Search PubMed⌕ Search

Biomedical subjects

S Sakata

Publications and source records attributed to S Sakata.

At least 127 records · Page 7Linked to original sources

A novel synthesis of antineoplastic 4'-thionucleosides using D-glucose as a chiral synthon.

We have synthesized 2'-deoxy-2'-methylene-4'-thiocytidine as a potential antineoplastic agent. Isopropylidene-3-O-benzylxylose, readily obtained from D-glucose in 5 steps, was converted to 1,4-anhydro-4-deoxy-4-thio-arabinitol. After manipulation at 2-position, unique Pummerer type glycosylation at the alpha-position of sulfoxides gave the target compound. Antineoplastic effect of this compound is also reported.

Antineoplastic Agents↗

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↗

In vitro and in vivo anti-herpes viral activities and biological properties of CV-araU.

We compared the in vitro and in vivo antiviral effects against herpes simplex virus type 1 (HSV-1) and other biological properties of 1-beta-D-arabinofuranosyl-5-[(E)-2-chlorovinyl]uracil (CV-araU) and 1-beta-D-arabinofuranosyl-5-[(E)-2-bromovinyl]uracil (BV-araU, sorivudine). Both CV-araU and BV-araU exhibited antiviral activities against HSV-1 in the cell culture derived from mouse, though the activities were lower than those seen in human cells. For intraperitoneal and intracerebral infections in mice with HSV-1 strain WT-51, both compounds, administered twice daily, were effective in increase in the survival rate at doses of 15 mg/kg and 30 mg/kg, respectively. In pharmacokinetic analysis, both drugs were absorbed well in the rat gastrointestinal tract following oral administration. There was no difference between the metabolism of orally administered CV-araU and BV-araU in rats. High levels of the corresponding base were found in plasma after oral administration of CV-araU and BV-araU, but much lower base levels were seen after intravenous doses. Both drugs were resistant to degradation by rat liver enzymes.

3T3 Cells↗

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↗

Erythropoietin response to acute hypobaric or anaemic hypoxia in gentamicin-administered rats.

In an attempt to assess the erythropoietin (Epo) production site(s) in rat kidney, Epo response to hypoxia and renal histopathological changes were studied in rats administered with graded doses of gentamicin. Male Sprague-Dawley rats of 9 to 11 weeks old were used. Following a 14-day subcutaneous administration (67.5 or 33.8 mg kg-1 day-1) of gentamicin, a nephrotoxic aminoglycoside, selective proximal tubular lesions were produced. These gentamicin-administered rats were compared with normal rats with respect to Epo response to hypoxia. Two different kinds of hypoxic load, either 0.35 atm hypobaric hypoxia (PIO2 = 46 torr) or acute anaemia (Ht: 29.3 +/- 0.2% and [Hb]: 9.7 +/- 0.3 g dl-1) by withdrawing of blood corresponding to 1-2% of body weight was used. During the hypoxic period of up to 48 h, the peak renal venous plasma Epo titres of 3.1 +/- 0.6 and 4.3 +/- 0.6 U ml-1 was observed at the 6th h in normal hypobaric hypoxic and anaemic rats, compared with the prehypoxic value of 0.7 +/- 0.1 U ml-1. The Epo titres then declined gradually. In the rats which were administered gentamicin, Epo response pattern was the same as that observed in the normal rats, but the peak value decreased significantly to 0.8 +/- 0.3 and 1.1 +/- 0.4 U ml-1 in hypoxic and anaemic rats (P < 0.05). Histological examination revealed the selective damage to renal proximal convoluted tubules. The Epo response was reduced by the tissue damages, and restoration of the gentamicin-induced tissue injury was accompanied with restored Epo response to hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

High affinity of blood for oxygen reduces oxygen uptake in contracting canine gracilis muscle.

To clarify the influence of blood flow with high-oxygen (O2)-affinity blood on oxygen consumption (VO2) in submaximally exercising skeletal muscle, we perfused the isolated dog gracilis (n = 8) contracting under 1 Hz stimulation alternatively with normal and high-O2-affinity blood, with a constant arterial O2 content (Ca,O2) and varying perfusion rates. The average P50 (oxygen partial pressure (PO2) for half-saturation at pH 7.40, PCO2 of 40 mmHg at 37 degrees C) of the high-O2-affinity blood prepared by carbamylation was 15.5 mmHg, and that of the normal blood 33.7 mmHg. With normal blood perfusion, the average VO2 above 6 ml min-1 (100 g)-1 of O2 delivery (Ca,O2 x flow) was 4.38 ml min-1 (100 g)-1 (range 4.17-4.68 ml min-1 (100 g)-1, and VO2 at the O2 delivery range of 6-5 and 4-2.5 ml min-1 (100 g)-1 decreased to 3.96 and 2.43 ml min-1 (100 g)-1, respectively. The PO2 of venous effluent (Pv,O2) at the O2 delivery of 6 ml min-1 (100 g)-1 was 33 mmHg. With low-P50 blood perfusion, VO2 was significantly less than with normal blood, both below the O2 delivery level of 6 ml min-1 (100 g)-1 and above it, even in the fairly high O2 delivery range of 8.5-12 ml min-1 (100 g)-1 (P < 0.05). Thus, high blood flow did not compensate for the reduced VO2 caused by high-O2-affinity blood. At values of Pv,O2 less than 33 mmHg, VO2 with low-P50 blood was not significantly different from that with normal blood (P > 0.05). The reduced VO2 in submaximally exercising skeletal muscle might be due to a slower O2 dissociation from the high-O2-affinity red cells and to a limited O2 diffusion resulting from the lower Pv,O2 value (which reflects mean end-capillary PO2).

Animals↗

Analysis of flow in a two-dimensional collapsible channel using universal "tube" law.

This paper presents an extension of the previous analyses on the collapsible tube-flow problem using a simplified model based on a two-dimensional channel conveying a one-dimensional flow. The main objective of the paper is to exploit the static and dynamic behavior of the model, by comparing with available experimental data and examining the accuracy of calculated results obtained for different numerical resolutions. The main revision from the previous analyses is the incorporation of a universal "tube" law that is valid for a wide range of positive and negative transmural pressure. Most of the numerical results agree qualitatively with the experimental observations. Self-excited high-frequency oscillation with very small amplitude of the membrane wall is however, predicted to occur in a flow range where the slope of the pressure drop curve is positive. It is seen that the high-frequency oscillation is associated with the motion of the separation point of the flow.

Compliance↗

[Five cases of tsutsugamushi disease].

We experienced 5 cases of tsutusgamushi disease from October to November 1993 at Hokusyo Central Hospital. All patients showed high fever, skin rash and eschar and four patients showed lymph node swelling. All cases were diagnosed serologically by indirect-immunofluorescence technique and treated with minocycline. In a survey of anti-Karp, Kato, Gilliam, Kawasaki, Kuroki antibodies, all patients showed the highest antibody titers against the Kawasaki strain and they were considered Kawasaki type. In Nagasaki Prefecture, the number of patients with tsutsugamushi disease has been increasing since 1982. We carried out immunologic and epidemiologic studies about this disease in Nagasaki Prefecture.

Adult↗

[Coexisting respiratory tract infection and bacteremia or sepsis caused by the same bacterium].

We experienced 12 patients who were suffering from bacteremia or sepsis and pneumonia or lung abscess coincidently caused by the same bacterium, during the 8 years from 1985 to 1992 a Hokusyo Central Hospital. All of them has some underlying diseases, and the average age was 73.6 years old. In ten out of 12 patients bacteremia or sepsis preceded the respiratory tract infection, and in 7 cases indwelling intravenous catheter was thought to be the port of entry of the bacteria. Respiratory tract infections were composed of pneumonia in 8 cases and lung abscess in 4 cases. Methicillin resistant Staphylococcus aureus (MRSA) was detected in 4 cases, Methicillin sensitive Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Pseudomonas aeruginosa were in 2 cases respectively, Citrobacter freundii and Methicillin resistant Staphylococcus spp. were in one cases respectively. Eight out of 12 cases died in spite of current antibiotics therapy, suggesting poor prognosis.

Aged↗

Plasma lipoprotein (a) levels and fibrinolytic activity in acute myocardial infarction.

To evaluate the effects of lipoprotein (a) [Lp (a)] on the fibrinolytic system in patients with acute myocardial infarction (AMI) who underwent thrombolytic therapy with recombinant tissue-type plasminogen activator, we examined serial changes in plasma levels of Lp (a), plasminogen activator inhibitor (PAI) activity, alpha 2-plasmin inhibitor-plasmin complex (PIC) and thrombin antithrombin III complex (TAT) in venous plasma samples from 25 patients with AMI for 3 weeks. Plasma Lp (a) levels were significantly increased 5, 7, and 14 days after admission and tended to decrease by the 21st day. On the other hand, the ratio of PIC/TAT was significantly increased on the 7th day and remained high for 3 weeks (p < 0.01), while plasma PAI activity was significantly decreased on the 5th day after admission (p < 0.01). Thus, plasma fibrinolytic function is impaired in the early phase after AMI, and gradually improves over the course of 3 weeks. The increase in plasma Lp (a) levels is, therefore, not accompanied by a significant decrease in plasma fibrinolytic function in patients with AMI.

Aged↗

Autoimmunity against thyroid hormones.

The presence of thyroid hormone autoantibodies (THAA) is a common phenomenon. More than 270 cases have been reported by the end of 1993 involving not only thyroidal but also nonthyroidal disorders. Clinically, THAA in a patient's serum produces variation in thyroid hormone metabolism and, in particular, may interfere with the radioimmunoassay (RIA) results of total or free thyroid hormone measurements, which can cause unusually high or low values of the hormones depending on the B/F separation method used. This in vitro interference can give clinicians confusing information about the patient's thyroid state. As a result, the patient may receive inappropriate treatment from physicians who are unaware of this disorder. The presence of THAA has been reported not only in humans but also in dogs, chickens, and rats. In this review article, clinical features of THAA and the mechanism of autoantibody production are discussed.

Adolescent↗

Possible gliclazide-induced water retention with azotemia.

An 80-year-old woman with diabetes mellitus was treated with gliclazide. Prior to the gliclazide administration, her urinary excretion of albumin, serum urea nitrogen and serum creatinine were normal. After the medication, oliguria, edema and azotemia developed. On the twenty-fourth day when the edema was severe and generalized, gliclazide administration was terminated. On the following day urinary volume increased suddenly (5,740 ml/day). Polyuria persisted for five days. Edema improved and urea nitrogen and creatinine were normalized thereafter. Though the mechanism is not known, the clinical course suggests that gliclazide is the principal causative factor in the water retention and azotemia in this patient.

Aged↗

[Chemical iodination of hormonogenic tyrosine residues of human thyroglobulin is critical for the production of anti-thyroglobulin autoantibody and for the induction of experimental autoimmune thyroiditis in mice].

There is evidence from animal models that the iodine content of thyroglobulin (Tg) may influence its antigenicity in thyroid autoimmunity. To elucidate the effect of iodination of hormonogenic sites of human Tg (hTg) on its autoantigenicity, a synthetic peptide (TB: hTg 2546-2571), containing two hormonogenic tyrosine residues of hTg, and a chemically-iodinated peptide (TB-I) were prepared. We immunized C3H/He (H-2k) mice, a high responder strain to Tg, and BALB/c (H-2d), a low responder strain, with TB or TB-I plus lipopolysaccharide. Lymph node cells from the two strains immunized with TB or TB-I proliferated in response to both TB and TB-I. Anti-Tg autoantibodies were detected in both strains when immunized with TB-I, while immunization with TB failed to produce anti-Tg antibodies. Furthermore, one of the C3H/He mice immunized with TB-I developed diffuse thyroiditis, but BALB/c mice did not. These findings indicate that the iodination of the hormonogenic tyrosine residues of hTg, in other words, the synthesis of mono- and di-iodotyrosine (MIT and DIT) residues, is necessary for the production of anti-Tg autoantibodies in high and low responder mice and for the induction of autoimmune thyroiditis in high responder mice.

Amino Acid Sequence↗

[On the localization of the binding site(s) of antibodies against TSH receptor using synthetic peptides].

In order to elucidate autoimmune B-cell recognition sites of human thyrotropin receptor (TSHR), nine overlapping synthetic peptides (residues 12-30, 24-44, 151-175, 171-195, 308-328, 324-344, 339-364, 359-380, and 375-399) were synthesized and biological activities of antibodies against each of the peptide were examined. It was shown that antibodies against TSHR 12-30, 24-44, 151-175, 171-195, 324-344, and 359-380 had thyroid stimulating antibody activity (TSAb), whereas antibodies against 339-364, 359-380, and 375-399 had thyroid stimulation blocking activity (TSBAb). From these results it was concluded that epitopes where TSH receptor antibodies with TSAb and TSBAb activities are bound are widely located in N-terminal, mid portion, and C-terminal regions.

Animals↗

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↗

Flounder growth hormone: isolation, characterization, and effects on growth of juvenile rainbow trout.

A highly purified growth hormone (GH) was isolated from the pituitary of the Japanese flounder (Paralichthys olivaceus) following extraction with alkaline solution, gel filtration on Sephadex G-75, and high-performance liquid chromatography (HPLC) on a reverse-phase column. Flounder GH (flGH) has a molecular weight of 20 kDa determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and an isoelectric point of 7.1 by gel electrofocusing. The complete amino acid sequence was determined by Edman degradation of the peptide fragments generated by enzymatic digestion and chemical cleavage. The flGH comprises 173 amino acid residues with pyroglutamate at the N-terminus. Compared with other fish GHs, flGH has an uninterrupted deletion of 14 amino acid residues near the C-terminus. flGH is the smallest of growth hormones so far reported and is a potent stimulator of growth in juvenile rainbow trout.

Amino Acid Sequence↗

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↗

High blood O2 affinity and relationship of O2 uptake and delivery in resting muscle.

To clarify the effects of high oxygen (O2) affinity of blood under stagnant hypoxic conditions, we studied the relationship between VO2 and O2 delivery (CaO2.flow) in isolated dog gracilis muscles perfused with low and normal P50 blood. The high affinity blood was prepared by either short-term incubation (P50 = 24.8 +/- 1.0 Torr) or long-term refrigerated storage (P50 = 19.5 +/- 1.5 Torr) with sodium cyanate. VO2 of the resting muscle was independent of O2 delivery above a critical level (0.45 ml.min-1.100 g-1), but was dependent on it below this level. The critical O2 delivery (0.45 ml.min-1.100 g-1), the maximal O2 extraction ratio (0.62), and the plateau VO2 (0.28 ml.min-1.100 g-1) in the present perfusions with low P50 blood were similar to those with normal blood. "Critical PvO2" (i.e. PvO2 at the critical O2 delivery) was 33 Torr in the perfusions with normal blood but only 19 Torr in the low P50 perfusions. The perfusion pressure-blood flow relationship was not influenced by the affinity change. These results suggest that the true critical PvO2 in resting muscle is lower than 19 Torr and hence that the decrease in VO2 in resting skeletal muscle under stagnant flow conditions is not caused by a decrease in PO2 driving pressure, but by a decrease in the surface area available for diffusion due to a closure of capillaries induced by the low perfusion pressure.

Animals↗