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Biomedical subjects

H Fujimaki

Publications and source records attributed to H Fujimaki.

At least 55 records · Page 3Linked to original sources

An antioxidant agent prevents NO2-induced inhibition of mast cell mediator release: evidence that the mechanism involves free radicals.

Previously we established that in vitro NO2 exposure induced inhibition of histamine release from rat peritoneal mast cells (PMC) stimulated with secretagogues such as compound 48/80 or substance P. To further explore the effects of NO2 exposure on mast cells, we investigated whether the addition of an antioxidant agent, 2-mercaptoethanol (2-ME), can prevent NO2-induced inhibition of mediator release from PMC. Histamine release from 5 ppm NO2-exposed PMC stimulated with 10 and 20 microM substance P was significantly inhibited compared with that from the controls. beta-Hexosaminidase release from 5 ppm NO2-exposed PMC stimulated with 20 microM substance P was also significantly inhibited. However, the inhibition of both histamine and beta-hexosaminidase release from exposed PMC was diminished by the addition of 5 mM 2-ME during NO2 exposure. Although IgE-mediated histamine release from NO2 exposed PMC was markedly inhibited, the addition of 5 mM 2-ME during NO2 exposure induced no inhibition of histamine release. These results suggest a possible relationship between NO2-induced inhibition of mast cell mediator release and production of free radicals by the action of NO2.

Animals↗

Impairment of humoral immune responses in mice exposed to nitrogen dioxide and ozone mixtures.

The relationship between immune defense mechanisms and environmental pollutants remains unknown because of uncertainty about the effects of combined or mixed pollutants. To investigate whether exposure to toxic gas mixtures change the effect of a single gas exposure on immune function, BALB/c mice were continuously exposed to 4.0 ppm nitrogen dioxide (NO2), 0.8 ppm ozone (O3), or the mixture of NO2 plus O3 for 3, 7, 14, and 56 days. Organ weights (lung, thymus, and spleen) and antibody responses to sheep red blood cells (SRBC), and to DNP-Ficoll were measured immediately after the exposure. Lung weights in mice exposed to O3 or the mixture were increased significantly in all exposure periods. The weights of thymus and spleen in mice exposed for 3, 7, and 14 days to the mixture were decreased. O3 exposure for 56 days showed significant decreases of the weights of both organs. Antibody response to SRBC in mice exposed for 3, 7, and 14 days to O3 or the mixture was markedly suppressed, but exposure to the mixture for 56 days did not show the suppression of anti-SRBC antibody response. No differences in anti-DNP antibody response between exposed and control mice were observed, except those exposed to O3 or the mixture for 14 days. These results suggest that mixed gas exposures variously modify the effects of a single gas exposure on antibody production in mice.

Air Pollutants↗

Effects of instillation of fly ash in the lung: physiochemical properties and immune responses.

In this study, we examined physiochemical properties of fly ash and aluminum silicate and investigated the effects of these compounds on IgE antibody production and macrophage response in the lung. Fly ash was round in shape, and aluminum silicate was indefinite in shape with respirable size. Both compounds consisted of alumina and silica as the main elements with respirable size. Enhanced IgE and IgG antiovalbumin (OA) antibody production was observed in mice first instilled intratracheally with the aluminum compounds and then given OA aerosol exposure. Histopathologic observations after instillation of fly ash and aluminum silicate showed that a large number of macrophages had ingested the compounds. However, the amount of free compound and the distribution of macrophages were different in mice given fly ash from those given aluminum silicate. These data indicate that particles of fly ash and aluminum silicate instilled into lung act as adjuvant for the production of IgE and IgG antibodies.

Administration, Inhalation↗

[Disorders of fluid and electrolyte metabolism in elderly diabetics].

Disorders of fluid and electrolyte metabolism in elderly diabetics were studied. High frequency of hyperkalemia (20.8%), hypomagnesemia (14.6%), hypocalcemia (13.7%), hyperphosphatemia (8.6%), hyponatremia (8.1%) and hyperchloremia (7.2%) was observed among 332 elderly diabetics. Furthermore, hyperkalemia, hyperphosphatemia, hyponatremia, hyperchloremia, hypercalcemia and hypermagnesemia were more frequent in diabetics with renal insufficiency (serum Cr greater than or equal to 1.5 mg/dl) than in diabetics with normal renal function (serum Cr less than or equal to 1.4 mg/dl). In addition, statistically significant negative correlation were observed between plasma glucose levels and serum levels of sodium and chloride in diabetics with normal renal function. These results clearly demonstrated that the most important causal factor of electrolyte disorders in elderly diabetics might be the renal dysfunction due to diabetic nephropathy and/or nephrosclerosis. Moreover, glucose intolerance is also one of the causal factors for hyponatremia and hypochloremia. Disorders of fluid and electrolyte metabolism were manifest in 31 diabetic patients with hyperosmolar non-ketotic coma. The frequency of patients with abnormally elevated serum levels of sodium, potassium and chloride, and patients with abnormally lowered serum levels of calcium was high in this morbid state. Water and sodium deficit, examined in 11 cases of hyperosmolar non-ketotic coma, was 4780 +/- 2100 ml (107 +/- 43 ml/kg body weight) and 290 +/- 170 mEq (6.8 +/- 4.2 mEq/kg body weight), respectively. However, no significant deficit of potassium was observed in the patients. Statistically significant positive correlations between water deficit and serum Cr levels and with serum effective osmolarity were observed. However, there were no significant correlations between water deficit and plasma glucose levels, serum sodium levels and serum osmolarity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Isolation and in vitro translation of mRNA from rat peritoneal mast cells and rat basophilic leukemia cells.

In the absence of any specific literature on the isolation of RNA from mast cells, our initial attempts established that unusual measures would be needed to prepare acceptable yields of high quality RNA from peritoneal mast cells of normal adult rats. Accordingly, we developed procedures for the isolation and characterization of RNA from rat peritoneal mast cells (PMC) and basophilic leukemia cells (RBL). The significant components of the procedures include: separation and removal of mast cell granules to minimize contamination of RNA with proteins and proteoglycans; use of bentonite in phenol extractions; and repetition of extractions and precipitation. The amounts of total RNA extracted from PMC were about 15% of those from RBL, although the percentage mRNA of total RNA in PMC and RBL was similar (1.8 and 2.0%). Ribosomal RNA banding patterns in agarose gel electrophoresis and in vitro translation experiments indicate that the isolated RNA can be employed for analysis of molecular mechanisms of mast cell function and heterogeneity.

Animals↗

Mast cell polymorphisms. Present concepts, future directions.

Although mast cells are widely distributed in the body, their functions are poorly known. The elucidation of mast cell function is complicated by growing evidence that mast cells are heterogeneous. Recent studies of mast cell ontogeny suggest that microenvironmental stimuli control the phenotypic expression of parts of the genome leading to subtype differences in a common lineage. Mast cells influence cell proliferation, differentiation, and activation in a range of target cells, although until recently they were considered important only in immediate hypersensitivity. However, they function in delayed-type hypersensitivity, potentiate cytotoxicity of eosinophils and macrophages, and are cytotoxic for certain targets themselves. Mast cell mediators influence blood flow and vascular permeability and facilitate angiogenesis. Numerous mast cell mediators are immunoregulatory. In vitro experiments have begun to investigate the role of mast cells in fibrotic diseases. Further knowledge of mast cell heterogeneity will provide the basis for new therapies in inflammatory diseases of the intestine and other organs.

Colitis, Ulcerative↗

Changes in delayed hypersensitivity reaction in mice exposed to O3.

BALB/c mice were continuously exposed to 0.8 ppm O3 for 1, 3, 7, and 14 days. Ozone exposure suppressed the delayed hypersensitivity (DH) reaction to sheep red blood cells (SRBC). The maximum effect was seen after 7 days of exposure. To estimate the suppression of the DH reaction by O3 exposure, the numbers of lymphocytes in thymus and blood of exposed mice were compared with those of control mice. A decrease in the numbers of lymphocytes in both thymus and blood was observed in O3-exposed mice. The percentage of T and B lymphocytes in blood of exposed mice was the same as that in blood of control mice. These results suggest that 0.8 ppm O3 exposure affects the T lymphocytes required for DH reactions.

Animals↗

Bone fracture in elderly female with primary hyperparathyroidism: relationship among renal function, vitamin D status and fracture risk.

Among 12 aged postmenopausal females with primary hyperparathyroidism, 5 had no bone fracture and 7 had fractures. Both serum 1,25 (OH)2D levels and creatinine clearance values in patients with fracture were significantly lower than those without fracture (p less than 0.025). In addition, significant positive correlation was observed between serum 1,25 (OH)2D levels and creatinine clearance values (p less than 0.05). These data suggest that decreased serum 1,25 (OH)2D level due to renal dysfunction may causally correlate to bone fracture in postmenopausal primary hyperparathyroidism.

Aged↗

Investigations of rat mast cell heterogeneity.

In the rat, two distinct mast cell subsets have been identified. One, represented by the easily accessible and purified peritoneal mast cell, differs from the other, the intestinal mucosal mast cell, in staining properties, fixation sensitivity, mediator content, and responsiveness to various secretagogues and antiallergic drugs. To investigate the molecular basis and control mechanisms of mast cell heterogeneity, we have initiated sodium dodecylsulfate polyacrylamide gel electrophoretic analysis of the constituents of rat peritoneal and intestinal mucosal mast cells; developed subcellular fractionation protocols to facilitate these comparisons; produced a mast cell specific rabbit antiserum, and established methods to isolate mast cell RNA. These approaches require refinement, but will prove to be useful in further investigations of mast cell biology.

Animals↗

Comparative induction of hepatic zinc-thionein and increase in tissue calcium by bacterial endotoxin in endotoxin-sensitive (C3H/HeN) and endotoxin-resistant (C3H/HeJ) mice.

Induction of zinc-thionein (Zn-Th) by endotoxin was studied in mice using an endotoxin-sensitive C3H/HeN strain and an endotoxin-resistant C3H/HeJ strain to find a relation between the sensitivity of these strains to endotoxin and the inducibility of hepatic Zn-Th by the endotoxin. Both strains of female mice were injected with endotoxin at two doses and the increase in hepatic Zn-Th levels was examined after 24 h. At the lower dose (0.25 mg/kg body weight), C3H/HeJ mice induced Zn-Th at a markedly lower level than C3H/HeN mice. However, both strains exhibited a comparable amount of Zn-Th when a higher dose (10 mg/kg body weight) of endotoxin was used. A parallel increase in hepatic calcium concentration was observed with the induction of hepatic Zn-Th in both strains. The injection of a spleen supernatant fraction from C3H/HeJ mice into C3H/HeN mice did not reduce the Zn-Th induction by endotoxin in C3H/HeN mice.

Animals↗

Induction of IgE antibody production to aerosolized ovalbumin in mice treated intratracheally with aluminum silicate.

Induction of IgE antibody production was studied in mice with aerosolized antigen exposure and intratracheal instillation of adjuvants. BALB/c mice were immunized intratracheally with 10 micrograms ovalbumin (OA) adsorbed with or without aluminum silicate as an adjuvant. A primary IgE antibody production was observed in mice immunized with OA plus adjuvant, but not with OA alone. In mice immunized with OA plus adjuvant, a secondary IgE antibody production was observed after a booster of OA aerosol exposure on day 28. Mice were instilled intratracheally with aluminum silicate or aluminum hydroxide (alum) and subsequently exposed to aerosolized OA for 30 min. Primary and secondary anti-OA IgE antibody productions were obtained in the groups instilled with the adjuvants. After the intratracheal instillation of alum, aluminum remained in the mice for a long period. These results suggest that the intratracheal instillation of adjuvants is effective in the induction of IgE antibody production by aerosolized antigen exposure.

Adjuvants, Immunologic↗

Enhanced IgE antibody production in mice injected with fly ash.

The adjuvant effect of fly ash injected via various routes on IgE antibody production was examined in mice. Primary anti-ovalbumin (OA) IgE antibody production was induced by intratracheal and intraperitoneal injection with fly ash and OA, but not by the intragastric route. Both the intratracheal and the intraperitoneal routes showed similar efficiency in inducing IgE antibody production. High secondary anti-OA IgE antibody response by exposure to aerosolized OA was also observed in mice primed with intratracheal instillation of fly ash plus OA. The activity to induce IgE antibody production by fly ash instillation was almost the same as that by aluminum silicate, studied previously. Primary and secondary anti-OA IgG antibody production was also stimulated by intratracheal instillation of fly ash. These results suggest that fly ash has an adjuvant activity in the induction of IgE and IgG antibody production in mice.

Adjuvants, Immunologic↗

Suppression of primary antibody response by a single exposure to cadmium in mice.

Suppression of primary antibody response to sheep red blood cells (SRBC) by a single intraperitoneal (i.p.) injection of cadmium into mice was investigated by the methods of in vitro plaque-forming cell (PFC) assay. BALB/c mice were given 1.8 mg cadmium/kg body weight, and 1, 2 or 7 days later, spleen cells from exposed and control mice were cultured with SRBC. PFC responses of all exposed groups were significantly suppressed compared to those of control groups. Addition of control adherent cells to spleen cells from exposed mice failed to recover control level. In the cell-reconstitution experiments, the activity of B-cell function from the exposed group was suppressed more by cadmium than that of T-cell function. These results suggest that the suppression of primary PFC response by cadmium exposure may be caused by the inactivation of B-cells.

Animals↗