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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 595 records · Page 33Linked to original sources

Membrane properties of rat substantia gelatinosa neurons in vitro.

1. The membrane properties of substantia gelatinosa (SG) neurons in an in vitro adult rat transverse spinal cord slice preparation with attached dorsal root have been examined. Intracellular recordings were obtained from identified SG neurons. 2. Seventy-six percent of SG neurons exhibited a time-dependent anomalous rectification (AR) when the membrane was hyperpolarized from the resting potential. The time-dependent AR was blocked by cesium (Cs+, 2 mM) but not by barium (Ba2+, 2 mM). Application of Cs+ itself caused membrane hyperpolarization in those SG neurons that expressed the time-dependent AR. The activation of the time-dependent AR was maximal at potentials 5-10 mV below the resting membrane potential. 3. In a few SG neurons, the current-voltage relationship revealed a marked inward rectification, even though there was no detectable time-dependent anomalous rectification during hyperpolarization. Analysis of the Ba2+- and Cs+-sensitivity of these neurons confirmed that SG neurons expressed two distinct ARs, one of which is fast and Ba2+-sensitive and the other of which is time-dependent and Ba2+-insensitive. 4. Fifty-one percent of SG neurons exhibited a transient outward rectification when hyperpolarizing current pulses were applied from potentials more positive than -60 mV or when depolarizing pulses were applied from potentials more negative than -65 mV. The transient outward rectification persisted for 0.3-2 s when hyperpolarizing pulses were applied at -55 mV. 5. The transient outward rectification was associated with a decrease in membrane resistance and was enhanced in low K+ solutions. 4-aminopyridine (4-AP, 2 mM) reversibly blocked the transient outward rectification. 6. The time-dependent anomalous and transient outward rectifying currents exerted opposite effects on the firing properties of SG neurons. Activation of the time-dependent AR increased neuronal excitability. In neurons that exhibited the time-dependent AR, membrane depolarization caused the appearance of a rebound depolarization that resulted in the generation of spikes with only a short delay after application of the depolarizing pulse. In contrast, the transient outward rectifying current markedly delayed spike firing in response to depolarizing pulses. This delay was blocked by application of 4-AP. 7. The diversity in response properties of subpopulations of SG neurons may result in part from this heterogeneity in membrane properties.

Animals↗

Primary afferent-evoked synaptic responses and slow potential generation in rat substantia gelatinosa neurons in vitro.

1. Primary afferent fiber-evoked synaptic responses and the mechanisms of spike and slow potential generation have been examined in adult rat substantia gelatinosa (SG) neurons in an in vitro transverse spinal cord slice preparation in which an attached dorsal root is retained. Intracellular recordings were made from SG neurons identified by morphological and electrophysiological criteria. Afferent fiber-evoked fast excitatory postsynaptic potentials (fast EPSPs) and slow EPSPs have been analyzed. 2. SG neurons had mean resting membrane potentials of -67.1 +/- 0.5 mV (mean +/- SE), mean input resistance of 257 +/- 17.7 (SE) M omega, and a mean time constant of 21.3 +/- 1.9 ms and exhibited spontaneous EPSPs. 3. Single low-intensity stimuli applied to the dorsal root using a suction electrode produced, in 70% of SG neurons, short-latency, presumed monosynaptic fast EPSPs which had a half decay time of 10-30 ms and an amplitude of 8-28 mV. The conduction velocity of afferent fibers evoking fast EPSPs was 2-7 m/s, corresponding to that of thinly myelinated A-delta-fibers. Dorsal root stimulation at higher intensities evoked, in 10% of SG neurons, long-latency and apparently monosynaptic EPSPs which had a time course and amplitude similar to that evoked by low-intensity stimulation. The conduction velocity of fibers evoking long-latency EPSPs was 0.4-2 m/s, suggesting that they constitute predominantly C-fibers. A-delta- and C-fiber-mediated fast EPSPs were detected in 20% of SG neurons examined. 4. Low-intensity stimuli produced slow EPSPs in 20% of SG neurons. Slow EPSPs were 3-15 mV in amplitude and of up to 2 min in duration. A-delta-fibers appeared to be responsible for the generation of slow EPSPs. Slow EPSPs were associated with an increase in membrane resistance and were decreased in amplitude with membrane hyperpolarization. 5. Action potentials in SG neurons had a mean amplitude of 76.3 +/- 1.1 mV and a mean duration of 1.0 +/- 0.07 ms. Na+ ions represent the main charge carrier during the rising phase of the action potential and Ca2+ ions contribute to the shoulder on the falling phase. 6. In 20% of SG neurons, subthreshold depolarizing pulses were followed by long-lasting slow-inactivating depolarizing potentials which were able to initiate spikes. The slow depolarizing potentials were blocked by TTX and enhanced by application of TEA and Ba2+, suggesting that Na+ and K+ are involved in this slow-inactivating potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Plasminogen phenotypes in a Japanese population. Four new variants including one with a functional defect.

Human plasminogen (PLG) phenotypes were investigated by polyacrylamide gel isoelectric focusing followed by immunoblotting. In 5,735 plasma samples from unrelated, healthy Japanese individuals, four new variants were detected and tentatively designated PLG AOsaka, PLG BOsaka, PLG MOsaka and PLG ANara. The plasminogen concentrations and activities of the PLG phenotypes were studied. In agreement with previous studies PLG M5 was found to have a decreased activity. The new variant PLG MOsaka had a very low activity and appears to be an abnormal plasminogen with a functional defect similar to that of PLG M5.

Gene Frequency↗

Thyroid-stimulating activity in sera of normal pregnant women.

To evaluate the effect of a thyroid stimulator on thyroid function in the sera of normal pregnant women, we measured thyroid-stimulating activity (TSA) using a highly sensitive bioassay based on cAMP accumulation in cultured rat FRTL-5 thyroid cells. Serum was pretreated with 10% polyethylene glycol (PEG), and the supernatant (PEG-pretreated serum) was then used in the following studies. FRTL-5 cells were preincubated in 5H medium and incubated for 2 h with PEG pretreated serum, and cAMP was measured. All 11 patients with untreated hyperthyroid Graves' disease with strongly positive thyroid-stimulating antibody activity had normal TSA, because only 5.6% of their immunoglobulin G was recovered in the PEG-pretreated serum. In 32 normal pregnant women, 29 (91%) had positive TSA. Their TSA showed statistically significant positive correlations with serum hCG and free T4 levels, and a negative correlation with serum TSH levels. Moreover, when hCG was absorbed from sera by incubation with the solid phase anti-HCG monoclonal antibody, a significant positive correlation was observed between the rate of decrease in hCG and that in TSA. In conclusion, 1) TSA exists in the sera of normal pregnant women, which reflects hCG itself; and 2) thyroid glands of normal pregnant women may be stimulated by TSA to induce a slight suppression of TSH but not sufficient to induce overt hyperthyroidism.

Adult↗

Induction of repressible acid phosphatase by unsaturated fatty acid in Saccharomyces cerevisiae.

We studied the induction of acid phosphatase (APase) by fatty acids in Saccharomyces cerevisiae. S. cerevisiae has two types of APase: constitutive and repressible enzymes. The synthesis of the latter APase is normally derepressed by depletion of inorganic phosphate (Pi) in the incubation medium. Of the saturated and unsaturated fatty acids tested, linoleic, linolenic and arachidonic acids induced the synthesis of APase even in the presence of a high concentration of Pi, whereas palmitic, stearic and oleic acids did not. De novo protein synthesis but not stimulation of secretion of the enzyme was required for the induction. Genetic analyses using plasmids carrying the genes, PHO5 and PHO3, that code for repressible APase and constitutive APase, respectively, showed that linolenic acid induced the formation of repressible APase. Linolenic acid inhibited the uptake of exogenous 32Pi and simultaneously lowered the intracellular level of Pi. These circumstances indicate that linolenic acid-induced derepression of repressible APase is primarily caused by a fall in the intracellular level of Pi. However, cells that had been preincubated in the presence of a high concentration of Pi produced APase shortly after the addition of linolenic acid. It is, therefore, suggested that, as well as a normal regulatory mechanism for derepression of repressible APase, a mechanism independent of the external level of Pi participates in the induction of repressible APase by linolenic acid.

Acid Phosphatase↗

Treatment of chronic osteomyelitis of the leg by peroneal myocutaneous island flap transfer.

We treated 11 patients with chronic osteomyelitis of the tibia or the foot by local excision and transfer of a peroneal myocutaneous island flap. This flap, pedicled proximally or distally on the peroneal artery and veins, provides viable muscle to fill the dead space in bone and skin to close the defect. Ten patients reviewed more than three years after operation were all free of drainage with no clinical or radiographic evidence of recurrence.

Adult↗

Decreased expression of hepatic epidermal growth factor receptor gene in diabetic mice.

The expression of hepatic epidermal growth factor (EGF) receptor gene was studied in genetically diabetic (C57BL/KsJ db/db) mice and streptozotocin-induced diabetic mice. The binding of 125I-labelled EGF to hepatic membrane preparations of genetically diabetic mice was only 35% of that of non-diabetic mice. Levels of EGF receptor messenger RNAs (10 and 6 kb) in the liver of the diabetic animals were also reduced by about 75%. In streptozotocin-induced diabetic mice, levels of hepatic EGF binding and messenger RNAs for EGF receptor were decreased to 27 and 30% of control levels respectively, at 5 weeks after injection of the drug. There were, however, no significant differences in levels of messenger RNAs for the structural protein beta-actin in the liver. In addition, levels of EGF receptor messenger RNAs in the kidney were similar between control and the two kinds of diabetic mice. Daily administration of insulin to the streptozotocin-induced diabetic mice increased the hepatic levels of EGF receptor messenger RNAs to almost normal levels. These results indicate that EGF binding to its receptor decreases in the liver of diabetic mice, involving alterations in the level of EGF receptor messenger RNAs, and that insulin is important for the regulation of EGF receptor gene expression in the liver but not in the kidney.

Actins↗

The regulation by thyroid hormones and androgen of epidermal growth factor synthesis in the submandibular gland and its plasma concentrations in mice.

The effects of androgen and thyroid hormones on epidermal growth factor (EGF) synthesis in the submandibular gland and on plasma EGF concentrations in mice were examined. Testosterone propionate was administered alone or in combination with L-thyroxine (T4) to female mice for 2 weeks. The submandibular EGF concentrations were increased by the administration of testosterone propionate in a dose-dependent fashion; the maximal increase, 20-fold, being produced by a dose of 2 mg every other day. The EGF levels were increased sevenfold by T4, which also enhanced the stimulatory effect of suboptimal doses of testosterone propionate. Cyproterone acetate, an anti-androgen, inhibited the testosterone propionate-induced increase, but not the T4-induced increase. Plasma EGF concentrations were raised by testosterone propionate but not by T4. Both hormones stimulated the accumulation of 4.7 kb preproEGF mRNA in the submandibular gland, which occurred almost in a parallel manner with the increase in submandibular EGF concentrations. These results suggest that EGF synthesis in the submandibular gland is regulated by alterations in the level of its mRNA by thyroid hormones and androgen, and that the rise in plasma EGF concentrations is under the influence of androgen but not of thyroid hormones.

Animals↗

Interaction of noradrenaline and dopamine in patients with essential hypertension or with pheochromocytoma.

To analyse the interaction of noradrenaline (NA) and dopamine (DA) release, the present study compared urinary outputs of total NA and DA as well as plasma levels of total NA and DA in normotensive (NT) subjects, in patients with essential hypertension (EHT) and in a patient with pheochromocytoma. Significant correlations between total NA and DA in urine were observed in NT subjects, in patients with EHT and in a patient with pheochromocytoma. A significant correlation was observed in plasma total NA and DA of blood collected from several veins except for the tumor vein, by indwelling catheter, in a patient with pheochromocytoma. These results suggest that DA is released from sympathetic nerve terminals in response to an augmented release of NA.

Adrenal Gland Neoplasms↗

Identification and characterization of an avian reovirus isolated from black-tailed gull (Larus crassirostris).

An isolated virus from the feces of nestlings of Black-tailed gulls living on the Kabu-Island, Hachinohe-city, Aomori-prefecture, was identified as an avian reovirus from its morphological, physicochemical and biological features. Serologically, the isolate has a 62% of relatedness to TS-17 strain, a prototype of avian reovirus in Japan. The isolate showed no significant virulences to one-day-old SPF chickens, and showed low mortalities to chicken embryos, although it formed remarkable lesion onto chorioallantoic membrane.

Animals↗

[A case of primary pulmonary hypertension with beneficial effect of oral long-acting prostaglandin E1 and nifedipine].

A 23-year-old female with moderate primary pulmonary hypertension (PPH) was treated by chronic oral administration of long-acting prostaglandin-E1 (PGE1) and nifedipine. Cardiac catheterization revealed evidence that both drugs had beneficial effects on this case. Total pulmonary resistance (TSR) decreased from 1089 to 955 dyne.sec.cm-5 by intravenous administration of PGE1 at a rate of 0.04 micrograms/kg/min and from 1089 to 710 dyne-sec-cm-5 by sublingual administration of nifedipine 10 mg respectively. After ten months of treatment with these two drugs, her pulmonary arterial pressure decreased from 85/40 (mean; 58) mmHg to 55/36 (mean; 45) mmHg, TSR decreased from 1089 to 829 dyne.sec.cm-5 and PaO2 in room air increased from 74.5 to 94.9 mmHg. Chest X-P and ECG revealed the decrease in the loading of the right ventricle. Thus, combined administration of PGE1 and nifedipine is expected to benefit PPH.

Administration, Oral↗

[Anatomical and clinical studies on peroneal vascularized composite tissue transfer].

An anatomical study of the peroneal artery and vein and their branches was carried out on 86 cadaver legs. The number of cutaneous branches was 4.8 +/- 1.4 per leg. The length of the cutaneous branches was 5.5 +/- 1.6 cm. The external diameters of cutaneous branches at the skin distribution site were 0.6 +/- 0.2 mm for the artery and 0.8 +/- 0.3mm for the vein. The peroneal vessels gave off communicating branches to anterior or posterior tibial vessels 6.1 +/- 2.4 cm proximal from the lateral malleolus. The range of rotation of 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 distal from the lateral malleolus. Based on the results obtained from these experimental studies, we have been performing peroneal vascularized tissue transfer since 1982. A total of 72 cases have been performed, and the results have been encouraging.

Adolescent↗

[Aberrant expression of major histocompatibility complex class II. (HLA-DR/DQ) antigens and proliferative nuclear antigen. (Ki-67) in renal tubular epithelial cells].

In an attempt to clarify the participations of cellular immunity in the development of tubulo-interstitial lesions, aberrant expressions of major histocompatibility complex (MHC) class II antigens and Ki-67 nuclear antigen on the renal tubular epithelial cells were studied. Ki-67 antigen was known to appear in all phases of cell cycle except for Go. Nine normal kidney specimens (4 males and 5 females) and 117 kidney specimens obtained from patients with kidney diseases (54 males and 63 females) were examined with the indirect immunofluorescence technique using murine monoclonal antibodies against HLA-DR (lal), HLA-DQ (Leu10) and Ki-67 nuclear antigen. Patients included 100 with glomerular diseases, and 16 with tubulo-interstitial diseases consisting of 4 acute tubular necrosis (ATN), 7 acute tubulo-interstitial nephritis (AIN), one renal allograft rejection and 4 sarcoidosis. In normal kidney, HLA-DR was solely noted in only two specimens (22.2%) at the basal portion of proximal tubular epithelial cells. In tubulo-interstitial diseases 11 (68.8%) out of 16 patients showed diffuse and intense expressions of HLA-DR concomitant with HLA-DQ in 6 of 13 (42.9%), and 11 of 13 (84.6%) were positive for Ki-67 nuclear antigen. Especially, in AIN and allograft rejection, intense expression of HLA-DR, DQ and Ki-67 nuclear antigen were observed in 100%, 86%, 100%, respectively. In ATN 3(75%) were positive for HLA-DR and Ki-67, but not for HLA-DQ. In contrast, only 12(15.6%). 2(2.6%) and 2(4.8%) of primary glomerular disease were weakly positive for HLA-DR, DQ and Ki-67 nuclear antigen, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparison of nisoldipine and atenolol in the treatment of essential hypertension.

The antihypertensive effects of nisoldipine, a calcium channel blocker, and atenolol, a beta-adrenergic blocker, were compared in patients with mild or moderate essential hypertension. Both drugs produced significant reductions in blood pressure from the 8th week through the end of the 12-week treatment period. The hear rate decreased significantly in the atenolol group but not in the nisoldipine group. Following oral administration of 50 mg of captopril, the rise in plasma renin activity was significantly smaller in both treatment groups than in normotensive controls. The magnitude of the pressor response during a hand-grip test tended to be smaller in both groups of patients than in the controls, with no significant difference between the treated groups. Although the plasma catecholamine concentration rose significantly in the control and nisoldipine groups, there were no significant intergroup differences in these parameters. The hemoglobin, GOT, creatinine, total cholesterol and serum sodium and potassium concentrations all decreased significantly in the nisoldipine group, although the values remained within normal limits. These results indicate that both nisoldipine and atenolol significantly suppress both plasma renin activity and the pressor response to stress leading to reduction of blood pressure.

Adult↗

[Endothelin and endogenous digitalis-like substance in cardiovascular regulation: a review].

Recent findings on endothelin, an endothelium-derived vasoconstrictor substance and endogenous digitalislike Na+, K+-ATPase inhibitor (s) obtained from animal and clinical experiments are reviewed. Endothelin is one of the most potent vasoconstrictive substances ever found; the pressor responses last for more than one hour after the bolus injection in rats. Because the pressor responses have not been attenuated by any known receptor-antagonists, the vasoconstriction is mediated by the endothelin receptors. Since messenger RNA for endothelin increases with thrombin, it may be involved in the damages of blood vessels. Radioimmunoassay for endothelin revealed that immunoreactive endothelin is increased in plasma of patients with chronic renal failure. Therefore, the plasma level of endothelin can be an index for some circulatory disorders. Since the Na+, K+-ATPase inhibitor cross-reacts with antidigoxin and antiouabain antibody, it is called a digitalis-like substance. We have demonstrated that cells containing the immunoreactive-substance to antidigoxin and antiouabain antibodies are restricted in the paraventricular and supraoptic nucleus of the hypothalamus, and that the plasma digoxinlike immunoreactivity increases with intracerebroventricular and intravenous infusions of hypertonic saline in rats. Because plasma concentrations of the immunoreactive substance significantly correlate with blood pressure, the substance seems to be involved in hypertension associated with excess intake of sodium salt.

Animals↗

Hypoxia in brain slices.

The effects of hypoxia on hippocampal CA1 neurones in tissue slices of the rat brain were studied in vitro by intracellular recording. In response to superfusion of a hypoxic medium equilibrated with 95%N2-5% CO2, a majority of the neurones showed a transient depolarization followed by a hyperpolarization of 5-15 mV in amplitude and 4-12 min in duration. The hyperpolarization was, in turn, followed by a slow depolarization which within 20 min of hypoxic exposure reached a plateau level of about 25 mV above the prehypoxic resting potential. Both the initial hyperpolarization and subsequent depolarization were associated with a reduction in membrane resistance. The hyperpolarization reversed in polarity at a membrane potential of -83 mV. There was an almost linear relationship between amplitude of the hyperpolarization and membrane potential. The hyperpolarization was markedly enhanced in potassium-free media and was depressed in high-potassium solution. Superfusion of ouabain (5-7 microM)-containing medium in normoxic conditions produced hyperpolarizing and depolarizing responses similar to those elicited by hypoxic exposure. The slow depolarization was also mimicked by elevation of the extracellular potassium concentration to 10-20 mM. Evoked i.p.s.p.s were abolished within 4 min of hypoxic exposure while evoked e.p.s. p.s were maintained for about 20 min of hypoxic superfusion. Soma spikes of the neurones elicited by a depolarizing pulse were also well preserved. Their threshold was, however, raised, concomitant with a decrease in the peak amplitude. In a minority of the neurones the slow depolarization was suddenly followed by a rapid depolarization, after which the neurones showed no functional recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗