[Emergency care of diabetics. 3. Hypoglycemia and unstable metabolic state (including self-determination of the blood glucose level)].
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Blood Glucose↗
Biomedical subjects
J Sato
Publications and source records attributed to J Sato.
Structural requirements of heparan sulfate for the binding to the tumor-derived adhesion factor/angiomodulin that induces cord-like structures to ECV-304 human carcinoma cells.
Tumor-derived adhesion factor/angiomodulin (AGM) is accumulated in tumor blood vessels and on the endothelial cell surface (Akaogi, K., Okabe, Y., Sato, J., Nagashima, Y., Yasumitsu, H., Sugahara, K., and Miyazaki, K. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 8384-8389). In cell culture, it promotes cell adhesion and morphological changes to form cord-like structures of the human bladder carcinoma cell line ECV-304. The cord formation is prevented by heparin, which inhibits the binding of AGM to ECV-304 cells. This observation suggests that AGM interacts with cell surface heparan sulfate (HS) proteoglycans. In this study, HS glycosaminoglycans and core proteins of integral transmembrane proteoglycans, syndecan-1 and -4, were identified by immunocytochemistry on ECV-304 cells, and the structural requirements for the interaction of HS with AGM were characterized. Inhibition experiments with sulfated polysaccharides and chemically modified heparin derivatives indicated that sulfate groups were essential for both AGM-HS binding and cord-like structure formation and that the rank order of the different sulfate groups in terms of their contribution was N-sulfate > 6-O-sulfate > 2-O-sulfate. The minimum size of heparin, a chemical analog of HS, required for the binding to AGM was a dodecasaccharide as determined by competition experiments using size-defined heparin oligosaccharides. Thus, a specific sulfation pattern in the HS of cell surface syndecans of ECV-304 cells is required for AGM binding and the morphological changes.
Animals↗
Acute changes in bladder volume produce minimal cardio-respiratory responses in lightly anesthetised humans.
PURPOSE: To examine whether changes in bladder volume elicit reflex cardiovascular and respiratory responses in humans under general anesthesia with sevoflurane and nitrous oxide. METHODS: Fourteen patients free of autonomic disorders were anesthetized with sevoflurane 0.5% and nitrous oxide 60% in oxygen that were approximately equivalent to 0.9 MAC. Warmed saline (6 ml x kg(-1), 37 degrees C) was instilled into the pre-emptied urinary bladder, and then the bladder was kept distended for five minutes. Following the distension, the instilled saline was drained to the pre-instilled volume of the bladder Arterial blood pressure, respiratory flow, and intra-vesicle pressure were continuously measured, and mean arterial pressure, pulse rate, respiratory rate, tidal volume, and minute ventilation were estimated offline from these signals. RESULTS: Bladder emptying produced small decreases in mean blood pressure (from 83.4+/-4.3 to 80.0+/-4.4 mm Hg, mean +/- SE, P = 0.017) and pulse rate (from 72.2+/-2.9 to 69.4+/-2.7 bpm, mean +/- SEM, P = 0.004). Only minimal respiratory reflexes were invoked by the bladder volume changes. CONCLUSION: In lightly anesthetized humans, the acute changes in bladder volume produce only mild cardiovascular and respiratory responses.
Adult↗
Gene transfer of endothelial nitric oxide synthase alters endothelium-dependent relaxations in aortas from diabetic rabbits.
AIMS/HYPOTHESIS: Cardiovascular disease is the leading cause of death in diabetes mellitus. Abnormal endothelium-dependent relaxation is observed both in humans and in animal models of diabetes mellitus and decreased bioavailability of nitric oxide (NO) is thought to be involved in this defect. Therefore, the aim of this study was to test whether adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) alters vascular reactivity of diabetic vessels. METHODS: Vascular reactivity was first assessed in thoracic aortas and carotid arteries from nine alloxan-induced diabetic (plasma glucose, 26.5 +/- 1.2 mmol/l; HbA1c, 6.4 +/- 0.3%) and nine control rabbits (plasma glucose, 11.1 +/- 1.3 mmol/l; HbA1c, 2.1 +/- 0.1%). Vascular reactivity was next examined in thoracic aortas of diabetic animals after ex vivo transduction with replication-deficient adenovirus encoding gene for eNOS (AdeNOS) or beta-galactosidase (Ad beta gal). RESULTS: After 10 weeks of hyperglycaemia, endothelium-dependent relaxation to acetylcholine was impaired in diabetic aorta, but was normal in carotid arteries from diabetic rabbits. In contrast, responses of both vessels to calcium ionophore and nitric oxide donor were normal. Histochemical staining for beta-galactosidase and immunohistochemistry for eNOS showed transgene expression in the endothelium and adventitia in Ad beta gal and AdeNOS transduced vessels, respectively. During submaximum contractions with phenylephrine, relaxations to low concentrations of acetylcholine (3 x 10(-8) to 10(-7) mol/l) were augmented in AdeNOS transduced diabetic vessels. CONCLUSION/INTERPRETATION: These findings suggest that adenovirus-mediated gene transfer of eNOS to diabetic aorta alters vascular reactivity.
Animals↗
Effects of lowering ambient temperature on pain-related behaviors in a rat model of neuropathic pain.
To clarify the mechanism by which changes in chronic pain are induced by cold environments, rats rendered neuropathic by a chronic constriction injury (CCI) to the sciatic nerve were exposed to low ambient temperature (LT; 7 degrees C decrease from 22 degrees C) in a climate-controlled room. LT exposure aggravated pain-related behaviors in CCI rats, i.e., decreased the threshold to von Frey hair and paw pressure stimulation, prolonged the duration of foot withdrawal to pinprick stimulation, and increased the cumulative duration of guarding posture. Lumbar sympathectomy (SYX) did not inhibit LT-induced augmentations of pain-related behaviors in CCI rats. LT exposure decreased the skin temperatures of both hind paws to the same degree in the sham-operated control and SYX rats, while in the CCI and SYX+CCI rats it caused a larger temperature decrease in the injured paw than in the uninjured one. These results indicate that LT exposure augments abnormalities in pain-related behaviors of neuropathic rats, and also suggest that sympathetic nervous activity is not a predominant factor in the augmenting mechanism.
Animals↗
Water content and thickness of the stratum corneum contribute to skin surface morphology.
Skin surface morphology has long been recognized as reflecting skin pathology. In the present study, we evaluated skin surface morphology using hairless mice under contrasting conditions of humidity. The skin surface microrelief was recorded with opaque quick-drying silicone rubber, and examined under a microscope. A binary image was produced by density slicing. Within 3 days of exposure to dry conditions, skin roughness was significantly increased. The skin roughness was partially mitigated by topical application of an aqueous solution of glycerol or hydration by immersion in water. A significant correlation between skin roughness and stratum corneum thickness was also observed. These results suggest that skin surface morphology is associated with both water content and thickness of the stratum corneum.
Administration, Topical↗
Migratory patterns of thoracic duct lymphocytes into bronchus-associated lymphoid tissue of immunized rats.
Lymphocytes continuously circulate between the bloodstream and lymphoid organs, and their migration into lymphatic tissues presumably occurs through selective mechanisms. Although bronchus-associated lymphoid tissue (BALT) is known as an inductive tissue of the common mucosal immune system, little is known about how effectively the lymphocytes in the blood vessels migrate into the BALT, thereby enabling the BALT to act as an effector tissue in the immunologic responses of the lungs. To analyze whether or not thoracic duct lymphocytes (TDL) from immunized and nonimmunized rats possess different migratory patterns to the BALT, 5-(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled TDL were injected into rats with BALT hyperplasia that was produced by intratracheal administration of TNP-KLH, and then the number of labeled cells in the BALT were examined by immunohistochemical methods. We studied the following three groups at 12 h after the injection: group A, intraintestinally immunized donors and intratracheally immunized recipients; group B, nonimmunized donors and intratracheally immunized recipients; group C (control group), nonimmunized donors and nonimmunized recipients. Time course studies 0.5, 4, 12, and 24 h after the injection were done in groups A and C. In a cytokinetic study, larger numbers of CFSE-labeled lymphocytes were found at 12 h and 24 h in group A than in group C. At 12 h after the injection, the absolute number of CFSE-labeled lymphocytes per BALT was significantly higher in group A than in group B (p < 0.05), and was lowest in group C. Histologically, there was a marked proliferation of high endothelial venules (HEV), with findings of adhesion and influx of lymphocytes inside the HEV in group A. These observations indicate that the immunized BALT actively recruits immunized TDL through a specific mechanism of lymphocyte-endothelium recognition in HEV, which partially explains the process of BALT development as an effector tissue for local immunity.
Animals↗
eNOS gene transfer to vascular smooth muscle cells inhibits cell proliferation via upregulation of p27 and p21 and not apoptosis.
OBJECTIVE: Smooth muscle cell (SMC) proliferation is a critical component of vascular diseases such as atherosclerosis and restenosis. Nitric oxide (NO) donors and gene transfer of endothelial nitric oxide synthase (eNOS) have been shown to inhibit SMC proliferation. NO may cause this effect by delaying cell cycle progression and/or induction of apoptosis. The aim of the current study was to examine the mechanism of eNOS-mediated inhibition of SMC proliferation. In addition, the effect of eNOS expression in vascular SMCs on the expression of the cyclin dependent kinase inhibitors, p27 and p21 was examined. METHODS: SMCs were transduced with an adenoviral vector encoding eNOS (AdeNOS) or beta-galactosidase (Ad beta Gal) at a multiplicity of infection of 100. Non-transduced cells served as additional controls. Transgene expression was sought by NADPH diaphorase staining, immunohistochemistry and Western Blotting. Functionality of the recombinant protein was assessed by measurement of cGMP. Cell cycle analysis was performed by flow cytometry and p27 and p21 expression were studied by western blot analysis. Apoptosis was sought by Annexin V staining and DNA laddering. RESULTS: eNOS expression was detected in transduced SMCs. cGMP levels were increased in eNOS-transduced compared to control cells. Expression of eNOS in SMCs resulted in a delay in cell cycle progression and upregulation of p27 and p21. There was no increase in apoptosis detected in eNOS transduced cells after 24 or 72 h. CONCLUSION: eNOS gene transfer to vascular SMCs inhibits cell proliferation via upregulation of p27 and p21 resulting in a delay in cell cycle progression.
Animals↗
Subacute hepatic failure associated with a new antidiabetic agent, troglitazone: a case report with autopsy examination.
An autopsy case of fatal subacute hepatic failure after administration of troglitazone is described. The liver dysfunction developed about five months after the patient, a sixty-three-year-old woman, had been initially treated with troglitazone. The patient developed hepatic failure and died despite various hepatic auxiliary treatments such as plasmapheresis. Autopsy findings revealed focal liver cell necrosis, cholestasis and steatosis with infiltration of lymphocytes and neutrophils and lack of regenerative activity. The causative mechanism of liver dysfunction may be metabolite aberration, as a result of accumulation of hepatotoxic metabolite(s), in a category of idiosyncratic liver injury. It is proposed to monitor liver function strictly and periodically for the diabetic patients prescribed troglitazone.
Chromans↗
Additive effects of estrogen deficiency and diabetes on bone mineral density in rats.
We investigated the combined effects of estrogen deficiency and diabetes on bone mineral density (BMD) and bone metabolism in rats. Ten-week-old, female rats were randomly divided into four groups: controls (C), an ovariectomized group (O), a streptozotocin-induced diabetic group (S), and a combined ovariectomy and streptozotocin-induced diabetic group (OS). The BMD of the lumbar spine and the femur were measured before grouping and at 23 weeks old. At the end of the experiment, blood samples were obtained via cardiac puncture, and bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP) and 1,25-dihydroxyvitamin D levels were measured. The rats in the C, O, S, and OS groups, in that order, had higher levels of BMD of the lumbar spine and femur at 23 weeks of age. The BGP levels in the S and OS groups were significantly lower than in C and O groups. Significantly higher 1,25-dihydroxyvitamin D was observed in the O group compared with the C, S and OS groups. No differences were obtained in TRAP among four groups. Our data suggest that the combined effects of estrogen deficiency and diabetes on BMD are not synergistic or counteractive but additive.
Alkaline Phosphatase↗
Effects of anti-VLA-4 monoclonal antibody treatment in murine model of allergic rhinitis.
In order to study the role of VLA-4 in allergic rhinitis, the effects of anti-mouse VLA-4 monoclonal antibody (mAb) were evaluated in a murine model. BALB/c mice were sensitized first by i.p. injections (general sensitization) and then by daily nasal dripping of antigen (local sensitization) before performing a nasal antigen challenge. The mAb was applied either before the antigen challenge (BC group), before the local sensitization (BL group) or before the general sensitization (BS group). The effects were evaluated in terms of antigen-induced early-phase nasal symptoms (sneezing), late-phase nasal eosinophilia and the serum level of antigen-specific IgE. Antigen-induced nasal eosinophilia was significantly (p = 0.009) reduced in the BL group but not in the BC group (number of eosinophils = 114 +/- 15.1, 244 +/- 52.8 and 347 +/- 50.5 in the BL, BC and control groups, respectively). The serum level of the specific IgE was also significantly (p = 0.038) reduced in the BL group but not in the BC group (optical density = 1.18 +/- 0.07, 1.28 +/- 0.13 and 1.58 +/- 0.14 in the BL, BC and control groups, respectively). The suppressive effect on sneezing was not significant in either the BL or BC groups. In the BS group, suppressive effects on antigen-induced nasal responses and the specific IgE level were not statistically significant. These findings suggest that VLA-4 plays an important role in the topical booster or priming effects during repeated nasal antigen exposures in pre-sensitized animals.
Animals↗
Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin.
We have previously demonstrated that oral administration of bovine lactoferrin (bLF) markedly increases CD4(+) and CD8(+) T cells and NK (asialoGM1(+) ) cells in the blood of tumor-bearing mice and enhances anti-metastatic activity. In this paper, we document that oral administration of bLF and bLF-hydrolysate (bLFH) is associated with strong increases in CD4(+) and CD8(+) T, as well as asialoGM1(+) cells in lymphoid tissues and lamina propria of the small intestine in mice, especially in tumor-bearing animals in which Co26Lu cells were implanted subcutaneously. Moreover, IgM(+) and IgA(+) B cells in lamina propria of the small intestine were also significantly increased by bLF and bLFH. Bovine apo-transferrin (bTF) did not exhibit such activity. In the colon, only CD8(+) cells were significantly increased by treatment with bLF, while asialoGM1(+) cells were significantly decreased. bLF and bLFH induced cytokines to activate T, B and asialoGM1(+) cells. Administration of bLF and bLFH, but not bTF, increased production of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and caspase-1 in the mucosa of the small intestine. Particularly high levels of IL-18 were found in the epithelial cells of the small intestine. Moreover, administration of bLF and bLFH, but not bTF, induced IFN-gamma presenting cells in the small intestine. Caspase-1, which processes proIL-18 to mature IL-18, was also induced in the epithelial cells of the small intestine following treatment with bLF and bLFH, but not with bTF. These results suggest that enhanced production of IL-18 and IFN-gamma and caspase-1 induction by treatment with bLF may be important for elevation of intestinal mucosal immunity.
Administration, Oral↗
Mean corpuscular volume may be a useful index of risk for colorectal adenoma in middle-aged Japanese men.
OBJECTIVE: It has been reported that alcohol intake and folate deficiency are associated with an increased risk of colorectal adenomas and carcinomas. Mean corpuscular volume (MCV) of red blood cells has been reported to be increased in these conditions. The purpose of this study was to assess the association between MCV and risk of colorectal adenoma. METHODS: The subjects were 497 middle-aged (45-65 yr old) men who underwent both barium enema examination and total colonoscopy. The subjects answered a questionnaire regarding their alcohol consumption history, and their blood samples were analyzed. The subjects were divided into four groups three times: with or without alcoholism, and with or without adenoma according to alcohol intake, and according to the MCV value. Various variables were compared among the groups, and the odds ratios of adenoma were calculated. RESULTS: The MCV was higher in the alcoholic group than in the nonalcoholic group (p < 0.01) and in patients with adenoma than in those without adenoma (p < 0.0001). When the subjects were stratified by alcohol intake, the MCV value had a higher significant difference than alcohol intake, between patients with adenoma and those without adenoma. As for the MCV value, the odds ratio (95% confidence interval) of adenoma was 1.00 (referent); (<92), 1.20 (0.71-1.69); (> or =92 but <95), 2.61 (2.07-3.15); (> or =95 but <98); and 3.62 (2.99-4.25); (> or =98). CONCLUSION: A high MCV value may be used as a simple index of the risk of colorectal adenomas, regardless of alcohol consumption.
Adenoma↗
Anti-idiotypic antibodies in patients with different clinical forms of paracoccidioidomycosis.
Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. Patients with PCM show a wide spectrum of clinical and pathological manifestations depending on both host and pathogen factors. Two clinical forms of the disease are recognized: the acute or juvenile form and the chronic or adult form. The major antigenic component of the parasite is a glycoprotein of 43 kDa (gp43). All patient sera present antibodies against gp43 (anti-gp43) and, as demonstrated before by our group, spontaneous anti-idiotypic (anti-Id) antibodies (Ab2) can be detected in patient sera with high titers of anti-gp43. Since it has been postulated that anti-Id antibodies may have a modulating function, we decided to purify and characterize anti-Id antibodies in this system. The possible correlation of Ab2 titers with different clinical forms of disease was also verified. Results showed that purified human anti-Id antibodies (human Ab2) recognized specifically the idiotype of some murine monoclonal anti-gp43 (17c and 3e) but not others (40.d7, 27a, and 8a). Spontaneous anti-Id antibodies were found in all clinical forms of disease. The majority of patients (88%, n = 8) with the acute form of PCM had high titers of Ab2. However, among patients with the multifocal chronic form of the disease, only 29% (n = 14) had high titers of Ab2; 70% (n = 10) of patients with the unifocal chronic form had low titers of Ab2. A correlation between Ab2 titers and anti-gp43 titers was observed before and during antimycotic treatment. Our results suggest that titers of anti-Id antibodies correlate with the severity of PCM in humans.
Adult↗
In vivo gene transfer of endothelial nitric oxide synthase to carotid arteries from hypercholesterolemic rabbits enhances endothelium-dependent relaxations.
BACKGROUND AND PURPOSE: Hypercholesterolemia is associated with abnormal endothelium-dependent vasorelaxation due to decreased nitric oxide bioavailability. Our aim was to examine the effect of adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) to the hypercholesterolemic rabbit carotid artery in vivo. In addition, we examined whether adenovirus-mediated gene transfer was associated with vascular dysfunction. METHODS: Rabbits were fed a 1% cholesterol diet for 4 weeks followed by a 0.5% cholesterol diet for 6 weeks. Vascular reactivity was assessed in nontransduced carotid arteries from chow- and cholesterol-fed animals. In addition, carotid arteries were surgically isolated, and 2 separate doses of adenoviral vectors encoding eNOS or beta-galactosidase (AdbetaGal) on the contralateral side were delivered to the lumen (1x10(10) and 5x10(10) pfu/mL). RESULTS: Abnormal acetylcholine-mediated endothelium-dependent vasorelaxation was detected in the carotid artery from cholesterol-fed animals, whereas responses to calcium ionophore A23187 and diethylamine NONOate were normal. Vascular reactivity was similar in nontransduced and AdbetaGal-transduced hypercholesterolemic vessels. In vessels transduced with eNOS, transgene expression was demonstrated by immunostaining in both the endothelium and the adventitia and by Western blot analysis. High-dose but not low-dose eNOS gene transfer enhanced endothelium-dependent relaxation in vessels from cholesterol-fed rabbits. CONCLUSIONS: Adenovirus-mediated gene transfer of eNOS to carotid arteries of cholesterol-fed animals improves endothelium-dependent relaxation when an optimal viral titer is administered.
Animals↗
Inhaled furosemide greatly alleviates the sensation of experimentally induced dyspnea.
Furosemide is known to influence the activity of vagally mediated mechanoreceptors in the airways. Because vagal afferent fibers may play an important role in modulation of the sensation of dyspnea, it is possible that inhaled furosemide may modify the sensation of dyspnea. In a double-blind, randomized, crossover study, we compared the effect of inhaled furosemide on dyspneic sensation with that of placebo. Severe dyspneic sensation was induced in 12 healthy subjects in two ways: (1) breathholding and (2) loaded breathing with a combination of inspiratory resistive load (240 cm H(2)O/L/s) and hypercapnia induced by extra mechanical dead space (0.26 L). Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale (dyspneic VAS). Breathholding times and changes in dyspneic VAS score during a 5-min period of loaded breathing were measured after inhalation of placebo and furosemide (40 mg). Total breathholding time after inhalation of furosemide (median, 93 [interquartile range, 78 to 112]s) was prolonged compared with the total breathholding time after placebo inhalation (67 [47-74]s). We also found that respiratory discomfort during loaded breathing after inhalation of furosemide develops more slowly and is less than that observed after inhalation of placebo. Our findings indicate that inhaled furosemide greatly alleviates the sensation of dyspnea induced experimentally by breathholding and by a combination of resistive loading and hypercapnia.
Administration, Inhalation↗
Increased numbers of dendritic cells in the bronchiolar tissues of diffuse panbronchiolitis.
Dendritic cells (DCs) are potent antigen-presenting cells (APCs); they are considered to be the most important APC in the lung. Recently, the number of DCs in the large airways was demonstrated to increase in patients with atopic asthma, leading to the concept that DCs play an important role in airway inflammation. However, little is known about the distribution of lung DCs in the small airways under other pathological conditions. The aim of the present study was to examine the distribution of DCs in the bronchiolar tissues in patients with diffuse panbronchiolitis (DPB), which is a chronic inflammatory disorder of the airways histologically characterized by peribronchiolitis. We investigated the distribution of DCs in the bronchiolar tissues of the lungs in 11 patients with DPB and 7 control subjects with normal lungs using immunohistochemical methods. Marked increases in the number of CD1a(+), CD1c(+), and CD83(+) DCs were found in both the bronchiolar epithelium and submucosal tissues of patients with DPB, compared with control subjects with normal lungs. The most striking increase occurred in the number of DCs expressing CD83, a marker of mature DCs, in the submucosal tissues of patients with DPB. The increases of these positive cells in patients with DPB were more marked in the submucosal tissues than in the epithelium. The bronchiolar epithelial cells in patients with DPB strongly expressed GM-CSF protein, which is an important cytokine for the differentiation and function of DCs, suggesting that the increased local production of GM-CSF may be responsible for the accumulation and differentiation of DCs in the bronchiolar tissues of patients with DPB. These results suggest that increased DCs in the bronchiolar tissues, together with their phenotypical maturation, may play an important role in the mucosal immune response in patients with DPB through their potent antigen-presenting function.
Adult↗
Inhibitory effect of dexamethasone palmitate-low density lipoprotein complex on low density lipoprotein-induced macrophage foam cell formation.
We used low density lipoprotein (LDL) as a carrier of site-specific delivery of drugs to atherosclerotic lesions, prepared a dexamethasone palmitate (DP)-LDL complex, and examined the effect of the DP-LDL complex on foam cell formation of macrophages in vitro. LDL was isolated from human plasma and the DP-LDL complex was prepared by incubation in the presence of Celite 545. The complex contained about 50 mol of DP in 1 mol of LDL. When macrophages were incubated with LDL for 48 h, cholesterol ester was accumulated in the macrophages, indicating foam cell formation. This accumulation of cholesterol ester was significantly inhibited by incubation with the DP-LDL complex. The potency of the DP-LDL complex was similar to that of dexamethasone alone. The DP-LDL complex also significantly attenuated the accumulation of cholesterol ester induced by incubation with LDL prior to the incubation with the DP-LDL complex. These findings indicated that the DP-LDL complex showed similar characteristics to LDL, and the DP-LDL complex inhibited the foam cell formation of macrophages in in vitro experiments. This DP-LDL complex has a possibility as a drug-carrier complex for use in atherosclerosis.
Animals↗