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Biomedical subjects

H Fujimaki

Publications and source records attributed to H Fujimaki.

At least 19 recordsLinked to original sources

Enhanced histamine release from lung mast cells of guinea pigs exposed to sulfuric acid aerosols.

To clarify the relationship between air pollution and mast cell response, the effects of sulfuric acid aerosols on histamine release from lung mast cells of guinea pigs were investigated. Guinea pigs were exposed to 0.3, 1.0 and 3.2 mg/m3 sulfuric acid (H2SO4) aerosols or 4 ppm nitrogen dioxide (NO2) for 2 and 4 weeks. After the exposure, lung mast cell suspensions were isolated by collagenase treatment and antigen- or A23187-induced histamine release was measured. Antigen-induced histamine release from mast cells was significantly enhanced by the exposure to 1.0 and 3.2 mg/m3 H2SO4 for 2 weeks, but exposure to H2SO4 for 4 weeks did not show the enhancement of antigen-induced histamine release. A23187-induced histamine release was significantly enhanced by the exposure to 1.0 mg/m3 H2SO4 or 4 ppm NO2 for 2 weeks, but suppression of histamine release from lung mast cells stimulated with A23187 was observed by the exposure to 3.2 mg/m3 H2SO4 for 4 weeks. The exposure to 0.3 mg/m3 H2SO4 showed no changes in antigen- and A23187-induced histamine release. The combination of 1.0 mg/m3 H2SO4 with 4 ppm NO2 for 2 weeks resulted in no changes in antigen- and A23187-induced histamine release. These results suggested that functional properties of lung mast cells may be altered by a low concentration of H2SO4 aerosol exposure.

Aerosols

Mast cell response to formaldehyde. 1. Modulation of mediator release.

To examine the effects of the atmospheric pollutant formaldehyde on functionally distinct mast cells, peritoneal mast cells (PMC), intestinal mucosal mast cells (IMMC) and mouse bone-marrow-derived mast cells (BMMC) were incubated with various concentrations of formaldehyde. Pretreatment for 30 min with up to 100 micrograms/ml formaldehyde was not cytotoxic to mast cells. Formaldehyde (1-10 micrograms/ml) alone induced low levels of histamine release (< 10%) from IMMC and BMMC. Antigen-induced histamine release was significantly increased in both PMC pretreated with low concentrations of formaldehyde (5-20 micrograms/ml) and BMMC pretreated with 10 micrograms/ml formaldehyde but decreased in PMC pretreated with a higher concentration (100 micrograms/ml) of formaldehyde. By contrast, antigen-induced histamine release was decreased in IMMC pretreated with formaldehyde in a dose-dependent manner. Histamine release stimulated with A23187 was also increased in PMC pretreated with a low concentration (10 micrograms/ml) of formaldehyde but decreased in those pretreated with a higher concentration (100 micrograms/ml) of formaldehyde. Pretreatment with 10 micrograms/ml formaldehyde significantly enhanced beta-hexosaminidase release from PMC stimulated with antigen or A23187. Compared to sham-treated PMC, PMC pretreated with formaldehyde expressed a markedly depressed natural cytotoxicity for the tumor target WEHI-164 (an assay of tumor necrosis factor alpha activity). These results suggest that formaldehyde modifies various mast cell functions through alterations in cellular metabolism. Such effects may be important in respiratory and other diseases associated with formaldehyde exposure.

Animals

Mast cell response to formaldehyde. 2. Induction of stress-like proteins.

Previously we established that immediately after pretreatment with low concentrations (5-10 micrograms/ml) of formaldehyde antigen- and ionophore-induced histamine secretion was enhanced from peritoneal mast cells (PMC) isolated from rats infected with Nippostrongylus brasiliensis. In contrast to immediately following pretreatment with low concentrations of formaldehyde, 3 h after a 30-min treatment with formaldehyde (10, 50 and 100 micrograms/ml) antigen-induced histamine secretion from PMC was significantly depressed, and 35S-methionine incorporation was also decreased. To further explore the effects of formaldehyde on mast cells, we investigated protein biosynthesis of PMC following formaldehyde treatment and compared this with the effects of hydrogen peroxide (H2O2) or heat treatment. One- and two-dimensional SDS-PAGE were used to assess the effects. Formaldehyde treatment induced the synthesis of 70- and 72-kD stress-like proteins in rat PMC. Pretreatment of PMC with 50 microM H2O2 and heat (45 degrees C) also induced proteins with the same molecular weight. Two-dimensional SDS-PAGE analysis established that formaldehyde-induced 70-kD proteins had the same pI values as 70-kD heat shock proteins previously observed in mammalian cells. These results suggest that formaldehyde, H2O2 and heat shock induce stress proteins in rat PMC. It will be important to establish whether or not these stress proteins are responsible for the functional alterations observed in the mast cells.

Animals

Relation between body size and bone mineral density with special reference to sex hormones and calcium regulating hormones in elderly females.

We studied the relation between body size and bone mineral density in elderly females. The study included a total of 93 ambulatory females aged over 60 years. They were divided into 3 groups according to their body mass index (BMI; kg/m2): slender group with BMI less than 20 (n = 28), normal group with BMI of 20 to 24.9 (n = 43) and obese group with BMI greater than or equal to 25 (n = 22). Fracture incidence, bone mineral density, calcium regulating hormones and steroid hormones were studied in an intergroup comparative manner. The incidence of vertebral fracture was found to be negatively correlated with BMI (the incidences of vertebral fracture in slender, normal and obese were 78.6, 48.8 and 22.7%, respectively) and bone mineral density was also BMI-related (0.390 +/- 0.016, 0.456 +/- 0.015 and 0.493 +/- 0.018 g/cm2, respectively: p less than 0.01 in ANOVA; mean +/- SE). The number of years after menopause was shorter in patients with a higher BMI. There was no intergroup difference in serum levels of PTH, vitamin D and estrogens. On the other hand, serum levels of calcitonin, DHEA, DHEAS, delta-4 androstenedione and testosterone were found to be higher in subjects with a higher BMI. From the present results, it seems that bone mineral density is supported not only by weight-bearing stress upon bone, but also by serum levels of calcitonin and androgens in obese females.

Age Factors

[The characteristics of metabolic acidosis in aged patients with chronic renal failure].

The present study was designed to clarify the characteristics of metabolic acidosis in aged patients with chronic renal failure. The subjects consisted of ambulatory cooperative patients (19 males and 18 females). Their values of creatinine clearance (Ccr) varied from 6.8 to 107.5 ml/min/1.73 m2. The relationship of Ccr to acid-base and electrolyte disturbances was investigated. The estimations of normal values in acid-base and electrolyte composition were based on the method of Hoffmann. The results are summarized as follows: 1. A high incidence of metabolic acidosis was demonstrated in patients whose Ccr values were below 20 ml/min/1.73 m2. 2. A significant positive correlation of Ccr values and plasma levels of bicarbonate (p less than 0.001) and a significant inverse correlation of Ccr values and serum levels of chloride (p less than 0.01) were observed. 3. The values of the anion gap did not change, irrespective of Ccr values. 4. Serum concentrations of potassium were inversely correlated with plasma levels of bicarbonate (p less than 0.01). Hyperchloremic normal anion gap acidosis with hyperpotassemia was the characteristic feature of metabolic acidosis in aged patients with chronic renal failure. The normal anion gap could be explained by normophosphatemia or mild hyperphosphatemia, even in the patients with advanced renal failure.

Acid-Base Equilibrium

Enhanced antibody production in W/Wv mice exposed to ozone.

To investigate the modulation of defense mechanisms by ozone (O3) exposure, mast-cell-deficient WBB6F1-W/WV and normal WBB6F1(-)+/+ mice were continuously exposed to 0.8 ppm O3 for 7 days. Although no differences in weights of lung, thymus and spleen were shown between exposed and control W/WV mice, antibody response to sheep red blood cells (SRBC) in exposed W/WV mice was markedly enhanced compared to control W/WV mice. In normal +/+ mice O3 exposure induced an increase in lung weight but did not enhance antibody production. These studies suggest that the susceptibility of W/WV mice to O3 may be different from that of +/+ mice.

Animals

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