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Biomedical subjects

M Ishimori

Publications and source records attributed to M Ishimori.

15 recordsLinked to original sources
PubMed2001

Morning granulocytopenia in a case of Graves' disease.

A 65-year-old woman with Graves' disease presented marked diurnal changes in white blood cell (WBC) and granulocyte counts. Granulocyte count was low and sometimes decreased to 0.2-0.3 x 10(9)/l in the early morning and increased in the afternoon irrespective of her thyroid status. She did not develop sore throat or fever during the investigation period. The present study indicates that these unusual diurnal changes in WBC and granulocyte counts should be considered in the differential diagnosis of agranulocytosis in Graves' disease patients treated with an antithyroid drug.

Aged↗
PubMed2000

Serum IgE response to orally ingested antigen: a novel IgE response model with allergen-specific T-cell receptor transgenic mice.

BACKGROUND: The mechanism by which orally ingested allergens elicit an IgE response remains unclear because there are few animal models available for investigation of this response. OBJECTIVE: We tried to develop a murine model suitable for investigation of the IgE response to orally ingested allergens, which would allow us to identify T cells that could promote IgE production. METHODS: Ovalbumin (OVA)-specific T-cell receptor transgenic mice were fed a diet containing OVA, and both the serum antibody response and cytokine production by splenocytes were examined. RESULTS: Oral administration of OVA to transgenic mice led to an increase in the levels of both antigen-specific IgE and total IgE in the sera. Subsequent intravenous challenge of OVA-fed transgenic mice with OVA resulted in anaphylactic shock. Analysis of cytokine production by splenocytes revealed that high IL-4-producing T cells appeared in the spleen 1 week after the start of feeding the OVA diet. T cells from these mice were found to promote IgE secretion by BALB/c B cells in vitro. This helper activity and the levels of IL-4 secretion were diminished after long-term feeding. These findings suggest the possibility that the orally ingested antigen elicited a response by a subpopulation of T cells that produce high levels of T(H2)-type cytokines and that promote IgE secretion, and these same T cells were tolerized by the orally ingested antigen. CONCLUSION: This experimental model with transgenic mice may be a useful tool for further studies of the cellular and molecular mechanisms of the T-cell and IgE responses to orally ingested antigens.

Administration, Oral↗
PubMed1999

Effects of long-term interferon-alpha treatment on glucose tolerance in patients with chronic hepatitis C.

BACKGROUND/AIMS: Interferon-a has been reported to acutely induce insulin resistance and glucose intolerance. The effects of long-term treatment with interferon-a on glucose metabolism remain unclear. METHODS: Thirty-two Japanese patients with chronic hepatitis C were given interferon-a (6x10(6)U/day) daily for 2 weeks and thereafter 3 times weekly up to 6 months. The patients received a 75-g oral glucose tolerance test before the treatment. Fifteen patients also had an intravenous glucose tolerance test for an assessment of insulin sensitivity with Bergman's minimal model. These tests were repeated 3 months after the treatment. RESULTS: Insulin sensitivity was not affected by the treatment (5.7+/-3.8 vs 5.2+/-3.8 10(-4) x min(-1) x mU(-1) x l , not significant) and a statistically significant but minimum decrease in area under the curve of plasma glucose (1012+/-332 vs 928+/-282 mmol x l(-1) x min, p<0.01) in a 75-g oral glucose tolerance test was noted. Acute insulin response to intravenous glucose tolerance tests (214+/-275 vs 294+/-334 mU x l(-1) x min, p<0.05) increased slightly. CONCLUSION: Contrary to the known acute metabolic effects, interferon-a therapy for 3 months in patients with chronic hepatitis C did not have deleterious effects on insulin sensitivity and glucose tolerance.

Adult↗
PubMed1999

Pharmacological treatments for GH-induced insulin resistance.

Troglitazone (T) and d-chiroinositol (DCI) have been reported to improve insulin resistance associated with obesity and NIDDM. We tested whether these compounds counteract the insulin antagonistic effects of recombinant human GH. Male Wistar rats were allocated to 4 different treatment groups, rhGH (n=8), rhGH+T (n=7), rhGH+DCI (n=8) and control (saline, n=8). rhGH (2 IU/100 g/day) was injected sc twice daily for 2 days. T and DCI were given (20 mg/day) po for 5 days preceding and 2 days along with rhGH. Euglycemic hyperinsulinemic clamp studies were done to assess the hepatic glucose output (HGO) and glucose disappearance rate (GDR). Fasting plasma glucose, insulin, serum FFA and basal HGO were similar in all 4 treatment groups. During the hyperinsulinemic clamp which raised plasma insulin levels to 7.2 +/- 0.4 ng/ml, HGO was suppressed in the control and rhGH+T treated rats but not in the rats treated with rhGH and rhGH+DCI. GDR decreased in the rats which received rhGH (18.1 +/- 5.8 vs 30.3 +/- 5.2 mg/kg/min) compared to the control rats. The rats given either T (24.7 +/- 2.7) or DCI (31.4 +/- 2.7) along with rhGH showed comparable GDR to the control rats. These results indicated that rhGH induced hepatic and peripheral insulin resistance. Troglitazone counteracted the insulin-antagonistic action of rhGH both in the liver and the peripheral tissues. DCI was effective in offsetting peripheral insulin resistance but without any effect on hepatic insulin resistance associated with rhGH treatment.

Animals↗
PubMed1998

Effects of troglitazone on hepatic and peripheral insulin resistance induced by growth hormone excess in rats.

It is well known that short-term growth hormone (GH) administration in humans and animals induces insulin resistance and glucose intolerance. The purpose of the present study was to clarify whether troglitazone, a new insulin-sensitizing drug of the thiazolidinedione class, counteracts the insulin antagonistic effects of recombinant human (rh) GH on glucose metabolism in rats. Male Wistar rats weighing 184 to 226 g were treated either with rhGH (n = 8) or rhGH plus troglitazone (n = 8). rhGH (20 IU/kg body weight/d) was given by subcutaneous injection twice daily for 2 days. Troglitazone was given at 100 mg/kg/d orally for 5 days before and 2 days during rhGH. Saline was injected to the control rats (n = 7). Euglycemic clamp studies with an insulin infusion rate of 8 mU/kg/min were performed in these rats after an overnight fast. Hepatic glucose output (HGO), glucose infusion rate (GIR), and glucose disappearance rate (GDR) were measured. Fasting levels of plasma glucose (6.6 +/- 0.1, 6.1 +/- 0.3, 6.5 +/- 0.2 mmol/L), insulin (187.5 +/- 24.1, 206.4 +/- 24.1, 182.3 +/- 31.0 pmol/L), and serum free fatty acid (FFA) (1.58 +/- 0.18, 1.43 +/- 0.16, 1.61 +/- 0.25 mEq/L) were comparable among rats treated with rhGH, rhGH plus troglitazone, and controls, respectively. Basal HGO was also comparable among the three treatment groups. HGO was suppressed significantly during the hyperinsulinemic glucose clamp in control rats, but not in rhGH rats. When troglitazone was coadministered with rhGH, suppressibility of HGO during the glucose clamp was comparable to that of controls. GIR (13.5 +/- 4.5 v 24.1 +/- 4.1 mg/kg/min) and GDR (18.1 +/- 5.8 v 30.3 +/- 5.2 mg/kg/min) were decreased by rhGH treatment compared with control values. They returned to normal levels in rats treated with both rhGH and troglitazone (GIR, 22.4 +/- 5.9; GDR, 24.7 +/- 7.1). From these results, it is evident that rhGH treatment impaired insulin's ability to suppress HGO and stimulate peripheral glucose utilization. Troglitazone could block the insulin antagonistic effects of GH on hepatic glucose output and peripheral glucose utilization.

Administration, Oral↗
PubMed1998

Effects of troglitazone on dexamethasone-induced insulin resistance in rats.

Troglitazone, a thiazolidinedione derivative, has been shown to counteract insulin resistance in obesity and non-insulin-dependent diabetes mellitus (NIDDM). To test its effects on dexamethasone-induced insulin resistance, we measured hepatic glucose production (HGP) and the insulin-stimulated glucose disposal rate (Rd) by a euglycemic-hyperinsulinemic glucose clamp technique coupled with 3-3H-glucose infusion in male Wistar rats treated with low-dose dexamethasone ([LoDex] 0.05 mg/kg/d, n = 7), high-dose dexamethasone ([HiDex] 0.1 mg/kg/d, n = 7), or dexamethasone plus troglitazone (LoDex + T, n = 8; HiDex + T, n = 6). Dexamethasone was injected subcutaneously for 4 days. Troglitazone was administered orally at 20 mg/d for 3 days before and for 4 days along with the dexamethasone treatment. The glucose clamp study was performed after an overnight fast in chronically catheterized conscious rats with a continuous insulin infusion of 57.4 pmol/kg/min. Basal HGP was comparable among the control (45.8 +/- 2.1 micromol/kg/min, n = 7), LoDex (47.9 +/- 4.7 micromol/kg/min), LoDex + T (46.0 +/- 2.6 micromol/kg/min), and HiDex + T (54.7 +/- 3.4 micromol/kg/min) groups. It increased about twofold in the HiDex group (80.1 +/- 5.2 micromol/kg/min, P < .05 v control). Under hyperinsulinemia, HGP was suppressed to a similar level in the control (11.3 +/- 8.8 micromol/kg/min), LoDex (10.2 +/- 8.4 micromol/kg/min), and LoDex + T (7.8 +/- 7.9 micromol/kg/min) groups. The suppressive effect of insulin on steady-state HGP during the clamp was impaired in HiDex (63.7 +/- 9.7 micromol/kg/min, P < .05) and HiDex + T (64.0 +/- 6.5 micromol/kg/min, P < .05). Rd decreased 27% in LoDex (81.5 +/- 5.8 micromol/kg/min, P < .05) and 36% in HiDex (71.3 +/- 9.4 micromol/kg/min, P < .05) compared with the controls (111.4 +/- 7.4 micromol/kg/min). Troglitazone prevented the decrease in Rd in LoDex + T (102.6 +/- 5.7 micromol/kg/min), but not in HiDex + T (67.0 +/- 6.4 micromol/kg/min). These results indicate that the development of peripheral insulin resistance was prevented by troglitazone in LoDex rats. Troglitazone may be a useful drug to treat steroid-induced diabetes.

Animals↗
PubMed1998

Recurrent hemithyroiditis: a case report.

We report on a girl with recurrent painful thyroiditis which involved the entire right thyroid lobe, but did not spread to the left thyroid lobe. She occasionally developed pain and swelling of the right side of the neck following symptoms of common cold over several years. During these attacks, the right thyroid lobe was enlarged, tender, and very soft, while the left thyroid lobe was not remarkable. Ultrasonic examination revealed that the entire right thyroid lobe was hypoechoic, but the entire left lobe was normal echoic. Serum C-reactive protein, white blood cell count, and erythrocyte sedimentation rate were increased during the attacks. The thyroiditis responded quickly to treatment with prednisolone and/or anti-inflammatory drugs, but the thyroiditis may have subsided spontaneously since the signs and symptoms of thyroiditis had subsided with only antibiotic therapy. After resolution of the thyroiditis, the echogenicity of the right lobe returned to near normal and the inflammatory findings became negative. During the investigation, thyroid function was normal except for when the thyroiditis was first diagnosed at another hospital with a serum TSH level of 0.1 mU/l. Serum thyroglobulin level was increased but returned to normal or decreased during and after attacks of thyroiditis. The mechanism(s) of the recurrent hemithyroiditis remains unknown, but the underlying disease appeared to be chronic thyroiditis since tests for anti-microsomal or anti-thyroid peroxidase antibodies were consistently positive during the course of her illness. The changes in the titers of these antibodies were not clear during and after the attacks of thyroiditis. In addition, the clinical course suggests that the present hemithyroditis can be induced by recurrent upper respiratory infection.

Adolescent↗
PubMed1997

A case of Graves' disease associated with painful thyroiditis.

We report on a 61-year-old woman with untreated Graves' disease associated with painful thyroiditis. On examination, the left lobe of the thyroid gland was firm and tender but the right lobe was not. A diagnosis of Graves' disease was made based on the results of thyroid function tests including the percentage of thyroidal radioactive iodine uptake (RAIU) and the presence of thyroid-stimulating antibodies (TSAb). However, ultrasonogram results and inflammatory findings (C-reactive protein concentration and erythrocyte sedimentation rate) also indicated the presence of inflammation in the thyroid gland. She was first treated with aspirin, and later with prednisolone. Her clinical course was similar to that in cases of subacute thyroiditis, but neither her HLA type nor aspiration cytology findings indicated the type of thyroiditis. With the resolution of the thyroiditis, her serum levels of thyroid hormone and TSAb decreased, although RAIU increased. Finally, she became euthyroid without antithyroid drug treatment. The serum levels of antithyroid antibodies, TSH-binding inhibitor immunoglobulins (TBII) and TSAb increased transiently and then decreased during the course of the illness, indicating that the mechanism(s) of the production and/or degradation of TBII and TSAb is similar to that for antithyroid antibodies in the present case. The present findings also indicate that remission may occur in some patients with Graves' disease after painful thyroiditis is resolved.

Female↗
PubMed1996

Adjuvant activity of diesel exhaust particulates (DEP) in production of anti-IgE and anti-IgG1 antibodies to mite allergen in mice.

The present study indicates that diesel exhaust particulates (DEP) and pyrene contained in DEP have an adjuvant activity on IgE and IgG1 antibody productions in mice immunized intranasally with a mite allergen. The effect of pyrene on IgE and IgG1 antibody productions in mice was investigated to clarify the relation between mite allergy and adjuvancy of the chemical compounds in DEP. Der f II, one of the major allergens of house dust mite (Dermatophagoides farinae), was used as a mite allergen. Mice were grouped, and immunized with 5 micrograms of Der f II alone, 5 micrograms of Der f II plus 200 micrograms of pyrene and 5 micrograms of Der f II plus 100 micrograms of DEP intranasally seven times at two week intervals. The separate groups of mice were also immunized with 10 micrograms of Der f II plus the same dose of adjuvants in the same way. The IgE antibody responses to Der f II in mice immunized with Der f II plus pyrene or Der f II plus DEP were markedly enhanced compared with those immunized Der f II alone. The anti-Der f II IgE antibody production increased with increasing the dose of Der f II from 5 micrograms to 10 micrograms in mice immunized with Der f II plus the same dose of adjuvants. The IgG1 antibody responses to Der f II in mice immunized with 10 micrograms of Der f II plus 200 micrograms of pyrene or 10 micrograms of Der f II plus 100 micrograms of DEP were extremely higher than those immunized with 10 micrograms of Der f II alone. In addition, when the peritoneal macrophages obtained from normal mice were incubated with pyrene or DEP in vitro, an enhanced interleukin-1 alpha production of the macrophages was observed. When the spleen lymphocytes obtained from the mice immunized with 10 micrograms of Der f II plus 100 micrograms of DEP or 10 micrograms Der f II plus 200 micrograms of pyrene were stimulated with 10 micrograms of Der f II in vitro, an enhanced IL-4 production of the lymphocytes was also observed compared with those immunized with Der f II alone. These results suggest that the adjuvancy of DEP and pyrene on the production of IgE and IgG1 antibodies to Der f II may be one of the factors responsible for an incidence of asthma caused by house dust mite.

Adjuvants, Immunologic↗
PubMed1996

Adjuvant activities of pyrene, anthracene, fluoranthene and benzo(a)pyrene in production of anti-IgE antibody to Japanese cedar pollen allergen in mice.

We have previously demonstrated that pyrene in diesel-exhaust particles (DEP) has an adjuvant activity on immunoglobulin E (IgE) antibody production in mice immunized with Japanese cedar pollen allergen (JCPA) or ovalbumin (OA) intraperitoneally. The present study is concerned with the adjuvant activity in IgE antibody production against JCPA of pyrene or DEP inoculated intranasally in mice. We show that anthracene, fluoranthene and benzo(a)pyrene in DEP have the ability to enhance anti-JCPA IgE antibody production in mice by intranasal immunization. Mice were grouped, immunized with 10 micrograms of JCPA plus 400 micrograms of pyrene, 10 micrograms of JCPA plus 100 micrograms of DEP, 10 micrograms of JCPA plus 2 mg of aluminum hydroxide and 10 micrograms of JCPA alone intranasally 7 times at 2 week intervals. Mice were also grouped, and immunized with JCPA (10 micrograms) plus 40 micrograms of anthracene, JCPA (10 micrograms) plus 400 micrograms of fluoranthene, JCPA (10 micrograms) plus 40 micrograms of benzo(a)pyrene, and JCPA (10 micrograms) plus 400 micrograms of pyrene and JCPA (10 micrograms) alone. We found that the IgE antibody responses to JCPA in mice immunized with JCPA plus pyrene, JCPA plus DEP or JCPA plus the three chemical organic compounds mentioned above were significantly enhanced compared with those immunized with JCPA alone. In addition, when the intraperitoneal macrophages obtained from the normal mice (unimmunized mice) were incubated with pyrene, anthracene, fluoranthene or benzo(a)pyrene in vitro, an enhanced chemiluminescence (CI) response and interleukin-1 alpha (IL-1 alpha) production of the macrophages was observed in each instance. These results suggest that in the production of IgE antibody to JCPA the adjuvancy of polycyclic aromatic hydrocarbons (PAHs) in DEP may be important in an attack of Japanese cedar pollinosis.

Adjuvants, Immunologic↗
PubMed1994

Increased insulin sensitivity in patients with aldosterone producing adenoma.

OBJECTIVE: Primary aldosteronism is a recognized endocrine cause of glucose intolerance. A blunted insulin response to glucose in patients with primary aldosteronism is well known, but insulin sensitivity has not been thoroughly determined. We investigated insulin sensitivity and insulin secretion in patients with aldosterone producing adenoma. DESIGN: Glucose tolerance and insulin responses to glucose were evaluated using a standard 75 g oral glucose tolerance test in patients with aldosterone producing adenoma before and after surgery, and in control subjects. Parameters for insulin resistance (HOMA-R) and pancreatic beta-cell function (HOMA-beta F) were derived from a homeostasis model assessment. PATIENTS: Fifteen patients with aldosterone producing adenoma and 41 control subjects with normal glucose tolerance matched for age and body mass index, were studied. Eight patients were re-evaluated after surgical removal of the adenoma. In 5 patients 125I-insulin binding to erythrocytes was also measured. MEASUREMENTS: Plasma glucose was measured by a glucose oxidase method. Plasma insulin, aldosterone and renin activity were measured by radioimmunoassay. RESULTS: Both fasting plasma glucose and insulin were lower in the patients than in the controls. Although the areas under the curve for plasma glucose during the oral glucose tolerance test did not differ, that for plasma insulin was less in the patients with hyperaldosteronism. Insulin sensitivity was increased in the patients, as evidenced by decreased HOMA-R compared with controls, while HOMA-beta F was comparable between the groups. 125I-insulin binding to erythrocytes was higher in 5 patients than in 19 normal controls. After surgical removal of adenoma, neither fasting plasma glucose nor the glucose area under the curve during the oral glucose tolerance test changed. However, fasting plasma insulin and the insulin area under the curve increased significantly. HOMA-R increased and HOMA-beta F remained unaltered. CONCLUSION: Insulin sensitivity was increased in untreated patients with aldosterone producing adenoma. Enhanced insulin receptor binding may contribute to this increased insulin sensitivity.

Adenoma↗