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Biomedical subjects

I Matsui

Publications and source records attributed to I Matsui.

At least 37 records · Page 2Linked to original sources
PubMed1995

Optimum pH control mechanism for porcine pancreatic alpha-amylase.

We studied the substrate-dependence of pH activity of porcine pancreatic alpha-amylase by using a series of p-nitrophenyl maltooligosaccharides. The mechanism controlling the optimum pH of mammalian alpha-amylase involved the reception and recognition of a substrate component at some other substrate binding sites, in addition to those at subsite 5 that were reported previously [K. Ishikawa et al., Biochemistry, 32, 6259-6265 (1993)].

Animals↗
PubMed1995

Transient hypothyroidism in a case of untreated Graves' disease.

We report the case of a 41-year-old female with untreated Graves' disease who developed transient hypothyroidism. The hypothyroid state was thought to be caused by silent thyroiditis, based on findings of a non-tender thyroid gland, suppressed thyroidal radioactive iodine uptake, normal white blood cell count and normal erythrocyte sedimentation rate, and ultrasonogram results. Silent thyroiditis may play a role in the development of Graves' hyperthyroidism. Results for TSH-binding inhibitor immunoglobulins (TBII), thyroid-stimulating antibodies (TSAb), anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were positive before the development of hypothyroidism. Their levels were decreased during and after the hypothyroid phase. These results suggest that the same or similar mechanism(s) were involved in the production of these different antibodies during the course of her illness.

Adult↗
PubMed1994

Roles of the aromatic residues conserved in the active center of Saccharomycopsis alpha-amylase for transglycosylation and hydrolysis activity.

The molecular structure of Saccharomycopsis fibuligera alpha-amylase was predicted by a homology-based modeling technique, and the amino acid residues composing the active site were displayed with color codes according to their order of conservation. We noticed two highly conserved aromatic residues located in the active center, tyrosine 83 (Y83) and tryptophan 84 (W84), and examined their roles in catalytic activity by site-directed mutagenesis. The W, leucine (L), and asparagine (N) mutants at Y83 and the L mutant at W84 showed remarkable enhancement of transglycosylation activity and complementary decreases in native hydrolysis activity. The phenylalanine (F) mutant at Y83 and the F and Y mutants at W84 only decreased hydrolysis activity. Mechanistic and kinetic studies of these mutants using a reducing-end-blocked substrate and a hydrolysis-specific substrate revealed a probable transglycosylation mechanism and critical contributions of the 83rd and 84th aromatic residues to efficient hydrolysis. Given that aromatic residues stack against the faces of sugars, we assumed that Y83 and, presumably, W84 play roles in the binding of oligosaccharide substrates through the stacking interaction and in the indirect fixation of the catalytic water molecule through hydrogen bonding with the hydroxyl of the bound substrates. Mutations to nonaromatic residues could cause slight changes in the binding topology of substrates to favor transglycosylation over hydrolysis.

Amino Acid Sequence↗
PubMed1994

Thyroid hormone autoantibodies in patients with Graves' disease: effect of anti-thyroid drug treatment.

We examined the effects of anti-thyroid drug treatment on serum autoantibodies against thyroid hormones (thyroid hormone autoantibodies, THAA), thyroglobulin (Tg) and thyroid peroxidase (TPO) in patients with Graves' disease by measuring each autoantibody level before and after treatment. Six patients among 40 untreated patients with Graves' disease had anti-thyroxine (T4) antibodies. One patient had both anti-T4 and anti-triiodothyronine (T3) antibodies. Thus the prevalence of THAA in untreated Graves' disease was 7 out of 40 (17.5%). Changes in T4-Ab levels after treatment varied. In five cases (cases 3-7) levels decreased 4-7 months after treatment. However, in the other two cases levels fluctuated 1, 3, 6 and 12 months after treatment. None of the previously THAA-negative patients became positive after treatment. Anti-Tg antibody (Tg-Ab) was positive in 34 out of 40 (85%) untreated cases and its level decreased in both THAA positive and negative patients after treatment. Anti-thyroid peroxidase antibody (TPO-Ab) was positive in 32 of the 40 (80%) untreated Graves' patients and its level significantly decreased after treatment. Our findings suggest that treatment with anti-thyroid drugs does not produce THAA in Graves' disease.

Adult↗
PubMed1994

Prevalence of thyroid hormone autoantibodies in healthy subjects.

OBJECTIVE: The prevalence of thyroid hormone autoantibodies in patients with thyroid disorders has been well described, although the results have been variable. However, the prevalence of thyroid hormone autoantibodies in apparently healthy subjects remains unknown and its determination was the main objective of this study. SUBJECTS AND METHODS: Sera obtained from 880 healthy subjects (365 men and 515 women) were examined for thyroid hormone autoantibodies by immune precipitation using radiolabelled thyroid hormones or thyroid hormone analogues. RESULTS: Anti-triiodothyronine (T3) and anti-thyroxine (T4) antibodies were detected in none (0%) and in 3 (0.34%), respectively, of the 880 individuals studied using radiolabelled thyroid hormones. Similar tests in 385 healthy subjects using radiolabelled thyroid hormone analogues (polyaminocarboxy T3 and T4) showed the presence of anti-T3 and anti-T4 antibodies in 3 (0.78%) and in 4 (1.04%), respectively. None of the subjects had both anti-T3 and anti-T4 antibodies. Thus, the prevalence of anti-T3 or anti-T4 antibodies among healthy population was concluded to be as high as 1.8%. Radiolabelled thyroid hormone analogue binding to purified immunoglobulin G (IgG), with or without the addition of an excess of unlabelled thyroid hormones, confirmed specific binding of thyroid hormones to the thyroid hormone autoantibody-positive IgGs. The presence and class specificity of thyroid hormone autoantibodies was confirmed by the Ouchterlony immunodiffusion/autoradiography method, which showed biphenotypic heavy chain (IgG and IgA) and kappa (kappa) light chain specificities. Serum concentrations of free thyroid hormones and TSH in thyroid hormone autoantibody-positive sera were within the normal range. CONCLUSIONS: These results indicate that the occurrence of thyroid hormone autoantibodies among the healthy Japanese population is fairly common. However, interference of thyroid hormone autoantibodies in the radioimmunoassay of free thyroid hormones is exceptional.

Adult↗
PubMed1993

Neurofibromatosis type 1 and childhood cancer.

BACKGROUND: Patients with neurofibromatosis type 1 (NF1) are prone to develop malignancy, particularly malignant schwannoma and glioma in adults. METHODS: To assess the risk for childhood malignancy in NF1, 26,084 patients with cancer younger than 15 years of age registered from 1969 to 1989 in the Japan Children's Cancer Registry were reviewed. The incidence of NF1 in each type of cancer was compared with that in the Japanese population. RESULTS: Fifty-six children with cancer had NF1 in the national registry. The incidence of NF1 (0.21%) was 6.45 times that of the expected estimated rate of 1 per 3000 in the Japanese population. These tumors tended to be type and site specific. The NF1 incidence was extremely high in optical nerve glioma (12.5%), other central nervous system gliomas (0.9%), and malignant schwannoma (31.4%). For nonneural tumors, NF1 incidence was increased in rhabdomyosarcoma (1.36%), particularly those in urogenital organs, and in myelogenous leukemia (0.27%). Epithelial carcinomas were not observed in the group of patients with NF1. CONCLUSION: The risk for glioma and malignant schwannoma increases in children and adults with NF1. Moreover, the risk for two childhood malignancies, myelogenous leukemia and rhabdomyosarcoma, increases in children with NF1. The NF1 gene seems to increase the risk not only for neural tumors but also for some non-neural tumors in an age-specific, organ-dependent pattern of carcinogenesis.

Adolescent↗
PubMed1993

Evaluation of thyroid function in patients with thyroid hormone autoantibodies.

Serum free thyroxine (FT4) levels were measured in patients with Hashimoto's thyroiditis and Graves' disease who were seropositive for thyroid hormone autoantibodies. The methods used were equilibrium dialysis/radioimmunoassay (FT4 by equilibrium dialysis, Nichols Institute) and FT4 analog radioimmunoassay (Amerlex MFT4) before and after treatment of sera with 12.5% polyethylene glycol (PEG). Furthermore, FT4 measurement in the PEG-treated sera was done using two other analog radioimmunoassays (DPC FT4 Kit and N-FT4 Corning). Serum thyrotropin (TSH) concentration before and after i.v. infusion of thyrotropin releasing hormone (TRH) was measured in five cases of Hashimoto's thyroiditis and four cases of Graves' disease with thyroid hormone autoantibodies. Although FT4 determination by analog tracer radioimmunoassays showed unusually high values for the hormone, results obtained by an equilibrium dialysis/radioimmunoassay method showed compatible values with basal TSH. Furthermore, FT4 concentrations measured with Amerlex MFT4 after treatment of sera with 12.5% PEG, correlated well with the values obtained by equilibrium dialysis/radioimmunoassay (r = 0.98, P < 0.001). Similar results were obtained with two other analog FT4 radioimmunoassays after treatment of sera with PEG. These results indicate that real FT4 values in patients with thyroid hormone autoantibodies are compatible with basal TSH concentrations. The presence of thyroid hormone autoantibodies per se does not affect the control mechanism of the hypothalamo-pituitary-thyroid axis. It was concluded that measurement of basal TSH as well as FT4 values by either equilibrium dialysis/radioimmunoassay or analog radioimmunoassays after PEG treatment provides clinicians with valid information for assessment of the precise status of thyroid function in patients with thyroid hormone autoantibodies.

Adolescent↗
PubMed1993

Substrate recognition at the binding site in mammalian pancreatic alpha-amylases.

Porcine and human pancreatic alpha-amylases (PPA and HPA, respectively) have five binding sites for hexose residues of substrates. As previously reported, when a substrate is too small to occupy subsite 5 of the alpha-amylases, the optimum pH for catalytic activity changes from neutral to acidic [Ishikawa, K., Matsui, I., Honda, K., & Nakatani, H. (1990) Biochemistry 29, 7119-7123]. We studied the mechanism by which the enzyme recognizes the substrate by using the synthetic substrates maltopentaose (G5) and its analogs 4-O-alpha-maltotetraosyl-D-xylose (G4-X), 4-O-alpha-maltotetraosyl-2-deoxy-D-glucose (G4-D), 3-O-alpha-maltotetraosyl-L- sorbose (G4-S), 4-O-beta-maltotetraosyl-D-glucose (G4 beta-G), alpha-maltotetraosyl-beta-D-fructose (G4-F), p-nitrophenyl alpha-maltotetraoside (G4-phi), and maltopentaitol (G4-GOH). The reducing-end residues of these substrates, relevant to subsite 5, are D-xylose (X), 2-deoxy-D-glucose (D), L-sorbose (S), D-glucose (G), alpha-D-fructofuranose (F), p-nitrophenyl (phi), and D-sorbitol (GOH), respectively. The optimum pH for catalytic activity on the substrates G5, G4-X, G4-D, G4-S, G4 beta-G, and G4-phi was neutral, while that for G4-GOH and G4-F was acidic. These results indicate that only six-membered-ring residues and a phenyl group are recognizable by subsite 5. The neutral pH profile for G4-phi suggests that steric compatibility of the substrates at subsite 5 is also important for the enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Two cases of Graves' disease with presentation of unilateral diffuse uptake of radioisotopes.

We present two cases of Graves' disease whose initial thyroidal scintiscan with 99mTcO4- (Case 1) and 123I (Case 2) showed unilateral diffuse uptake of radioisotopes. Initial diagnosis was possibility of malignancy in Case 1 and Graves' disease or Plummer's disease in Case 2. Both cases underwent right hemithyroidectomy. Histopathology of the resected thyroid gland in both showed hyperplastic columnar epithelium and infiltrative lymphocytes which was compatible with Graves' disease. Twenty seven (Case 1) and eight months (Case 2) after operation, both presented with thyrotoxic symptoms associated with enlarged left lobe, increased serum free thyroid hormone concentrations, suppressed TSH concentration, increased thyroidal 123I uptake in the remaining left lobe, and positive thyrotropin receptor antibodies. Both cases were successfully treated with methimazole. It was concluded that initial radioisotope uptake as well as scintigram in rare subgroup of patients with Graves' disease could be similar with that of non-autoimmune autonomous goiter (Plummer's disease).

Animals↗
PubMed1993

Preliminary report: suspicion of hearing-loss at age 0-1 years by TV viewing attitude.

To determine any difference of TV viewing attitude between normal and hearing-loss children, 14 normal and 8 sensory impaired infants/toddlers were observed separately in a playroom with a TV set showing a 12-min videotape. All children enjoyed TV and showed clear differences in TV viewing behavior between hearing-loss and auditory normal children. At the beginning of their favorite programs or changes in programs, normal infants/toddlers were quickly aware of the TV sound and turned toward the TV set, where as hearing-loss children remained unaware. Our observation proved the intact hearing of two clients who had not responded to regular infant auditory tests. Moreover, we surveyed 65 hearing-loss children. Only 21% of them began to watch TV at 0 year of age, 50% at 1 year. They did it apparently later than normal infants who began to watch TV mostly before 1 year of age in the Japanese general population. From fitting with a hearing aid, however, most of them began to enjoy TV, watch it longer, have their favorite programs (music, songs, etc.) and turn to face the TV whenever a favorite program began. This suggests hearing acuity is important to enjoy TV. Since TV is already familiar and attractive to most any children, it is a useful and sensitive tool for early detection of hearing-loss children at 6-18 months of age.

Child Behavior↗
PubMed1993

Immune recognition of hormonogenic sites of human thyroglobulin: studies of Graves' sera and a murine monoclonal antibody with thyroid hormone antibody activity.

We synthesized four peptides (HTg-1, 1-10; HTg-2, 2547-2558; HTg-4, 2592-2603 and HTg-6, 2737-2748) and two peptides (HTg-3, 2582-2591 and HTg-5, 2687-2694) with or without hormonogenic acceptor tyrosine of human thyroglobulin (hTg). They were iodinated with 127I or 125I. 127I-labeled peptides were tested for their ability to displace 125I-T4 binding to thyroid hormone autoantibodies (THAA) in two cases of Graves' disease and to a murine anti-hTg monoclonal antibody with anti-T4 activity (mAb). 125I-labeled peptides were tested for the direct binding to the aforementioned antibodies. None of the peptides displaced 125I-T4 binding to THAA or to a mAb, or exhibited increased binding to THAA and to a mAb. 125I-T4 binding to a mAb was equally displaced by hTgs obtained from a normal thyroid gland (NTg) and a case of Hürthle cell adenoma with undetectable iodine content (CTg). 125I-T4 binding to serum gamma globulin in each patient's serum was completely displaced by NTg, but CTg displaced 125I-T4 binding 2% and 5% in Case 1 and Case 2, respectively. It was speculated that the mAb recognizes a topological epitope around the hormonogenic site of hTg, while that of THAA in our two cases recognizes only T4 or an iodine dependent topological epitope(s) of hTg.

Animals↗
PubMed1993

Biological activities of rat antisera raised against synthetic peptides of human thyrotropin receptor.

Twenty three male Wistar rats were divided into five groups and were immunized with five overlapping synthetic peptides (Group I (n = 5), peptide 12-30; Group II (n = 5), 24-44; Group III (n = 4), 308-328; Group IV (n = 5), 324-344; and Group V (n = 4), 339-364) of human thyrotropin receptor (TSHR), which had been conjugated with rabbit serum albumin. Sera obtained 34 days after the first immunization were investigated for their ability to displace 125I-TSH binding to thyrotropin receptor (thyrotropin binding inhibitor immunoglobulins (TBII)). In addition, biological activity, namely thyroid stimulating (TSAb) or blocking (TSBAb) activities in them were tested with cultured porcine thyroid cells. TBII activities in Group I, II, III, IV, and V rats were 12.6 +/- 4.1% (range 9.2-17.2%), 16.3 +/- 4.0% (range 11.7-22.0%), 16.7 +/- 4.9% (range 13.2-20.1%), 14.5 +/- 5.7% (range 8.1-19.0%), and 13.8 +/- 6.3% (range 8.1-14.3%), respectively, which were not significantly different from control rat sera (12.3 +/- 6.7%, range 1.2-20.1%). TSAb activities in Group I, II, III, IV, and V rats were 608 +/- 675% (range 275-1813%), 234 +/- 26% (range 209-265%), 313 +/- 175% (range 187-568%), 190 +/- 63% (range 145-301%), and 134 +/- 24% (range 107-158%), respectively. TSAb activities in Group I, II, III, and IV rats were significantly higher than those from control rat sera (P < 0.01) while those of Group V were not significantly different from control rat sera. None of the rats in each group exhibited TSBAb activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

A mutant alpha-amylase with enhanced activity specific for short substrates.

The 210th lysine (K210) at the active site in Saccharomycopsis fibuligera alpha-amylase was altered to arginine (R) or asparagine (N) by site-directed mutagenesis. Replacement of K210 by R strengthened the 7th and weakened the 8th subsite affinities. K210 was found to contribute to both the 8th and the 7th subsites. The catalytic activity of the K210R enzyme for the hydrolysis of maltose (G2) was three-times higher than that of the native enzyme due to an increase in the affinity of the 7th subsite adjacent to the catalytic site, whereas the activity of the K210N enzyme for G2 was decreased to 1% of that of the native enzyme by a reduction in the 7th subsite affinity.

Amylose↗
PubMed1992

Alteration of bond-cleavage pattern in the hydrolysis catalyzed by Saccharomycopsis alpha-amylase altered by site-directed mutagenesis.

The 210th lysine (K) residue in the Saccharomycopsis alpha-amylase (Sfamy) molecule was replaced by arginine (R) and asparagine (N) residues by site-directed mutagenesis. The influences of the replacements on the bond-cleavage pattern for several substrates were analyzed. Both mutant enzymes, K210R and K210N, cleave mainly the first glycosidic bond from the reducing end of maltotetraose (G4), while the native enzyme hydrolyzes mainly the second bond from the reducing end. We changed successfully the major cleavage point in the hydrolysis reaction of G4. The 8th subsite affinities of the K210R and K210N enzymes are calculated to be +2.52 and -0.01 kcal/mol, respectively, whereas that of the native enzyme is +3.32 kcal/mol as reported in the previous paper. These affinity values suggest that the K210 residue composes the 8th subsite, one of major subsites, and that a positively charged amino residue is necessary for the 8th subsite affinity. The K210N enzyme is found to be less active for short substrates like maltotetraose (G4) than for long substrates like amylose A (approximately G18). The reduced catalytic activity specifically for the short substrates is also attributable to the remarkable decrease in the affinity of the 8th subsite.

Amino Acid Sequence↗
PubMed1992

Multi-functional roles of a histidine residue in human pancreatic alpha-amylase.

Functional roles of histidine residues at the active site in human pancreatic alpha-amylase were examined by protein engineering. Three histidine residues at 101, 201, and 299 were converted to asparagine residues, respectively. It was found that His201 played multi-functional roles concerning so many functions; substrate binding, control of optimum pH, change in substrate specificity, activation by chloride ion, and inhibition by a proteinaceous inhibitor.

Binding Sites↗
PubMed1992

Biological activities of rabbit antibodies against synthetic human thyrotropin receptor peptides representing thyrotropin binding regions.

Recently, we have shown that the thyrotropin (TSH) binding regions of human thyrotropin receptor (TSHR) reside in two areas within residues 12-44 and 308-344. Serial antisera were raised against four overlapping synthetic peptides representing these two regions of TSHR (peptides 12-30, 24-44, 308-328, and 324-344) and were investigated for their ability to stimulate or block the cultured porcine thyroid cells. In addition, serum concentrations of triiodothyronine (T3) and thyroxine (T4) in serial sera obtained from each rabbit were examined. It was shown that residues of 12-30 and 324-344 of TSHR, respectively, are the site (at least a part of the site) where stimulating (TSAb) and blocking type (TSBAb) immunoglobulins are directed.

Amino Acid Sequence↗
PubMed1992

Non-suppressed thyroidal radioactive iodine uptake (RAIU) in thyrotoxic phase in a case of subacute thyroiditis with thyroid-stimulating antibodies (TSAb).

In this paper, we report a 49-year-old female with subacute thyroiditis who had thyroid-stimulating antibodies (TSAb) and thyroid-stimulation-blocking antibodies (TSBAb) in serum. Although she was in the thyrotoxic phase and TSH was suppressed in May, 1990, her radioactive iodine uptake (RAIU) was not suppressed (35.5%) and a thyroid scan disclosed a diffuse goiter with no defect. Serum assays revealed the presence of TSAb, but TSBAb were negative. In August, 1990, the right lobe became undetectable by thyroid scan when the RAIU was 20.7% with the TSH level remaining suppressed. At that time, TSAb were negative, while TSBAb were positive. When the RAIU was 31.1% in October, 1990, both thyroid lobes became visible and the TSH level was normalized. TSBAb became negative, and although TSAb reappeared it later became undetectable. These results indicate that the changes in the patient's thyroid scan and RAIU were attributable to the presence of TSAb.

Autoantibodies↗