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Biomedical subjects

H Tada

Publications and source records attributed to H Tada.

At least 253 records · Page 14Linked to original sources

A high concentration of glucose alters the production of tPA, uPA and PAI-1 antigens from human mesangial cells.

To elucidate a role of tPA, uPA and PAI-1 for the development of diabetic glomerulosclerosis, the effect of high glucose concentration on the production of both basal and thrombin-mediated tPA, uPA and PAI-1 antigens from human mesangial cells was investigated. The culture of mesangial cells in the presence of high glucose (33 mM) for 11 days resulted in an increase in the synthesis of tPA and uPA when compared with that in normal glucose concentration (5 mM). In contrast, the cells grown in high glucose produced less PAI-1 than those in normal glucose. Thrombin stimulated dose-dependently the production of tPA, uPA and PAI-1 from the cells grown in either 5 or 33 mM glucose. However, the magnitude of the increase in tPA, uPA and PAI-1 from the cells grown in high glucose was less than that in normal glucose. These results suggest that the plasmin activity in mesangial cells may increase under a high glucose condition, leading to increased proteolysis of mesangial matrix. In addition, either fibrinolysis or proteolysis mediated by thrombin may be altered by high glucose concentration. Therefore, it is postulated that the turnover of mesangial matrix may be increased in diabetic nephropathy.

Cells, Cultured↗

Effects of chronic diabetes on the responsiveness to endothelin-1 and other agents of rat atria and thoracic aorta.

1. Plasma endothelin-1 level as well as plasma lipid and glucose levels was markedly elevated in the rats treated with streptozotocin 8 weeks earlier. 2. Positive inotropic response, which was significantly greater than that in the age-matched control, was produced by endothelin-1 in the left atria isolated from diabetic rats. On the other hand, the contractile response of thoracic aorta to endothelin-1 was conversely attenuated in the diabetic rats. Such contrasting effects of diabetes between the atrial and aortic muscles were observed in the responsiveness to other contractile drugs. Endothelium-dependent relaxation in the thoracic aorta was also significantly attenuated in diabetic rats. However, the basal twitch contraction of left atria, the chronotropic responses to endothelin-1, isoproterenol and carbachol and the relaxation of the aorta by papaverine were not affected by diabetes. 3. These results suggest that the contractile responsiveness of atrial and aortic muscles and the endothelial functions significantly alter during diabetes for 8 weeks.

Animals↗

Staurosporine can inhibit the G1-S transition induced by a calcium channel agonist by blocking the pathway independent of phorbol ester-sensitive protein kinase C in rat thyroid cells (FRTL-5).

IGF-I, when added to TSH-primed FRTL-5 cells, can induce a long lasting Ca2+ influx followed by the DNA synthesis. BAY K8644, a Ca2+ channel agonist, can also induce the DNA synthesis in TSH-treated cells. Staurosporine, which is known to be a potent inhibitor of protein kinase C(PKC) strongly inhibited the DNA synthesis caused by these two reagents. However, in PKC-down regulated cells, IGF-I and BAY K8644 could also evoke the DNA synthesis and the inhibitory effect of staurosporine persisted. These inhibitory effects did not relay on inhibition of the Ca2+ influx induced by BAY K8644. Thus these results demonstrate that staurosporine acts at a point distal to Ca2+ influx to inhibit G1-S transition and this staurosporine-sensitive pathway possibly mediates the mitogenic signal in PKC-independent manner.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Differentiation of postpartum thyrotoxicosis by serum thyroglobulin: usefulness of a new multisite immunoradiometric assay.

Destruction-induced thyrotoxicosis and Graves' thyrotoxicosis must be differentiated, since they are treated differently. To find a useful marker, we examined serial changes in serum thyroglobulin (Tg) concentrations in 20 patients with postpartum thyroid disease (9, euthyroid Hashimoto's disease; 11, Graves' disease in remission in early pregnancy). Serum Tg was measured by a new multisite immunoradiometric assay that allows little influence of anti-Tg autoantibodies. Eight women developed destruction-induced thyrotoxicosis 1 to 4 months postpartum, 6 had relapse of Graves' thyrotoxicosis 2 to 4 months postpartum, and 6 remained euthyroid. In destruction-induced thyrotoxicosis, serum Tg 2 months before the onset was 13.3 +/- 11.4 micrograms/L, then clearly increased 1 month before (34.5 +/- 31.9 micrograms/L) and was even higher at the onset of thyrotoxicosis (116.5 +/- 137.1 micrograms/L). In contrast, serum Tg increased only at the onset in Graves' thyrotoxicosis (from 25.9 +/- 25.2 micrograms/L 1 month before to 76.1 +/- 75.3 micrograms/L at the onset, p < 0.05). There was no difference in serum Tg level at the onset between the two disorders. However, when data were expressed as the percent increase from the level one month before, and the cut-off value were taken at 150%, all 7 patients above the cut-off developed destruction-induced thyrotoxicosis, and 6 of 7 below had recurrent Graves' thyrotoxicosis. Thus, serial measurement of serum Tg is useful for the differentiation of destruction-induced thyrotoxicosis from Graves' thyrotoxicosis after delivery.

Adult↗

Prediction of post-partum Graves' thyrotoxicosis by measurement of thyroid stimulating antibody in early pregnancy.

OBJECTIVE: Autoimmune thyroid diseases often occur after delivery. However, it has been difficult to predict who will develop Graves' thyrotoxicosis after delivery. We tried to establish a systematic method for predicting post-partum onset of Graves' thyrotoxicosis. DESIGN: We followed up the pregnant women with antithyroid microsomal antibody (MCAb) from early pregnancy to the post-partum period and analysed the relation between the activities of thyroid stimulating antibodies (TSAb) in early pregnancy and post-partum occurrence of Graves' disease. PATIENTS: Seventy-one women with positive MCAb in early pregnancy were studied. They were randomly selected from 262 MCAb-positive subjects found in 3405 consecutive early pregnant women who attended our maternity clinic during the last ten years. MEASUREMENTS: MCAb was measured with a commercially available agglutination kit. For 71 MCAb-positive subjects, TSH-binding inhibitory immunoglobulin (TBII) and TSAb were measured in early pregnancy, and serially until 6 months after delivery for the subjects with either positive TBII or TSAb. Thyroid function and goitre size were recorded at every observation. RESULTS: Among the 71 subjects, 7 showed positive TSAb in early pregnancy without any thyroid dysfunction; all 7 developed thyroid dysfunction in the post-partum period. Five of them (70% of TSAb-positive subjects) developed Graves' disease, two showing persistence and three transiently. None of 64 TSAb-negative subjects developed Graves' thyrotoxicosis, though 44 developed various types of thyroid dysfunction as a result of post-partum autoimmune thyroiditis. CONCLUSION: The individuals at high risk of post-partum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of TSAb. Overall occurrence of post-partum Graves' disease in the general population is estimated above 0.54%, that is, one in 200 post-partum women may develop Graves' thyrotoxicosis, although thyrotoxicosis may be transient in half of the patients.

Autoantibodies↗

Relationship between intracellular period modulation and external environment change in Physarum plasmodium.

The relationship between intracellular period modulation and external environment change was investigated from the viewpoint of internal information coding in Physarum plasmodium. For the external conditions, concentration changes of attractant (galactose) and repellent (KCl) were used, and the internal responses were measured as the thickness oscillation of the plasmodium. (i) Period of the intracellular oscillation decreased when the concentration of attractant was increased and when the concentration of repellent was decreased. (ii) The period increased when the attractant was decreased and when the repellent was increased. (iii) The larger concentration change induced the larger period modulation. (iv) These responses were observed when the change of concentration was greater than a threshold value. From these results, it was clarified that the relative change in environmental condition is encoded on the relative period modulation in intracellular oscillation. This means that the period change does not directly represent the environment itself but represents the change of its condition. Thus, it is further suggested that the plasmodium estimates the environmental condition based on the relationship between the previous external condition and the present one.

Animals↗

Prevalence of postpartum onset of disease within patients with Graves' disease of child-bearing age.

To assess the prevalence of postpartum onset of disease among the patients with Graves' disease, we performed a retrospective examination of 289 consecutive female patients with Graves' disease who attended our thyroid clinic. Of these patients, 92 were female of child-bearing age (20-39 y.o.) who have had one or more deliveries, and at least 37 patients revealed clear evidences of postpartum onset of the disease. That is, at least 40% of Graves' patients of 20-39 y.o. developed their disease during the postpartum period.

Adult↗

A case of hyperthyroidism due to pituitary resistance to thyroid hormone.

A fifteen-year-old male was admitted to our hospital because his thyroid function showed a lack of TSH suppression in the face of elevated thyroid hormone. This patient complained of heat intolerance, palpitation and hand tremor. Peripheral indices of thyroid hormone action indicated a hypermetabolic state. Serum TSH did not respond sufficiently to TRH stimulation, suggesting TSH-secreting pituitary adenoma. However, sellar CT scan and MRI images did not demonstrate any pituitary adenoma. Moreover, the serum TSH alpha-subunit concentration was not high and serum TSH was partially suppressed by the administration of T3. Furthermore, the results of single stranded conformation polymorphism (SSCP) suggested the existence of mutation(s) in the exon 7 of T3 receptor beta (TR beta) gene of this patient. These findings support the diagnosis of pituitary resistance to thyroid hormone.

Adenoma↗

Change in serum concentration of insulin-like growth factor II (IGF-II) in patients with thyroid disease.

We investigated the serum concentration of IGF-II in patients with thyroid diseases (25 with untreated Graves' patients, 30 with hypothyroidism, 23 with thyroid adenoma) and in 72 healthy adults as normal controls, by a sensitive radioimmunoassay of serum IGF-II. Thyroid hormones are known to increase IGF-I production in the liver through the enhancement of GH secretion. In case of IGF-II, however, knowledge has been rather limited. The mean +/- SD concentration in healthy subjects was 556 +/- 94 micrograms/L with neither sex nor age dependence. In untreated Graves' patients, serum IGF-II levels (675 +/- 129 micrograms/L) were significantly (P < 0.01) higher than in normal controls, and significantly lower in patients with hypothyroidism (460 +/- 106 micrograms/L; P < 0.01). Thyroid hormones revealed positive correlation with the IGF-II concentration.

Adult↗

Reducing effect of nadolol on serum levels of free thyroid hormones in hyperthyroidism.

We evaluated the effect of the beta-adrenergic receptor blocking agent nadolol on serum levels of free thyroid hormones in 20 untreated patients with Graves' disease, aged between 17 and 57 years (mean +/- SD, 32.9 +/- 10.5). All the patients were treated with 30 mg of nadolol alone once-daily for 2 weeks, and clinical and laboratory parameters before and after the treatment were compared. Systolic blood pressure was depressed significantly (P < 0.001) from 132.7 +/- 11.1 mmHg to 122.8 +/- 10.9 mmHg. The resting pulse rate was also reduced significantly (from 110.3 +/- 9.2/min to 86.0 +/- 13.2/min, P < 0.001). Serum free thyroxine levels were reduced significantly from 7.1 +/- 3.1 ng/dl to 5.7 +/- 3.6 ng/dl (P < 0.05) and serum free triiodothyronine levels were reduced from 21.9 +/- 5.6 pg/ml to 17.2 +/- 6.9 pg/ml (P < 0.01). In the present study, the beta-adrenergic receptor blocking agent nadolol was newly found to have a reducing effect on serum free thyroxine, as well as free triiodothyronine concentrations.

Adolescent↗

Genistein but not staurosporine can inhibit the mitogenic signal evoked by lithium in rat thyroid cells (FRTL-5).

Long-term administration of lithium is one of the well-known causes of goiter. It can stimulate DNA synthesis in rat thyroid cells (FRTL-5) treated with thyroid-stimulating hormone (TSH). To investigate the mitogenic signal transduction system activated by lithium, lithium-induced DNA synthesis and Ca2+ influx were studied using two protein kinase inhibitors, genistein as a specific tyrosine kinase inhibitor and staurosporine as a potent inhibitor of protein kinase C. Genistein but not staurosporine blocked the DNA synthesis induced by lithium in TSH-primed cells but neither compound had any effect on the Ca2+ entry stimulated by lithium. Genistein clearly attenuated the phosphotyrosine content of the 175 kDa substrate in the presence of lithium but staurosporine failed to do so. Moreover, lithium could also stimulate DNA synthesis in protein kinase C down-regulated cells. These data demonstrate that lithium may require the activation of a particular genistein-sensitive kinase, possibly a tyrosine kinase, to induce cell proliferation. It is suggested that the phorbol ester-sensitive protein kinase C family might not participate in the mitogenic signal transduction pathway activated by lithium.

Alkaloids↗

Abundant existence of 40kD-cdc2-related protein in rat thyroid cells.

The cdc2 kinase family is known to be one of the important factors for cell proliferation in both yeast and mammalian cells. By using polyclonal antibodies against PSTAIRE region of cdc2HS, we studied the amount of cdc2-related kinases in the rat thyroid cell line, FRTL-5, during the cell cycle. The immunoreactive protein with molecular weight 34kD was hardly detectable, instead, 40kD protein exists constantly in amount through G0 phase to S phase. Further, it did not decrease when the cells were cultured in serum- and hormone-free medium. Moreover, we observed an increase of this protein in the nuclear fraction as the cells enter S phase. On the contrary, we could not detect any immunoreactive 40kD protein in primary cultures of rat thyroid cells. These results may indicate abundant existence of this protein might concern cell cycle regulation of FRTL-5 or its immortal feature.

Animals↗

Phorbol ester inhibits DNA synthesis induced by interleukin-6 in TSH-pretreated FRTL-5 cells.

Combination of TSH and Interleukin-6 (IL-6) can stimulate DNA synthesis in FRTL-5 cells. Phorbol 12-myristate 13-acetate (PMA) stimulates G0 to G1 transition but inhibits G1 to S transition in these cells. We studied the effect of IL-6 on DNA synthesis in TSH-pretreated FRTL-5 cells in the presence or absence of PMA. IL-6 induced DNA synthesis when it was added to TSH-pretreated cells. Further, PMA inhibited the DNA synthesis induced by IL-6. These data might suggest that in FRTL-5 cells IL-6 can show its mitogenic effect in G1 phase of their cell cycle progression.

Animals↗

[Side effects of interferon on endocrine and respiratory system in 545 cases of chronic hepatitis C].

We investigated the side effects of interferon (IFN) on the endocrine and respiratory system in 545 cases of chronic hepatitis C. Eleven of 494 (2.2%) patients with chronic hepatitis C who were treated with natural or recombinant interferon (IFN) developed thyroid disease while on treatment. Eight patients developed hyperthyroidism and 3 patients developed hypothyroidism. All 11 patients required definitive therapy, who became euthyroid after the therapy. Two patients received nIFN alpha and one patient received rIFN alpha 2b developed diabetes mellitus. Two patients received rIFN alpha 2a and rIFN alpha 2b, respectively, developed interstitial pneumonia 12 weeks and 24 weeks later, respectively. One patient showed positive reaction for RA test and LE factor and positive LE cell, and complained of fever, arthralgia and dry cough. These phenomenon disappeared after the cessation of IFN therapy.

Adult↗

Serum concentrations of apolipoproteins in patients with thyroid dysfunction.

We measured serum concentrations of apolipoproteins (apo A-I, A-II, B, C-II, C-III and E) in patients with thyroid disease (hyperthyroidism; n = 44, hypothyroidism; n = 15) and in normal subjects (n = 89). We found that apoA-II, B and C-III concentrations revealed significant difference among three groups of the normal (apoA-II; 31.4 +/- 4.9 mg/dl, apoB; 85.8 +/- 16.3 mg/dl, apoCIII; 7.45 +/- 2.99 mg/dl), hyperthyroidism (apoA-II; 29.8 +/- 5.4, apoB; 63.4 +/- 18.9, apoC-III; 6.28 +/- 2.45) and hypothyroidism (apoA-II; 27.5 +/- 5.3, apoB; 108.0 +/- 30.9, apoC-III; 9.43 +/- 2.74). Thyroid hormones showed clear negative correlation to apoB (r = 0.70, p < 0.001). Furthermore, apoC-III was also found to be negatively correlated with thyroid hormone concentrations (r = 0.47, p < 0.001).

Adult↗

The pedicle latissimus dorsi transfer for reconstruction of the plexus brachialis and brachium.

To reconstruct the area from the brachial plexus to the upper arm, pedicle latissimus dorsi muscle transfer was performed in 16 patients. Nine patients underwent functional bipolar transfer for reconstruction of elbow flexion. The surgical results were satisfactory in 6 patients, but were unsatisfactory in 3 because of an incorrect preoperative assessment of the strength of the latissimus dorsi muscle and an unsuitable length of transferred muscle in 2 patients, and because of progression of spastic paralysis caused by cervical myelopathy in the third patient. Seven patients with skin loss and an unstable scar underwent aesthetic unipolar transfer in which the exposed nerve, neurovascular bundle, bone, and joint were covered by a musculocutaneous flap with good vascularity. The surgical results were successful in all 7 patients. Infection was present before transfer in 4 of the 16 patients, but it was successfully treated by simultaneous radical debridement of the infected wound and latissimus dorsi transfer.

Adolescent↗

Coexistence of paraneoplastic sensory neuronopathy and Lambert-Eaton myasthenic syndrome in a small cell lung cancer patient.

The present report is on a 72-year-old male patient with combined paraneoplastic sensory neuronopathy (PSN) and Lambert-Eaton myasthenic syndrome (LEMS) with small cell lung cancer. He noticed a painful paresthesia of the legs which advanced over seven days, and both hands became numb and painful. Three months later, he was found to have small cell lung cancer by mediastinoscopic examination. PSN was diagnosed by clinical symptoms and anti-Hu antibody, and LEMS was diagnosed by the waxing phenomenon on an electromyogram (incremental in compound muscle action potential up to 120%) and autoantibody against the presynaptic voltage-gated calcium channel. High titers of anti-Hu antibody were detected in the serum (1:12800) and cerebrospinal fluid (1:320). Although a partial response to chemoradiotherapy was obtained, the neurologic symptoms of PSN did not improve. The anti-Hu antibody titers obtained on five different occasions during the patient's clinical course did not change. The patient died from respiratory arrest six months after the initiation of therapy. To the best of the authors' knowledge, this combined form of disease, confirmed by both clinical and laboratory tests, is the rarest case ever to be reported.

Aged↗