Successful treatment of DIC with a serine proteinase inhibitor.
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Aged↗
Biomedical subjects
M Kagami
Publications and source records attributed to M Kagami.
Glandular and extraglandular expression of costimulatory molecules in patients with Sjögren's syndrome.
OBJECTIVES: To investigate the expression and regulation of CD80, CD86, and CD28 costimulatory molecules in sialoadenitis and interstitial nephritis in patients with Sjögren's syndrome (SS). METHODS: Expression of CD80, CD86, and CD28 molecules was studied by immunohistochemical staining of lip biopsy specimens obtained from patients who had sialoadenitis associated with SS, and renal biopsy specimens obtained from patients who had interstitial nephritis associated with SS. To elucidate the mechanism of de novo expression of CD80 and CD86 antigens, their induction by cytokines in human salivary duct cell line (HSG) and renal cortical epithelial cells (HRCE) by cell enzyme linked immunosorbent assay (ELISA) was quantitatively investigated. RESULTS: In patients with severe sialoadenitis, CD80 and CD86 were strongly expressed on ductal epithelial cells. In contrast, these antigens were not found in the minor salivary glands of normal subjects or of patients with mild sialoadenitis. Some infiltrating cells expressed CD28. In patients who had interstitial nephritis associated with SS, some tubular epithelial cells expressed CD86 but not the CD80 antigen. Unstimulated HSG cells did not express CD80 or CD86. Interferon gamma (IFNgamma) consistently up regulated levels of CD80 and CD86. In contrast, tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), IL2, and IL4 had no effect on either CD80 or CD86 levels. Unstimulated HRCE did not express CD80 or CD86. IFNgamma consistently up regulated CD86 expression. No CD80 expression was found on tubular cells. TNFalpha, IL1beta, IL2, and IL4 had no discernible effects. CONCLUSIONS: Salivary ductal cells in patients with SS can express CD80 and CD86 costimulatory molecules in response to IFNgamma. Tubular epithelial cells in patients who have interstitial nephritis associated with SS express only CD86 molecules. In patients with SS, salivary ductal cells and tubular epithelial cells may activate infiltrating CD28 positive T lymphocytes by presenting antigens to T cells, potentially leading to tissue destruction.
Adult↗
[Chronotherapy of bronchial asthma: circadian rhythms in asthmatic symptoms. Report I: Survey on chronobiology acrophase of asthmatic symptoms].
We conducted a questionnaire survey on the onset time and frequency of asthmatic symptoms in adults with bronchial asthma who were regular clinic attendees in 17 sites in Chiba Prefecture, and analyzed 513 respondents. As a result, the frequency of wheezing was 54.6%, the highest of all symptoms. Feeling of chest discomfort was 32.2%, followed by asthma attack (13.8%), cough (8.7%) and dynpnea (6.8%). Asthmatic symptoms were highest from midnight to early morning, with the peak at around 4 o'clock am. The same pattern was seen regardless of the severity and types of asthma. This survey also showed that conventional anti-asthmatic therapies decreased the frequency of nightly asthmatic symptoms from the baseline: 7 times or more per week reduced from 44.9% to 16.1%, 3 times or more per week from 76.8% to 40.4%, and at least once per week from 94.4% to 71.5%. The results suggest that it is important to take another therapeutic strategy, which can administer medications at the appropriate time according to the circadian rhythms in asthmatic patients to better control asthma.
Adult↗
[Chronotherapy of bronchial asthma: circadian rhythms in peak expiratory flow. The report II: Circadian rhythms of peak expiratory flow in asthmatic patients and effect of sustained-release theophylline on various types of the circadian rhythms].
We monitored peak expiratory flow (PEF) in outpatients with adult bronchial asthma in 17 sites in Chiba prefecture 4 times daily for 2 weeks, using a peak flow meter to categorize the patients by circadian patterns of PEF. Then a sustained-release theophylline preparation formulated for once-daily dosing was administered to these patients grouped to examine the effect of the drug on circadian rhythms in PEF. Analysis was performed in 215 of total 245 patients enrolled as a result of excluding 30 ineligible patients. 187 patients (87.0%) exhibited a certain rhythm in their PEF, and 28 patients (13.0%) did not show any particular rhythm. These 187 patients with a certain rhythm in PEF were grouped into 63 patients (29.3%) of morning-dip type, 83 patients (38.6%) of peak type, 7 patients (3.3%) of evening-dip type, and 34 patients (15.8%) of flat type. And there were no trough-type patients. Uniphyl tablets were administered once a day at a daily dosage of 400 mg after supper to 124 patients of the above 187 patients grouped according to circadian patterns of PEF. Uniphyl was particularly effective in the morning-dip type and the peak type. This result suggests that it is necessary to take circadian rhythms of PEF into consideration in drug therapy for patients with bronchial asthma.
Adolescent↗
Effect of YM-126414 on glucose uptake and redistribution of glucose transporter isotype 4 in muscle cells.
We discovered a novel compound, YM-126414 [1,3, 3-trimethyl-2-(2-phenylaminovinyl)-3H-indolium perchlorate], which stimulates glucose uptake in skeletal muscle cells in vitro. This compound increased the rate of consumption of glucose by C2C12 mouse myoblast cells in a dose-dependent manner (EC(50)=10 nM). To investigate the mechanism of this stimulation, we determined the redistribution of insulin-regulatable glucose transporter isotype 4 (Glut4). When fully differentiated C2C12 cells stably expressing myc-tagged Glut4 protein were treated with YM-126414, redistribution was dramatically increased in a dose-dependent manner (EC(50)=21 nM). These results indicate that YM-126414 is a novel glucose uptake stimulator for muscle cells by causing up-regulation of Glut4 redistribution in differentiated muscle cells. Our findings for the in vitro effects of YM-126414 suggest a direction for the development of new drugs for the treatment of type 2 diabetes.
Animals↗
Metastatic breast carcinoma masquerading as primary colon cancer.
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Barium Sulfate↗
Regulation of CD69 expression on eosinophil precursors by interferon-gamma.
The purpose of this study was to determine whether interferon-gamma (IFN-gamma) induced CD69 expression by eosinophil precursors. Eosinophil precursors were induced from CD34+ cord blood cells using recombinant human interleukin-3 (IL-3) and interleukin-5 (IL-5). On day 14 of culture, cells constitutively expressed CD69 and the IFN-gamma receptor (IFN-gammaR). Stimulation with IFN-gamma for 24 h did not affect IFN-gammaR expression by the cells. On the other hand, IFN-gamma significantly upregulated CD69 expression by the precursors after 24 h of incubation. A specific JAK2 inhibitor (AG-490) caused a concentration-dependent suppression of IFN-gamma-induced CD69 expression by the precursors. In conclusion, these results indicate that IFN-gamma induces CD69 expression by eosinophil precursors via the activation of JAK2.
Antigens, CD↗
Clinicopathologic prognostic factors in patients with Borrmann type 4 gastric cancer: univariate and multivariate analyses.
BACKGROUND: Advanced gastric cancer is classified into four Borrmann types, types 1 to 4. Type 4 is a relatively undifferentiated carcinoma with little or no gland-forming capability. Despite recent advances in the diagnosis and surgical management of gastric cancer, most tumors of Borrmann type 4 are not detected at an early stage and the prognosis remains poor; the five-year survival rate after gastric resection ranges from 10 to 20 percent. We evaluated the affects of several clinicopathologic variables on the 5-year survival rate after resection of Borrmann type 4 gastric cancer. METHODS: Data on clinical characteristics were obtained from the records of patients who underwent gastric resection between 1985 and 1995 at the Department of Surgery, Sendai National Hospital, and follow-up data were obtained from our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides. The relationship between clinicopathologic variables and 5-year survival rate was estimated by the Kaplan-Meier survival curve and the logrank test. Multivariate Cox's proportional hazards regression analysis was then performed to determine which variables were independent prognostic factors. RESULTS: Eighty-seven patients with Borrmann type 4 gastric cancer underwent a resection during the study period at our hospital. The overall 5-year survival rate was 14.8%. The relationship between clinicopathologic variables and 5-year survival rate was determined by constructing a Kaplan-Meier survival curve. Tumor location (upper, middle and distal vs whole stomach, p=0.0214), lymph node metastasis, capillary microinvasion, and peritonitis carcinomatosa (absent vs present, p<0.05) significantly influenced survival. When multivariate analysis using Cox's proportional hazards regression of 5-year survival was performed, capillary microinvasion, peritonitis carcinomatosa (absent vs present) and tumor location (distal vs whole stomach) emerged as the statistically significant independent prognostic factors associated with long-term survival. CONCLUSION: Capillary microinvasion and the presence or absence of peritonitis carcinomatosa are more powerful predictors of 5-year survival than is lymph node metastasis. Patients with gastric cancer of the whole stomach have a poorer prognosis than do those with carcinoma in the antrum of the stomach.
Adult↗
Role of JAK2 signal transductional pathway in activation and survival of human peripheral eosinophils by interferon-gamma (IFN-gamma).
The purpose of this study was to determine whether the JAK pathway is involved in eosinophil activation and survival through IFN-gamma receptor signalling in human peripheral eosinophils. Eosinophils were purified from the blood of six atopic disease patients by anti-CD16 magnetic bead-negative selection. IFN-gamma significantly up-regulated survival and CD69 expression in 24-48 h cultured eosinophils. Further, IFN-gamma induced tyrosine phosphorylation of JAK2 in eosinophils, as indicated by Western blot analysis. Finally, the specific JAK2 inhibitor AG-490 inhibited the tyrosine phosphorylation of JAK2, IFN-gamma-induced survival and CD69 expression in eosinophils. In conclusion, these results indicate that IFN-gamma induces eosinophil survival and CD69 expression through the activation of JAK2 in peripheral eosinophils, suggesting that JAK2 may play a significant role in eosinophil regulation by IFN-gamma-IFN-gammaR interaction.
Adolescent↗
Eosinophil activation and in situ interleukin-5 production by mononuclear cells in skin lesions of patients with drug hypersensitivity.
In order to determine the inflammatory mechanisms of skin lesions in patients with drug hypersentivity, we examined eosinophil activation and interleukin-5 (IL-5) production in infiltrating lymphocytes. First, we showed that the number of peripheral eosinophils and the level of serum IL-5 at the eruption-active stage were both significantly higher than those in healed skin eruptions. Histological and immunohistological examination revealed that CD4+ T cells and eosinophils significantly more densely infiltrated drug eruptions than control skin lesions. The infiltrating eosinophils were also shown to be activated by immunostaining using anti-secreted formed eosinophilic cationic protein monoclonal antibody. The expression of mRNA for IL-5 in the infiltrating mononuclear cells at drug eruptions was shown by in situ hybridization. These results suggest that infiltrating CD4+ T cells might regulate both peripheral and tissue eosinophils and facilitate allergic inflammation at drug eruptions by means of IL-5 production.
Adult↗
[Sensitivity of sputum eosinophil cationic protein level for monitoring asthmatic patients with normal peak expiratory flow].
Previous studies have shown that eosinophils and eosinophil cationic protein (ECP) levels in the sputum of patients with asthma closely reflect inflammatory activity of the bronchial mucosa. We examined whether the ECP level or eosinophil count in induced sputum provides information useful in determining whether to taper the dose of medications or to terminate treatment especially with inhaled corticosteroids in patients with well controlled asthma. We studied 15 adults with asthma who consistently maintained a peak expiratory flow (PEF) value within 80% or more of their predicted value (green zone) for at least 4 weeks with no asthmatic symptoms. All patients underwent at least two hypretonic saline inhalation tests. Forty sputum samples were obtained for evaluation of cell count and ECP level. Before the tests, patients were requested to record asthmatic symptoms, medications received, and morning and evening PEF values in a diary for more than 3 months. The relations among clinical and laboratory variables, including symptoms scores, medication scores, asthma scores (= symptom scores + medication scores). PEF values, forced expiratory volume (FEV1.0) during the test, and sputum eosinophil count or sputum ECP, were analyzed. The sputum ECP level correlated significantly with the percentage of eosinophils in the sputum (rs = 0.783). There were also significant correlations between the sputum ECP level and the mean weekly symptom scores (rs = 0.500-0.510), medication scores (rs = 0.510-0.540), and asthma scores (rs = 0.509-0.548). However, there were no significant correlations among sputum ECP level, mean morning PEF or evening PEF, daily variation in PEF, and FEV1.0. We conclude that the sputum ECP level is a sensitive laboratory variable useful in monitoring the presence of eosinophilic inflammation in the bronchial mucosa of patients with bronchial asthma, especially those who have mild or no symptoms with normal PEF.
Adult↗
A patient with non-A, non-B, non-C hepatitis-associated aplastic anemia recovered promptly following immuno-suppressive therapy, including antithymocyte globulin.
A 21-year-old male patient with non-A, non-B, non-C acute hepatitis was complicated by hepatitis-associated severe aplastic anemia during hospitalization for active hepatitis. He was promptly diagnosed and treated with methylprednisolone, anabolic steroids, cyclosporin A, granulocyte colony-stimulating factor (G-CSF), and antithymocyte globulin (ATG). He responded quickly to the immuno-suppressive therapy and was transfusion independent after 25 days and granulocyte colony-stimulating factor independent at 57 days after ATG therapy. Although the etiology of hepatitis-associated aplastic anemia is still controversial, the authors emphasized the importance to carefully follow non-A, non-B, non-C hepatitis patients without aplastic anemia for more than three months after hepatitis episodes in order to improve outcome of this lethal disease.
Adult↗
Sro7p, a Saccharomyces cerevisiae counterpart of the tumor suppressor l(2)gl protein, is related to myosins in function.
Yeast SRO7 was identified as a multicopy suppressor of a defect in Rho3p, a small GTPase that maintains cell polarity. Sro7p and Sro77p, a homologue of Sro7p, possess domains homologous to the protein that are encoded by the Drosophila tumor suppressor gene lethal (2) giant larvae [l(2)gl]. sro7Delta sro77Delta mutants showed a partial defect of organization of the polarized actin cytoskeleton and a cold-sensitive growth phenotype. A human counterpart of l(2)gl could suppress the sro7Delta sro77Delta defect. Similar to the l(2)gl protein, Sro7p formed a complex with Myo1p, a type II myosin. These results indicate that Sro7p and Sro77p are the yeast counterparts of the l(2)gl protein. Our genetic analysis revealed that deletion of SRO7 and SRO77 showed reciprocal suppression with deletion of MYO1 (i.e., the sro7Delta sro77Delta defect was suppressed by myo1Delta and vice versa). In addition, SRO7 showed genetic interactions with MYO2, encoding an essential type V myosin: Overexpression of SRO7 suppressed a defect in MYO2 and, conversely, overexpression of MYO2 suppressed the cold-sensitive phenotype of sro7Delta sro77Delta mutants. These results indicate that Sro7 function is closely related to both Myo1p and Myo2p. We propose a model in which Sro7 function is involved in the targeting of the myosin proteins to their intrinsic pathways.
Actins↗
Heterogeneous expression of tumor necrosis factor-alpha receptors I and II on human peripheral eosinophils.
BACKGROUND: Expression of the tumor necrosis factor-alpha receptor by human eosinophils has not been determined. We examined the surface expression and mRNA for tumor necrosis factor-alpha receptors I and II (TNF-alphaRI and TNF-alphaRII) on peripheral eosinophils. METHODS: Eosinophils were obtained from 17 asthma patients and 3 healthy volunteers. Flow cytometry was used to examine receptor expression, and the reverse transcriptase-polymerase chain reaction was used to examine receptor mRNA expression. RESULTS: Flow cytometry revealed that 16 out of 20 subjects had eosinophils expressing TNF-alphaRI and 18 subjects had eosinophils expressing TNF-alphaRII. All eosinophils expressed at least one receptor. The mRNA for TNF-alphaRII was detected in all eosinophils examined, but the signals for TNF-alphaRI mRNA were only found in cells expressing this receptor. CONCLUSIONS: Human peripheral eosinophils show heterogeneous expression of TNF-alphaRI and TNF-alphaRII.
Adolescent↗
Interferon-gamma receptor beta-chain expression and formation of alpha- and beta-chain complexes after receptor conjugation on human peripheral eosinophils.
BACKGROUND: It has been unclear whether or not the interferon-gamma receptor (IFN-gammaR) on human peripheral eosinophils is completely functional. Accordingly, we examined the expression of IFN-gammaR alpha- and beta-chains and the association of the two chains after binding of IFN-gamma to the receptor. METHODS: Peripheral blood eosinophils were obtained from 8 patients (bronchial asthma, n=6, and hypereosinophilic syndrome, n=2), and expression of the alpha- and beta-chain was investigated by flow cytometry with specific antibodies. Expression of mRNA for the alpha- and beta-subunits was also investigated by the reverse transcriptase-polymerase chain reaction. RESULTS: Eosinophils from all the patients were positive for both the alpha- and beta-chains by flow cytometry. In addition, mRNA for both chains was detected by the polymerase chain reaction. Furthermore, coprecipitation of the alpha- and beta-chains was only found after eosinophil stimulation with IFN-gamma. CONCLUSIONS: Human peripheral eosinophils apparently express both the alpha- and beta-chains of the IFN-gammaR, and the two chains may only form the receptor complex after ligand binding.
Adolescent↗
Expression of cell adhesion molecules in tubulointerstitial nephritis associated with Sjögren's syndrome.
The tissue distribution of cellular adhesion molecules (ICAM-1, ELAM-1, VCAM-1) was studied in specimens from six normal human kidneys and in six biopsies from kidneys with tubulointerstitial nephritis associated with Sjögren's syndrome. In addition, the expression of cellular adhesion molecules was examined both in four renal biopsies from cases of tubulointerstitial nephritis of diverse pathogenesis and in six lip biopsies from cases of Sjögren's syndrome. ICAM-1 was expressed on vascular endothelial cells in normal kidneys, in all specimens of tubulointerstitial nephritis and in salivary glands. On tubular epithelial cells, ICAM-1 appeared slightly in normal kidneys; otherwise tubular epithelial ICAM-1 was observed in and around the foci of cellular infiltration in all cases of tubulointerstitial nephritis. ELAM-1 and VCAM-1 were observed on the newly generated vessels in massive cellular infiltrates in some cases of tubulointerstitial nephritis associated with Sjögren's syndrome; by contrast, they were not seen in normal kidneys and in cases of tubulointerstitial nephritis of diverse pathogenesis. In the lip biopsies from salivary glands, ICAM-1 was observed on ductal epithelial cells in and around the foci of cellular infiltration, and ELAM-1 and VCAM-1 occasionally appeared on the newly generated vessels in massive cellular infiltrates. Chronic and progressive inflammation may be facilitated by such ELAM-1 and VCAM-1 expression on newly generated vessels. The adhesion molecules were thought to play a role in the pathogenesis of tubulointerstitial nephritis and sialoadenitis associated with Sjögren's syndrome. It was thus concluded that the same inflammatory process that took place in the salivary glands to induce the characteristic tissue change of Sjögren's syndrome likely was operative in the renal tubulointerstitial tissue as well.
Adolescent↗
Human peripheral eosinophils express functional interferon-gamma receptors (IFN-gammaR).
In order to determine whether or not IFN-gammaR is associated with regulatory mechanisms on human eosinophil function, we examined the expression of functional IFN-gammaR on human peripheral eosinophils. In this study, peripheral blood eosinophils were obtained from seven normal controls and 12 patients (bronchial asthma, n = 9, and hypereosinophilic syndrome (HES), n = 3), and the purity of eosinophils was 97.11 +/- 2.31%, n = 19. We first showed that anti-IFN-gammaR alpha-chain MoAb reacted with all tested eosinophils of both normal controls and patients by flow cytometry analysis. We also showed expression of mRNA for the alpha-chain of IFN-gammaR in all purified eosinophils of six individuals. Further, to characterize IFN-gammaR on eosinophils, we did binding experiments with 125I-IFN-gamma on purified peripheral eosinophils. The linear Scatchard plot indicated a single type of high-affinity binding sites (dissociation constant (Kd) = 3.89-4.95 x 10(-10) M, numbers of binding sites = 183-233/cell, n = 3). To determine whether IFN-gammaR on eosinophils is functional, we examined surface eosinophilic cationic protein (ECP) and CD69 induction after IFN-gammaR ligation with recombinant human IFN-gamma (rhIFN-gamma) on eosinophils by flow cytometry. rhIFN-gamma stimulation significantly induced both ECP and CD69 expression on the 2-18 h-cultured eosinophils in a dose-dependent manner. Further, the effects of rhIFN-gamma stimulation were significantly blocked by both a neutralizing anti-IFN-gamma MoAb and a blocking anti-IFN-gammaR MoAb. These results suggest that human peripheral eosinophils express functional IFN-gammaR.
Adolescent↗
IL-5 but not interferon-gamma (IFN-gamma) inhibits eosinophil apoptosis by up-regulation of bcl-2 expression.
In order to determine regulatory mechanisms of eosinophil apoptosis, we examined the effect of recombinant IL-5 and interferon-gamma (IFN-gamma) on eosinophil apoptosis and bcl-2 expression. rhIL-5 (2.5 ng/ml) significantly inhibited eosinophil apoptosis in 96 h in vitro culture compared with medium only-cultured eosinophils (89.4 +/- 3.6% versus 31.3 +/- 12.2% (mean +/- s.d.); n = 7, P < 0.05). Further, rhIL-5 significantly increased bcl-2 protein and mRNA expression on cultured eosinophils. A phosphorothioate antisense oligonucleotide targeted at the ATG translation initiation codon of bcl-2 (10(-5) M) could significantly block the supportive effect of rhIL-5 (0.25 ng/ml) for eosinophil survival compared with sense cDNA of bcl-2 on 96 h culture (inhibition rate 28.01 +/- 4.56% versus 0.07 +/- 1.73%; n = 4, P < 0.05). In contrast, rhIFN-gamma (100 U/ml) significantly inhibited eosinophil apoptosis on 96 h in vitro culture (72.7 +/- 10.5%; n = 7, P < 0.05), but did not significantly up-regulate bcl-2 protein and mRNA. These results indicate that IL-5 has inhibitory effects on eosinophil apoptosis by regulation of bcl-2 expression.
Apoptosis↗