Biomedical subjects
Publications and source records attributed to M Yoshimura.
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1. The type of endothelin (ET) receptor located on the myenteric neurones of guinea-pig ileum was determined by receptor autoradiography and function of the receptor was examined by release experiments of acetylcholine (ACh) from the longitudinal muscle myenteric plexus (LM-MP) preparations. 2. Specific [125I]-ET-1 binding sites were distributed in muscle layers, myenteric and submucous plexuses, and mucosa layers. High-grain densities were detected in both myenteric and submucous plexuses. 3. Binding in the myenteric plexus was abolished by incubation with either IRL 1620 (endothelin ETB receptor agonist) or BQ 788 (endothelin ETB receptor antagonist), but not with BQ 123 (endothelin ETA receptor antagonist). The [125I]-IRL 1620 binding sites were evident in the myenteric plexus. Thus, the endothelin receptor located on the myenteric neurones is of the ETB type. 4. ET-1 (10(-10)-3 x 10(-8) M) and ET-3 (10(-10)-3 x 10(-8) M) evoked 3H outflow from LM-MP preparations of ileum preloaded with [3H]-choline, in a concentration-dependent manner. There was no significant difference between maximum amounts of ET-1-evoked and ET-3-evoked 3H outflow. 5. ET-1 and ET-3 evoked outflow of 3H was BQ 788-sensitive, but BQ 123-insensitive. Both evoked outflows of 3H were Ca(2+)-dependent and tetrodotoxin-sensitive. 6. These results indicate that the endothelin ETB receptor is located on the enteric cholinergic neurones and that stimulation evokes the release of ACh.
The regional cerebral blood flow (rBCF) values measured by stable xenon-enhanced computed tomography (Xe XT) and by radioactive xenon-133 single photon emission computed tomography (Xe SPECT) were compared in 16 patients with cerebral infarct. On the non-lesion side Xe SPECT recorded 10.7% higher rCBF values than Xe CT in the anterior cerebral artery territory, while Xe CT recorded 9.6% higher values than Xe SPECT in the middle cerebral artery territory. These differences were not statistically significant. Although the rCBF values were almost the same, no correlation was found between the two methods in the posterior cerebral artery territory and the basal ganglia. Only hemispheric CBF on the non-lesion side showed the same value and a good correlation between the Xe CT and the Xe SPECT. There was a good correlation in the hemispheric CBF values on the lesion side, too. The difference of rCBF between the non-lesion side and the lesion side was expressed smaller in the Xe SPECT than in the Xe CT. This is in agreement with the previous reports that Xe SPECT overestimates the flow in the low flow areas. The higher rCBF values in the anterior cerebral artery territory measured by the Xe SPECT was ascribed to the artifact from the radioactivities in the inhalation mask and the air passages as reported previously. In conclusion, there is no good correlation between the rCBF values measured by the Xe CT and by the Xe SPECT. Only hemispheric CBF shows a good correlation between the two methods.
Effects of acetylcholine (ACh) on L-type Ca2+ current (ICa) were examined in isolated atrioventricular (AV) node cells exhibiting spontaneous contractions and pacemaker current (If). ACh at a saturating concentration of 10 microM reduced basal ICa by 48 +/- 6%. The ACh effect was abolished by dialysis with 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase inhibitor, or guanosine-5'-O-(2-thiodiphosphate). Dialysis with guanosine 3',5'-cyclic monophosphate (cGMP) or NG-monomethyl-L-arginine (L-NMMA) and application of the cGMP-dependent protein kinase inhibitor KT-5823 (1 microM) did not affect ACh inhibition of ICa. Nitric oxide donor 3-morpholinosydnonimine (100 microM) and type III phosphodiesterase (PDE) inhibitor trequinsin (10 nM) enhanced basal ICa by 10-20%, whereas type IV PDE inhibitor Ro-20-1724 (30 microM) together with trequinsin caused a large ICa stimulation comparable to that by 3-isobutyl-1-methylxanthine (IBMX). These findings indicate that ACh inhibits basal ICa primarily by suppressing cAMP synthesis and that these cells have a potent type III and IV PDE activity to determine the basal cAMP concentration. When ICa was stimulated by IBMX (100 microM), the inhibitory effect of ACh was slightly reduced by L-NMMA, cGMP, and methylene blue but not by KT-5823 or Ro-20-1724. ACh hardly inhibited, or even enhanced, IBMX-stimulated Ica when forskolin (3 microM) was coapplied or the IBMX concentration was increased to 500 microM. These findings suggest that cAMP is degraded in the presence of 100 microM IBMX to some extent. Type II PDE, for which IBMX has a relatively high inhibitor constant, seems to contribute partially to the cAMP degradation.
Here we report on the presence of proliferating cell nuclear antigen (PCNA) in human leptomeninges from 35 normal subjects with ages ranging from 57 to 94 years. Strong immunoreactivity with PC10 (a monoclonal antibody to PCNA) was detected in the nuclei of meningothelial cells, smooth muscle cells of leptomeningeal vessels, and ependymal cells. An immunoblot of leptomeningeal homogenate with PC10 showed the presence of a single band at 35 KD, the expected molecular mass of PCNA. Ki-67, another marker for cell proliferation, was undetectable in human leptomeninges. These observations point to isolated PCNA expression in tissue in which cells are not actively proliferating.
To investigate the possible humoral factor(s) influencing thyroid cell activity in chronic renal failure, we measured serum activity which stimulates or inhibits the [3H]thymidine incorporation by using a cultured functioning rat thyroid cell line (FRTL-5 cells) in 17 patients on hemodialysis and 19 healthy controls. Polyethylene glycol-treated serum was centrifuged and FRTL-5 cells were cultured with the supernatant. Thyroid stimulating activity was determined by [3H]thymidine incorporation after incubation for 72 h. There was no significant difference in [3H]thymidine incorporation between cultures incubated with patient and normal serum, suggesting the absence of the stimulating activity. But when patient serum was added to cultures together with 20 or 50 microU/ml of TSH, the TSH-stimulated increase in [3H]thymidine incorporation was significantly decreased, indicating the presence of thyroid inhibiting activity, which possibly inhibits the thyroid cell growth. This activity was not significantly altered by hemodialysis. No significant correlation was observed between this activity and serum levels of thyroid hormones or the iodine concentration. Patients on hemodialysis therefore have serum thyroid inhibiting activity which is nondialysable, differs from iodine, and could influence the thyroid cell growth.
Plasma free T4 (FT4) concentrations could be increased during hemodialysis in patients with chronic renal failure (CRF) because an increase in non-esterified fatty acids (NEFA) could interfere with the binding of T4 to thyroxine-binding globulin. To evaluate the effect of hemodialysis on the FT4 concentration in patients with CRF, we measured the FT4 in 39 patients with CRF by four assay methods including equilibrium dialysis, the 125I-T4 analog method and enzyme immunoassay. The addition of the fatty acid sodium oleate to normal pooled sera led to a marked increase in FT4 as measured by equilibrium dialysis (Model FT4). A moderate increase in the serum FT4 concentration also was observed with an IMX enzyme immunoassay kit, whereas the Coat-A-Count analog method demonstrated no interference by sodium oleate. The mean serum FT4 prior to hemodialysis measured by equilibrium dialysis did not differ significantly from that in the normal control, although those measured by analog methods (Coat-A-Count and Amerlex) and IMX were subnormal. The FT4 by IMX were albumin-dependent, and the values decreased as the samples were serially diluted, but Model FT4 was not affected by the albumin level or the serial dilution. FT4 by Model FT4 showed a marked increase beginning 10 min after the start of dialysis, and it correlated well with the plasma concentration of NEFA and the NEFA/albumin molar ratio. The other three assay methods, including one which is not affected by NEFA, did not show a change in FT4 at 10 min, but a significant increase of 11 to 17% was observed by the end of dialysis. The TSH concentration decreased significantly during hemodialysis. These data suggest that (1) the low serum FT4 in hemodialysis patients measured by some immunoassay methods may be an underestimation due to the low albumin level; (2) FT4 actually increases during hemodialysis due to the actual increase in NEFA, although the marked increase in FT4 during hemodialysis as measured by equilibrium dialysis is an overestimation due to the in vitro generation of NEFA; and (3) one should beware of aberrations in thyroid hormone parameters during hemodialysis and potential complications.
Streptococcus pneumoniae is a major pathogenic organism of community-acquired bacterial pneumonia as well as otitis media and bacterial meningitis. Recently penicillin- or multiply resistant pneumococci have been isolated worldwide. In this study we examined the susceptibility tests of 11 antibiotics with the total of 63 clinically isolated pneumococci, using a broth microdilution method. Most of pneumococci were isolated from respiratory specimens. According to NCCLS standard, all these pneumococci were classified as follows: PCG-susceptible S. pneumoniae (PSSP, MIC < or = 0.06 micrograms/ml), PCG-intermediately resistant S. pneumoniae (PISP, 0.12 < or = MIC < or = 1.0 micrograms/ml), and PCG-highly resistant S. pneumoniae (PRSP, MIC > or = 2.0 micrograms/ml) were 45 (71.4%), 14 (22.2%) and 4 isolates (6.4%), respectively. Forty-four percent of isolates from children under 10 years and 29% from outpatients were PISP or PRSP. Resistance to erythromycin (EM) clindamycin (CLDM) or minocycline (MINO) was significantly recognized, but not correlated with that to PCG. On the other hand, the resistance to beta-lactam antibiotics were correlated with that to PCG. Seventeen isolates (27%) were resistant to two or more antibiotics among PCG, EM, MINO, ofloxacin (OFLX), and sulfamethoxazole-trimethoprim (ST). In pneumococcal infection, we always have to pay a careful attention to susceptibility test before we choose antibiotics.
Urinary free dopamine (DA) is derived from DA synthesized or converted from circulating DOPA in renal proximal tubules, and plays an important role for diuresis and natriuresis. As plasma free DA is in tiny amounts near detectable range, a large amount of free DA in urine is tubular origin, but not from circulating DA. In the present study, we hypothesized that urinary free dopamine (U-f-DA) can be used as the marker of renal function. We speculated that U-f-DA may decrease in the damage of renal tubules or renal disorder. To evaluate clinical significance of U-f-DA, we used serum creatinine levels as the index of renal function. As the urinary parameter of renal function, we measured U-f-DA, alpha(1)-microglobulin (U-alpha(1) MG), beta(2)-microglobulin (U-beta(2)MG) and N-acetyl-beta-D-glucosaminidase (U-NAG) in spot urine samples of 154 outpatients (male; 76, female; 78). Each values are rectified by creatinine (Cr) concentration in urine. U-f-DA was negatively correlated with the serum level of creatinine, U-alpha(1)MG and U-beta(2)MG. The receiver operating characteristic (ROC) curve analysis was used for their comparison in evaluation of urinary marker of renal function. In this analysis, area under the curve (AUC) of U-f-DA is best among other markers of renal function. AUC of U-f-DA/Cr, U-alpha(1)MG/Cr, U-beta(2)MG/Cr, U-NAG/Cr were 0.82, 0.57, 0.72, 0.62 in male, 0.92, 0.72, 0.81, 0.57 in female, respectively. These results suggest that the measurement of U-f-DA is superior marker of renal function to the determination of U-alpha(1)MG, U-beta(2)MG and U-NAG.
The introduction of D1A dopamine receptors and mu-opioid receptors into HEK 293 cells that were also transiently transfected with adenylyl cyclase cDNA imparted to dopamine and to mu-opioid receptor agonists the ability to modulate the activity of the expressed adenylyl cyclase. Dopamine added to cells expressing D1A receptors and type V adenylyl cyclase significantly stimulated type V enzyme activity. The concomitant addition of morphine produced a dose-dependent inhibition of dopamine-stimulated type V adenylyl cyclase activity. On the other hand, if the HEK 293 cells were transfected with cDNA for type VII adenylyl cyclase instead of the type V isoform, morphine stimulated this adenylyl cyclase activity beyond the stimulation produced by dopamine. Both the inhibitory and stimulatory effects of morphine were blocked by naloxone or pretreatment of the transfected HEK 293 cells with pertussis toxin. When expressed in the HEK 293 cells, the alpha subunit of transducin, which is considered to be the putative scavenger of the beta gamma subunits of G proteins, suppressed the stimulatory effect of morphine on type VII adenylyl cyclase. We also expressed the adenylyl cyclases in cells that were transfected with D1A receptor and G beta 1 and G gamma 2 cDNAs. Dopamine was more efficacious in stimulating type VII adenylyl cyclase activity in cells concomitantly transfected with the beta gamma subunit cDNAs than in cells not transfected with these G protein subunits. Transfection with beta gamma subunit cDNAs did not affect dopamine stimulation of type V adenylyl cyclase activity, and morphine-induced inhibition of type V adenylyl cyclase activity was still evident in cells cotransfected with the alpha subunit of transducin. These data support the contention that the effects on type VII adenylyl cyclase activity mediated through the G1/G(o) proteins may depend on the actions of the beta gamma subunits. The same is not the case for type V adenylyl cyclase. Our data demonstrate that both qualitative and quantitative responses to mu-opioid receptor stimulation depend on the isoform of adenylyl cyclase expressed in neurons or other cells of the body.
1. Since endothelium-derived nitric oxide (NO) is a potent vasodilator and degraded into nitrous ions, we measured the serum nitrate ion (NO3-) and the amount of urinary excretions of NO3- as an index for endogenous NO to ascertain whether NO formation is augmented in patients with chronic liver diseases. 2. Using inpatients suffering from chronic liver diseases, serum levels and urinary excretions of NO3- were measured by using high-performance liquid chromatography with an anion exchange column. 3. Among the four patient groups of normal controls, and those with chronic liver diseases such as chronic active hepatitis, compensated cirrhosis, and decompensated cirrhosis the serum level of NO3- showed the highest level in a patient group with decompensated cirrhosis. The amount of urinary excretion of NO3- was significantly increased in both groups of patients with liver cirrhosis compared with the control group and patients with chronic active hepatitis. Patients with chronic active hepatitis did not show any difference between the normal control group. The amount of urinary excretion of NO3- correlated significantly and negatively with the level of serum albumin (P < 0.05) and counts of platelets (P < 0.01) in patients with compensated cirrhosis. 4. These findings suggest that the production of endogenous NO is augmented in patients with liver cirrhosis, particularly in a decompensated subgroup. Increases in the production of endogenous NO correspond to the progress of liver cirrhosis, but not in patients with chronic hepatitis.
Nine children with congenital rubella syndrome were examined with respect to the relation between clinical symptoms and the findings of computed tomography (CT, 9/9 cases) and magnetic resonance imaging (MRI, 7/9 cases). All patients had deafness, and three had relatively severe sequelae in the central nervous system (CNS), such as mental retardation (MR), cerebral palsy (CP) or microcephaly. In four patients, dilatation of the lateral ventricles was found by CT; in four patients, low-density areas were noted in the periventricular white matter and/or the subcortical white matter; one patient showed a spotty calcified area in the lenticula. No abnormal findings were found by CT in other three patients. MRI in seven children demonstrated areas of prolonged T1 and T2 relaxation times in the white matter in all of them. In relation to clinical symptoms, five patients without dilatation of the lateral ventricles had no sequelae except deafness. On the other hand, in four patients with dilation of the lateral ventricles, three had MR, CP or microcephaly. This study showed that there was a close relation between the ventricular dilatation and sequelae with in CNS, whereas abnormal intensity areas in the white matter found by MRI were not related well to the sequelae of CNS.
Although free and conjugated dopamine (DA) constitutes most of plasma and urine catecholamine pool, the diagnostic significance of DA estimation for the evaluation of illness is not clear. Plasma free DA is mainly derived from the peripheral sympathetic nerve terminals and the released DA is converted to conjugated DA and to DA metabolites. The free DA concentration in plasma is trace in amount. Urinary free DA is mainly derived from renal tubular cells, and urinary conjugated DA is derived from filtrated DA at glomerulus. We investigated clinical significance of plasma free and conjugated DA and urinary excretion of free and conjugated DA in patients with chronic renal failure before and after renal transplantation. Marked elevation of plasma conjugated DA in patients with renal failure disappeared after hemodialysis or transplantation, like clinical picture of creatinine and blood urea nitrogen. Increases of urinary excretion of free and conjugated DA and of urinary volume were augmented in these patients after renal transplantation. The augmented excretion of urinary free DA resulted from the transplanted renal tubules, which indicate the functional fixation of transplanted kidneys into host patients. These results suggest that the estimations of plasma conjugated DA and urinary excretion of free DA are an important index for the evaluation of renal transplantation and renal function.
We investigated the antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro. First, Staphylococcus aureus samples were obtained using stamp agar medium from inflammatory lesions of 29 adult patients with atopic dermatitis before and after a single photochemotherapy. Therapy was oral PUVA (30 mg 8-methoxypsoralen, 8MOP plus 5J/cm2 UVA), topical PUVA (0.3% 8MOP plus 200 mJ/cm2 UVA) or UVB (80 mJ/cm2) irradiation. The number of S. aureus on the lesions was significantly reduced, even after a single treatment with all therapies. Reductions (mean +/- SD) were 69.3 +/- 26.9%, 76.3 +/- 31.3% and 83.8 +/- 18.5%, respectively. Secondly, we investigated the effect of PUVA (0.001% 8MOP plus 10, 20, 30, 40, or 50 mJ/cm2 UVA) and UVB (10, 30, 50, or 100 mJ/cm2) irradiation on the proliferation of S. aureus in vitro. PUVA and UVB treatment markedly inhibited the proliferation in a dose-dependent manner. These results seem to indicate the possibility that the antimicrobial effect of UV radiation contributes to successful photochemotherapy in patients with atopic dermatitis.
Estrogens have been reported to influence endothelial functions. This article's aim is to examine whether endothelium-dependent vasodilation of brachial arteries is changed in parallel with the physiological variation of the ovarian hormones during the menstrual cycle in young healthy female subjects. With high-resolution ultrasonography, we measured the diameter and blood flow of brachial arteries at rest, during reactive hyperemia, and after sublingual nitroglycerin administration in 15 young healthy female subjects (mean 29.6 +/- 2.6 years). All female subjects were studied in each of three different phases of one menstrual cycle (M, menstrual phase; F, follicular phase; L, luteal phase). The increase in arterial diameter during reactive hyperemia was lowest in the menstrual phase and highest in the follicular phase (4.9 +/- 0.8% in M; 14.1 +/- 0.9% in F; 9.2 +/- 1.1% in L; p < 0.005 between any two means among the groups). No significant difference was apparent in the percentage of increase in blood flow during reactive hyperemia among the three phases. The percentage of increase in arterial diameter after nitroglycerin administration also was not significantly different among the three phases of the cycle. The serum estradiol level was lowest in the menstrual phase and was highest in the follicular phase (17.5 +/- 1.6 pg/ml in M, p < 0.0005, M versus F and L; 107.8 +/- 18.0 pg/ml in F, p < 0.05, F versus L; 74.4 +/- 7.3 pg/ml in L). The serum level of nitrite-nitrate, measured by the Griess reaction, was highest in the follicular phase and was lowest in the menstrual phase of the three different phases (40.4 +/- 7.9 mumol/l in M, p < 0.01, M versus F, and p < 0.05, M versus L; 106.7 +/- 17.6 mumol/l in F, p < 0.05, F versus L; 62.2 +/- 6.2 mumol/l in L). In conclusion, a significant variation of the endothelium-dependent vasodilation parallels the levels of serum estradiol and nitrite-nitrate during the menstrual cycle in female subjects.
We performed bronchial reconstruction by several unusual procedures and succeeded in preserving lung function, which was proven with spirometry and treadmill exercise test. Type 1 (n = 2): Anastomosis between the left main bronchus and upper segmental bronchus with lower lobectomy and lingulectomy. Type 2 (n = 2): Anatomosis between the left main bronchus and basal segmental bronchus with upper lobectomy and superior segmentectomy acompanied by vascular reconstruction. Type 3 (n = 4): Anastomosis between the right main bronchus and lower bronchus with upper and middle lobectomy, accompanied by vascular reconstruction in 2 cases. One patient required completion pneumonectomy but the others had uneventful postoperative courses and maintained better lung function than expected, although the amount of preserved lung tissue was limited. There may be a great difference in the postoperative quality of life if pneumonectomy can be avoided, even though the preserved segments are few. Surgeons should reconsider the choice of pneumonectomy for interlobar tumors invading another lobe, especially in the case of N0 or N1 squamous cell carcinoma.
The well-known Minamata disease was caused by mercury; the Itai-Itai disease by cadmium; and lead poisoning by gasoline additives. Following our previous investigation on heavy metal concentrations in the umbilical cords in 1980, total mercury, cadmium and lead concentrations in the umbilical cords (from 20 males and 20 females) have been measured in 1990 for comparison in the present study. The changes in metal concentrations in 1980 and 1990 were: from 0.007 +/- 0.005 microgram/g to 0.011 +/- 0.008 microgram/g for total mercury; from 0.019 +/- 0.016 microgram/g to 0.006 +/- 0.005 microgram/g, from 0.151 +/- 0.123 microgram/g to 0.046 +/- 0.038 microgram/g for lead. Total mercury accumulated in the umbilical cords increased to approximately 1.6-fold, while cadmium and lead decreased to approximately 1/3-fold during these 10 years.
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