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Biomedical subjects

N Shimojo

Publications and source records attributed to N Shimojo.

At least 91 records · Page 5Linked to original sources
PubMed1993

Regulation of renal cytochrome P450s by thyroid hormone in diabetic rats.

Effects of thyroid hormone treatment on renal P450 expression in the diabetic rats were investigated. Diabetes produced by streptozotocin induced CYP4A2 and P450 K-2 (similar form with CYP2C23) but not P450 K-4 (similar form with CYP4A8) and induced lauric acid hydroxylation activity. The serum thyroid hormone level was decreased with diabetes. Treatment of diabetic rats with thyroid hormone (T3) as well as with insulin reversed the increase in the levels of CYP4A2 and P450 K-2. Thyroidectomy also induced CYP4A2 and P450 K-2 in the rat kidney. The increase was reversed by treatment of thyroidectomized rats with T3. These findings suggest that expression of CYP4A2 and P450 K-2 in rat kidney is suppressively regulated by thyroid hormone and the decrease in thyroid hormone level in the diabetic state affects the levels of CYP4A2 and P450 K-2.

Animals↗
PubMed1993

Changes in amounts of cytochrome P450 isozymes and levels of catalytic activities in hepatic and renal microsomes of rats with streptozocin-induced diabetes.

Hepatic microsomal cytochrome P450s, which are involved in the metabolism of drugs, hormones, prostaglandins and fatty acids, change when animals develop diabetes. We studied changes in cytochrome P450 isozymes in both hepatic and renal microsomes of rats with diabetes caused by streptozocin, and compared the results with changes in catalytic activities in the microsomes. In hepatic microsomes of diabetic rats, the amount of cytochrome P450 2E1, an acetone-inducible isozyme, was two and a half times that of control rats, and that of P450 4A2, a major renal isozyme, was three times that in the controls. The amounts of cytochrome P450s 2A1, 2C6, 2C7, 3A2 and 4A3 increased in hepatic microsomes of diabetic rats, and P450 2C11 decreased. Treatment with insulin restored these to the levels in the controls. The catalytic activities of aniline hydroxylation, 7-ethoxycoumarin O-dealkylation, testosterone 2 beta, 6 beta, 7 alpha, and 16 beta-hydroxylation, and omega-, (omega-1)-hydroxylation of lauric acid were high in the hepatic microsomes of diabetic rats, and testosterone 2 alpha and 16 alpha-hydroxylation activities were low. In renal microsomes of diabetic rats, cytochrome P450s 2E1, 4A2 and K-4 were induced, and omega- and (omega-1)-hydroxylation activities were high. These changes were reversed by insulin treatment. The induction and suppression of cytochrome P450 isozymes in diabetic rats were consistent with the changes in the catalytic activities. In both hepatic and renal microsomes, P450s 2E1 and 4A2 were induced, altered metabolism of ketones and fatty acids in diabetes may contribute to these changes.

Animals↗
PubMed1993

A common T-cell epitope between human thyroglobulin and human thyroid peroxidase is related to murine experimental autoimmune thyroiditis.

We have investigated functional common T-cell epitopes between human thyroglobulin (hTg) and human thyroid peroxidase (hTPO) in mice. Four hTg peptides, Tg-P1, Tg-P2, Tg-P3 and Tg-P4, in which 5 amino acid residues are identical to those of hTPO, and 1 hTPO peptide, TPO-P4 relevant to Tg-P4, were prepared. Among these peptides, only Tg-P4 (residues 2730-2743) and TPO-P4 (residues 118-131) were highly antigenic and both peptides shared the common T-cell epitope. In addition, when the spleen cells from mice immunized with mouse Tg (mTg) were restimulated in vitro by Tg-P4 or TPO-P4 as well as by mTg, these cells transferred thyroiditis to naive recipient mice. These findings indicate that this common T-cell epitope between hTg and hTPO is immunogenic and related to the development of murine experimental autoimmune thyroiditis.

Amino Acid Sequence↗
PubMed1993

[Analysis of ovalbumin-specific T cell lines established from patients with hen egg allergy].

Ten ovalbumin (OVA)-specific T cell lines (TCLs) were established from peripheral blood mononuclear cells of 6 patients with hen egg allergy, and the antigen recognition of these TCLs was characterized. Two OVA epitopes were determined by use of 3 synthetic OVA peptides which have been known as murine T cell epitopes. Blocking of antigen-specific T cell proliferation by anti-HLA class II monoclonal antibodies suggest that all 3 HLA class II molecules could act as restriction elements for T cell recognition of OVA. This is the first demonstration of OVA epitopes recognized by T cells in patients with hen egg allergy, as far as we know.

Cell Line↗
PubMed1993

Electrochemical assay system with single-use electrode strip for measuring lactate in whole blood.

We have developed an assay system for measuring lactate in whole blood, consisting of a single-use strip of an enzyme-coated electrode and a small meter. The electrode strip is made of three plastic films: a cover sheet, a spacer, and an insulation layer printed with electrodes that are coated with lactate oxidase (EC 1.1.3.x) and ferricyanide as an electron mediator. The meter measures the magnitude of the anodic current of the reduced mediator by the enzymatic reaction and displays the lactate concentration 60 s after a blood sample (5 microL) is applied. The calibration curve was linear up to 20 mmol/L, and the between-run CVs at three concentrations were 1.7-8.4%. Lactate concentrations determined by this method (y) in blood samples from healthy individuals before and after exercise agreed with the results obtained by the conventional enzymatic method (x): y = 0.97x - 0.3, Sy/x = 0.7. This assay provides a rapid and convenient test for measuring blood lactate concentrations.

Biosensing Techniques↗
PubMed1993

Characterization of a thyroiditis-inducing thyroglobulin-specific T-cell clone restricted by the H-2 molecule of a low responder mouse strain.

We established a thyroglobulin (Tg)-specific, thyroiditis-inducing T-cell clone, B12G, from B6C3F1 mice by the immunization of mouse Tg with lipopolysaccharide (LPS) from Klebsiella strain LEN (O3:K1). B12G was Thy-1.2+, CD3+, CD4+, CD18+, and CD8-, and could transfer thyroiditis to recipient mice after in vitro stimulation with mouse or bovine Tg. Histological examination showed severe thyroiditis with predominant infiltrations of polymorphonuclear cells; few mononuclear cells were observed. B12G proliferated in response to bovine, mouse, porcine, and rat Tg in the presence of irradiated spleen cells, but did not respond to chicken or human Tg. H-2b, a low-responder haplotype of experimental autoimmune thyroiditis, governed the response of the clone to Tg. B12G produced interleukin-4 (IL-4) and IL-6, but not IL-2 or interferon-gamma (IFN-gamma), on stimulation with mouse Tg. These findings were different from characteristics of previously reported Tg-specific T-cell clones from high-responder mice in terms of epitope specificity and cytokine production pattern, raising the possibility that the specificities and functions of T cells involved in the development of autoimmune thyroiditis in low-responder mice differ from those in high responders.

Animals↗
PubMed1992

Fetal scalp and umbilical artery blood lactate measured with a new test strip method.

OBJECTIVE: To compare the measurement of lactate in fetal scalp and umbilical artery blood by a new dry reagent strip method with a commercially available enzymatic method using plasma (Monotest). DESIGN: Comparative study. SUBJECTS: Fetal scalp blood samples were obtained during labour from 24 fetuses and umbilical artery blood samples were obtained at birth in a further 51 deliveries. RESULTS: The concentration of lactate in scalp and umbilical artery blood measured by the reagent strip method correlated well (r = 0.94, P less than 0.001 and 0.95, P less than 0.001 respectively) with the enzymatic plasma method. The paper strip method tended to give lower readings than the enzymatic method when the fetal haematocrit was greater than or equal to 50%. CONCLUSIONS: The new dry reagent strip method which takes only 1 min to carry out and requires only 20 microliters of blood seems to be handy and reliable. This system provides a convenient and rapid test for measuring fetal blood lactate.

Evaluation Studies as Topic↗
PubMed1992

Detection of house dust mite (HDM)-specific IgE antibodies on nasal mast cells from asthmatic patients whose skin prick test and RAST are negative for HDM.

Mast cells are found in nasal smears of pediatric patients with perennial bronchial asthma whose skin prick test and radioallergosorbent test (RAST) are negative for inhalant allergens. IgE antibodies were demonstrated on these mast cells by monoclonal anti-human IgE antibodies, whereas IgG antibodies were not detected by monoclonal anti-IgG antibodies. In order to pursue the causative allergen for asthma in these patients, binding potential between IgE antibodies on nasal mast cells and house dust mite (HDM), the most prevalent aeroallergen, was examined by an immunochemical technique. Out of 9 patients whose skin prick test and RAST were negative for HDM, 7 were found to have HDM-specific IgE antibodies on their nasal smear mast cells. None of these 7 patients had IgE antibodies to cedar pollen, a negative control aero-allergen, on their mast cells. Specific binding of HDM on the mast cells was further confirmed by the fact that nasal mast cells from patients with egg allergy bound egg white but not HDM on their surface. Preincubation of mast cells with anti-IgE antibodies inhibited binding of HDM on the mast cells, indicating that HDM was bound to surface IgE antibodies on the mast cells. These experiments enabled us to expeditiously identify sensitization to an inhalant allergen, such as HDM, in young asthmatic patients whose allergen cannot be found by conventional laboratory diagnostic procedures.

Allergens↗
PubMed1992

[Development of automated lactate analyzer with continuous blood sampling for monitoring blood lactate and its application for the testing of physical exercise].

The anaerobic threshold is useful for estimating the intensity of physical exercise. It is shown as either an increase in blood concentrations of lactate or a disproportionate increase in ventilation. We developed a lactate analyzer based on an electroenzymatic method with a continuous blood sampling system through a double-lumen catheter. Ascorbic acid, bilirubin, hemoglobin, creatinine, uric acid, and glucose did not interfere the results. The lactate concentrations in blood samples from healthy subjects during physical exercise correlated well (r = 0.993) with results measured by the conventional enzymatic method. We measured the concentrations of blood lactate with a use of this lactate analyzer to see the anaerobic threshold in nine healthy volunteers during exercise on a treadmill with an increasing workload. The point at which lactate concentrations started to increase was detected easily. The anaerobic threshold identified as a disproportionate increase in ventilation was seen at almost the same time. We conclude that the lactate analyzer, with a continuous blood sampling system, can measure precisely concentrations of lactate in blood and can detect the anaerobic threshold during physical exercise.

Adult↗
PubMed1992

[Diagnosis of food allergy based on rectal mucosal cytology].

We performed rectal and/or oral challenge tests on 8 patients with suspected but unproven diagnosis of food allergy based on detailed medical history and findings from radioallergosorbent tests (RAST). The cells appearing in the rectal mucosal smear serially for 48 hours after allergen challenge were examined. The following results were obtained: 1) Significant numbers of not only eosinophils but also mast cells appeared in the rectal smears after challenges with suspected-food allergens, but not with unrelated foods. This confirmed the antigen-specificity of the method. 2) In some cases, the appearance of mast cells and eosinophils was bimodal, suggesting the existence of a later allergic response in addition to an immediate-type reaction. 3) The food-specific appearance of mast cells and eosinophils was observed in association with clinical symptoms after challenge, even in patients whose IgE antibodies to the allergen were negative or commercially unavailable. In conclusion, we propose that rectal mucosal cytology in conjunction with rectal and/or oral challenge tests is a reliable and objective method to diagnose unproven or suspected food allergy.

Child↗
PubMed1992

[Allergy to casein hydrolysate formula. A study of sensitizing allergen].

A six-month old baby, who had been fed for 2 months with casein hydrolysate formula (MA-1) for treatment of milk allergy, developed diarrhea. The baby's RAST score for milk was negative. IgE antibodies to MA-1 but not to MA-1 depleted of lipid (fat-free MA-1), were demonstrated by enzyme-linked immunosorbent assay (ELISA). It was confirmed by the appearance of numerous mast cells and eosinophils in a rectal smear taken after challenge with MA-1 (but not detected after challenge with fat-free MA-1) that some component in the lipid of MA-1 must be an allergen in this patient.

Caseins↗
PubMed1992

[Autoimmune response to thyroglobulin. Proliferative response to thyroglobulin fragments in low responder mice].

Thyroglobulin (Tg) is one of the major thyroid autoantigens involved in autoimmune thyroiditis. The immune response of mice to Tg is genetically controlled by H-2-linked genes. To elucidate the regulation mechanism of autoimmune response to Tg in low responder mice, we studied the proliferative response of lymph node cells (LNC) to mouse Tg (MTg) and enzyme-digested MTg fragments. MTg was treated with Staphylococcus aureus V8 protease followed by separation of the fragments into 6 fractions (Fr1-Fr6: 264,000-17,000) by high performance liquid chromatography (HPLC), LNC from MTg immunized CBA/N (H-2k) mice, a high responder strain, proliferated in response to MTg and all fractions (Fr1-Fr6) of MTg fragments in vitro. In contrast, LNC from MTg immunized BALB/c (H-2d) and B10 (H-2b) mice, low responder strains, did not respond to native Tg but responded well to some smaller Tg fractions (Fr3, 4, 5). In addition, when BALB/c mice were immunized with MTg Fr4 with a molecular weight of 63,000, LNC from BALB/c mice proliferated in response to MTg as well as MTg Fr4. These findings suggest that T cells which are capable of responding to Tg do exist even in low responder mice and that the activation of these autoreactive T cells is suppressed by a regulatory cell subpopulation in low responder mice.

Animals↗
PubMed1991

Distribution of manganese in rat pancreas and identification of its primary binding protein as pro-carboxypeptidase B.

Distribution of manganese (Mn) and its binding to specific proteins were examined in rat pancreas. A MnCl2 solution was injected subcutaneously into Wistar rats daily at a single dose of 15 mg of Mn/kg body weight for 10 days and the animals were killed 1 day after the last injection. The concentration of Mn in the pancreas increased considerably from 1.4 +/- 0.2 (control) to 13.3 +/- 3.7 micrograms/g wet tissue by the repeated injection of Mn. The distribution of Mn in the soluble fraction of the pancreas (170,000 g supernatant) was determined on a gel-filtration column (Asahipak GST-520) using an h.p.l.c.-inductively coupled argon plasma atomic-emission spectrometry (i.c.p.) technique. The metal was eluted as a single peak in the high-molecular-mass protein fraction, where Mn had been observed as a small peak in the control profile, suggesting that the administered Mn was bound to the same Mn-binding component as that in the control. On the basis of enzymic and chemical characterization of the protein, it was identified as a zymogen of carboxypeptidase B (pro-carboxypeptidase B, pro-CPB). The elution profiles of the protein by h.p.l.c.-i.c.p. indicated that Mn and zinc (Zn) were bound to the zymogen with a molar ratio of 1:4 in normal rat pancreas. Mn bound to the zymogen was easily replaced by Zn in vitro, suggesting that Mn was bound to the Zn-binding site and that the binding affinity to Zn was higher than that to Mn. The present results indicate that pro-CPB is the primary Mn-binding protein in the pancreas of control and also Mn-administered rats.

Amino Acid Sequence↗
PubMed1991

Changes in element concentration and distribution in breast-milk fractions of a healthy lactating mother.

Daily changes in components of breast milk with number of days of lactation after delivery were demonstrated by determining concentrations and distributions of several elements simultaneously. Concentrations of calcium, copper, magnesium, phosphorus, sulfur, and zinc were determined simultaneously by inductively coupled argon plasma-atomic-emission spectrometry (ICP) for whole milk and milk fractions (skimmed milk and whey) collected from 2 to 196 d postpartum from a healthy lactating mother. Calcium and phosphorus concentrations increased in transitional milk. With days postpartum, the other elements decreased from the highest concentrations in colostrum milk, the modes of decrease being characteristic for each element. Distributions of copper, iron, phosphorus, sulfur, and zinc in whey were determined on a gel-filtration column by HPLC with ICP detection (HPLC-ICP method). Distributions of the five elements and absorbance peaks at 254 and 280 nm changed dramatically day by day at the beginning (colostrum milk), resulting in constant distributions after 30 d (mature milk). These results suggest the important roles of daily changing constituents in breast milk, especially in colostrum milk, in the nutrition of the newborn. Several element peaks on a gel-filtration column were identified by comparison with standard samples.

Adult↗
PubMed1991

Lactate analyzer with continuous blood sampling for monitoring blood lactate during physical exercise.

To monitor changes in the concentration of blood lactate during physical exercise, we used an automated lactate analyzer based on an electro-enzymatic method with continuous blood sampling through a catheter. The lactate concentration was measured every 2 min; between measurements, the instrument was calibrated with a lactate standard. Ascorbic acid, bilirubin, hemoglobin, creatinine, uric acid, and glucose did not interfere with the measurements. The lactate concentrations in blood samples from apparently healthy subjects before and after exercise correlated well (r = 0.993) with results by the conventional enzymatic method. We measured the blood lactate concentrations in nine apparently healthy volunteers during exercise on a treadmill with an increasing workload. The point at which lactate concentrations started to increase was detected easily. Thus, the lactate analyzer is suitable for monitoring changes in blood lactate concentrations during exercise.

Autoanalysis↗