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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 559 records · Page 31Linked to original sources

The vasculature of the peroneal tissue transfer.

Peroneal vascularized composite-tissue transfer has many useful applications and advantages. An anatomic study of the peroneal artery and vein and their branches was carried out on 80 adult cadaver legs. The number of cutaneous branches averaged 4.8 +/- 1.4 per leg. The length of the cutaneous branches averaged 5.4 +/- 1.5 cm. The external diameters of cutaneous branches at the skin distribution site were 0.6 +/- 0.2 mm for the artery and 0.8 +/- 0.3 mm for the vein. The communicating branches were branched at anterior or posterior tibial vessels 6.1 +/- 2.4 cm proximal to the lateral malleolus. The range of rotation of the island flap when transposed proximally was 14.3 +/- 3.3 cm proximal from the head of the fibula, and when transposed distally, the range of rotation was 16.9 +/- 5.3 cm distally.

Aged↗

Intracerebroventricular infusions of insulin increase vasopressin release in rats.

1. The role of cerebral insulin or insulin-like immunoreactive substance (ILI) on arginine-vasopressin (AVP) release using rats was investigated. Feeding rats with a high salt diet for 4 weeks significantly decreased the contents of ILI in both the hypothalamus and pituitary gland. Intracerebroventricular infusions of insulin (4 and 40 micrograms/min for 30 min) increased plasma AVP concentrations dose-dependently without hypoglycaemia, but decreased hypothalamic and pituitary contents of AVP. 2. These results indicate that ILI in the brain may play a role in the secretion of AVP, and that this mechanism could be operated to control a water-sodium balance.

Animals↗

Role of dopaminergic mechanisms in the kidney for the pathogenesis of hypertension.

1. To estimate the role of renal dopaminergic mechanisms in the pathogenesis of hypertension, patients with essential hypertension and animal models of hypertension were investigated. 2. Impaired dopaminergic activity in kidneys for natriuresis was observed in patients with 'salt-sensitive' hypertension and with low-renin hypertension. 3. Decreased dopaminergic activity in kidneys was observed in the Dahl S-rats without salt loading. 4. In spontaneously hypertensive rats, renal dopamine synthesis was enhanced whereas there was a decrease of adenylate cyclase activity in renal tubules. 5. Demonstration of impaired dopaminergic mechanisms in kidneys of human and animal hypertension suggests that renal dopaminergic mechanisms play an important role in development of hypertension.

Animals↗

Amino acid-mediated EPSPs at primary afferent synapses with substantia gelatinosa neurones in the rat spinal cord.

1. Fast excitatory postsynaptic potentials (EPSPs) evoked by stimulation of A delta and C fibres were examined by intracellular recording from substantia gelatinosa (SG) neurones in a transverse slice preparation of adult rat spinal cord. 2. Single low-intensity stimuli applied to the dorsal root activated A delta fibres and evoked monosynaptic EPSPs in 70% of SG neurones. In 5% of SG neurones, increasing the intensity and duration of stimulation evoked solely C fibre-mediated EPSPs. About 20% of neurones received both A delta and C fibre input from primary afferents. 3. Low concentrations of tetrodotoxin (TTX, approximately 50 nM) blocked EPSPs evoked by stimulation of A delta fibres without affecting those evoked by C fibre stimulation. Higher concentrations of TTX (500 nM) also blocked C fibre-evoked responses. 4. EPSPs evoked by A delta and C fibre stimulation reversed in polarity at membrane potentials near 0 mV, similar to the reversal potential of spontaneous EPSPs and of the potential change evoked by exogenous glutamate. 5. A delta and C fibre-evoked EPSPs were depressed by kynurenate and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); C fibre-evoked EPSPs appeared to be less sensitive. 6. In the presence of TTX, only 50% of SG neurones were depolarized by L-glutamate. However, neurones which exhibited no direct response to L-glutamate received afferent-evoked EPSPs which were sensitive to CNQX. In sensitive neurones, the depolarization evoked by L-glutamate was depressed by only approximately 15% in the presence of CNQX, whereas afferent-evoked EPSPs recorded from the same neurone were almost completely suppressed. Combined application of DL-2-amino-5-phosphonovaleric acid (APV) and CNQX depressed the response to L-glutamate by only approximately 25%. 7. These findings suggest that A delta and C fibres use L-glutamate or a related amino acid as a transmitter at synapses with substantia gelatinosa neurones. The postsynaptic actions of this transmitter are mediated predominantly by non N-methyl-D-aspartic acid (NMDA) receptors. The failure of CNQX and APV to completely block the L-glutamate-evoked depolarization of substantia gelatinosa neurones raises the possibility that exogenously applied L-glutamate activates a non-NMDA receptor distinct from that which mediates the actions of the synaptically released afferent transmitter.

2-Amino-5-phosphonovalerate↗

Hormonal induction of beta-casein gene expression: requirement of ongoing protein synthesis for transcription.

Hormonal induction of beta-casein gene expression was studied using a two-step culture of mouse mammary explants and RNA blotting analysis. The explants prepared from pregnant mice were cultured first for 4 days under nonlactogenic conditions to reduce the initial level of beta-casein transcripts and then induced to express beta-casein gene in the presence of insulin, hydrocortisone, and PRL for up to 3 days. Among the six different combination of hormones tested in the first incubation period, the combinations of insulin and epidermal growth factor was found to reduce the residual level of beta-casein transcripts in cultured explants to a nearly undetectable level and allow the highest induction in the second incubation period. The increase in beta-casein transcripts was detected as early as 30 min of induction with insulin, hydrocortisone, and PRL, and its level increased more than 100-fold over the initial level at 24 h. The increase in beta-casein transcripts was blocked by concomitant addition of the protein synthesis inhibitors cycloheximide or puromycin with the three hormones. Cycloheximide inhibited the increase in beta-casein gene transcription that was elicited by insulin, hydrocortisone, and PRL, but did not alter the stability of beta-casein transcripts. These results suggested that protein synthesis was required for hormonal activation of beta-casein gene transcription.

Animals↗

Synergistic effect of thyroid hormone and thyrotropin on iodothyronine 5'-deiodinase in FRTL-5 rat thyroid cells.

The effects of T3 and T4 on the iodothyronine 5'-deiodinase (5'-D) activity in FRTL-5 rat thyroid cells were investigated. T3 and T4 stimulated the 5'-D activity in a dose-dependent manner. Kinetic studies showed that the stimulation of the 5'-D by T3 was associated with an increase in maximum velocity (Vmax) in [11.9 +/- 0.2 (mean +/- SE) and 25.4 +/- 0.9 pmol I-released/mg protein.min, respectively, in control and cultured with 10(-9) M T3 for four days] but without a change in apparent Michaelis-Menten constant (Km) (94.8 +/- 5.3 nM and 105.4 +/- 12.1 nM, respectively). Furthermore, cycloheximide (5 microM) completely abolished the stimulatory effect of T3 on the 5'-D activity. T3 and T4 also enhanced the 5'-D activity stimulated by TSH in a dose-dependent manner. Kinetic studies showed that the stimulatory effect of T3 on the 5'-D stimulated by TSH was again associated with an increase in Vmax (86.0 +/- 4.0 and 166.5 +/- 1.9 pmol I- released/mg protein.min, respectively, cultured with 0.3 U/liter TSH and cultured with TSH plus 10(-9) M T3 for four days) without a change in apparent Km (114.0 +/- 7.4 nM and 111.6 +/- 12.5 nM, respectively). Cycloheximide (5 microM) completely abolished the stimulatory effect of TSH plus T3 on the 5'-D activity. There were no significant differences observed between cells cultured with TSH and with TSH plus T3 in either the intra- or extracellular cAMP contents. Furthermore, T3 enhanced the 5'-D activity stimulated by (Bu)2 cAMP. These results strongly suggest that T3 or T4 was synergistic with TSH in stimulating the 5'-D activity in FRTL-5 cells, and that cAMP production would be an important component of the synergism.

Animals↗

Graves' immunoglobulin G stimulates iodothyronine 5'-deiodinating activity in FRTL-5 rat thyroid cells.

To elucidate the effect of Graves' immunoglobulin G (IgG) on iodothyronine deiodination in the thyroid, we examined the characteristics of iodothyronine 5'-deiodinating (I-5'-D) activity in FRTL-5 rat thyroid cells and the effect of Graves' IgG on its activity. FRTL-5 cells were sonicated and incubated with 0.5 mumol/L rT3 with a tracer amount of [125I]rT3 in 0.1 mol/L phosphate buffer containing 1 mmol/L EDTA and 0.5 mmol/L dithiothreitol. The released 125I- was separated by Dowex-50WX2 column and counted. The amount of I- released was tissue, incubation time, temperature, and pH dependent, strongly suggesting that the reaction is enzymatic. The activity was completely inhibited by propylthiouracil. The Km value for rT3 was approximately 0.32 microM when analyzed by Lineweaver-Burk plot. TSH, dibutyl cAMP, and Graves' IgG induced I-5'-D activity in a dose-dependent manner. However, cycloheximide (5 mumol/L) abolished the stimulating effects of these agents on I-5'-D activity. These results suggest that TSH, dibutyl cAMP, and Graves' IgG induced I-5'-D activity through the synthesis of new enzyme protein. A significant positive correlation between thyroid-stimulating antibody activity assayed by measuring cAMP production using FRTL-5 cells and I-5'-D activity induced by the Graves' IgG in 10 patients with untreated Graves' disease was observed (r = 0.79; P less than 0.01). The present findings suggest that type I iodothyronine 5'-deiodinase exists in FRTL-5 rat thyroid cells and that Graves' IgG as well as TSH stimulate the activity at least in part by activating adenylate cyclase.

Animals↗

Measurement of digital arterial pressure in patients with essential hypertension.

In 8 normotensive volunteers, digital blood pressure was determined, and the value was compared to direct brachial arterial pressure and to that measured by a conventional, indirect Korotkoff-method in the upper arm. The correlation coefficient was determined by changing blood pressure with intravenous administration of vasoconstrictors, sublingual nitroglycerin, and stress tests. Although the absolute value of the digital blood pressure was slightly lower than direct arterial pressure, the correlation between the two determinations was highly significant. The difference in readings between direct and digital arterial pressure was not significant even when the pressure was fluctuated with administration of vasoactive drugs and stress tests. In 2 of 6 volunteers the photosignals of the digital arterial pulses became too small to measure pressure 30 min after they entered in a cold room. However, the digital/brachial blood pressure difference did not alter even when the signals became small during the cold exposure in the remaining 4 subjects. Afterward, the subjects visited our outpatient clinic, where their digital blood pressure was taken. The value was compared with the indirect, contralateral brachial blood pressure. The absolute difference between the readings increased significantly when hypertension advanced. Among the patients (WHO, stage I) treated with antihypertensive drugs, the digital/arm pressure gap was the greatest in patients treated with beta-adrenergic blockers, diuretics and calcium channel blockers in decreasing order. These results indicate that digital blood pressure is influenced by the severity of hypertension and drugs; i.e., hypertensive vascular injury and/or atherosclerosis lowers the peripheral blood pressure leading to impaired peripheral tissue perfusion in the hypertensive patient, and beta-adrenergic blockers may deteriorate peripheral circulation in spite of their hypotensive effects.

Adult↗

Intracerebroventricular injections of endothelin increase arterial pressure in conscious rats.

We investigated the possible effects of endothelin (ET) on the central regulation of arterial pressure by injecting ET intracerebroventricularly (ICV) into conscious rats. ICV injections of ET caused dose-dependent elevation of arterial pressure and increase of heart rate. The first reaction was abolished by bunazosin, an alpha 1-adrenergic blocker, injected intravenously. However, the increase in arterial pressure and heart rate caused the rats, injected with ET ICV, to roll to the left on their long axis for 20-30 min, followed by prolonged sedation. Furthermore, the pressor responses and tachycardia were significantly attenuated by the ICV pretreatment with nicardipine, a calcium channel blocker, and nicorandil, a nitrate derivative, respectively. These results suggest that ET may elevate the intracellular Ca2+ concentration ([Ca2+]i) of sympathetic nerve activity regulatory neurons of the brain, leading to an accelerated outflow of sympathetic nerve activity and cause the elevation of arterial pressure.

Adrenergic alpha-Antagonists↗

A sensitive and practical bioassay for thyrotropin (TSH): comparison of the bioactivity of TSH in normal subjects and in patients with primary hypothyroidism.

To study the possible correlation between the bioactivity ratios of the serum TSH and serum thyroid hormone concentrations in patients with primary hypothyroidism, the bioactivity of TSH in these patients was determined by means of a sensitive and practical bioassay and the results were compared to those in normal subjects. Sample sera were obtained from 11 patients with primary hypothyroidism and 9 normal subjects. TSH was extracted from the serum with anti-human TSH monoclonal antibody-coated tubes. The bioassay for TSH was performed by measuring the amount of cAMP released into the medium from cultured FRTL-5 cells incubated with the TSH extract. Linear relations were found between the serum TSH values, measured by the immunoassay, and the bioactivity of the TSH, measured by the present assay, in normal subjects (y = 1.13 x-0.3, r = 0.89, p less than 0.01) and in patients with primary hypothyroidism (y = 0.90 x + 0.7, r = 0.93, p less than 0.01). Moreover, the regression line in patients with primary hypothyroidism was not significantly different from that in normal subjects based on the analysis of covariance. The present findings suggest that the bioactivity of TSH is consistent with the immunoreactivity of TSH in patients with primary hypothyroidism as well as in normal subjects.

Adult↗

Human chorionic gonadotropin promotes thyroid growth via thyrotropin receptors in FRTL-5 cells.

To ascertain the presence of thyroid growth-promoting activity (TGA) in the sera of pregnant women, we measured TGA in the sera of pregnant women by means of a bioassay based on [3H]-thymidine [( 3H]Tdr) incorporation in cultured rat FRTL-5 thyroid cells. Furthermore, to elucidate the mechanisms of human chorionic gonadotropin (hCG) in promoting the thyroid growth, we evaluated the effects of blocking type TSH receptor antibody (blocking IgGs) from patients with primary hypothyroidism on the activity of hCG. After the PEG-pretreated serum or the serum plus blocking IgGs was incubated for 72 h at 37 degrees C with FRTL-5 cells and [3H] Tdr, [3H] Tdr incorporated in the cells was counted. Although 9 normal pregnant women had normal TGA, two patients with hydatidiform mole, whose hCG levels were 966,500 and 497,100 IU/L, had positive TGA, but the activity showed normal when analyzed with the addition of a blocking IgG. hCG also showed a dose-dependent increase in [3H]Tdr incorporation, and it was inhibited by the addition of blocking IgGs. Furthermore, the inhibition of hCG-induced [3H]Tdr incorporation by 16 blocking IgGs correlated with their TBII and the inhibition activity of hCG-induced cAMP accumulation. Analysis by the Lineweaver-Burk plots of dose response curves of TSH- and hCG-induced [3H]Tdr incorporation showed the same inhibition pattern as with the addition of the same blocking IgGs. In conclusion, 1) hCG-related TGA exists in the sera of some patients with hydatidiform mole; and 2) hCG and the sera of some patients with hydatidiform mole promote thyroid growth, at least in a part, via TSH-receptors in FRTL-5 cells.

Adolescent↗

Thyroid-stimulating activity of human chorionic gonadotropin in sera of normal pregnant women.

To ascertain the thyrotropic activity of human chorionic gonadotropin in sera of normal pregnant women, we examined the adenylate cyclase activation in the cultured FRTL-5 cells by extracted hCG from 7 normal pregnant women. hCG was extracted from the sera using anti-hCG-beta subunit monoclonal antibody-coated microwells, eluted with 2 mol/l guanidine-HCl, and reconstituted with hypotonic Hanks' solution. FRTL-5 cells were precultured in 5H medium, incubated for 2 h with the serum extracts, and the cAMP released into the medium was measured. hCG levels in serum extracts ranged from 1100 to 6800 IU/l; values corresponded to 1.4-19.8% compared with those in the original serum samples. Addition of the extracts to FRTL-5 cells resulted in significant increases in the cAMP accumulation, ranging from 9.8 to 59.0 nmol/l. cAMP levels were also increased in a dose-dependent manner by adding purified hCG as well as crude hCG and hTSH to FRTL-5 cells. These findings suggest that the thyroid gland of normal pregnant women may actually be stimulated by hCG itself.

Adult↗

[Pathophysiological analysis and treatment of arrhythmias, using Holter electrocardiography].

Using Holter electrocardiography, the primary factors affecting the occurrence and severity of ventricular premature systoles (VPS) and the method of treatment of VPS in patients having no apparent heart disease were examined. Pathological significance of catecholamines on the occurrence of VPS was studied in 182 patients. The close correlation between the severity of VPS and the total amount of urinary norepinephrine excretion demonstrated in this study suggests that the occurrence of VPS in patients with no apparent underlying heart disease, especially those over 40 years of age, may be mediated by enhanced endogenous catecholamine activities. This assumption is further substantiated by the fact that beta adrenoceptor blockade was effective against VPS in patients excreting high amounts of catecholamines, but not in patients with normal catecholamine excretion. Antiarrhythmic efficacy of class IA (disopyramide), IB (aprindine, mexiletine), II (propranolol), III (amiodarone) and IV (verapamil) drug was studied in 110 patients having more than 1,000 VPS per day. Judging from these results, we may conclude that: 1) VPS with short coupling intervals should be treated with class I drugs such as mexiletine which have a fast kinetics of unbinding from the inactivated state, 2) VPS with intermediate or long coupling intervals should be treated with class I drugs such as disopyramide and aprindine, which have a slow kinetics of unbinding from the inactivated state, 3) class II drug, propranolol, was effective against VPS associated with an increased sympathetic tone, 4) class III drug, amiodarone, was the most potent antiarrhythmic agent against any type of VPS, and 5) class IV drug, verapamil, appeared effective against VPS in elderly patients.

Adult↗

Competitive action of a biological response modifier, PSK, on a humoral immunosuppressive factor produced in tumor-bearing hosts.

We investigated the effect of PSK, a protein-bound polysaccharide obtained from the basidiomycetes Coriolus versicolor, on an immunosuppressive factor produced in tumor-bearing animals. Oral administration of PSK suppressed the growth of the tumor in C3H/He mice bearing X5563 plasmacytoma or MH134 hepatoma, but affected mice bearing MM102 mammary tumor little. PSK prevented the reduction in splenic lymphocyte blastogenesis caused by phytohemagglutinin that occurs in mice bearing X5563 tumors or MH134 hepatoma. The lymphocyte blastogenesis affected little by tumor or PSK in mice bearing MM102 tumors. The effect of sera on the blastogenesis of lymphocytes caused by phytohemagglutinin was different with different tumors in the C3H/He mice. Serum of mice bearing X5563 tumors inhibited blastogenesis, but serum of mice bearing MH134 hepatoma or MM102 tumors promoted it. The sera of mice bearing MH134 hepatoma contained both inhibitory and promotive factors; those of mice bearing X5563 tumors contained an inhibitory factor, and those of mice bearing MM102 tumors contained a promotive factor. The oral administration of PSK reduced the inhibition caused by the sera of mice bearing X5563 tumors. The promotive activity of sera from mice bearing MH134 hepatoma was augmented by PSK; that of sera in mice bearing MM102 tumors was not affected by PSK. Living Bacillus Calmette-Guérin did not have such effects in any of these mice. Serum immunosuppressive activity was also reduced by PSK in various tumor lines of rodents. These results suggest that PSK acts by reducing the activity of immunosuppressive factors produced in tumor-bearing hosts.

Administration, Oral↗

[Pathophysiology and laboratory examinations of essential hypertension--a review of recent topics].

Since the pathogenesis of essential hypertension has not yet been clarified, laboratory examinations are needed to identify secondary hypertension and to classify the patients with essential hypertension into subclasses. We reviewed the recent topics on hypertension-research related to laboratory examinations such as 1) recording of arterial pressure, 2) plasma renin activity and digitalis-like substances as the cause of essential hypertension, and 3) atrial natriuretic polypeptides and endothelin, as possible indices of atherosclerosis, one of major complications of hypertension.

Atrial Natriuretic Factor↗