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Biomedical subjects

F Gejyo

Publications and source records attributed to F Gejyo.

At least 91 records · Page 5Linked to original sources

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1998)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 18 institutions around the entire Japan, 532 strains of presumably etiological bacteria were isolated mainly from the sputa of 438 patients with lower respiratory tract infections during the period from October in 1998 to September in 1999. MICs of various antibacterial agents and antibiotics were determined against 85 strains of Staphylococcus aureus, 100 strains of Streptococcus pneumoniae, 96 strains of Haemophilus influenzae, 75 strains of Pseudomonas aeruginosa (non-mucoid strains), 6 strains of Pseudomonas aeruginosa (mucoid strains), 38 strains of Moraxella subgenus Branhamella catarrhalis, 26 strains of Klebsiella pneumoniae etc., and the susceptibilities of 517 strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 60.0%. Vancomycin (VCM) and arbekacin (ABK) showed the most potent activities against MRSA. But one of MRSA showed resistance to ABK with the MIC of 64 micrograms/ml. The sensitive strains of MRSA to VCM have decreased. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP) + PC-resistant S. pneumoniae (PRSP) have increased in 46.0% for 1998 comparatively from 30.9% of 1997's. But PRSP decreased, and PISP increased into 39.0% of 1998 years from 19.8% of 1997's. Panipenem (PAPM), imipenem (IPM) and faropenem (FRPM) showed the most potent activities against S. pneumoniae with MIC80s of 0.125 microgram/ml or below. Against H. influenzae and M. (B.) catarrhalis, almost all the drugs showed good activities. The sensitive strains of them against ceftazidime (CAZ) decreased in 1997, but those have increased in 1998. Inversely, the susceptibility of them against cefotiam (CTM) had been higher in 1997, but those have been lower in 1998. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and nonmucoid strains). All drugs except ampicillin (ABPC) were active against K. pneumoniae. A quite few of K. pneumoniae showed low susceptibilities. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 48.6% of all the patients showing a slight increase in every year. About the proportion of diagnosed diseases as follows: Bacterial pneumonia was the most frequent with 40.2%. The ratio of it has increased slightly, and the increased rate was 10% in patients with ages over 70 years compared with the results in 1997. Chronic bronchitis have decreased slightly with 27.6% in 1998. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these were almost same number in bacterial pneumonia. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 26.7%, H. influenzae 23.8%, S. aureus 13.3% and M. (B.) catarrhalis 10.8%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa (both mucoid and non-mucoid) was not affected. The frequencies of P. aeruginosa was 45.5% after administration over 15 days. The frequencies of S. pneumoniae decreased upon administration of antibiotics, these were only 4.5% over 15 days. The frequencies of H. (

Anti-Bacterial Agents↗

[Efficacy of sustained-released theophylline on peak expiratory flow rate in asthmatic patients].

Nocturnal worsening is an important problem in asthma management. We evaluated the efficacy of two sustained-released theophylline formulations, administered twice-a-day (TD) and once-a-day (UP). In 20 asthmatic patients with low peak expiratory flow rate (PEF) in the morning (< 80% of predicted) administered TD (mean dose 475 mg/day) for 2 weeks, we evaluated PEF, diurnal variability of PEF, symptom score, results of spirometry and serum theophylline concentration (STC) and then changed theophylline, from TD to UP (mean dose 470 mg/day) for 2-4 weeks. PEF in the morning was higher during the UP period (mean +/- SD: 335 +/- 110 L/min) than during the TD period (mean +/- SD: 308 +/- 95 L/min) (p < 0.05), and diurnal variabirity of PEF was lower during the UP period (17.1 +/- 8.0%) than TD period (22.9 +/- 13.4%) (p < 0.05). However, there were no changes in PEF at night or daytime, symptom score, spirometry parameters or STC during the study period. The improvement in morning PEF observed in this study was consistent with the differences in pharmacokinetics between the two theophylline formulations. Morning PEF was increased during the UP period, probably because STC in the early morning during the UP period was higher than STC during the TD period.

Adult↗

[Obstructive sleep apnea syndrome in a patient with superior vena cava syndrome caused by lung cancer].

A 48-year-old man was treated with chemotherapy and irradiation therapy for superior vena cava syndrome (SVCS) caused by adenocarcinoma of the lung, and his symptoms subsided temporarily. However, the same symptoms recurred, and severe snoring during sleep and daytime hypersomnolence developed. Obstructive sleep apnea syndrome (OSAS) was diagnosed by respiratory inductive plethysmography. After chemotherapy, the symptoms of edema of the face and arms, snoring, and daytime somnolence tendency were alleviated, and the patient's apnea hypopnea index decreased remarkably. In addition, lateral cephalograms disclosed improved patency of the upper respiratory tract and dilation of the soft palate. These findings suggested a relationship between SVCS and OSAS. OSAS may cause a deterioration of circulatory dynamics and the quality of life when it develops secondary to SVCS. Therefore, it is necessary to determine whether OSAS is present and accordingly provide suitable treatment in patients with SVCS.

Adenocarcinoma↗

Interaction between A beta(1-42) and A beta(1-40) in Alzheimer's beta-amyloid fibril formation in vitro.

We analyzed the interaction of two kinds of amyloid beta-peptides (A beta), i.e., A beta(1-42) and A beta(1-40), in the kinetics of beta-amyloid fibril (fA beta) formation in vitro, based on a nucleation-dependent polymerization model using fluorescence spectroscopy with thioflavin T. When 25 microM A beta(1-42) was incubated with increasing concentrations of amyloidogenic A beta(1-40), the time to proceed to equilibrium was extended dose-dependently. A similar inhibitory effect was observed when 45 microM A beta(1-40) was incubated with increasing concentrations of A beta(1-42). On the other hand, when 50 microM of nonamyloidogenic A beta(1-40) was incubated with A beta(1-42) at a molar ratio of 10:1 or 5:1, A beta(1-42) initiated fA beta formation from A beta(1-40). The lag time of the reaction shortened in a concentration-dependent manner, with A beta(1-42). We next examined the seeding effect of fA beta formed from A beta(1-42) (fA beta(1-42)) on nonamyloidogenic A beta(1-40). When 50 microM of nonamyloidogenic A beta(1-40) was incubated with 10 or 20 microg/mL (2.2 or 4.4 microM) of fA beta(1-42), the fluorescence showed a sigmoidal increase. The lag time of the reaction was shortened by fA beta(1-42) in a concentration-dependent manner. However, the time to proceed to equilibrium was much longer than when an equal concentration of fA beta formed from A beta(1-40) (fA beta(1-40)) was added to A beta(1-40). The fluorescence increased hyperbolically without a lag phase when 25 microM A beta(1-42) was incubated with 10 or 20 microg/mL (2.3 or 4.6 microM) of fA beta(1-40), and proceeded to equilibrium more rapidly than without fA beta(1-40). An electron microscopic study indicated that the morphology of fA beta formed is governed by the major component of fresh A beta peptides in the reaction mixture, not by the morphology of preexisting fibrils. These results may indicate the central role of A beta(1-42) for fA beta deposition in vivo, among the different coexisting A beta species.

Alzheimer Disease↗

The role of Pseudomonas aeruginosa elastase as a potent inflammatory factor in a rat air pouch inflammation model.

Pseudomonas aeruginosa, an opportunistic pathogen, can cause life threatening infections in patients compromised by underlying respiratory disease like bronchiectasis, cystic fibrosis and diffuse panbronchiolitis. Most strains of P. aeruginosa produce some kind of protease with broad substrate specificities during the infectious state in the host. P. aeruginosa elastase, one of the strongest exotoxins, has a tissue-damaging proteolytic activity and is capable of degrading such plasma proteins as immunoglobulins, complement factor and cytokines. The present study focused on the effect of P. aeruginosa elastase and was designed to evaluate the neutrophil accumulation at the inflammation site mediated by P. aeruginosa elastase in the inflammatory response in the host. An air pouch model in rats, considered as a useful model of inflammation, was used to analyze the number of leukocytes, the volume of exudate and the concentration of interleukin-8 after the injection of P. aeruginosa elastase into the pouch cavity. The number of neutrophils and the volume of exudate in the pouch cavity increased significantly at 4 h, peaked at 8 h in a dose-dependent manner and then decreased at 24 h. The concentration of interleukin-8 in pouch fluid peaked 4 h earlier than the peak of the neutrophil number. The enzymatic activity of P. aeruginosa elastase seemed to reinforce the inflammation process. The influence of lipopolysaccharide contamination was negligible. Although these observations were made in the subcutaneous cavity, they indicate that P. aeruginosa elastase plays a role as an immunoprovocative factor in the inflammatory response in cases of infection with P. aeruginosa.

Air↗

Successful adoptive immunotherapy of murine poorly immunogenic tumor with specific effector cells generated from gene-modified tumor-primed lymph node cells.

We previously reported that cytokine gene transfer into weakly immunogenic tumor cells could enhance the generation of precursor cells of tumor-reactive T cells and subsequently augment antitumor efficacy of adoptive immunotherapy. We investigated whether such potent antitumor effector T cells could be generated from mice bearing poorly immunogenic tumors. In contrast to similarly modified weakly immunogenic tumors, MCA102 cells, which are chemically induced poorly immunogenic fibrosarcoma cells transfected with cDNA for IL-2, IL-4, IL-6, IFN-gamma, failed to augment the host immune reaction. Because priming of antitumor effector T cells in vivo requires two important signals provided by tumor-associated Ags and costimulatory molecules, these tumor cells were cotransfected with a B7-1 cDNA. Transfection of both IFN-gamma and B7-1 (MCA102/B7-1/IFN-gamma) resulted in regression of s.c. tumors, while tumor transfected with other combinations of cytokine and B7-1 showed progressive growth. Cotransfection of IFN-gamma and B7-1 into other poorly immunogenic tumor B16 and LLC cells also resulted in the regression of s.c. tumors. Cells derived from lymph nodes draining MCA102/B7-1/IFN-gamma tumors showed potent antitumor efficacy, eradicating established pulmonary metastases, but this effect was not seen with parental tumors. This mechanism of enhanced antitumor efficacy was further investigated, and T cells with down-regulated L-selectin expression, which constituted all the in vivo antitumor reactivity, were significantly increased in lymph nodes draining MCA102/B7-1/IFN-gamma tumors. These T cells developed into potent antitumor effector cells after in vitro activation with anti-CD3/IL-2. The strategy presented here may provide a basis for developing potent immunotherapy for human cancers.

Animals↗

Lipid-binding proteins in rat and human kidney.

BACKGROUND: The kidney metabolizes actively lipophilic molecules. Several species of lipid-binding proteins (LBPs) have been well characterized, including fatty acid-binding proteins (FABPs), acyl-CoA binding protein (ACBP), sterol carrier protein 2 (SCP2), cellular retinol binding protein (CRBP), and phosphatidylinositol transfer protein (PITP). METHODS: To clarify which LBPs are expressed in isolated rat glomeruli (RG), cultured rat mesangial cells (RMC) and human kidney, RT-PCR, immunoblot analysis and immunohistochemistry were performed. RESULTS: Protein and mRNA expression of heart type (H-) FABP was found in RMC, but not in RG. Immunohistochemistry using antihuman H-FABP antibody revealed that an H-FABP like protein was present in the capillary wall and distal tubules of human glomeruli. Immunoblot analysis using the antibody showed that a 110-kDa protein related to H-FABP was present in human isolated glomeruli but not in any other tissues tested including blood, liver, and heart, and that the 14-kDa protein, H-FABP itself was localized in the distal tubules of human kidney. mRNA for SCP2, ACBP and PITP was detected in RG and RMC. CRBP and mRNA was detected in RG but not RMC. CONCLUSIONS: A variety of lipid-binding proteins are present in rat glomeruli. In human glomeruli, a novel 110-kDa H-FABP-related protein is localized specifically in the capillary wall.

Animals↗

A common mutation of cholesteryl ester transfer protein gene in dialysis patients.

BACKGROUND: In patients on maintenance hemodialysis, a decreased concentration of high-density lipoprotein cholesterol (HDL-C) is an apparent independent risk factor for vascular disease (VD). A common missense mutation of cholesteryl ester transfer protein (CETP) gene, D442G (Asp442 to Gly), increases HDL-C levels, but the mutation may also diminish the activity of reverse cholesterol transport. METHODS: We compared the genotype distribution of the D442G polymorphism and postprandial serum lipid levels between patients with and without VD in 414 hemodialysis patients. RESULTS: Serum levels of total cholesterol and HDL-C did not differ in patients with the mutation [group M (+)] and without the mutation [group M (-)] and in patients with and without VD. However, patients with below median HDL-C levels (< 45 mg/dl) had a significantly higher prevalence of VD than those with above median HDL levels (26.0 vs. 15.2%, P < 0.01). Moreover, in this low-HDL-C subgroup, group M (+) patients had a significantly higher prevalence of VD than group M (-) patients (54.5 vs. 24.4%, P < 0.05). In the subgroup, group M (+) patients with VD had higher levels of total cholesterol and a higher atherogenic index than those without VD, whereas group M (-) patients with VD had lower levels of total cholesterol and a lower atherogenic index than those without VD. CONCLUSIONS: The D442G mutation may be a risk factor for atherosclerotic complications in dialysis patients with HDL-C levels below 45 mg/dl. Atherogenic lipid profiles may promote atherosclerosis in the patients with the mutation, but not in those with no mutation.

Adult↗

Apolipoprotein E phenotypes in hemodialysis patients.

BACKGROUND: Apolipoprotein (apo) E polymorphism consists of three major isoproteins (E2, E3, and E4). Because of their difference in a lipid-modulating effect, the polymorphism has been reported to affect the morbidity of atherosclerosis in general population. Therefore, in hemodialysis (HD) patients, the apo E polymorphism may also modulate serum levels of cholesterol and susceptibility to atherosclerotic vascular disease. METHODS: We determined apo E phenotypes in 493 HD patients and 422 controls. We also investigated vascular risk profile and measured postprandial serum levels of lipids and apos in the dialysis patients. RESULTS: We found a similar phenotype distribution and allele frequency between HD patients and healthy controls. Serum levels of total cholesterol, triglyceride, and apo A I, A II, and C III did not differ significantly among patients with phenotypes apo E2/3, E3/3, and E3/4. Patients with apo E3/4 had significantly lower levels of high-density lipoprotein cholesterol, significantly higher levels of low-density lipoprotein cholesterol (LDL-C), and a higher atherogenic index than those with apo E2/3 (LDL-C, 100 +/- 30 vs. 82 +/- 35 mg/dl, P < 0.01; the index, 3.3 +/- 1.7 vs. 2.3 +/- 1.3, P < 0.01). Patients with apo E3/4 showed a tendency toward higher levels of apo B than patients with apo E2/3 or apo E3/3. Multiple logistic regression analysis revealed that age and diabetes mellitus, but not apo E phenotypes, were independent risk factors for vascular disease. CONCLUSIONS: Apo E polymorphism modulates cholesterol metabolism in dialysis patients but appears to have little association with the prevalence of atherosclerotic complications in the patients.

Age Factors↗

Immunotherapy of disseminated fibrosarcoma in mice using IL-2-producing tumor cells: studies on its mechanism and specificity.

Genetically modified, IL-2-producing tumor cells have been shown to regress in vivo and immunize mice against subsequent challenge with parental tumor. We investigated whether IL-2-producing tumor cells may serve as immunotherapy of established tumors in mice. MCA 205 and MCA 203, weakly immunogenic murine sarcomas of B6 origin, were transfected with the pBMGNeo-mIL-2 vector containing the murine IL-2 cDNA. Mice receiving intraperitoneal injections of the parental sarcoma cells developed ascites and died within 4 weeks. The intraperitoneal injection of IL-2-producing tumor cells significantly prolonged survival and, moreover, significantly reduced the number of established pulmonary metastases. The specificity of this effect was indicated by the unaltered course of disease in mice that were injected with unrelated IL-2-producing tumor cells. FACS analysis of peritoneal cells obtained from treated mice showed a predominance of Vbeta3-positive cells. In a 4 h 51Cr release assay, these Vbeta3-positive cells exhibited tumor-specific cytotoxicity and also nonspecific effector cells are shown to be involved in tumor rejection.

Animals↗

Significance of serum pepsinogens and their relationship to Helicobacter pylori infection and histological gastritis in dialysis patients.

BACKGROUND: Previous investigations reported that patients undergoing dialysis therapy had significantly higher serum pepsinogen (PG) levels than patients with normal renal function. However, in dialysis patients, the relationship between serum PG levels and Helicobacter pylori infection remains unknown. METHODS: Sixty three maintenance dialysis patients (54 haemodialysis and nine continuous ambulatory peritoneal dialysis) who required endoscopic examination were enrolled in the study. Sixty four age- and sex-matched patients with normal renal function served as controls. We performed endoscopic examination and obtained both the gastric antral and corpus mucosa for histopathological evaluation and H. pylori identification. Twenty three patients on dialysis underwent H. pylori eradication therapy. RESULTS: In dialysis patients, H. pylori-positives had significantly higher serum PG II levels than H. pylori-negatives (26.6+/-21.5 vs 14.1+/-7.1 ng/ml, P<0.05), but no significant difference was found in serum PG I between H. pylori-positives and H. pylori-negatives (228.8+/-158.5 vs 179. 4+/-113.5 ng/ml). There was no significant difference in serum PG II between dialysis patients and controls (19.9+/-16.5 vs 18.6+/-14.9 ng/ml), while serum PG I levels were significantly higher in dialysis patients than in controls (201.7+/-136.8 vs 77.6+/-85.8 ng/ml, P<0.05). Serum PG II levels, but not those of PG I, significantly correlated with the inflammation and activity scores of antrum in dialysis patients, and these scores were highly influenced by H. pylori infection. Dialysis patients in whom H. pylori was eradicated successfully showed significant reductions of serum PG II levels but not of PG I. CONCLUSIONS: In dialysis patients, high serum levels of PG II, but not PG I, are significantly related to H. pylori infection and mucosal inflammation. A significant decrease in serum PG II levels could be used as a predictor of the eradication of H. pylori infection in dialysis patients.

Aged↗

High frequency of antibody activity against ribosomal protein S10 in anti-Sm sera from patients with systemic lupus erythematosus.

This study was carried out to clarify the frequency of detection of antibody activity to ribosomal protein S10 (anti-S10) in patients with systemic lupus erythematosus (SLE) with anti-Sm antibodies (anti-Sm), and clinical differences between anti-Sm-positive SLE patients with and without anti-S10. Twenty-seven of 31 serum samples containing anti-Sm reacted with ribosomal protein S10 along with Sm core proteins B/B' and D (87.1%). Four serum samples containing anti-Sm against only B/B' but not D did not react with S10 (12.9%). Patients who had both anti-Sm and anti-S10 showed lower serum complements levels, high frequency of skin lesion and anti-double-stranded DNA antibody. Many anti-Sm antibodies may recognize B/B', D, and S10 simultaneously, and such antibodies may appear in active disease.

Antibody Specificity↗

The leukotriene B4 receptor antagonist ONO-4057 inhibits nephrotoxic serum nephritis in WKY rats.

To evaluate the role of leukotriene B4 (LTB4) in glomerulonephritis, this study was conducted to examine whether ONO-4057, an LTB4 receptor antagonist, moderated nephritis caused by the injection of nephrotoxic serum (NTS) into Wistar-Kyoto rats. Rats were given intraperitoneal injections of ONO-4057 or phosphate-buffered saline 24 h before the injection of NTS. These rats subsequently received equal doses of ONO-4057 or phosphate-buffered saline 3 h and 1, 2, 3, 4, 5, and 6 d later. Compared with the control groups, ONO-4057 treatment significantly reduced proteinuria and hematuria, suppressed the glomerular accumulation of monocytes/macrophages, and reduced the formation of crescentic glomeruli in a dose-dependent manner. These results suggest that LTB4 is responsible for the crescentic formations and renal dysfunction associated with NTS nephritis. The LTB4 receptor antagonist ONO-4057 may thus be beneficial in the treatment of crescentic glomerulonephritis.

Animals↗

A cholesteryl ester transfer protein gene mutation and vascular disease in dialysis patients.

Among patients undergoing maintenance hemodialysis, a decreased high-density lipoprotein cholesterol (HDL-C) concentration is among the most common abnormalities of lipid metabolism and apparently is an independent risk factor for vascular disease. A common missense mutation of cholesteryl ester transfer protein gene, D442G (Asp 442 to Gly), increases HDL-C levels through the reduced activity of cholesteryl ester transfer from HDL to VLDL, but the mutation also may lead to reduced activity of reverse cholesterol transport. To investigate the effect of the D442G polymorphism on atherosclerotic complications in dialysis patients, the genotype and allele frequency of the polymorphism were determined in 414 unselected dialysis patients and 220 control subjects, and postprandial serum lipid levels were measured in the dialysis patients. A similar genotype distribution was found between hemodialysis patients and healthy control subjects, and in dialysis patients with and without vascular disease. Serum levels of total cholesterol and HDL-C did not differ between patients with and without the mutation and in patients with and without vascular disease. However, patients with sub-median HDL-C levels (<45 mg/dl) had an independent odds ratio of 1.8 for vascular disease (95% confidence interval, 1.04 to 3.2; P < 0.05). In this low-HDL-C subgroup, patients with the D442G mutation had a significantly higher prevalence of vascular disease than those with no mutation (54.5% versus 24.4%; P < 0.05), and an independent odds ratio of 4.9 (95% confidence interval, 1.05 to 22.65; P < 0.05). In conclusion, the D442G mutation is an independent risk factor for atherosclerotic complications in dialysis patients with HDL-C levels below 45 mg/dl.

Adolescent↗

Structural analysis of the amyloidogenic kappa Bence Jones protein (FUR).

Patients with systemic amyloidosis associated with multiple myeloma (AL-amyloidosis) exhibit immunoglobulin light chains and fragments which have been identified as amyloid protein. Since a relatively small proportion of patients with multiple myeloma develop AL-amyloidosis, comparison of the amino acid sequence of the amyloidogenic and non-amyloidogenic immunoglobulin light chains and the structural characterization of the amyloid proteins are required to understand the relationship between structure and amyloidogenicity. We determined the primary structure of a kappa I-type Bence Jones protein obtained from a patient (FUR) who had systemic AL-amyloidosis associated with multiple myeloma. We identified eight amino acid replacements unique to this patient among the amyloidogenic kappa I-light chains, and which are also rare among the known kappa type light chains of humans. Three of these substitutions were within the framework regions and may act to destabilize the structure to promote a putative amyloidogenic conformation. In contrast to light chain fragments in the urine, which were processed in the variable region, mass spectrometric analysis of the fibril proteins isolated from lingual amyloid deposits in this patient, revealed that they were all truncated within the constant region and corresponded to residues 1-125, 1-144, and 1-210. Inspection of the predicted three-dimensional model of this protein suggested that these fragments may be generated by a protease specific for the N-terminal sides of basic amino acids. These findings suggest that amino acid substitutions at highly conserved residues may convert non-amyloidogenic to amyloidogenic immunoglobulin light chain proteins.

Aged↗