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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 37 records · Page 2Linked to original sources

Apolipoprotein-E phenotype and basal activity of low-density lipoprotein receptor are independent of changes in plasma lipoprotein subfractions after cholesterol ingestion in Japanese subjects.

We investigated whether the apolipoprotein-E (apoE) phenotype and the basal activity of low-density lipoprotein (LDL) receptor, which were reported to be the major determinants for increase in plasma LDL levels by cholesterol ingestion, have the same role in Japanese subjects whose diet is low in fat and cholesterol. Cholesterol (750 mg/d) was added to the ordinary diet as a dried egg-yolk supplement for 4 wk to 110 subjects. Plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions were measured at the beginning and end of the test period. Phenotyping of apoE was determined by an isoelectric focusing-immunoblotting method, and LDL receptor activity in lymphocytes was determined by flow cytometry. Plasma levels of cholesterol in less-dense LDL (LDL(1)) and less-dense high-density lipoprotein (HDL(2)) were slightly but significantly increased, 3.4% and 4.1%, respectively, by cholesterol ingestion, but the increases were not statistically significant in any of E2, E3, and E4 groups. The distribution of the apoE phenotype was equivalent in all three LDL-cholesterol groups (no change, increase, and decrease by cholesterol ingestion). Plasma levels of LDL, LDL(1), and LDL(2) cholesterol were not significantly increased in the three groups of subjects with lymphocyte LDL-receptor activities (low, medium, and high). As with apoE phenotype, LDL-receptor activities were the same in all three LDL-cholesterol groups. In addition, there were no significant correlations between LDL-receptor activity and changes in plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions. Therefore, we concluded that cholesterol ingestion significantly increases plasma levels of less-dense LDL and HDL, but neither apoE phenotype nor basal LDL-receptor activity explain the variability in changes in plasma lipoprotein subfractions by cholesterol ingestion in Japanese subjects.

Apolipoproteins E↗

Severe metabolic acidosis and heart failure due to thiamine deficiency.

We report the case of a male patient with severe metabolic acidosis and heart failure caused by thiamine deficiency. He was admitted in August 1998 to the Tokai University Oiso Hospital because of severe dyspnea. The patient was diagnosed with heart failure and metabolic acidosis of unknown causes based on arterial blood gas analysis, chest x ray, and ultrasonic echocardiographic examinations. Our previous experience in treating a patient with thiamine deficiency caused by total parenteral nutrition without thiamine supplementation suggested that this patient was deficient in thiamine. The serum thiamine level was low and the lactate level was high. After intravenous administration of thiamine, the acidosis and heart failure disappeared. Dietary analysis showed that thiamine intake was low (0.32 mg/1000 kcal/d). Thiamine deficiency should be included in the differential diagnosis when encountering cases of heart failure with severe metabolic acidosis, even in developed countries.

Acidosis↗

Long-term outcome of endoscopic biopsy and subsequent nephroureterectomy for upper urinary tract tumor.

BACKGROUND: Upper urinary tract tumors can be biopsied using a flexible ureterorenoscope. This study examined retrospectively possible adverse effects of this procedure on patient outcome. METHODS: The study subjects consisted of 16 consecutive patients with renal pelvic tumor (n = 13) and upper ureteral tumor (n = 3). All subjects underwent endoscopic biopsy of their tumor and subsequent total nephroureterectomy between 1989 and 1995. The follow-up period ranged from 4.1 to 9.5 (mean 5.2) years. RESULTS: The overall 5-year survival rate was 87.0%, being 100% in 12 patients with tumors of grade 1 or 2. In contrast, of four patients with grade 3 tumor, three (75%) developed systemic lymphogenous and/or multiple lung metastases within 1 year postoperatively. CONCLUSIONS: The excellent patient outcomes deny any adverse effect of endoscopic biopsy on patients with grade 1 or 2 tumor. However, the endoscopic procedure should be performed prudently when a high grade tumor is suspected.

Aged↗

Topical application of acidic bupivacaine to the lumbar ganglion induces mechanical hyperalgesia in the rat.

UNLABELLED: To investigate the neurologic mechanisms of acidic local anesthetic-induced low back pain in humans, we administered bupivacaine and buffered saline at acidic or alkalinized pH at the L5 dorsal root ganglion (DRG) of rats via a hole drilled through the transverse process covering the DRG. Behavioral changes were tested before and after bupivacaine or saline administration. Results indicate that acute single-dose infusion of the DRG with bupivacaine (0.5%) at acidic pH (5.5) induced ipsilateral mechanical hyperalgesia that lasted for 7 days. Acute infusion of alkalinized bupivacaine (pH 7.2), however, caused only minor hyperalgesia that lasted <3 days. Similar results were obtained when bupivacaine was replaced with saline. Alternatively, chronic delivery of acidic saline to the DRG via a subcutaneously implanted osmotic pump resulted in a significant decrease in the withdrawal threshold on the ipsilateral hind paw that lasted for 10 days. In rats receiving chronic treatment of the DRG with alkalinized saline, mechanical hyperalgesia lasted for only 3 days. The results demonstrated that acidic bupivacaine deposited at the DRG causes pain and hyperalgesia when the effects of the local anesthetic have dissipated. These findings may explain the limited therapeutic effects of some acidic local anesthetics used for management of cancer-related and chronic back pain. IMPLICATIONS: Acidic bupivacaine administered at the L5 lumbar ganglion causes pain and hypersensitivity of the hind paw in the rat. These findings may explain the limited therapeutic effects of some acidic local anesthetics used for treatment of cancer-related and chronic back pain.

Administration, Topical↗

Transvaginal ultrasound of urethral sphincter at the mid urethra in continent and incontinent women.

PURPOSE: Few studies are available on imaging the urethral sphincter. We performed transvaginal ultrasonography to examine the muscle in continent and incontinent women. MATERIALS AND METHODS: Transvaginal ultrasonography was performed using a 7.5 MHz. transrectal probe in 19 continent and 69 incontinent supine women. Incontinent cases were classified as urge (14) and stress (55), and included urethral hypermobility (22) and intrinsic sphincter deficiency (33). Cadaver specimens were also examined to confirm the anatomy of ultrasound images. RESULTS: Transvaginal ultrasonography showed the urethra as a round structure consisting of a relatively high echogenic central zone and a relatively low echogenic peripheral zone. Matching ultrasound images with the anatomy of cadaver specimens indicated that the peripheral zone represents rhabdosphincter most reliably at the lateral aspects. Thus, its thickness was measured at the 9 o'clock position of the mid urethra. Mean thickness plus or minus standard error of mean was significantly decreased in stress incontinence compared with continence and urge incontinence (2.14 +/- 0.04, 2.78 +/- 0.08 and 2.87 +/- 0.11 mm., respectively, p <0. 001), while in intrinsic sphincter deficiency it was thinner than in hypermobility (2.00 +/- 0.05 versus 2.35 +/- 0.06 mm., p <0.01). There was no difference in central zone thickness according to continence status. CONCLUSIONS: Urethral structures may be visualized by transvaginal ultrasonography. The rhabdosphincter image was thinner in stress incontinence, especially in intrinsic sphincter deficiency. Transvaginal ultrasonography may be a useful clinical test for examining the morphology of the urethral sphincter muscle in women.

Cadaver↗

Enhancement of goblet cell hyperplasia and airway hyperresponsiveness by salbutamol in a rat model of atopic asthma.

BACKGROUND: Goblet cell hyperplasia (GCH) is a prominent feature in animal models of atopic asthma produced by immunisation and following multiple challenges with antigens. The aim of this study was to examine the effect of a beta(2) agonist on the development of GCH induced by the immune response. METHODS: Brown Norway rats were immunised and challenged with an aerosol of ovalbumin for four weeks. Salbutamol (0.5 mg/kg/day) or vehicle was continuously delivered for the four weeks using a subcutaneously implanted osmotic minipump. The density of goblet cells, other morphological changes, and airway responsiveness to methacholine were evaluated 24 hours after the final challenge. RESULTS: Treatment with salbutamol induced a more than twofold increase in the mean (SE) number of goblet cells (53.7 (7.3) vs 114.5 (11.8) cells/10(3) epithelial cells, p<0.01) while it did not significantly influence airway wall thickening and eosinophilic infiltration. Airway responsiveness to methacholine expressed as the logarithmic value of the concentration of methacholine required to generate a 50% increase in airway pressure (logPC(150)Mch) was also enhanced by the beta(2) agonist (-0.56 (0. 21) vs -0.95 (0.05), p<0.05). Additional experiments revealed that the same dose of the beta(2) agonist alone did not cause GCH in non-immunised rats and that the enhancement of GCH by salbutamol was completely abolished by simultaneous treatment with methylprednisolone (0.5 mg/kg/day). CONCLUSIONS: These data suggest that salbutamol enhances goblet cell hyperplasia and airway hyperresponsiveness in this rat model of atopic asthma.

Adrenergic beta-Agonists↗

Essential role for extracellular Ca(2+) in JNK activation by mechanical stretch in bladder smooth muscle cells.

Mechanical stretch has been implicated in phenotypic changes as an adaptive response to stretch stress physically loaded in bladder smooth muscle cells (BSMCs). To investigate stretch-induced signaling, we examined the mitogen-activated protein kinase (MAPK) family using rat primary BSMCs. When BSMCs were subjected to sustained mechanical stretch using collagen-coated silicon membranes, activation of c-Jun NH(2)-terminal kinase (JNK) was most relevant among three subsets of MAPK family members: the activity was elevated from 5 min after stretch and peaked at 10 min with an 11-fold increase. Activation of p38 was weak compared with that of JNK, and ERK was not activated at all. JNK activation by mechanical stretch was totally dependent on extracellular Ca(2+) and inhibited by Gd(3+), a blocker of stretch-activated (SA) ion channels. Nifedipine and verapamil, inhibitors for voltage-dependent Ca(2+) channels, had no effect on this JNK activation. Moreover, none of the inhibitors pertussis toxin, genistein, wortmannin, or calphostin C affected stretch-induced JNK activation, indicating that G protein-coupled and tyrosine kinase receptors are unlikely to be involved in this JNK activation. On the other hand, W-7, a calmodulin inhibitor, and cyclosporin A, a calcineurin inhibitor, prevented JNK activation by stretch. These results suggest a novel pathway for stretch-induced activation of JNK in BSMCs: mechanical stretch evokes Ca(2+) influx via Gd(3+)-sensitive SA Ca(2+) channels, resulting in JNK activation under regulation in part by calmodulin and calcineurin.

Animals↗

Multidisciplinary treatment of advanced testicular tumor with bulky liver metastasis.

A 21-year-old man with far-advanced nonseminomatous germ cell tumor of the left testis is presented. He had multiple bulky metastases in the liver and retroperitoneum with an extraordinarily elevated serum alpha-fetoprotein (23,500 ng/ml). He received multidisciplinary treatment consisting of systemic chemotherapy, cytoreductive left hepatic lobectomy, percutaneous ablation therapy, transarterial chemoembolization, and external beam irradiation for median segments of the liver. The efficient combination treatment normalized the tumor markers within 6 months and has maintained complete serological remission for 4.7 years.

Adult↗

Effects of low-dose pravastatin on plasma levels of lipids and apolipoproteins in Japanese type II hyperlipoproteinemic subjects with apolipoprotein E phenotype E3/2, E3/3, and E4/3.

Effects of 12 weeks of treatment with pravastatin at a dose of 20 mg/day were compared in subjects with type II hyperlipoproteinemia with apo+(lipoprotein) E phenotype E3/2, E3/3, and E4/3. There were no differences in age, body mass index, smoking status, complications, or plasma levels of lipids and apoproteins, except the higher levels of apo E in E3/2 subjects (n = 11) than in E3/3 subjects (n = 84) and E4/3 subjects (n = 28). Plasma levels of low-density lipoprotein cholesterol (LDL-C) were reduced by 47% +/- 8% (mean +/- SD) in E3/2 subjects, 36% +/- 10% in E3/3 subjects, and 26% +/- 12% in E4/3 subjects after 12 weeks of treatment with pravastatin (all p < 0.0001). Plasma levels of apo B were decreased by 40% +/- 12% in E3/2 subjects, 27% +/- 10% in E3/3 subjects, and 18% +/- 14% in E4/3 subjects after 12 weeks of treatment with pravastatin (all p < 0.0001). The reduction in plasma levels of LDL-C and apo B was most marked in E3/2 subjects, next in E3/3 subjects, and smallest in E4/3 subjects. The authors conclude that treatment with pravastatin at a dose of 20 mg/day in Japanese subjects is equally effective as 40 mg/day in Western subjects, and apo Epolymorphism is a factor to determine the efficacy of pravastatin in Japanese subjects.

Adult↗

[Development of theme in radiochemistry].

The disintegration rates of 222Rn and its daughters in natural water were determined successfully by the use of the integral counting method with a liquid scintillation spectrometer. A significant advantage of this method is its freedom from the quenching effect. Moreover, when plural alpha-, and beta-emitters are present, their total amounts can be determined. The simple extrapolation of integral counting curve to zero pulse-height, however, do not give the true disintegration rate for the soft beta-emitters (Emax < 200 keV), because the liquid scintillator (LS) has a relatively high detection threshold. Therefore, the zero detection threshold of the liquid scintillation spectrometer was determined by measuring standard 3H samples, and a modified integral counting method which extrapolates the integral counting curve to the zero detection threshold was proposed. The method has been successfully applied to various beta-emitters, 222Rn samples, and coloured samples of beta-emitters, giving more accurate absolute disintegration rate than the conventional integral counting method and the efficiency tracing method. In the course of the study determining 222Rn by liquid scintillation counting, we observed unexpected phenomena; the air luminescence from gaseous space above LS, and the temperature dependence of pulse-height spectra. As for the former phenomenon, we proposed a method for correcting errors due to air luminescence, a method for determining alpha-emitters by the air luminescence, and a rapid calibration method for 222Rn detectors. As for the latter phenomenon, we observed that the pulse-height spectra for alpha, and beta-emitters in LS are shifted toward higher pulse-height with decreasing temperature. We found that the fluorescence intensities of the solvent of LS (toluene) is promoted at lower temperatures, and that not only toluene, but also the fluorescence intensity of a number of aromatic hydrocarbons and aliphatic hydrocarbons show the same effect as toluene. Other unexpected results are existence of metals in number of enzymes, and discrepancies between the experimental value for Kurie plot of allowed beta-emitters and the value which would be expected according to Fermi's theory, the results of which would affect the transmission probability of potential barrier for alpha-particles.

Fluorescence↗

Wavelength-specific activation of MAP kinase family proteins by monochromatic UV irradiation.

The depletion of stratospheric ozone causes related increase in UV light below about 310 nm, which significantly affects biological and ecological systems. To understand the wavelength-specific effects of UV light, Molt4 cells (human T lymphoma cells) were irradiated with a series of monochromatic UV lights and the activities of three members of the mitogen-activated protein (MAP) kinase group were examined. Extracellular signal-regulated kinase was specifically activated within 1 min after UV irradiation in the range 320-360 nm. In contrast, P38 kinase was activated by 270-280 nm light with a peak at 1 min after irradiation. c-Jun N-terminal kinase activation was observed in a narrow range of UV light with a sharp peak at 280 nm occurring in 10 min. JNK translocated from the cytosol to the nucleus upon irradiation, while P38 remained in the cytosol even after UV irradiation. The activation of three MAP kinases was prevented by antioxidant reagents, suggesting that an oxidative signal initiates these responses. These results confirm that UV light affects various cellular functions through the activation of intracellular signaling systems including MAP kinase family proteins. However, the UV-induced activities of the separate MAP kinases show distinctly different dose, time and wavelength dependencies.

Cell Line↗

Tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp. MK993-dF2. I. Taxonomy, isolation, physico-chemical properties and biological activities.

Tyropeptins A and B, new proteasome inhibitors, were isolated from the culture broth of Kitasatospora sp. MK993-dF2. They were purified using ethyl acetate extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and HPLC. Tyropeptin A inhibited the chymotrypsin-like (ChT-L) and trypsin-like (T-L) activities of 20S proteasome with IC50 values of 0.1 microg/ml and 1.5 microg/ml respectively, but did not inhibit the peptidylglutamyl-peptide hydrolyzing (PGPH) activity of 20S proteasome at a concentration of 100 microg/ml. The inhibitory activities of tyropeptin A were about two times as strong as that of tyropeptin B. Taxonomy of the producing strain is also described.

Animals↗

Electromyographic study of the striated urethral sphincter in type 3 stress incontinence: evidence of myogenic-dominant damages.

OBJECTIVES: To determine the electromyographic features of the striated urethral sphincter in patients with type 3 stress incontinence (SI) due to intrinsic sphincteric deficiency (ISD). METHODS: We performed electromyography (EMG) of the striated urethral sphincter muscle and urodynamic studies in a total of 51 women, 41 female patients with type 3 SI and 10 women with normal urinary control (NUC). The results were analyzed in both groups, and the correlation of EMG findings with the patient characteristics and urodynamic parameters was evaluated. RESULTS: Motor unit potentials (MUP) of SI patients showed significantly shorter duration (P = 0.0014), lower amplitude (P = 0.0008), and larger number of phases (P = 0.0022) compared with those in the NUC group. Thirty (73%) of the SI patients showed an obvious low amplitude (less than 350 microV)/short duration (less than 4.5 milliseconds)/polyphasic pattern and early recruitment of interference activity with low amplitude at voluntary contraction of the striated sphincter, both indicating existence of myogenic damages. These patients showing myogenic damages had significantly lower Valsalva leak point pressure (P = 0.002) and more leakage in the pad-weigh test (P = 0.010) compared with the SI patients without myogenic damage findings. CONCLUSIONS: These results suggested that myogenic-dominant damages of the striated urethral sphincter may contribute to the etiology of ISD in most patients with type 3 SI.

Aged↗

Enhanced phospholipase C activity in the cultured skin fibroblast obtained from patients with coronary spastic angina: possible role for enhanced vasoconstrictor response.

OBJECTIVES: We measured phospholipase C (PLC) activity in the cultured skin fibroblasts obtained from patients with and without coronary spasm and examined its correlation with coronary artery vasomotility. BACKGROUND: Coronary artery vasomotility is enhanced in coronary spastic angina (CSA), but no information is available for the intracellular signaling. In spontaneously hypertensive rats, PLC activity in the skin fibroblasts has been shown to be enhanced. METHODS: Skin fibroblasts obtained from 24 patients with CSA-14 with organic coronary artery disease (CAD) and 12 control subjects--were cultured by the explant method. Activity of PLC was determined by incubating the membrane fraction with 3H-phosphatidyl inositol bisphosphate and by quantifying 3H-inositol trisphosphate. In patients with CSA and control subjects, the relations between PLC activity and coronary artery basal tone and constrictor response to intracoronary acetylcholine (ACh) were examined. RESULTS: Activity of PLC (pmol/protein [mg] per min) was 1.74+/-0.19 in patients with CSA; 0.90+/-0.12 in patients with CAD; and 0.65+/-0.07 in control subjects (p<0.001, patients with CSA vs. patients with CAD and control subjects; p = NS, patients with CAD vs. control subjects). According to the Lineweaver-Burk plot, Michaelis constant (micromol/liter) of PLC was 28+/-4 in patients with CSA; 49+/-14 in patients with CAD; and 56+/-10 in control subjects (p<0.05, patients with CSA vs. control subjects), whereas the maximal velocity was not different between the three groups. There were significant positive correlations between PLC activity and both basal tone (p = 0.0108) and response to ACh (p = 0.0053). Western blot analysis using membrane fraction demonstrated that 89% of PLC isoenzymes detected was of the delta1 isoform. CONCLUSIONS: Because the PLC activity measured was genetically defined and was positively correlated with coronary artery vasomotility, enhanced PLC activity may be involved in the pathogenesis of coronary spasm.

Angina Pectoris, Variant↗

Stability-instability transitions in silicon crystal growth.

In order for a crystal to grow, source atoms must be incorporated into the underlying lattice. Typically, this process occurs on the surface in one of two modes: either through island nucleation or through step flow. However, a third, morphologically unstable growth mode has been predicted. Monitoring the surface of ultraflat substrates with an in situ scanning electron microscope, we prove that for the (111) face of silicon there is a transition from stable step flow to morphological instability and then to island nucleation.

Journal Article↗