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Biomedical subjects

H Sagara

Publications and source records attributed to H Sagara.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Basic and clinical studies of pazufloxacin on infectious enteritis research group of T-3761 on infectious enteritis].

A clinical study was carried out on pazufloxacin (PZFX) in 137 patients including shigellosis, Salmonella enteritis, enteropathogenic Esherichia coli enteritis and cholera, and carriers of these pathogens. Antibacterial activity of PZFX against clinical isolates, fecal concentration of PZFX and effects of PZFX on fecal microflora were also investigated. The overall clinical efficacy rate was 97.2%. The bacteriological efficacy rates were 98.2% against Shigella spp., 81.8% against Salmonella spp., 50% against Vibrio cholerae O1, and 100% against E. coli, V. parahaemolyticus, Aeronomas spp., Plesionomas shigelloides and V. cholerae non-O1, respectively. Side effect (epigastralgia) was observed in 1 of 130 cases (0.8%). The rate of abnormal laboratory findings was 11.2% (11/98). These were mainly elevation of GOT and/or GPT and increased eosinophils. The clinical usefulness rate was 95.2%. The MIC90 values of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The results of fecal drug concentration and the effects on fecal microflora in one patient were compatible with those obtained in healthy volunteers.

4-Quinolones↗
PubMed1996

[Clinical study of prulifloxacin on infectious enteritis. Japan Research Committee of Prulifloxacin, Research Group on Infectious Enteritis].

Prulifloxacin (PUFX), a new quinolone antimicrobial agent, was administered to a total of 122 patients and carriers to investigate its clinical efficacy, safety and usefulness in infectious enteritis (bacillary dysentery, enteritis caused by Salmonella spp. and enteropathogenic E. coli, cholera and so on). In addition, the minimum inhibitory concentration (MIC) of UFX (active compound) was determined against each clinical isolate, and compared with that of ciprofloxacin (CPFX), ofloxacin (OFLX), tosufloxacin (TFLX) and nalidixic acid (NA). The correlation between the concentration of UFX in feces and the change of the fecal microflora were also investigated when PUFX was administered to the patients with acute infectious enteritis. A daily dose of 400 mg of PUFX was administered orally in two divided doses (morning and evening) for 5 days, with the exception of 7 days administration against salmonella enteritis and 3 days administration against cholera. 84 cases were adapted for evaluating the usefulness. The clinical efficacy was 100% in all the enteritis except salmonella enteritis, in which it was 88.9% (8/9 cases). On the bacteriological efficacy, the elimination rate was 100% in all isolates except Salmonella spp., in which it was 75.0% (12/16 cases). As for the adverse effect, uriticaria in moderate degree was observed in 1 (0.9%) of 109 cases. Abnormal changes in laboratory findings were seen in 3 (3.0%) of 100 cases, consisting of 1 with eosinophilia and 2 with elevated S-GPT, although they were all slight in degree. The usefulness rate was 65.5% (55/84 cases) for "very useful" and 95.2% (80/84 cases) for "very useful" and "useful". MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae, was 0.025, 0.05, 0.025 and 0.05 microgram/ml, respectively. These values were the same as those of CPFX and TFLX, and superior to OFLX and NA. UFX concentrations in feces followed by administration of PUFX in 3 cases with acute infectious enteritis were higher than that of MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae. The changes of the fecal microflora, which influence the efficacy and safety of PUFX, were not observed.

Adult↗
PubMed1996

Sialyl Lewis X analog inhibits eosinophil accumulation and late asthmatic response in a guinea-pig model of asthma.

Preferential eosinophil accumulation is characteristic of airway inflammation in asthma. Although little is known about its mechanism, the effect of a sialyl Lewis X analog on airway eosinophilia was examined in a guinea-pig model of asthma. Guinea-pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed striking airway eosinophilia and a late asthmatic response. In contrast, when guinea-pigs were pretreated intravenously with sialyl Lewis X analog (LX 0104) 1 h before antigen challenge, both eosinophil infiltration in the tracheal wall and the late asthmatic response were significantly inhibited in a dose-dependent manner. In a further in vitro study, LX 0104 significantly suppressed the adhesion of human and guinea-pig eosinophils to human umbilical vein endothelial cells activated with interleukin-1 beta. These results suggest that LX 0104 plays a critical role in antigen-induced airway eosinophilia and the late asthmatic response.

Animals↗
PubMed1996

Comparison of adhesion molecule expression on light and normal-density eosinophils from patients with eosinophilia.

Increased numbers of light-density eosinophils (LDEs) are observed in the blood of patients with eosinophilia and are associated with disease activity. LDEs are thought to be metabolically more activate than normal-density eosinophils (NDEs). Recent studies suggest that cytokine-induced eosinophil activation is associated with adhesion molecule expression. The activated state of LDEs may result from increased expression of adhesion molecules. This study compared the expression of eosinophil adhesion molecules on LDEs and NDEs from various diseases characterized by eosinophilia. Expression of very late antigen-4 (VLA-4), lymphocyte function-associated antigen-I (LFA-1) and macrophage antigen-1 (Mac-1) on eosinophils from patients with eosinophilia was increased compared with those from healthy subjects. Mac-1 expression on LDEs was higher than on NDEs. These results suggest that VLA-4 plays a role in selective migration of eosinophils into the inflammatory tissue, and that Mac-1 is associated with activation of eosinophils in eosinophilic diseases.

Cell Adhesion Molecules↗
PubMed1996

Role of interleukin-4 and vascular cell adhesion molecule-1 in selective eosinophil migration into the airways in allergic asthma.

Recent in vitro studies have suggested that interleukin-4 (IL-4) may be involved in the preferential migration of eosinophils into the airways in allergic asthma through its capacity to selectively increase vascular cell adhesion molecule-1 (VCAM-1) expression on vessels. To test this hypothesis, we studied the expression of VCAM-1, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) on vascular endothelium in bronchial mucosal biopsies from 20 allergic asthmatics using an immunohistochemistry technique and related the observations to IL-4 levels in bronchoalveolar lavage (BAL) fluid simultaneously obtained and to eosinophil infiltration in the bronchial mucosa. IL-4 was detectable in BAL fluid from nine subjects (range, 15.1 to 110 pg/ml in 20-fold concentrated BAL fluid) (IL-4-positive asthmatics) but unmeasurable in the remaining 11 subjects (IL-4-negative asthmatics). The IL-4-positive asthmatics showed a significantly increased expression of VCAM-1 but not E-selectin and ICAM-1 on vessels as compared with both IL-4-negative asthmatics (P < 0.001) and diseased control subjects (P < 0.001). In asthmatics, VCAM-1 expression was positively correlated with BAL IL-4 levels (rs = 0.89; P < 0.0001). Moreover, there was a significant correlation between the endothelial expression of VCAM-1 and the number of eosinophils, but not neutrophils, in the bronchial submucosa (r2 = 0.76; P < 0.001). A significant correlation was also found between BAL IL-4 levels and the number of eosinophils. These results suggest that IL-4 is a VCAM-1-selective activator also in human airways and the VCAM-1-dependent pathways play a role in selective migration of eosinophils into the airways in allergic asthma, and support the hypothesis described above.

Adult↗
PubMed1996

The effect of anti-VLA-4 monoclonal antibody on eosinophil accumulation and leukotriene production in nasal mucosa.

Eosinophil derived leukotrienes and platelet activating factor are known to cause nasal swelling. Toxic proteins induce nasal hyperreactivity to non-specific stimuli including histamine. Recent studies strongly suggest that very late activation antigen-4 (VLA-4) on the eosinophil surface plays a prominent role in the recruitment of eosinophils from blood vessels and eosinophil locomotion in inflammatory tissues. To test this hypothesis, we examined the effect of a monoclonal antibody (mAb) to VLA-4 on eosinophil accumulation in nasal mucosa after antigen challenge in a guinea pig model. Here we have demonstrated that the mAb depressed the eosinophil accumulation in nasal mucosa. In addition, we have shown that this mAb also inhibited eosinophil activation and leukotriene production. Our results raise a possibility that eosinophils might be activated during the journey from bloodstream to inflammatory tissues by the adhesion to endothelial cells and fibronectin. VLA-4 might act as a signalling as well as an adhesion receptor on eosinophils.

Animals↗
PubMed1996

[PAF receptor antagonist in asthma therapy].

Platelet-activating factor (PAF), proposed as an important inflammatory mediator in asthma, reproduces several of the features of asthma, such as micro vascular leakage, mucus secretion, broncoconstriction, and possibly increased airway responsiveness. The recognition that PAF may be a central mediator in asthma has been a relatively recent event, so that those interested in asthma research may be unfamiliar with the chemistry, biochemistry and biology of this material. It seemed appropriate therefore to assemble a group of expert investigators to make presentations and to discuss the current status of PAF research with a specific bias toward asthma. In this way, it has been possible to focus upon PAF in asthma and to provide the necessary background for consideration of the effects of existing antiasthma drugs to suppress pulmonary responses to PAF. The capacity of existing antiasthma drugs to suppress pulmonary responses to PAF implies that this will be necessary feature of many of the newer antiasthma drugs and this knowledge allows a more balanced judgment of the prospects for PAF receptor antagonists in this disease.

Animals↗
PubMed1996

[The expression of adhesion molecules on eosinophils from atopic and non-atopic subjects].

The accumulation of eosinophils in the airway is one of the characteristics seen in patients with chronic asthma. There is now considerable evidence that airway eosinophilia is associated with the development of late asthmatic response (LAR) and bronchial hyperresponsiveness. In this study, we observed PAF induced up-regulation of inducible adhesion molecules Mac-1 and LFA-1 beta on eosinophils of atopic patients compared with non-atopic and normal subjects. In conclusion, we found that adhesion molecule expression is different between atopic and non-atopic patients. Therefore, adhesion molecule expression is thought to be important in the prolonging and pathogenesis of allergic inflammation.

Adult↗
PubMed1995

[Permeability to horseradish peroxidase of the ciliary muscle vessels of squirrel monkeys].

The morphology and permeability to horseradish peroxidase (HRP) of the ciliary muscle capillaries of squirrel monkeys were studied. The endothelial cells of the capillaries were of the continuous type and the interendothelial clefts were closed by a zonula occludens. Many vesicles were present in the cytoplasm of the endothelial cells. In addition to these vesicles, large vacuole-like structures, 100-500 nm in diameter, were observed in the cytoplasm of capillary endothelium, especially in the circular and radial ciliary muscles. When HRP was perfused into the anterior chamber, the 3,3'-diaminobenzidine reaction product was observed in the lumen of the ciliary muscle vessels after 30 minutes. When HRP was administered intravenously, the reaction product was observed among the muscle fiber bundles after 15 minutes. In both cases, the reaction products were also present in the cytoplasmic vesicles and vacuole-like structures, suggesting that these structures are involved in the bidirectional transport of HRP between interstitium and blood.

Animals↗
PubMed1994

[Basic and clinical studies of fleroxacin on infectious enteritis. Research Group of AM-833 on infectious enteritis].

A clinical study was conducted on fleroxacin (FLRX) in 143 patients and carriers with infectious enteritis (shigellosis, Salmonella enteritis, Campylobacter enteritis, pathogenic Escherichia coli enteritis, Vibrio parahaemolyticus enteritis, cholera, multiple bacterial infections, pathogen-negative enteritis). Furthermore, its antibacterial activity against clinical isolates, fecal concentration and effect on fecal microflora were conducted. FLRX was administered orally in doses of 200 mg once a day (200 mg group) or 300 mg once a day (300 mg group) for 3 days to cholera, for 7 days to Salmonella enteritis and for 5 days to the other infectious enteritis. The clinical efficacy rates were 100% in both the 200 mg and 300 mg groups. The bacteriological efficacy rates were 100% against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and V. cholerae O1, and 63.6% against Campylobacter spp. in the 200 mg group. The rates of the 300 mg group were 93.3% against Shigella spp., and 100% against Campylobacter spp. and pathogenic E. coli. As adverse effects, skin rash was observed in 1 case each in both groups (1.1%, 2.1%). Abnormal laboratory findings consisted of 1 case of increased eosinophils and 1 case of elevated GOT and GPT levels in the 200 mg group (2.8%), and 1 case of elevated GPT in the 300 mg group (2.9%). The clinical usefulness rates were 92.9% and 93.3% in the 200 mg and 300 mg groups, respectively. Antibacterial activity was somewhat inferior to that fo ciprofloxacin and equal to or better than that of norfloxacin, demonstrating MIC90 values against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and Campylobacter spp. of 0.1, 0.2, 0.1, 0.2 and 0.78 micrograms/ml, respectively. Peak fecal concentrations of the drug were 49.0 micrograms/g and 274.4 micrograms/g in the 200 mg group, and 43.3 micrograms/g and below the detection limit (5.0 micrograms/g) in the 300 mg group. With respect to fecal microflora (4 cases), a decrease in Enterobacteriaceae was observed in 3 cases during dosing. But this change showed a tendency to recover after completion of dosing. No effects were observed on anaerobic bacteria.

Adolescent↗
PubMed1994

The eta isoform of protein kinase C is localized on rough endoplasmic reticulum.

The eta isoform of protein kinase C, isolated from a cDNA library of mouse skin, has unique tissue and cellular distributions. It is predominantly expressed in epithelia of the skin, digestive tract, and respiratory tract in close association with epithelial differentiation. We report here that this isoform is localized on the rough endoplasmic reticulum in transiently expressing COS1 cells and constitutively expressing keratinocytes. By the use of polyclonal antibodies raised against peptides of the diverse D1 and D2/D3 regions, we found that immunofluorescent signals were strongest in the cytoplasm around the nucleus and became weaker toward the peripheral cytoplasm. Under immunoelectron microscopic examination, electron-dense signals were located on the rough endoplasmic reticulum and on the outer nuclear membrane which is continuous with the endoplasmic reticulum membrane. However, no signals were detected in the nucleus, inner nuclear membrane, smooth endoplasmic reticulum, Golgi apparatus, mitochondria, or plasma membrane. Treatment of the cells in situ with detergents suggested association of the isoform of protein kinase C with intracellular structures. By immunoblotting, a distinct single band with an M(r) of 80,000 was detected in whole-cell lysate and in rough microsomal and crude nuclear fractions, all of which contain outer nuclear membrane and/or rough endoplasmic reticulum. We further demonstrated the absence of a nuclear localization signal in the pseudosubstrate sequence. The present observation is not consistent with the report of Greif et al. (H. Greif, J. Ben-Chaim, T. Shimon, E. Bechor, H. Eldar, and E. Livneh, Mol. Cell. Biol. 12:1304-1311, 1992).

Amino Acid Sequence↗
PubMed1994

[Shigellosis].

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Adult↗
PubMed1994

[Typhoid fever].

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Humans↗
PubMed1994

[Shigellosis].

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Child↗
PubMed1994

[Typhoid fever].

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Humans↗
PubMed1993

Transfusion-associated graft-versus-host disease.

We reported two patients showed similar clinical course after blood transfusion. Case 1 was 74-year-old female, received transfusion of 200 ml of whole blood from her son, because of hemorrhagic shock for fematemesis from gastric ulcer. After transfusion, she died of liver dysfunction and severe aplastic anemia. Case 2 was a 73-year-old male, received transfusion of three unites of concentrated red blood cells for anemia following the orthopaedic treatment. High fever and erythema was appeared suddenly after transfusion. He died of liver dysfunction and the autopsy was performed. In case 1 the diagnosis was transfusion-associated graft-versus-host disease (GVHD) and in case 2 drug-induced-aplastic anemia (DIAA) was suspected. Differentiating the diagnosis between GVHD and DIAA is clinically difficult.

Aged↗
PubMed1993

[Multicenter study of the effects of sulbactam/cefoperazone on bacterial infections in the fields of internal medicine focused mainly on respiratory infections in Tochigi Prefecture].

Clinical effects of sulbactam/cefoperazone (SBT/CPZ) was studied on variety of bacterial infections in the fields of internal medicine focused mainly on respiratory infections. The total 135 infections were consisted of 103 respiratory infections, 15 urinary tract infections, 4 sepsis, 7 biliary tract infections, and 6 other infections, of which 86 patients had underlying diseases. The daily doses of SBT/CPZ were 2 to 6 g divided into 2 to 3 times i.v. or d.i.v., and the duration of administration was from 3 to 35 days. The clinical effects were judged by the attending doctors based on the changes in fever, cough, rales, chest rentogenograms, white blood cell counts, CRP values, ESR, etc. The total efficacy rate was 76.9%, and 69.0% of the isolated organism was eradicated by SBT/CPZ. The side effect was noted in 1 case, and the abnormal laboratory findings were noted in 1 case, however it was difficult to determine whether they were due to SBT/CPZ. These results suggest that the clinical usefulness of SBT/CPZ for the infections in the fields of internal medicine.

Adult↗