < 0.01) was observed with use of both tracers, with the maximal decrease (average 37% with alpha-[13C]ketoisocaproate as the precursor) occurring by middle age and with no further changes thereafter. In contrast, plasma concentrations of fibrinogen increased with age (P < 0.002). There was no age-related change in synthesis rate and concentrations of albumin. An age-related decline in fibrinogen FSR, but not FSR of albumin, indicates a differential effect of age on synthesis rate of these two liver proteins. This study also demonstrated that the increased circulating levels of fibrinogen represent a slower rate of disposal of fibrinogen rather than an increased production rate.

Adult↗
PubMed1998

[Energy expenditure in patients with pulmonary emphysema].

We evaluated resting energy expenditure (REE) using canopy mode indirect calorimetry in 21 ambulatory, clinically stable outpatients with pulmonary emphysema (age: 69.3 +/- 8.4, %IBW: 79.3 +/- 12.5, FEV1: 0.98 +/- 0.36) and compared it with that of a 14 age-matched healthy controls (age: 71.1 +/- 6.0, %IBW: 94.5 +/- 13.4). We also compared REE in malnourished patients (%IBW < 90; 73.0 +/- 7.6, N = 14) and normonourished patients (%IBW > or = 90; 92.0 +/- 5.6, N = 7). We examined the relation ship between %REE (REE/REEpred. x 100) and measurements of lung function tests in 21 emphysema patients using single regression analysis. The REE of the patient group was significantly higher than that of the control group (%REE; 115.9 +/- 12.0 vs 86.5 +/- 8.7, p < 0.01). The REE of the malnourished patient subgroup was significantly higher than that of the normonourished patient subgroup (%REE; 121.9 +/- 7.9 vs 109.9 +/- 9.2, p < 0.01). There were no significant differences in FEV1(L), RV/TLC(%), TLC(pred.%) or DLco/VA (pred.%) between the two patient subgroups. The REE of the normonourished subgroup was significantly higher than that of control group (%REE; 109.1 +/- 9.2 vs 86.5 +/- 8.7, p < 0.01). There were significant relations hips among %REE and FEV1, %FVC, FEV1% G, %DLco/VA and RV/TLC (p < .05). These findings suggest that elevated REE may have a significant relation ship with abnormal lung function, and that elevated REE may be a cause of malnutrition in clinically stable patients with pulmonary emphysema.

Aged↗
PubMed1998

[Thoracoscopic lung volume reduction surgery for emphysema].

In recent years, several institutions have been performing lung volume reduction surgery (LVRS) for emphysema, and have reported that LVRS is effective for patients with emphysema that is resistant to other forms of therapy. However, questions remain about the relationship between the extent of resection and the therapeutic benefits. In our study, 15 men with emphysema underwent thoracoscopic LVRS. We analyzed the effects of LVRS on pulmonary function, exercise performance, and subjective symptoms after both bilateral and unilateral procedures. The patients who underwent the bilateral procedure, demonstrated significantly improved pulmonary function and exercise performance and relief of their subjective symptoms. Those who underwent the unilateral procedure, demonstrated significantly improved pulmonary function and relief of their subjective symptoms. Forced expiratory volume in 1.0 second increased by an average of 51% after the bilateral procedure, and 17% after the unilateral procedure. We conclude that thoracoscopic LVRS is an effective treatment for emphysema, especially with the bilateral procedure.

Aged↗
PubMed1997

Sodium/hydrogen exchanger gene defect in slow-wave epilepsy mutant mice.

The "housekeeping" sodium/hydrogen exchanger, NHE1, mediates the electroneutral 1:1 exchange of Na+ and H+ across the plasma membrane. NHE1 is ubiquitous and is studied extensively for regulation of pHi, cell volume, and response to growth factors. We describe a spontaneous mouse mutant, slow-wave epilepsy, (swe), with a neurological syndrome including ataxia and a unique epilepsy phenotype consisting of 3/sec absence and tonic-clonic seizures. swe was fine-mapped on Chromosome 4 and identified as a null allele of Nhe1. Mutants show selective neuronal death in the cerebellum and brainstem but otherwise are healthy. This first example of a disease-causing mutation in an Nhe gene provides a new tool for studying the delicate balance of neuroexcitability and cell survival within the CNS.

Animals↗
PubMed1997

Airway inflammation in COPD assessed by sputum levels of interleukin-8.

STUDY OBJECTIVE: To assess the characteristics of airway inflammation in patients with COPD. METHODS: We measured the sputum concentration of interleukin-8 (IL-8), a chemokine involved in the migration and activation of neutrophils and eosinophils. We also measured myeloperoxidase (MPO) as a parameter of neutrophil activity and eosinophil cationic protein (ECP) as a parameter of eosinophil activity. Spontaneous sputum samples were obtained from 33 patients with stable COPD and 30 patients with asthma. Induced sputum samples were obtained from 12 normal control subjects. RESULTS: The sputum concentration of IL-8 was significantly higher in the patients with COPD than in the patients with asthma or in the control subjects (p<0.0001). Concentrations of MPO and ECP were significantly higher in the patients with COPD than in the control subjects but did not differ significantly between the patients with COPD and those with asthma. In the patients with COPD, the sputum concentration of IL-8 was significantly correlated with the concentration of MPO (r=0.55, p<0.001) and of ECP (r=0.53, p<0.01). The sputum concentration of IL-8 was negatively correlated with FEV1/FVC (r=-0.78, p<0.0001) in the COPD group. CONCLUSIONS: Results suggest the activation of both neutrophils and eosinophils in the airways of patients with COPD. It appears that IL-8 plays a primary role in this activation. The sputum concentration of IL-8 appeared to be closely associated with the degree of airflow obstruction in patients with COPD and may serve as a marker in evaluating the severity of airway inflammation, which is a risk factor for COPD.

Adult↗
PubMed1997

[Exercise performance and body composition in patients with chronic obstructive pulmonary disease].

Malnutritions is one cause of exercise intolerance in patients with chronic obstructive pulmonary disease. We studied the relation between exercise limitation and body composition in 20 clinically stable patients with chronic obstructive pulmonary disease. Maximal work capacity was measured during incremental exercise on a cycle ergometer, along with maximal oxygen uptake. Anaerobic threshold was determined by the V-slope method. Bone mineral content, lean mass, and fat mass were assessed by dual-energy X-ray absorptiometry. Bone mineral content and lean mass were significantly lower in moderately malnourished patients (%IBW < 80) than in well-nourished patients (%IBW > or = 90). Fat mass was significantly lower in mildly malnourished patients than in well-nourished patients. Maximal work capacity, maximal oxygen uptake, and anaerobic threshold correlated significantly with lean mass, but not with fat mass. These data suggest that lean mass is one determinant of exercise capacity in patients with chronic obstructive pulmonary disease.

Aged↗
PubMed1997

[A case of Mycobacterium intracellulare infection associated with sinobronchial syndrome].

The patient was 71-year-old male with a history of sinobronchial syndrome since 8 years ago. He has been suffering from cough, sputum and upper abdominal discomfort since January 1994. He was diagnosed as an early gastric cancer by endoscopy, and his chest X-ray film showed an infiltrative shadow in the right upper lung field. A smear of the sputum specimen was positive for acid fast bacilli, which were later identified as Mycobacterium intracellulare. In this case, before the Mycobacterium intracellulare infection, it was confirmed that his mucociliary transport was severely impaired by using aerosol inhalation cine-scintigraphy. This case suggests that an impairment of the local defence mechanisms may play an important role in the pathogenesis of Mycobacterium intracellulare infection.

Aged↗
PubMed1997

[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↗
PubMed1997

[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↗
PubMed1997

[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↗