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Biomedical subjects

T Yoshimi

Publications and source records attributed to T Yoshimi.

At least 73 records · Page 4Linked to original sources

[Mutations of glucokinase gene in Japanese subjects with NIDDM].

Glucokinase has been proposed to play an important role as a glucose sensor in pancreatic beta-cells. Mutations in the glucokinase gene have been shown to be the major cause of maturity-onset diabetes of the young (MODY) in Caucasian subjects. In population-association study with microsatellite DNA polymorphisms in Japanese subjects with NIDDM, a negative association was evident between NIDDM and the glucokinase gene locus, although contradictionary results were present. Using PCR-SSCP analysis, no glucokinase mutation, which induces changes in amino acid residues, was identified in Japanese subjects with classical late-onset NIDDM. These results suggest that mutations in this gene are not the major cause of common form NIDDM in Japanese.

Asian People↗

Effects of high-molecular-weight sodium hyaluronate on experimental osteoarthrosis induced by the resection of rabbit anterior cruciate ligament.

Sodium hyaluronate (HA) with a molecular weight of 202 x 10(4) (HA-202) was administered into the right knees of mature rabbits for the treatment of experimental osteoarthrosis induced by resection of the anterior cruciate ligament. At six and 12 weeks after the initiation of administration, the test group was compared with a group administered physiological saline solution to determine the effects on articular cartilage and synovial tissue. In both the six- and the 12-week period, cartilage degeneration proceeded with the lapse of time in both groups; however at 12 weeks, the efficacy of HA-202 in inhibiting degeneration was clearly observed at the lateral condyle of the femur and tibia where relatively marked degeneration was observed in the saline group. A comparison was also made among three groups administered HA-95 (sodium hyaluronate with a molecular weight of 95 x 10(4)), HA-202, and saline, respectively, for 12 weeks. The saline group showed the greatest cartilage degeneration accompanied by complete disorganization of the cartilage layer and the disappearance of chondrocytes. The degeneration was less in the HA groups, and it was more significantly inhibited in the HA-202 group than in the HA-95 group.

Animals↗

Effect of high-molecular-weight sodium hyaluronate on immobilized rabbit knee.

Experimental osteoarthrosis of the knee joint was induced in rabbits using a polyethylene binding brace. A 1% solution of sodium hyaluronate (HA) of molecular weight 1.73 x 10(6) (HA-173) was administered intraarticularly at a dosage of 0.1 ml/kg body weight twice a week. Changes in articular cartilage and synovial membrane, and joint contracture were compared with a saline control group at intervals throughout a six-week period of immobilization. In all groups, articular cartilage degeneration and joint contracture progressed with time but were inhibited by the administration of HA-173. Additionally, the results of a 1% solution of HA of molecular weight 9.8 x 10(5) (HA-98), a 1% solution of HA of molecular weight 2.02 x 10(6) (HA-202), and saline, each administered twice a week for five weeks at a dose of 0.1 ml/kg body weight, were compared. It was clear that the articular cartilage degeneration was significantly inhibited by HA as compared with saline, and that the effect was more potent with the higher molecular weight, HA-202, than with HA-98. Furthermore, joint contracture was inhibited by HA, and the effect was more potent with the higher molecular weight, HA-202, than with HA-98.

Animals↗

Changes in fibrinolytic parameters in male patients with type 2 (non-insulin-dependent) diabetes mellitus.

We examined changes in fibrinolytic parameters in male patients with diabetes mellitus (DM) and controls. DM patients were divided into three groups: patients without retinopathy, patients with simple retinopathy, and patients with proliferative retinopathy. Plasma levels of t-PA (tissue plasminogen activator) and t-PA-PAI-1 (plasminogen activator inhibitor-1) complex increased with increase in age, but those of PAI-1 (total and free) did not change in controls. On the other hand plasma levels of PAI-1 decreased with increase in age in DM patients. Plasma levels of t-PA, t-PA-PAI-1 complex, free and total PAI-1 increased with increase in body mass index in controls, but no significant changes were shown in these parameters in DM patients. When compared with controls, plasma levels of t-PA, t-PA-PAI-1 complex and PAI-1 were lower in DM patients. Plasma levels of UK (urokinase) and Lp(a) were higher in DM patients. ELT (euglobulin clot lysis time) was significantly shorter in DM patients than in controls. Patients without retinopathy showed increased fibrinolytic activities compared with those with retinopathy due to the increased levels of t-PA in plasma. These results seem to indicate that blood vessels release larger amounts of t-PA at the early stage of DM, then release being impaired at its advance stage. It is also suggested that the regulatory control mechanisms of fibrinolytic activity associated with mechanisms of fibrinolytic activity associated with change in age and body mass index are different between patients with DM and normal people.

Adult↗

The effect of MCI-9042 on serotonin-induced platelet aggregation in type 2 diabetes mellitus.

MCI-9042, a potent inhibitor of 5HT2 receptor, was used to examine its effects on serotonin induced-aggregation of platelets obtained from patients with type 2 diabetes mellitus (DM). The extent of platelet aggregation induced by serotonin increased in DM patients without retinopathy, but the increase was further significant in DM patients with retinopathy. MCI-9042 as well as ketanserin, inhibited significantly serotonin induced-aggregation of platelets obtained from DM patients with retinopathy. MCI-9042 dose dependently inhibited platelet aggregation induced by serotonin and collagen. These results suggest that serotonin which may be released from platelets of DM patients may activate platelets together with collagen exposed on atherosclerotic endothelium and that MCI-9042 may be inhibitory to enhanced platelet aggregability under these conditions.

Adult↗

Transitional expression of neural cell adhesion molecule isoforms during chicken embryonic myogenesis.

The neural cell adhesion molecule, NCAM, is known to be expressed in chicken muscle as at least three principal molecular forms (molecular masses of 155 kDa, 145 kDa, and 120 kDa). They are generated from a single gene by alternative splicing. To distinguish these molecular species and to investigate their expressions in muscle differentiation during chicken embryonic development, we prepared antipeptide antibodies against three different domains of the NCAM. The antibody named MSD<+> was designed to detect muscle-specific domain (MSD) which was inserted into a muscle-specific NCAM by alternative splicing. The locus encompassing the MSD insertion site was detected with the antibody named MSD<->, and cytoplasmic sites near the transmembrane region were detected with the antibody named CYT. Immunoblot analysis utilizing the peptide antibodies prepared here revealed that, of three NCAMs, two isoforms, 155 kDa and 120 kDa, were recognized with the antibody MSD<+> and the same 155-kDa and the other 145-kDa molecule were recognized with the antibody CYT. The antibody MSD<-> was capable of detecting all three isoforms of the NCAM. Expression of the 120-kDa form with MSD but lacking a cytoplasmic tail increased but that of the 145-kDa form with cytoplasmic tail but lacking MSD declined during embryonic day 5 to day 18. The 155-kDa form NCAM with both MSD and cytoplasmic tail was expressed specifically and transiently during embryonic day 11 to day 14 in chick muscle; this period coincides with the period of extensive myotube formation. Thus, this largest isotype seems to play an important role in muscle differentiation.

Amino Acid Sequence↗

Testosterone normalizes plasma vasopressin response to osmotic stimuli in men with hypogonadism.

We studied plasma vasopressin concentrations during hypertonic saline infusions in 5 men with hypogonadism and 10 normal men to investigate the effect of gonadal steroid on hypothalamo-neurohypophyseal function. All the subjects received the infusion of 5% saline, and plasma vasopressin concentrations were determined by radioimmunoassay (RIA). Three of the 5 men were patients with isolated hypogonadotropic hypogonadism (IHH) and the other two were patients with Klinefelter's syndrome. None of them had any symptoms of diabetes insipidus. Although there was no difference between basal plasma osmolality in the patients and the normal subjects (287.2 +/- 2.1 vs. 285.3 +/- 1.8 mmol/kg), the basal level of plasma vasopressin in the patients was lower than that in the normal subjects (0.62 +/- 0.17 vs. 1.36 +/- 0.15 pg/ml, P < 0.05). Hypertonic saline infusion revealed varying degrees of subnormal vasopressin responses in the patients except one patient with Klinefelter's syndrome. The mean vasopressin response to osmotic stimuli (delta plasma vasopressin/delta plasma osmolality) in the 5 patients was lower than in the normal subjects (0.04 +/- 0.01 vs. 0.16 +/- 0.02, P < 0.05). Three patients with IHH and one patient with Klinefelter's syndrome were re-examined after pulsatile gonadotropin-releasing hormone (GnRH) infusion or testosterone enanthate i.m. injection. After the treatment with testosterone or GnRH, the response of plasma vasopressin to hypertonic saline infusion was normalized in three patients who had subnormal vasopressin response before treatment (delta plasma vasopressin/delta plasma osmolality: 0.04 +/- 0.01 vs. 0.09 +/- 0.01, P < 0.05). These results suggest that testosterone improves the subnormal vasopressin response to osmotic stimuli in men with hypogonadism.

Adolescent↗

[Medical management after pituitary surgery].

Although the majority of patients with pituitary tumor, undergoing transsphenoidal microsurgery, have a low incidence of hormonal deficiency after surgery, the endocrinological evaluations should be carefully done before and after surgery. Glucocorticoid replacement is necessary in patients with Cushing's disease during and after surgery as well as those with adrenal insufficiency. Repeated CRF test is useful to assess the secondary adrenal insufficiency of Cushing's disease after surgery. Patients with impaired secretion of both ACTH and TSH should receive glucocorticoid replacement before thyroid hormone replacement in order to avoid adrenal crisis. A combination of CRF, GRF, TRH and GnRH is a safer and more reliable test to evaluate pituitary function than the conventional triple test consisting of insulin, TRH and GnRH, especially in patients predicted to have pituitary-adrenal insufficiency. Diabetes insipidus(DI), immediately after pituitary surgery, should be treated with subcutaneous injection of Pitressin. Even if patients seem to have recovered from DI several days after surgery, they must be monitored closely because of the incidence of triphasic DI. Less attention has been given to replacement for GH deficiency in adults. Recent reports revealed that GH replacement in adults with GH deficiency decreases visceral fat tissue and increases plasma calcium, phosphorus, osteocalcin and procollagen III levels. GH replacement will become more popular even in adults. Many options and technological advantages in the diagnosis and treatment of pituitary tumors have developed in a decade. In the near future, post-operative patients with pituitary tumors must be cared for in view of the "quality of life".

Adenoma↗

Blood serotonergic mechanisms in type 2 (non-insulin-dependent) diabetes mellitus.

Serotonin (5-hydroxytryptamine, 5HT) is believed to play a role in vasospasm and increased platelet aggregability that in turn could contribute to atherosclerosis. The present study was designed to evaluate a possible participation of serotonin in the development of vascular complications in diabetes mellitus. Whole blood and plasma serotonin, the platelet uptake and release of the amine and serotonin- induced platelet aggregation were studied in 32 patients with Type 2 diabetes. The patients were divided into three groups according to the presence and advancement of retinopathy. Mean levels of blood serotonin content were significantly lower in diabetic patients. The concentration of the amine in the plasma was markedly increased in diabetes. It was correlated with vascular changes of the retina. We established that platelets from diabetic patients took up less serotonin when compared to the control group. Concomitantly enhanced spontaneous release of 5HT from platelets was observed. The platelets of diabetic patients showed increased response to serotonin. There was a relation between serotonin-induced aggregation and the presence of retinopathy. These results suggest that serotonin may be involved in the pathogenesis of diabetic vasculopathy.

Adult↗

Increased level of atrial natriuretic peptide messenger RNA in the hypothalamus and brainstem of spontaneously hypertensive rats.

OBJECTIVE: The aim of this study was to investigate atrial natriuretic peptide (ANP) gene expression in the central nervous system (CNS) during hypertension. METHODS: We measured and compared immunoreactive atrial natriuretic peptide (irANP) and ANP messenger RNA (mRNA) in the hypothalamus and brainstem of 17-week-old spontaneously hypertensive rats (SHR) with those of age-matched Wistar-Kyoto (WKY) rats using ribonuclease (RNase) protection assay for ANP mRNA and a specific radioimmunoassay for irANP. RESULTS: RNase protection assay revealed that the concentrations of ANP mRNA in the hypothalamus and brainstem of SHR were higher than those of WKY rats. IrANP concentrations in the hypothalamus and brainstem of SHR were determined by a specific radioimmunoassay and found to be higher than those of WKY rats. Elevated mRNA levels in the hypothalamus and brainstem of SHR indicated that increased level of irANP in the CNS resulted from increased synthesis of ANP. CONCLUSION: We propose that increased synthesis of brain ANP in SHR may reflect a compensatory mechanism induced by hypertension.

Animals↗

Plasma free fatty acids, inhibitor of extrathyroidal conversion of T4 to T3 and thyroid hormone binding inhibitor in patients with various nonthyroidal illnesses.

In order to clarify the role of free fatty acid (FFA) in thyroid hormone abnormalities in patients with nonthyroidal illness, thyroid function, FFA, inhibitor of extrathyroidal conversion of T4 to T3 (IEC) and thyroid hormone binding inhibitor (THBI) were studied in 99 patients with various nonthyroidal illnesses including diabetes mellitus (DM) (n = 35), liver cirrhosis (LC) (n = 33), chronic obstructive pulmonary disease (COPD) (n = 17) and chronic heart failure (CHF) (n = 14). Patients were divided into three groups based on the level of serum T3: Group I (T3 < 50 ng/dl), Group II (50 < or = T3 < 80) and Group III (80 < or = T3). Serum T4, FT3 and the T3/T4 ratio decreased significantly in the order Group III, Group II and Group I (Group III > II > I). The plasma FFA level was 0.91 +/- 0.12 mmol/l in Group I (P < 0.05, vs. Group III), 0.65 +/- 0.06 in Group II and 0.54 +/- 0.04 in Group III, respectively. The incidence of positive IEC was 80.0% in Group I (P < 0.05, vs. Group III), 53.7% in Group II (P < 0.05, vs. Group III) and 34.2% in Group III. However, IEC was not correlated with the serum T3 concentration. The incidence of positive THBI was 80% in Group I (P < 0.05, vs. Group III), 68.3% in Group II and 47.4% in Group III, but THBI was not correlated with the serum T4 level. Positive correlations were observed among FFA, IEC and THBI (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗