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Biomedical subjects

T Sakurada

Publications and source records attributed to T Sakurada.

At least 163 records · Page 9Linked to original sources
PubMed1990

Substance P-like immunoreactivity, choline acetyltransferase activity and cholinergic muscarinic receptors in Alzheimer's disease and multi-infarct dementia.

Substance P-like immunoreactivity, choline acetyltransferase (ChAT) activity and muscarinic cholinergic receptors were measured in brains from 9 individuals with senile dementia of the Alzheimer type (AD), 4 individuals with multi-infarct dementia (MID), 6 individuals with mixed type of dementia (AD/MID) and 9 controls. The ChAT activity was markedly reduced (50-60%) in the hippocampus of all demented brains. The number of muscarinic cholinergic receptors was reduced only in the MID and AD/MID brains. No significant difference in substance P-like immunoreactivity was measured in 4 regions of AD brains in comparison to controls. In the combined MID plus AD/MID groups a significant reduction in substance P-like immunoreactivity (-35%) was measured in the hippocampus while no change was found in the frontal cortex, amygdala and caudate nucleus. The findings support the assumption of differences in selectivity of damage between AD and AD/MID, MID.

Aged↗
PubMed1990

N-terminal substance P fragments inhibit the spinally induced, NK 1 receptor mediated behavioural responses in mice.

N-terminal fragments of substance P (SP) were tested for antagonism against the aversive responses induced in mice by various tachykinin receptor agonists, somatostatin and bombesin. When co-administered with SP intrathecally, low doses (1.0-4.0 pmol) of SP (1-7) or SP (1-8) reduced the SP-induced behavioural responses of scratching, biting and licking. Aversive responses induced by two other neurokinin (NK) 1 receptor agonists, Septide and physalaemin, were also dose-dependently decreased by the simultaneous injection of small doses of SP (1-7) or SP (1-8). Aversive responses induced by 400 pmol of NK A were also significantly reduced by co-administration of SP (1-7) or SP (1-8). No significant effects of the N-terminal fragments were observed against the aversive responses elicited by NK A (300 pmol), eledoisin, NK B, somatostatin or bombesin. These results suggest that the behavioural antagonism produced by SP (1-7) and SP (1-8) may be limited to the NK 1 receptor at the spinal level in mice.

Animals↗
PubMed1990

N-terminal tetrapeptide of dermorphin and D-Arg-substituted tetrapeptides: inactivation process of the antinociceptive activity by peptidase.

Degradation products of the N-terminal tetrapeptide of dermorphin, H-Tyr-D-Ala-Phe-Gly-OH (ALPG) and D-Arg2-substituted tetrapeptide analogs of dermorphin, H-Tyr-D-Arg-Phe-Gly-OH (ARPG), H-Tyr-D-Arg-Phe-Gly-NH2 (TDAPG-NH2) and H-Tyr-D-Arg-Phe-beta-Ala-OH (TDAPA) by enkephalin degrading enzymes were studied by using reversed-phase high-performance liquid chromatography. After 5 and 25 hr incubations of the peptides with solubilized enzymes of mouse brain or spinal cord, liberation of the appreciable Tyr1 residue was observed in ALPG but not in ARPG, TDAPG-NH2 and TDAPA. When ARPG and TDAPG-NH2 were incubated with enzymes for 25 hr, a main degradation product was the N-terminal tripeptide produced from the hydrolysis of Phe3-Gly4 bond. Conversely, TDAPA did not produce the N-terminal tripeptide after 25 hr incubation with enzymes. In the enzyme assay, Tyr1-D-Arg2 bond of ARPG, TDAPG-NH2 and TDAPA was more stable than that of ALPG to the cleavage by aminopeptidase M (AP-M). Phe3-Gly4 bond of ALPG, ARPG and TDAPG-NH2 were easily hydrolyzed by carboxypeptidase Y (CP-Y) within 3 hr incubation, whereas the hydrolysis of Phe3-beta-Ala4 bond of TDAPA by CP-Y was not observed after 3 hr incubation. The present results and previous behavioural data suggest that a potent and prolonged antinociceptive activity of the D-Arg-substituted tetrapeptides is mainly attributed to the stability of Tyr1-D-Arg2 bond against aminopeptidase of peptidases.

Amino Acid Sequence↗
PubMed1990

Erythrocyte zinc in hyperthyroidism: reflection of integrated thyroid hormone levels over the previous few months.

Red blood cell (RBC) zinc (Zn) concentration was measured by atomic absorption spectrophotometry in 28 healthy volunteers, in 46 patients with hyperthyroidism, and in 6 patients with hypothyroidism. The mean (+/- SD) RBC Zn concentration in euthyroid controls was 11.4 +/- 1.5 mg/L RBC, and the normal range defined as the mean +/- 2 SD was 8.5 to 14.3 mg/L RBC. The mean RBC Zn in patients with hyperthyroidism was decreased to 6.4 +/- 1.6 mg/L RBC, and 43 (93%) had low values. The mean RBC Zn in patients with hypothyroidism was not different from that in the controls. There was a significant negative correlation between the concentrations of RBC Zn and those of both plasma thyroxine (T4; r = -0.73) and plasma 3,5,3'-triiodothyronine (T3; r = -0.70). After the treatment of 17 hyperthyroid patients with antithyroid drugs, both mean plasma T4 and T3 levels became normal within 4 weeks, but the normalization of RBC Zn lagged about 2 months behind them. The RBC Zn levels significantly correlated with both the plasma T4 and T3 levels obtained 0, 4, 8, and 12 weeks prior to the RBC sampling, and the highest correlation was observed between the RBC Zn levels and plasma T4 and T3 levels measured 8 weeks previously. These data suggest that RBC Zn concentration in hyperthyroid patients reflects a patient's mean thyroid hormone level over the preceding several months as glycosylated hemoglobin level does in diabetic patients.

Adult↗
PubMed1990

Spinal antinociception: comparison of a dermorphin tetrapeptide analogue, [D-arginine2, sarcosine4]-dermorphin (1-4) and morphine in rats.

Intracerebroventricular injections of [D-arginine2, sarcosine4]-dermorphin (1-4) (DAS-DER 1-4) and morphine produced a dose-dependent inhibition of the tail-flick response to thermal stimulation. The ED50 value for each drug was 3.23 (1.35-7.73) nmol/rat and 32.0 (13.3-76.6) nmol/rat, respectively. When injected into the spinal subarachnoid space, the ED50 value was 0.035 (0.015-0.086) nmol/rat for the tetrapeptide and 11.9 (5.7-25.2) nmol/rat for morphine, respectively. Antinociception induced by DAS-DER 1-4 and morphine, through the intracerebroventricular and intrathecal routes, was clearly reduced by pretreatment with a small dose of naloxone. After spinal transection, the antinociceptive potency of systemically-administered morphine was significantly reduced while that of DAS-DER 1-4 was unaltered. The activity of DAS-DER 1-4 and morphine was also reversed by naloxone in spinal animals. It is concluded that DAS-DER 1-4, a dermorphin analogue, has a minor supraspinal action but acts mainly at the level of the spinal cord, in contrast to the action of morphine.

Analgesics↗
PubMed1990

Phosphoramidon potentiates mammalian tachykinin-induced biting, licking and scratching behaviour in mice.

The effects of peptidase inhibitors were examined upon behavioural responses including scratch, bite and lick produced by intrathecal (IT) injection of substance P (SP) and neurokinin A (NK A) in mice. Phosphoramidon (0.002-2.0 nmol), an endopeptidase-24.11 inhibitor, simultaneously injected with SP or NK A, remarkably enhanced and prolonged SP- or NK A-induced behavioural response in a dose-dependent manner. The behavioural response to SP was significantly increased by 2.0 nmol of bestatin, an aminopeptidase inhibitor, but not by 1.0 nmol. Captopril, an angiotensin-converting enzyme inhibitor, was without effect on both tachykinin-induced responses. When phosphoramidon was injected together with bestatin and captopril which have no significant effect alone, SP- or NK A-induced behavioral response was significantly increased. These data suggest that endopeptidase-24.11 may be an important enzyme responsible for terminating of SP- or NK A-induced behavioral response at the spinal cord level.

Aggression↗
PubMed1990

Thyroid function in patients with myotonic dystrophy.

In order to investigate endocrine disturbances in patients with myotonic dystrophy (MD), 12 patients and 20 normal controls were studied. All patients were clinically euthyroid and there were no significant differences between circulating levels (mean +/- SD) of T4 (114.7 +/- 26.8 vs 129.9 +/- 28.3 nmol/l), FT4 (16.6 +/- 4.5 vs 18.4 +/- 3.8 pmol/l), T3 (1.61 +/- 0.29 vs 1.86 +/- 0.33 pmol/l), TSH (2.7 +/- 1.3 vs 2.4 +/- 1.4 mU/l), TBG (26.7 +/- 5.5 vs 27.6 +/- 4.9 mg/l), T4/T3 (84.3 +/- 18.4 vs 82.1 +/- 15.3), and FT4/FT3 (0.28 +/- 0.05 vs 0.33 +/- 0.08). Serum FT3 (4.3 +/- 1.4 pmol/l) in patients were significantly lower than those (5.3 +/- 0.9 pmol/l) in normal controls (P less than 0.02). Thyroidal 131I-uptakes (8.7 +/- 4.3%) in patients were significantly lower than those (25.8 +/- 7.4%) in controls (P less than 0.01). The mean maximal TSH responses following TRH stimulation were significantly less in patients with MD (11.4 +/- 4.5 vs 17.0 +/- 6.2 mU/l; P less than 0.02). Neither circulating thyroid microsomal nor thyroglobulin antibodies were detectable in the 11 patients tested. Serum thyroglobulin concentrations were within the normal range in all patients but one. In conclusion, it is suggested that normal levels of serum T4, T3, FT4, TSH, TBG, T4/T3 and FT4/FT3, slight but significant decrease of serum FT3, reduced TSH response to TRH and a decrease of thyroidal radioiodine uptake might be due to a slight functional failure of TSH secretion in patients with myotonic dystrophy.

Adult↗
PubMed1990

The effects of substance P analogues on the scratching, biting and licking response induced by intrathecal injection of N-methyl-D-aspartate in mice.

1. Intrathecal (i.t.) administration of N-methyl-D-aspartate (NMDA) elicited a dose-dependent behavioural response consisting of licking, biting and scratching in mice. 2. Repeated i.t. injections of 0.4 nmol NMDA, at 5 min intervals, resulted in the rapid development of desensitization to this NMDA-induced behavioural phenomenon. 3. The NMDA-induced response was dose-dependently inhibited by the simultaneous injection of a selective NMDA-receptor antagonist, D-2-amino-5-phosphonovaleric acid. 4. The substance P (SP) analogues [D-Pro2, D-Trp7,9] SP and [D-Arg1, D-Trp7,9, Leu11] SP (spantide) inhibited NMDA-induced behavioural responses in a dose-dependent manner. However, [D-Phe7, D-His9] SP (6-11), a SP analogue selective for neurokinin1 (NK1) receptors, failed to inhibit NMDA-induced responses even at a dose of 4.0 nmol. 5. These results indicate that NMDA-induced behavioural responses are mainly mediated through NMDA receptors without affecting NK1 receptors in the spinal cord.

2-Amino-5-phosphonovalerate↗
PubMed1990

Erythrocyte zinc concentration in patients with subacute thyroiditis.

We have recently reported that red blood cell (RBC) zinc (Zn) in patients with hyperthyroidism reflects a patient's integrated thyroid hormone level over the previous few months. In the present paper RBC Zn concentrations were measured in 10 patients with subacute thyroiditis whose total plasma T4 and T3 levels were elevated. The values were compared with those obtained in 10 patients with untreated Graves' disease, whose plasma T4 concentrations were elevated to the same level as in the former group. The RBC Zn concentration was normal in 9 of 10 patients with subacute thyroiditis, but was depressed in all patients with Graves' disease. The mean (+/- SE) RBC Zn in patients with subacute thyroiditis was 162 +/- 9 mumol/L, significantly (P less than 0.001) higher than that in Graves' disease (87 +/- 5 mumol/L). During prednisolone treatment the RBC Zn in patients with subacute thyroiditis remained at the normal level and did not change significantly, although it was slightly decreased at 2 and 4 weeks of treatment. On the other hand, the RBC Zn in patients with Graves' disease was significantly increased at 8 weeks of treatment and reached the normal range in 12 weeks. These results suggest that elevation of plasma thyroid hormone concentrations in patients with subacute thyroiditis is transient and does not cause any significant change in the RBC Zn concentration.

Adult↗
PubMed1990

The influence of immunosuppressive acidic protein on the activity of peripheral K-lymphocytes in subacute thyroiditis.

We previously reported that immunosuppressive acidic protein (IAP), an alpha 1-acid glycoprotein, is increased during the acute phase of subacute thyroiditis (SAT). In this study we measured the percentage and absolute number of peripheral K-cells using a plaque-forming cell technique to investigate immunological abnormalities associated with SAT. Additionally, we investigated the relationship between IAP and peripheral K-cell activity. In normal controls, a sex-related difference in the percentage of K-cells among total lymphocytes was present; the percentage was significantly lower in women (mean +/- SD, 5.0 +/- 2.0%; n = 12; P less than 0.01) than in men (8.4 +/- 2.9%; n = 13). However, there was no difference (0.153 +/- 0.073 x 10(9)/L in five females; 0.173 +/- 0.054 x 10(9)/L in seven males) in the absolute number of peripheral K-cells. During the acute phase of SAT, the percentage (2.4 +/- 1.9% in 16 females; 2.7 +/- 1.0% in 3 males) and absolute number (0.058 +/- 0.048 x 10(9)/L in 11 females) of K-cells were significantly lower than those in normal controls. These values returned to normal during the recovery phase, although their mean values were still lower than those in normal controls. In female patients with Graves' disease, the percentage (2.2 +/- 1.8% in 11 females) and absolute number (0.038 +/- 0.033 x 10(9)/L in 11 females) of K-cells were significantly lower than those in normal controls; in male patients, the percentage (4.2 +/- 2.7% in 5 males) was lower than that in normal controls, but the absolute number (0.136 +/- 0.114 x 10(9)/L) of K-cells was not significantly different. Serum IAP values during the acute phase of SAT showed a significant negative correlation with the percentage of K-cells (r = -0.66; P less than 0.01). The number of K-cells from a normal subject decreased significantly when these lymphocytes were incubated with sera from patients with SAT, and the mean inhibition rate of K-cells by serum samples from 13 SAT patients during the acute phase was higher than that during the recovery phase (68.0 +/- 21.0 vs. 38.0 +/- 23.0%; P less than 0.01). Purified IAP inhibited the activity of K-cells from normal subjects dose dependently. These results suggest that 1) there may be inhibitory factors for the antibody-dependent cell-mediated cytotoxicity of peripheral K-cells in the serum of patients with SAT, and 2) IAP may be one of these inhibitory factors.

Acute-Phase Reaction↗
PubMed1990

Thyroxine 5'-deiodinase in human anterior pituitary tumors.

The activity of T4 5'-monodeiodinase (5'D) in the pituitary was measured in 12 patients with pituitary adenoma (3 patients with acromegaly, 2 with prolactinoma, 1 with Cushing's disease, 1 with TSH-producing tumor, and 5 with nonfunctioning tumor) and, as a control, in a patient who died of parotid cancer. The pituitaries, obtained at operation or autopsy, were homogenized in 0.1 mol/L potassium phosphate buffer, pH 7.0, and centrifuged at 800 x g. Supernatants were incubated with [125I]T4 and 20 mmol/L dithiothreitol (DTT) at 37C for 90 min. T4 5'-D was measured by the release of 125I- with the ion exchange method. The activity of T4 5'-D in the pituitaries from patients with prolactinoma and parotid cancer was dependent on protein concentration, incubation time, incubation temperature, and T4 concentration, and was labile to prior heating at 70 C for 30 min. T4 5'-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited 95% by 0.1 mmol/L iopanoic acid. The apparent Km and maximum velocity for T4 5'-D in homogenates of prolactinoma at 20 mmol/L DTT were 11 nmol/L and 1.54 pmol/mg protein.h, respectively. This reaction followed sequential-type reaction kinetics when the DTT concentration was varied. All other homogenates of pituitary tumors, except two nonfunctioning tumors, also demonstrated T4 5'-D activity. These results indicate that 1) the human pituitary express a low Km and PTU-insensitive T4 5'-D activity which is very similar to the type II enzyme activity in the rat pituitary; and 2) various types of pituitary tumor cells contain T4 5'-D activity.

Acromegaly↗
PubMed1990

Replacement of L-T4 suppository in MMI treated rabbits.

L-T4 suppositories containing 50, 100 or 200 micrograms of L-T4 were given to rabbits treated with MMI. The serum T4 gradually increased within 3.5 and 6.5 hours following the use of 100 and 200 micrograms of L-T4 suppositories, respectively, without an acute increase in serum T3. The increase in serum T4 continued up to 48 hours. The area under the curve (AUC) for serum T4 was evidently dose-dependent. It is concluded from these results that the T4 suppository will be useful as a replacement therapy for patients with hypothyroidism.

Animals↗
PubMed1990

[Analysis of cellular proteins in 9,10-dimethyl-1,2-benzanthracene induced hamster tongue carcinoma and dysplastic lesions by two-dimensional gel electrophoresis].

The cellular proteins of hamster tongue squamous cell carcinoma and epithelial dysplastic lesions induced by 9,10-dimethyl-1,2-benzanthracend (DMBA) were analyzed by two-dimensional isoelectric focusing-sodium dodecyl sulfate gel electrophoresis. Many of the polypeptides were common to these lesions. However, there were thirteen main polypeptides which differed between normal tongue mucosa and tongue carcinoma. In the carcinoma, eight polypeptides (5.2/53 K, 5.8/47 K, 6.9/46 K, 6.9/50 K, 7.1/55 K, 7.2/46 K, 7.3/75 K, 7.4/48 K, pI/MW) were decreased and three polypeptides (4.9/32 K, 6.3/50 K, 7.2/60 K) were increased in an amount. The remaining two polypeptides (4.8/37 K, 4.9/36 K) that were not normally present were appeared in carcinoma, but these two new polypeptides were not specific to carcinoma because they were also present in dysplastic lesions. There were marked differences in the polypeptide between various degree of dysplastic lesions and carcinoma on the one hand and normal mucosa on the others. These results suggests that two-dimensional electrophoresis may have usefulness in further research on transformations from normal mucosa to malignant cancer cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

[Long-term results of total correction of tetralogy of Fallot less than 2 years old].

Between April 1972 and March 1979, eighteen total correction for tetralogy of Fallot less than 2 years old were performed with a mortality rate of 11.1%. The valved patch made of autologous pericardium was utilized for right ventricular outflow reconstruction in 12 of 16 survivors. Late (from 10 to 17 postoperative year) results of the all survivors were studied on functional and clinical status, hemodynamics and cardiac functions, and also, were compared with that of the patients above 2 years of age. All of them were in NYHA class I with no physical exercise limitation. Chest X-ray showed nearly normal CTR of 51.7%. ECG showed complete or incomplete RBBB in 14 patients and LAD in 3 of them, whereas no ventricular arrhythmia. Cardiac catheterization and cineangiography revealed that they had quite satisfactory hemodynamics and cardiac functions despite their moderate pulmonary regurgitation. In comparison with the older patient group, this younger one had a tendency to take superior results in all parameters of cardiac functions and clinical status. These excellent long term results seem to come from their young and less degenerative myocardium at the time of surgery.

Adolescent↗
PubMed1990

[Surgical treatment of impending rupture of aortic arch aneurysm associated with ischemic heart disease].

A 58-year-old man with thoracic aneurysm was admitted because of progressive chest oppression, back pain and the rapidly grown mediastinal mass lesion in his chest X-ray. Aortography and computed tomography revealed impending rupture of saccular aortic arch aneurysm. Emergency operation, consisted of aortic arch replacement under selective cerebral perfusion and CABG with the left IMA, was performed successfully. His postoperative course was uneventful without any neurological deficit. Postoperative angiography demonstrated successful reconstruction of the aortic arch and the patent IMA graft.

Aorta, Thoracic↗
PubMed1990

[Clinical study on the use of retrograde cardioplegia with St. Thomas' Hospital solution].

One hundred and three consecutive patients with aortic valve disease and twenty seven patients with ischemic heart disease of severe critical coronary stenosis or left main trunk stenosis underwent open heart operations with the use of retrograde cardioplegic technique for myocardial protection. Under complete cardiopulmonary bypass, a balloon catheter was inserted into the coronary sinus through small right atriotomy and secured in place. Retrograde cardioplegia was accomplished using cold St. Thomas' Hospital solution by drip method at height of 60 to 80 cm with topical saline slush. Cardiac resuscitation was very easy and acceptable hemodynamics were obtained in all patients. Even in 8 patients in which aortic crossclamping time was above 180 minutes cardiac recovery was excellent except one who needed IABP support. Eight patients in aortotomy group were died postoperatively from the reasons unrelated to myocardial protection. Postoperative hemodynamic data and enzymatic analyses of CK-MB revealed good myocardial protective effects. Retrograde cardioplegia with the use of cold St. Thomas' Hospital solution is thus an effective alternative of myocardial protection in aortic valve surgery or aortotomy surgery and in coronary revascularization for multiple coronary stenoses or left main trunk lesions.

Adult↗
PubMed1990

[Coronary revascularization using an internal mammary artery-saphenous vein composite graft in a patient with severely calcified ascending aorta].

A 52-year-old woman with angina pectoris resulted from complete obstruction of left coronary ostium required double-vessel bypass. Because of severely calcified ascending aorta, avoidance of aortic cross-clamping was needed for the prevention of embolic injury and aortic dissection. Internal mammary artery (IMA)-saphenous vein (SV) composite graft under hypothermic ventricular fibrillation was successfully performed without any complication. IMA-SV composite graft is a good alternative in a case of insufficient IMA length and limited site for proximal vein graft anastomosis, which can avoid or reduce the manipulation of diseased ascending aorta.

Aortic Diseases↗