The accumulation of eosinophils in the airway is one of the characteristics seen in patients with bronchial asthma. One of the newly developed anti-asthma drugs (controller), nedocromil sodium (nedocromil) is known to suppress the influx of eosinophils into allergic lesions. However, little is known about this mechanism. Therefore, in this report we investigated the effects of nedocromil on Mac-1 expression on PAF-stimulated eosinophils, and adhesion molecule expression on endothelial cells stimulated by either IL-1 beta or IL-4. We also investigated the eosinophil chemotaxis. A significant suppression of the Mac-1 expression on PAF-induced eosinophils was observed at both concentrations of 10(-5) and 10(-7) M of nedocromil. The expression of adhesion molecules, particularly ICAM-1 and E-selectin, on IL-1 beta-stimulated human umbilical vascular endothelial cells (HUVEC) was significantly suppressed at these concentrations, whereas the VCAM-1 expression was not changed. No significant suppression of VCAM-1 expression on IL-4-stimulated HUVEC was observed, although there was a tendency of suppression at these concentrations. On the other hand, the expression of the E-selectin molecule was significantly suppressed by nedocromil even under resting (non-stimulated) condition. PAF-induced eosinophil chemotactic activities were also suppressed at these concentrations in a dose-dependent manner. These results suggested that nedocromil suppressed the influx of eosinophils to inflammatory lesions by inhibiting not only the expression of the Mac-1 on eosinophils and of E-selectin and ICAM-1 molecules on HUVEC, but also the eosinophil chemotactic activities.

Anti-Asthmatic Agents↗

PubMed1998

A novel member of the Ig superfamily, RPE7, expressed on the retinal pigment epithelial cell and Müller cell of the bovine retina.

The retinal pigment epithelium of the vertebrate eye plays a major part in the maintenance of ocular function. To identify molecules involved in the exertion of their physiological functions, monoclonal antibodies against bovine retinal pigment epithelial cells were made. Analysis by immunofluoresence and immunoelectron microscopy showed that one of the monoclonal antibodies named anti-RPE7 stained the cell surface of retinal pigment epithelial cells and Müller cells. The anti-RPE7 antibody was revealed to recognize molecules of 45-55 kDa by Western blot analysis. Molecular cloning of the RPE7 cDNA and sequence analysis of the amino acids revealed that protein RPE7 belonged to the Ig superfamily. The high homology of RPE7 with metalloproteinase inducer suggests that the protein RPE7 might play a role in the matrix (interphotoreceptor matrix and basement membranes) remodeling as well as in retinal pigment epithelial cell migration under pathological conditions.

Amino Acid Sequence↗

PubMed1998

Defective degranulation and calcium mobilization of bone-marrow derived mast cells from Xid and Btk-deficient mice.

Regulation of adhesion and degranulation of mast cells plays an important role in allergy and inflammation. We investigated a possible role of Bruton's tyrosine kinase (Btk) in the regulation of adhesion and degranulation by using bone marrow-derived mast cells from X-linked immunodeficiency (Xid) and Btk-deficient mice. Cross-linking of the high affinity IgE receptor (Fc epsilonRI) and steel factor (SLF) induced indistinguishable adhesive responses of mast cells to fibronectin in kinetics, and these adhesive responses were comparable among wild type, Xid, and Btk-deficient mast cells. Cross-linking of Fc epsilonRI, but not SLF triggered degranulation of bone marrow-derived mast cells. However, Fc epsilonRI-induced degranulation was impaired in Xid and Btk-deficient mast cells. Calcium influx induced by Fc epsilonRI cross-linking and SLF were also reduced in Xid and Btk-deficient mast cells. Degranulation and calcium influx were reduced more severely in Btk-deficient than in Xid mast cells. Consistently, cross-linking Fc epsilonRI and SLF augmented Btk kinase activities transiently. Inositol triphosphate (IP3) production was also severely reduced in Btk-deficient mast cells, indicating Btk play a critical role of Fc epsilonRI-induced IP3 production. The differential sensitivity of wortmannin on calcium influx in wild type and Xid mast cells suggested that the activation of phosphatidylinositol 3 kinase (PI 3-kinase) was required in calcium influx. Furthermore, abnormal secretory granules with translucent contents and variable in size were observed both in Xid and Btk-deficient mast cells. Our study demonstrated a critical role of Btk in regulating intracellular calcium and granule exocytosis.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed1998

[A case of imported paratyphoid fever associated with Giardia lamblia and Isospora belli infection].

We report a case of imported paratyphoid fever associated with Giardia lamblia and Isospora belli infection. The patient was a 23-year-old Japanese female with complaints of high grade fever and diarrhea after 10 days traveling to Nepal. Salmonella Paratyphi A was isolated from the blood and fecal cultures on admission and Ciprofloxacin of 200 mg tid was administered for 14 days. Fecal examination revealed cysts of G. lamblia at the same time and metronidazole of 250 mg tid for 7 days was effective for their eradication. During the follow-up studies oocysts of I. belli were found and cotrimoxazole of 960 mg bid for 10 days was effective for their eradication. Fecal examinations on parasites which is rare in Japan such as I. belli are recommended to the cases returning from tropical areas.

Adult↗

PubMed1998

[A case of AIDS complicated with isosporiosis as initial manifestation].

We reported a Thailander patient with isosporiasis accompanied by AIDS. The 34-year-old male, who had been living in Japan for six years, was admitted to our hospital complaining of diarrhea and body weight loss. After admission the patient developed acute renal failure due to dehydration resulting from diarrhea. Laboratory findings on admission showed neither significant microorganisms nor parasite ova in the stool. The patients was given both an intestinal drug and an antibacterial agent, but is vain. Frequent stool examinations disclosed Isospora oocyst in the feaces. Co-trimoxazole was administered resulting in remarkable diarrheal improvement. Renal function was also improved without dialysis. Although isosporiasis is rarely found in Japan, it is stressed that in the AIDS patient with persistent diarrhea who may develop a parasitic disease as did in this case, frequent fecal examinations should be conducted.

AIDS-Related Opportunistic Infections↗

PubMed1998

[Correlation between apoptotic index, bcl-2 protein expression and progression and prognosis in breast carcinoma].

Apoptosis is considered to play a critical role in tumorigenesis. It has been shown that apoptosis is controlled by both pro-oncogenes bcl-2, c-myc and tumor-suppressor genes p53. We determined the apoptotic index (AI) on light microscopy and detected immunohistochemically the expression of bcl-2 and p53 in patients with breast cancer. The correlations between AI and clinicopathological factors, bcl-2 and p53 were also analyzed. Our results showed that bcl-2 expression was down-regulated in the process from normal breast epithelial cells to intraductal carcinoma and from intraductal carcinoma to invasive carcinoma. We failed to detect p53 protein in normal breast epithelial cells, and p53 positivity was 24% and 30% in intraductal and invasive cancer tissues, respectively. Moreover, AI was significantly associated with histological grade, mitotic index, and bcl-2 and p53 expression. In univariate analyses, lower AI and bcl-2 expression was significantly predictive of a better prognosis for both disease-free survival and overall survival. These results suggest that apoptosis and apoptosis-related gene (bcl-2, p53) are related to progression and prognosis in breast cancer.

Adult↗

PubMed1998

Asthma, adenosine, mast cells and theophylline.

Many clinical trials have suggested that theophylline has anti-inflammatory properties in the treatment of bronchial asthma. Proposed mechanisms of theophylline inhibition include phosphodiesterase inhibition, an adenosine receptor antagonist, the increase of circulating adrenaline, mediator antagonist and inhibition of calcium ion influx. Further to these observations we report on the inhibition by theophylline of NF-kappaB, a key transcription factor found in human purified mast cells, which plays a role in the transcription of TNF alpha, GM-CSF, and IL-8 within this cell. The suppression of NF-kappaB activation, indicates that theophylline, in addition to its bronchodilator activities, has the potential for anti-inflammatory activity.

Adenosine↗

PubMed1997

[Emerging infectious diseases--New-type cholera].

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4-Quinolones↗

PubMed1997

Differentiation and morphogenesis in pellet cultures of developing rat retinal cells.

We previously developed a reaggregate cell culture system (pellet cultures) in which retinal neuroepithelial cells proliferate and give rise to rod photoreceptor cells (rods) in vitro (Watanabe and Raff, 1990, Neuron 4:461-467). In the present study, we analyzed cell differentiation and morphogenesis in pellet cultures by using both cell-type-specific markers with immunofluorescence and electron microscopy. We demonstrated that, in addition to rods, the other major retinal cell types, including amacrine cells, bipolar cells, Müller cells, and ganglion cells were all present in the pellets, where most were able to develop from dividing precursor cells in vitro. The different cell types in the pellets became organized into two distinct structures: dark rosettes and pale rosettes. The cellular composition of these structures indicated that the dark rosettes correspond to the outer nuclear layer and the pale rosettes to the inner nuclear layer of the normal retina. Ultrastructural studies have indicated that the thin layer of neuronal processes surrounding the dark rosettes correspond to the outer plexiform layer, and the central region of the pale rosettes correspond to the inner plexiform layer of the normal retina. Other features of normal retinal development also occurred in the pellets, including programmed cell death and the formation of inner and outer rod cell segments and synapses. Thus, pellet cultures provide a convenient way to study different aspects of retinal development where one can control the size and the cellular composition of the initial reaggregate.

Animals↗

PubMed1997

[Simple method for typing human immunodeficiency virus type I (B, E) by PCR and chronological change of distribution of subtype (B to E) in Japan].

We analyzed the clade distribution of B and E in HIV-1 isolates in Japan by a nested PCR method using 5'-CCCACAAGATTTAAATATG-3' of the gag gene as clade B primer and 5'-CCCACAAGATTTAAACTCC-3' of the gag gene as clade E primer. Seventy-two anti-HIV-1 confirmatory positive serum samples were collected during a period of 1991-1996 in two hospitals in Yokohama City. Peripheral blood mononuclear cells were obtained from the buffy coat of these samples and extracted DNA were used for nested PCR. The 72 cases comprised of 11 Japanese hemophiliacs, 14 Japanese male homosexuals, 19 Japanese male heterosexuals, 5 Japanese female heterosexuals and 23 Thai female heterosexuals. Of these 36 were clade B and 35 were clade E and one case showed positive PCR results for both B and E primers. Almost all male Japanese hemophiliacs and homosexuals in our sample have clade B, while the female Thai heterosexuals have clade E, irrespective of the year of isolation. As for Japanese male heterosexuals, through 1993, clade B was predominant but since 1994, the predominate clade switched to clade E. Although the number of Japanese female heterosexuals in our sample is small, clade B was isolated in 2 cases even after 1994.

Female↗

PubMed1997

A monoclonal antibody against very late activation antigen-4 inhibits eosinophil accumulation and late asthmatic response in a guinea pig model of asthma.

Preferential eosinophil accumulation is a characteristic of airway inflammation in asthma. Although little is known about its mechanism, recent in vitro observations suggest that the very late activation antigen-4 (VLA-4, CD49d/CD29) and vascular cell adhesion molecule-1 (VCAM-1) adhesion pathway may be involved in specific eosinophil migration. To test this hypothesis, we studied the effect of an anti-VLA-4 monoclonal antibody (mAb) on the airway eosinophilia in a guinea pig model of asthma. Guinea pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed a striking airway eosinophilia and late asthmatic response (LAR). In contrast, when guinea pigs were pretreated intravenously at 2 h before antigen challenge with a rat antimouse VLA-4 mAb, PS2/3, cross-reacting with guinea pig eosinophils and lymphocytes, eosinophil, basophil and lymphocyte infiltration in the tracheal wall was significantly inhibited as well as LAR in a dose-dependent manner. These results suggest that VLA-4 plays a critical role in antigen-induced airway eosinophilia and LAR.

Animals↗

PubMed1997

Comparison of platelet-activating factor receptor mRNA levels in peripheral blood eosinophils from normal subjects and atopic asthmatic patients.

Platelet-activating factor (PAF) modulates the functions of eosinophils, which play an important role in allergic inflammation, through a specific receptor(s) expressed on the cell surface. We compared expression levels of mRNA for the PAF receptor (PAF-R) in peripheral blood eosinophils from atopic asthmatic patients with those from normal healthy subjects using a relative quantification method based on the reverse transcription-polymerase chain reaction (RT-PCR). We found that the levels of PAF-R mRNA in eosinophils from the patients were significantly higher than those in normal subjects. These results suggest that the increased expression of PAF-R in eosinophils may be relevant to the pathogenesis of atopic asthma.

Adult↗

PubMed1996

Theophylline at therapeutic concentration suppresses PAF-induced upregulation of Mac-1 on human eosinophils.

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Asthma↗