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Biomedical subjects

S Sakata

Publications and source records attributed to S Sakata.

At least 271 records · Page 15Linked to original sources

A case of Graves' disease with anti-triiodothyronine antibodies.

A case of Graves' disease with high serum thyroxine (T4) and low triiodothyronine (T3) levels which was therefore initially diagnosed as a T4-thyrotoxicosis is reported. Examination of the serum from the patient showed the presence of unusual protein which bound T3. It was later confirmed as IgG class anti-T3 antibodies. In addition to treatment with methylmercaptoimidazole (MMI), the patient was treated with prednisolone for 30 days (total amount 500 mg). Titers of anti-T3 antibodies in the sera were unchanged before and after prednisolone treatment. Our present case indicates that it is clinically important to bear the presence of autoantibodies in mind to account for a possible error in measuring T3 and T4 by radioimmunoassay (RIA). In the case that RIA determination gives an unexpectedly high or low T3 and/or T4 value, the presence of autoantibodies to them should be considered and a test for them is recommended.

Antibodies, Anti-Idiotypic↗

Production of anti-human thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with human thyroglobulin.

Two rabbits (TG-1, TG-2) were immunized with human thyroglobulin (HTg) and bled serially. Antisera were obtained at different times after the first immunization and kept separately and studied. In both rabbits production of anti-HTg, and anti-thyroid hormone antibodies such as anti-thyroxine (T4) and anti-triiodothyronine (T3) antibodies was observed. Binding parameters of anti-HTg antibodies with HTg, T4, and T3 were calculated in two selected antisera (70-day and 249-day). The Scatchard's plots of these antibodies were all curve-linear and were analyzed in two components: one, higher binding constant (Ka1) and smaller binding capacity (Cap1) and the other, lower binding constant (Ka2) and larger binding capacity (Cap2). Ka1 values of anti-HTg, anti-T4, and anti-T3 antibodies in sera from TG-1 obtained from 70-day and 249-day bleeding were 1.1 X 10(10) M-1, 6.0 X 10(9) M-1. 7.9 X 10(8) M-1 and 1.7 X 10(10) M-1, 6.5 X 10(9) M-1, 1.0 X 10(9) M-1, respectively. Those from TG-2 were 1.7 X 10(10) M-1, 1.8 X 10(9) M-1, 6.4 X 10(8) M-1 and 2.0 X 10(10) M-1, 3.1 X 10(9) M-1, 1.6 X 10(9) M-1, respectively. The significance of the production of anti-HTg and anti-thyroid hormone antibodies in rabbits immunized with HTg in relation to the antigenic structure of HTg molecule was discussed.

Animals↗

Regional difference in sympathetic vasoconstrictor tone in conscious rats.

Regional differences in sympathetic vasoconstrictor tone were studied in conscious rats. In each rat an electromagnetic flow probe was chronically implanted around the common carotid, superior mesenteric, or renal artery, or the terminal aorta. An indwelling catheter for the measurement of arterial pressure was inserted into the terminal aorta via the right femoral artery. Peripheral resistance was calculated by dividing arterial pressure by flow. The per cent decrease in peripheral resistance on the ganglion blockade with hexamethonium bromide was used as a measure of regional sympathetic vasoconstrictor tone. A significant decrease in peripheral resistance, assumed to indicate a substantial tonic discharge to resistance vessels, was observed in conscious rats only in the carotid and renal areas and not in the superior mesenteric and hindquarter (supplied by the terminal aorta) areas. Since ganglion blockade also diminished the sum of the mean regional flows, cardiac output was estimated to decrease on the ganglion blockade. This suggests that capacitance vessels are also receiving a sizable vasoconstrictor tone, because the ganglion blockade did not elevate right atrial pressure. Pentobarbital anesthesia markedly inhibited the assumed tone to the renal area and was estimated to newly generate a tone to the hindquarters.

Animals↗

A pressor response to vibration in conscious rats.

Cardiovascular response in an alerted state induced by vibration was studied in conscious rats by giving a to-and-fro movement to their cages for 30 sec. Cardiac output, superior mesenteric flow, and hindquarter flow were observed with chronically implanted electromagnetic flow probes and arterial pressure with an indwelling catheter. Arterial pressure, heart rate, cardiac output and hindquarter flow increased and superior mesenteric flow decreased with vibration. The increase in heart rate was still present after adrenalectomy, but was abolished by beta-adrenoceptor blockade propranolol. The increase in hindquarter flow was greatly diminished by propranolol or after adrenalectomy, but was still present in adrenalectomized rats after alpha-adrenoceptor blockade phentolamine. The decrease in superior mesenteric flow in vibration was abolished by phentolamine. It was diminished by adrenalectomy. These findings indicate that the cardiovascular response to vibration includes excitation of the cardiac sympathetic nerves, adrenomedullary secretion, and excitation of sympathetic vasoconstrictor fibers and exercise hyperemia in skeletal muscles.

Animals↗

Autoantibodies against thyroid hormones or iodothyronine. Implications in diagnosis, thyroid function, treatment, and pathogenesis.

The presence of antithyroid hormone autoantibodies in the sera of patients with thyroid and nonthyroid disorders is a well-known condition. When circulating thyroid hormones bind to the patients' immunoglobulins, serum levels of total and free thyroid hormones are often in discordance with clinical features. This problem occurs because the autoantibodies can interfere with radioimmunoassays. To avoid inappropriate treatment of such patients, it is clinically important to consider the presence of autoantibodies in patients with unexpectedly high or low total and free thyroid hormone values. We have reviewed the English and Japanese literature, both case reports and basic works, and summarize the incidence of antithyroid hormone autoantibodies, clinical features, effects on appropriate testing of the hypothalamic-pituitary-thyroid axis, diagnostic methods for confirming their presence of autoantibodies, treatment of patients with these disorders, and possible pathogenetic mechanisms.

Autoantibodies↗

Enhancement of erythroid differentiation in clones of human leukemic cell line K562 by fetal calf serum.

Clone cells of K562 that are able to synthesize hemoglobin spontaneously on a relatively high level were obtained by cell-cloning technique. The clone cell proliferated 25 times by day 6 in culture, and the growth rate was not affected by changing the dose of fetal calf serum (FCS) from 5% to 30%. On the other hand, the erythroid differentiation could be linearly enhanced by increasing dosage of FCS, reaching a maximum after four days in culture. The wild-type K562 cells were also slightly stimulated to synthesize hemoglobin by adding FCS (30% final concentration). The enhancing effect of 30% FCS on the erythroid differentiation in the clone cells was greater than that of 12.5 microM hemin, while in the wild-type cells the relationship was reversed. There were no effects of erythropoietin (Epo) on the hemoglobin synthesis in either the clone cells or the wild-type cells. When various kinds of sera were added to the standard culture of the clone cells, only FCS had the enhancing effect. These results suggest that spontaneous erythroid differentiation is not induced by hemin or Epo in FCS but by FCS-specific substance(s).

Adult↗

[Optimization of treatment planning for radiation therapy].

There are two problems to be solved to apply quantitative optimization for treatment planning of radiation therapy. Firstly, an objective function which estimates both biological effect of non-uniform dose distribution and dose response relationship has to be developed. Secondly, precise radiobiological and clinical data are required to derive and justify the objective function. Hence, it is important to decrease the errors in dose measurement and calculation and to clarify the factors in data analysis. In this article, the methods of optimization reported in the past were reviewed and some subjects for future studies were discussed.

Humans↗

[Radiotherapy of carcinoma of the larynx--dose and function preservation].

Relationship between irradiated dose and function preservation of the larynx in patients of laryngeal carcinoma (T1-T3) treated with radiotherapy were analysed and discussed. Local control rate for T1 and T2 lesion was highest in the dose range of 65-70 Gy. But in T3 lesion, especially of supraglottic cancer, the dose range to obtain highest local tumor control rate is above 76 Gy and higher than in case of T1 and T2 lesions. Laryngeal edema was seen in patients who were delivered the dose of 80 Gy. But total laryngectomy could be avoided by conservative therapy. Necessity of induction chemotherapy for advanced cases was also discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Intraoperative radiotherapy for advanced carcinoma of the pancreas.

A detailed retrospective analysis of the efficacy of intraoperative radiotherapy (IOR) in advanced carcinoma of the pancreas is presented. During a 10-year period from 1973 through 1982, 70 patients with advanced carcinoma of the pancreas were treated by multimodal methods, separate or combined therapy of surgery, IOR, and chemotherapy in two different institutions. Among these, 33 patients underwent IOR, mostly combined with additive surgery. A single dose of 20.1 to 40.0 Gy with 8 to 25 meV electrons was delivered through radiation cones ranging from 6 to 10 cm in diameter. Excellent relief was noticed in 50% of the patients who had complained of pain. Among Stage IV patients, a significant difference of survival rate was observed between IOR and control groups (P less than 0.05); the mean survival time of the IOR group was 4.6 +/- 2.6 (SD) and that of the control group 2.5 +/- 1.4 (SD) months. Intraoperative radiotherapy proved to be effective in prolonging the survival of patients with advanced stage of the lesion.

Adult↗

[Investigations on the mechanism(s) of the production of anti-thyroid hormone antibodies 3:Production of anti-rabbit thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with rabbit thyroglobulin].

Recently, the presence of anti-thyroid hormone antibodies has been reported in many cases of thyroidal and non-thyroidal disorders. In order to elucidate the immunological mechanism(s) in the production of anti-thyroid hormone antibodies, we immunized outbred rabbits and mice with different H-2 and Igh allotypes with human thyroglobulin (HTg) and showed that the production of both anti-HTg and anti-thyroid hormone antibodies is genetically controlled. In our present study, rabbit thyroglobulin (RTg) was purified from 4 rabbit thyroid glands and was immunized in two rabbits (RG-I, RG-2). The two rabbits were then serially bled and tested for the presence of anti-RTg and anti-thyroid hormone antibodies. In both rabbits, the production of anti-RTg and anti-thyroid hormone antibodies was observed. The binding constant of anti-RTg, anti-T4 and anti-T3 antibodies in RG-1 were 6 X 10(9)M-1, 9.5 X 10(8)M-1, 4.6 X 10(8)M-1, and those in RG-2 were 6.5 X 10(9)M-1, 5.6 X 10(8)M-1, 1.6 X 10(8)M-1, respectively. These results further strengthen the possibility that the antigen of the anti-thyroid hormone antibodies observed in various disorders so far reported is the HTg molecule. In addition, the fact that anti-RTg antibodies had a higher binding constant and capacity than anti-thyroid hormone antibodies suggests that the antigenic site(s) of RTg, which contains thyroid hormones, is not highly immunogenic.

Animals↗

In vitro and in vivo antiviral activity of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and related compounds.

BV-araU and related compounds such as CV-araU, IV-araU and BV-araUMP showed marked activity against herpes simplex virus type 1 (HSV-1) in human embryonic lung fibroblast cells. BV-araU, CV-araU and BV-araUMP were also effective in mice infected intracerebrally with HSV-1. Especially, when mice were infected with a low dose of virus, both intravenous and oral treatment with BV-araU proved capable of increasing the mean survival time and decreasing the final mortality of the infected mice. The in vivo anti-HSV-1 activity of BV-araU was comparable to that of BVDU. BV-araU exhibited little toxicity for mice.

Animals↗

Further improvement in preparation and some properties of native alpha and beta chains from canine hemoglobin treated with p-chloromercuribenzoate.

The alpha and beta chains were prepared from canine hemoglobin by a modification of the method of Bucci and Fronticelli ((1965) J. Biol. Chem. 240, PC551-552) which involved treatment of hemoglobin with an excess of p-chloromercuribenzoate (pCMB), separation of the mercurated chains by chromatography on a DE-32 column with a salt gradient at pH 8.6, and regeneration of sulfhydryl groups of the chains with 2-mercaptoethanol. The SH titer was two per heme for both the regenerated alpha and beta chains. The titer decreased to four per tetramer of hemoglobin after equimolar recombination of both chains. Measurements of the absorption spectrum and oxygen binding showed that the chains were in a native state.

Amino Acids↗

Serum thyroglobulin concentration in normal pregnancy.

We measured the levels of serum thyroglobulin (Tg) in 52 pregnant females at various stages and compared them with those of 15 age-matched nonpregnant females. Serum Tg was measured by a solid-phase immunoradiometric assay. In pregnant females, mean serum Tg levels at the first, second, early third, and late third trimesters were 8.4 (range; 1.3-18.0), 9.2 (1.7-25.6), 10.1 (1.8-22.8), and 12.1 ng/ml (5.3-25.2), respectively. The statistical comparison was made after logarithmic transformation of the data. The mean value only at the late third trimester was significantly higher than that of controls (mean; 6.0 ng/ml, range; 1.5-23.6), but each value was within the normal range. Although serum Tg levels have been reported to be high at the end of pregnancy, our results indicate that the Tg levels in females could be clinically interpreted without regard to the coexistence of pregnancy.

Adult↗

Theoretical consideration of the effects of dilution on estimates of free thyroid hormones in serum.

When concentrations of free thyroid hormones in serum are measured by equilibrium dialysis, the serum sample is diluted by dialysis buffer, resulting in a new equilibrium for distribution of these hormones that differs from that in the original serum sample. We have derived a mathematical formulation, based on an equilibrium model for multiple ligands and multiple binding sites, to determine the effect of dilution on the concentrations of free hormones in serum. Computer simulations based on the formulation indicate that both free thyroxin (T4) and free triiodothyronine (T3) are decreased by dilution of serum, free T3 being affected more than free T4. This dilution-related decrease is more prominent in hyperthyroidism than in euthyroidism, and even more striking for sera in which binding capacities for thyroid hormones are decreased (e.g., in thyroxin-binding globulin deficiency or hypoalbuminemia). These simulations can provide a basis for minimizing experimental errors in the estimates of concentrations of free thyroid hormones by equilibrium dialysis.

Blood Proteins↗