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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 451 records · Page 25Linked to original sources

Discrete expression of Ca2+/calmodulin-sensitive and Ca(2+)-insensitive adenylyl cyclases in the rat brain.

Physiological studies and inferences from invertebrate models implicate Ca2+/calmodulin-sensitive adenylyl cyclase with memory processes. However, Ca2+/calmodulin-insensitive adenylyl cyclase also occurs in brain, and its neuronal functions are less clear. Two oligonucleotide probes, based on rat cDNAs for Types I and II adenylyl cyclase, which appear to correspond to these functional forms, were used to conduct in situ hybridization analysis of the relative abundance and localization of these two species in the rat brain as a first step in evaluating their neuronal role. Quite discrete patterns of expression were encountered; in some areas, both species were co-expressed, but in others, little overlap was observed. The differential expression of the two mRNAs suggests that discrete roles may be fulfilled by the two adenylyl cyclases in neural tissues.

Adenylyl Cyclases↗

The unusual development of empyema with multiple alveolobronchiolar fistulae 8 years after non-curative resection and radiation for lung cancer: report of a case.

We present herein the case of a man who developed empyema with multiple lung fistulae 8 years after receiving postoperative radiation for a residual tumor on the bronchial stump. The patient was successfully managed with two-stage surgery, involving an open window thoracotomy, followed by omental flap transfer. This case documents how postoperative radiotherapy that was effective following non-curative resection was also responsible for the development of empyema. Furthermore, although the empyema was successfully treated using the omentum, a small free space remained in the thorax, which resolved within 2 months.

Aged↗

Effects of fasting on distribution and excretion of lead following long-term lead exposure in rats.

Lead was given to rats through drinking water containing 100 ppm lead acetate for 20 days. Delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes was significantly lower (p < 0.05) at 20 days after Pb treatment. Erythrocytic ALAD activity was significantly lower (p < 0.05) in fasted rats than in fed rats with or without Pb pretreatment. Serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase activities after 6 days of fasting were significantly higher (p < 0.05) in Pb pretreated rats than in other groups (Pb nontreated fed and fasted rats, and Pb pretreated fed rats). Long periods of fasting strongly enhanced these serum-enzymes elevations induced by lead. Maximum Pb concentrations and total amount in feces increased in rats fasted for 3 days regardless of Pb pretreatment. On the other hand, total amount of Pb in feces of rats fasted for 6 days were not significantly different from the other groups because their fecal volume decreased to about 1% of fed rats. The Pb concentrations of liver, kidney, spleen, and femur increased significantly in Pb pretreated rats compared to in controls, but there were no significant differences between the fed and fasted rats.

Alanine Transaminase↗

The prevalence and retention of lead pellets in Japanese quail.

Thirty-six Japanese quail (18 control birds, 18 lead-dosed birds) were used. The 18 quail were dosed with #4 lead weight that were orally inserted into the proventriculus. Delta-aminolevulunic acid dehydrase (ALAD) activity in erythrocytes in the dosed quail decreased 90% (p < 0.01) after one week as compared with the undosed quail. This inhibition of ALAD activity in erythrocytes indicates lead exposure. Radiographics were obtained at 0, 1, 4, 9, 22, and 32 days. The lead pellets remained in the gizzard and became smaller in 4 days. At day 22, after the lead treatment, in 8 quail of the treated quail 12, the lead pellets disappeared. At day 32, all lead pellets disappeared. These findings indicate that the ingested lead pellets are absorbed gradually in the intestine. The lead concentrations in the blood, liver, kidney, and femur of the lead-dosed quail were significantly higher than in the undosed quail until the 6th week. At week 2, the lead concentration of the proventriculus, gizzard, gizzard contents, duodenum, small intestine, and cecum in the dosed quail was significantly higher. Lead concentration of feces was significantly higher at weeks 2 and 4 (p < 0.01). Throughout this study, no lead pellets were found in the feces.

Animals↗

Membrane properties and dendritic arborization of the intermediolateral nucleus neurons in the guinea-pig thoracic spinal cord in vitro.

The morphological and electrophysiological properties of neurons in the intermediolateral nucleus (IML) were studied in the transverse and longitudinal slice of guinea-pig thoracic spinal cord (T2-T3) using intracellular staining and recording techniques. Two morophologically different types of neurons were observed: fusiform cells with craniocaudally oriented dendrites, and multipolar cells with dendrites diffusely extending in the IML. The ratio of fusiform to multipolar cells was 4:1. The fusiform cells were identified as sympathetic preganglionic neurons (SPNs) by their antidromic responses to stimulation of the ventral root exit zone, while the multipolar cells were not antidromically activated by stimulation of this site. Both cell types showed similar resting membrane potential and input resistance. The tonic responses of these neurons to hyperpolarizing current pulses were characteristically different: the SPNs had a marked hyperpolarizing sag at the break of the pulse, caused by an A current, while the unidentified neurons showed no A current. In addition, the SPNs had much longer duration of spike and afterhyperpolarization, as well as lower frequency of spontaneous or current-evoked firing, than the unidentified neurons. These observations suggest that, in the absence of the criterion of antidromic activation by stimulation of the axon, it is still possible to differentiate SPNs from other IML neurons on the basis of morphological and electrophysiological properties of the neuron.

Animals↗

The distribution of excitatory amino acid receptors on acutely dissociated dorsal horn neurons from postnatal rats.

Excitatory amino acid receptor distribution was mapped on acutely dissociated neurons from postnatal rat spinal cord dorsal horn. N-methyl D-aspartate, quisqualate and kainate were applied to multiple locations along the somal and dendritic surfaces of voltage-clamped neurons by means of a pressure application system. To partially compensate for the decrement of response amplitude due to current loss between the site of activation on the dendrite and the recording electrode at the soma, a solution containing 0.15 M KCl was applied on the cell bodies and dendrites of some cells to estimate an empirical length constant. In the majority of the cells tested, the dendritic membrane had regions of higher sensitivity to excitatory amino acid agonists than the somatic membrane, with dendritic response amplitudes reaching more than seven times those at the cell body. A comparison of the relative changes in sensitivity between each combination of two of the three excitatory amino acid agonists along the same dendrite showed different patterns of agonist sensitivity along the dendrite in the majority of the cells. These data were obtained from dorsal horn neurons that had developed and formed synaptic connections in vivo. They demonstrate that in contrast to observations made on ventral horn neurons, receptor density for all the excitatory amino acid receptors on dorsal horn neurons, including the N-methyl-D-aspartate receptor, are generally higher on the dendrites than on the soma. Further, these results are similar to those obtained from dorsal horn neurons grown in culture.

Animals↗

Blind patch-clamp recordings from substantia gelatinosa neurons in adult rat spinal cord slices: pharmacological properties of synaptic currents.

Whole cell patch-clamp recordings were made from substantia gelatinosa neurons in the thick slice of the adult rat spinal cord, which retained an attached dorsal root to study the pharmacological properties of spontaneous and primary afferent fibre-evoked synaptic currents. The majority of substantia gelatinosa neurons tested exhibited miniature excitatory postsynaptic currents in the presence of tetrodotoxin (0.5 microM). Stimulation of primary afferent A delta fibres evoked monosynaptic and/or polysynaptic excitatory postsynaptic currents. In Mg(2+)-containing solution, 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) abolished the evoked excitatory postsynaptic currents and the miniature excitatory postsynaptic currents. 2-Amino-5-phosphonovaleric acid (50-100 microM) had little effect on the miniature excitatory postsynaptic current. In Mg(2+)-free solution, however, 6-cyano-7-nitroquinoxaline-2,3-dione reduced but did not abolish the miniature excitatory postsynaptic currents, leaving the miniature excitatory postsynaptic currents with a small amplitude and a slow time course, which were abolished by 2-amino-5-phosphonovaleric acid. At holding potentials more positive than -60 mV, stimulation of A delta fibres evoked outward postsynaptic currents in 11 out of 28 substantia gelatinosa neurons. The evoked inhibitory postsynaptic currents were abolished in seven out of 11 neurons by either strychnine (0.5 microM) or bicuculline (10 microM), and in the remaining four neurons by the combination of both antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

Free peroneal and its composite flap: a distant donor for head and neck reconstruction.

Free peroneal or its composite flap from the leg has been transferred in four patients for oro-mandibular and hypopharyngeal defects following surgery for malignancy. These flaps were successfully transplanted in all patients: two cases of free peroneal flap and two of free fibular graft with skin with no resulting problems with the leg. The peroneal osteocutaneous flap offers the following advantages: The axial vessels are preferable for microvascular surgery. Two flaps can be used with two cutaneous branches. A flap measuring up to 16 x 4.5 cm can be utilized with primary closure at the donor site. A long bone can be obtained together with skin. Surgery on the neck and harvesting of the flap can be done at the same time. The donor site is not conspicuous.

Aged↗

Suppression of rat thyrotroph and thyroid cell function by tumor necrosis factor-alpha.

We studied the effect of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma) on the function of thyroid cells and pituitary thyrotrophs. In FRTL-5 rat thyroid cells, both human and murine TNF-alpha inhibited basal and TSH-stimulated [125I]iodide transport. IL-1 shared this action with TNF-alpha, but was less potent. IL-1 and IFN-gamma did not cause a further reduction of TNF-alpha-induced inhibition of [125I]iodide transport. TNF-alpha, phorbol ester 12-myristate 13-acetate (PMA), and calcium ionophore (CI) A23817 all inhibited [125I]iodide transport, but high doses of PMA and CI also blocked the inhibitory action of TNF-alpha on [125I]iodide transport. Inhibition of protein kinase A and protein kinase C by H7 or HA inhibited TSH-stimulated iodide transport, but did not block the TNF-alpha action, suggesting that the mechanism of TNF-alpha action on thyroid cells is independent of protein kinase A and C. In pituitary cells, both human and murine TNF-alpha did not affect basal TSH secretion, but TNF-alpha reduced TRH-stimulated TSH secretion. This study provides further in vitro evidence that TNF-alpha inhibits the function of the hypothalamus-pituitary-thyroid axis acting directly on both the pituitary and thyroid glands.

Animals↗

Digoxin-like immunoreactivity may contribute to hyperinsulinemia-associated hypertension in patients with glucose intolerance.

The role of endogenous digitalis-like factors in the pathogenesis of the hypertension associated with impaired glucose tolerance was investigated by measuring plasma digoxin-like immunoreactivity (DLI). Mean blood pressure correlated significantly with the obesity index, serum insulin-like immunoreactivity (IRI), and plasma DLI concentrations in subjects with impaired glucose tolerance (IGT). Plasma DLI concentrations also correlated significantly with the obesity index and serum IRI concentrations. Because increased insulin has been proposed to promote sodium reabsorption, sodium retention in turn has presumably caused an increase of natriuretic, digitalis-like factors reflected by the increased plasma DLI concentrations in patients with IGT. Consequently, increased DLI may contribute to the elevated arterial pressure in patients with hyperinsulinemia.

Adult↗

Impaired coronary flow reserve immediately after coronary angioplasty in patients with acute myocardial infarction.

OBJECTIVE: To examine coronary flow reserve immediately after emergency coronary angioplasty in patients with acute myocardial infarction. DESIGN: A 3 F coronary Doppler catheter was used to measure coronary blood flow velocity in the infarct artery and in the non-infarct artery. Maximal hyperaemia was produced by 10 mg of intracoronary papaverine and coronary flow reserve was calculated. PATIENTS: 11 patients with acute myocardial infarction undergoing both emergency coronary angioplasty (4.7 (3.6) h after the onset of chest pain (mean (SD))) and at follow up catheterisation 16 (4) days after angioplasty. SETTING: Hiroshima City Hospital. RESULTS: There was no stenosis of > or = 50% in the coronary artery of interest. Immediately after coronary angioplasty the mean (1 SD) coronary flow reserve of the infarct artery was significantly less than that of the non-infarct artery (1.4 (0.4) v 2.8 (0.8), p < 0.001). At follow up catheterisation the coronary flow reserve of the infarct artery increased almost to the value of the non-infarct artery (2.8 (1.2) v 3.1 (0.8) p = NS). CONCLUSION: The coronary flow reserve in the infarct region was severely impaired immediately after reperfusion, even with a widely patent infarct artery. This could restrict the beneficial effects of reperfusion therapy, especially when there is a severe residual stenosis.

Adult↗

Different secretion patterns of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart failure.

BACKGROUND: The plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in relation to the severity of congestive heart failure (CHF). This study was designed to examine whether the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles. METHODS AND RESULTS: We measured plasma levels of ANP and BNP in the aorta in 20 patients with mitral stenosis (MS) in whom atria are mainly overloaded, 30 patients with dilated cardiomyopathy (DCM) in whom both atria and ventricles are overloaded, and 20 control subjects during cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) was significantly higher in the MS and DCM groups (16.7 +/- 4.7 mm Hg and 15.1 +/- 7.7 mm Hg, respectively) than in the control group (7.2 +/- 1.1 mm Hg, p < 0.01), whereas there was no significant difference between the MS and DCM groups. Left ventricular end-diastolic pressure (LVEDP) was significantly higher in the DCM group than in the MS group (16.4 +/- 7.8 mm Hg versus 7.6 +/- 2.0 mm Hg, p < 0.01), and the level was comparable between the MS and control groups (7.6 +/- 2.0 mm Hg versus 6.8 +/- 1.2 mm Hg, p = NS). The plasma ANP level was significantly higher in the MS and DCM groups (356 +/- 169 pg/ml and 331 +/- 323 pg/ml, respectively) than in the control group (98 +/- 41 pg/ml, p < 0.01), whereas there was no significant difference between the MS and DCM groups. The plasma BNP level was significantly higher in the DCM group than in the MS group (333 +/- 405 pg/ml versus 147 +/- 54 pg/ml, p < 0.01), and the level was significantly higher in the MS group than in the control group (147 +/- 54 pg/ml versus < 10 pg/ml, p < 0.01). The plasma levels of ANP and BNP had a highly positive correlation with PCWP in the DCM group (p < 0.01). On the other hand, in the MS group, the plasma ANP level had a highly significant correlation with PCWP (p < 0.01) but the plasma BNP level did not. CONCLUSIONS: We conclude that plasma levels of BNP mainly reflect the degree of ventricular overload and that the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.

Adult↗

Increased plasma levels of brain natriuretic peptide in patients with acute myocardial infarction.

BACKGROUND: Brain natriuretic peptide is a novel natriuretic peptide that is secreted predominantly from the ventricles, and its plasma levels have been shown to be markedly increased in patients with chronic congestive heart failure. This study was designed to examine the plasma levels of brain natriuretic peptide as well as atrial natriuretic peptide in patients with acute myocardial infarction. METHODS AND RESULTS: We examined the plasma levels of brain natriuretic peptide as well as atrial natriuretic peptide in 50 consecutive patients (36 men and 14 women; mean age, 66 years) with acute myocardial infarction over the time course of 4 weeks. The plasma level of brain natriuretic peptide was significantly increased on admission in patients with acute myocardial infarction compared with controls (92 +/- 28 versus 5.2 +/- 0.5 pg/mL, P < .01) and reached the peak level of 319 +/- 58 pg/mL at 16.4 +/- 0.7 hours after admission. Thereafter, the level decreased and then again increased, forming the second peak of 277 +/- 66 pg/mL on day 5. The level then decreased gradually but was still much higher in the fourth week than that of controls (149 +/- 47 versus 5.2 +/- 0.5 pg/mL, P < .001). On the other hand, the plasma atrial natriuretic peptide level already had been increased at the time of admission compared with controls (116 +/- 14 versus 39.5 +/- 2.6 pg/mL, P < .01) and decreased thereafter, again increasing and making a small peak on day 2 to 3. The time course of the plasma brain natriuretic peptide level could be divided into two patterns: a monophasic pattern with one peak at about 16 hours after admission and a biphasic pattern with two peaks at about 16 hours and 5 days after admission. There were significantly more patients with anterior infarction, congestive heart failure, higher level of maximal creatine kinase-MB isoenzyme, and lower left ventricular ejection fraction in the biphasic group than in the monophasic group. CONCLUSIONS: We conclude that the plasma level of brain natriuretic peptide is increased markedly in patients with acute myocardial infarction and may reflect the degree of left ventricular dysfunction in these patients.

Aged↗

Estimation of sulphoconjugated catecholamine concentrations in plasma by high-performance liquid chromatography.

Free and sulphoconjugated catecholamine (CA) concentrations were measured in plasma using a fully automated and sensitive analyser equipped with a three-column system of high-performance liquid chromatography (HPLC). Although the free dopamine (DA) concentration has been below the detection limit of HPLC analysers thus far available, this new CA analyser can measure as little as 0.03 nmol/L. For the estimation of sulphoconjugated CA, we performed enzymatic deconjugation with arylsulphatase prior to HPLC analysis. The difference between free and total concentrations represents that of sulphoconjugated CA. The intraassay coefficient variation was less than 2.2% for free noradrenaline (NA) and adrenaline (A), 12.62% for free DA, and less than 4.3% for total A, and DA. These assays of free and sulphoconjugated CA are simple and can be performed routinely by a suitably equipped laboratory.

Adult↗

Activation of the thyrotropin (TSH) receptor by human chorionic gonadotropin and luteinizing hormone in Chinese hamster ovary cells expressing functional human TSH receptors.

It is well known that peptide heterogeneity exists in the hCG-beta subunit in pregnancy and in patients with trophoblastic diseases. To elucidate the differences in thyrotropic activity of hCG molecules, we examined cAMP accumulation and TSH receptor binding of intact hCG, hLH, and a recombinant hCG that lacked the C-terminal extension on the beta-subunit, hCG (alpha wt/beta delta T), using Chinese hamster ovary (CHO) cells transfected with hTSH receptors. hLH, which shares 85% sequence identity with the hCG-beta molecule except for the C-terminal amino acid residue extension of the hCG-beta subunit, bound to the TSH receptor and stimulated adenylate cyclase about 10 times more potently than hCG on a molar basis. This was consistent with the result that cAMP stimulation by mutant hCG (alpha wt/beta delta T) was greater than intact hCG. hLH also increased iodide uptake and thymidine incorporation in FRTL-5 rat thyroid cells more potently than intact hCG. These results demonstrate that hLH is a more potent TSH than hCG and that the C-terminal extension of the hCG beta-subunit can interfere with hCG interaction with the hTSH receptor. hCG lacking the C-terminal extension of the beta-subunit occurs in the mixture of heterogeneous hCG molecular forms of pregnancy and trophoblastic diseases and may contribute to the hyperthyroidism in patients with hydatidiform mole, choriocarcinoma, and hyperemesis gravidarum.

Analysis of Variance↗

Measurement of erythrocyte Na,K-ATPase activity in normal pregnant women.

To investigate the peripheral metabolic status during normal pregnancy, we measured the number of erythrocyte Na,K-ATPase units as well as the cation transport activity of the pump from 32 normal pregnant women and 12 normal controls. The number of pump units determined by maximal ouabain binding to erythrocyte in normal pregnancy was significantly higher than that in normal controls (mean +/- SEM: 0.52 +/- 0.03 vs. 0.39 +/- 0.04 pmol/10(9)RBC, P < 0.05). The total cation transport activity of the pump measured by 86Rb uptake also significantly increased during pregnancy (98.9 +/- 6.4 vs. 73.1 +/- 5.4 nmol/10(9) RBC, P < 0.01). However, the mean cation transport activity per pump unit, which was presumed to be an indicator of the peripheral metabolic status, was unchanged in any of three trimesters when compared with that in normal controls. Serum FT4 levels measured by two different methods were significantly lower in the third trimester than in the first trimester (P < 0.01). In conclusion, erythrocyte Na, K-ATPase activity per pump unit is normal in pregnant women, suggesting that the peripheral metabolic status in pregnancy seems to be normal. Increases in both the number and function of the pump may be influenced by factors other than thyroid function.

Adult↗

Correlation of orbital muscle changes evaluated by magnetic resonance imaging and thyroid-stimulating antibody in patients with Graves' ophthalmopathy.

To evaluate the relationship between eye changes and autoantibody to the thyrotropin receptor in patients with Graves' disease, we evaluated the eye changes using magnetic resonance imaging and the results were correlated with thyroid-stimulating antibody, thyrotropin binding inhibitor immunoglobulin and thyroid growth activity. Subjects were 15 patients with Graves' disease who had Graves' ophthalmopathy, including exophthalmos and other signs and symptoms, and nine patients without ophthalmopathy; all were maintained in a euthyroid state by antithyroid drugs. The thyrotropin-binding inhibitor immunoglobulin was measured by a kit, and thyroid-stimulating antibody and thyroid growth activity were evaluated by cyclic adenosine 3',5'-monophosphate production and [3H]thymidine incorporation, respectively, by cultured functional rat thyroid lined cells. The sum of the swelling ratios (muscle thickness to the diameter of the optic nerve) of the four extraocular muscles correlated well with the degree of exophthalmos. The thyrotropin-binding inhibitor immunoglobulin was positive in nine out of 15 patients with ophthalmopathy; however, no correlation was observed between the activity and exophthalmos or muscle swelling. No significant correlation was observed between muscle changes and thyroid growth activity either. On the other hand, thyroid-stimulating antibody (642 +/- 91%) in Graves' patients with ophthalmopathy was significantly (p < 0.02) higher than that (315 +/- 84%) in patients without ophthalmopathy. Moreover, the level of stimulating activity in Graves' patients with ophthalmopathy showed a significant (p < 0.02) positive correlation with the sum of the swelling ratios of the individual eight eye muscles. These results suggest that thyroid-stimulating antibody has a close relation to Graves' ophthalmopathy.

Adolescent↗