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Biomedical subjects

Y Abe

Publications and source records attributed to Y Abe.

At least 649 records · Page 36Linked to original sources

Increased plasma endothelin concentrations in patients with acute heart failure after myocardial infarction.

We have investigated the relationship between plasma endothelin (ET) concentrations and several clinical characteristics in 31 patients with acute myocardial infarction (MI). ET levels were also measured in 10 age-matched healthy subjects, 9 patients with unstable angina, and 20 patients with chronic heart disease. In patients with MI, although no significant relationship was observed between plasma ET concentrations and measured hemodynamic parameters, plasma levels were higher in patients with pulmonary congestion than in those without this complication (1.61 +/- 0.29 vs 1.21 +/- 0.33 fmol/ml; p < 0.01). No significant difference in plasma ET levels was found between cardiac and peripheral sampling sites (pulmonary artery; 1.07 +/- 0.28, right atrium; 1.02 +/- 0.28, peripheral artery; 1.12 +/- 0.23, peripheral vein; 1.14 +/- 0.38 fmol/ml: N.S.), or among patients with uncomplicated MI, unstable angina (1.00 +/- 0.32 fmol/ml), and healthy subjects (1.01 +/- 0.29 fmol/ml). Increased level were observed in patients with decompensated heart failure due to chronic heart disease, but were not found in patients without pulmonary congestion (1.62 +/- 0.60 vs 1.11 +/- fmol/ml; p < 0.01). These observations suggest that plasma ET concentrations are elevated in the presence of congestive heart failure or severe ventricular depression, but are not persistently increased by myocardial ischemia per se.

Acute Disease↗

Effects of NG-nitro-L-arginine on isolated rabbit afferent arterioles.

We examined the effects of NG-nitro-L-arginine (L-NNA) on isolated rabbit afferent arterioles to confirm that nitric oxide is released at the resistance vessel level in the kidney. We microdissected the superficial afferent arterioles from the kidneys of New Zealand White rabbits. Each afferent arteriole was cannulated with a micropipette system, and the intraluminal pressure was set at 80 mmHg. By our methods, we found that norepinephrine (NE) decreased the lumen diameter of the afferent arterioles in a dose-dependent manner, and acetylcholine increased the lumen diameter of NE-constricted afferent arterioles. L-NNA (10(-4) M) gradually decreased the lumen diameter of afferent arterioles from 21.5 +/- 0.9 to 18.6 +/- 0.9 microns in 20 min, but NG-nitro-D-arginine (10(-4) M) did not affect them (from 21.8 +/- 1.3 to 21.8 +/- 1.5 microns). L-Arginine (10(-2) M) restored the lumen diameter of L-NNA-contracted afferent arterioles to the control levels. These findings indicate that the isolated afferent arteriole has the ability to release or to synthesize and release nitric oxide under basal conditions and that this basal release of nitric oxide plays an important role in the basal tone of the afferent arteriole.

Acetylcholine↗

The incidence of vertical transmission of hepatitis C virus.

This study was undertaken to clarify the incidence of the vertical transmission of hepatitis C virus (HCV). During the third trimester, 2015 pregnant women were examined as to anti-HCV antibodies. Anti-HCV antibody seropositive women were examined for HCV-RNA in peripheral blood at labor and in breast milk. Their offspring were also examined for HCV-RNA in umbilical cord blood and peripheral blood one week after birth and during subsequent outpatient visits. The following results were obtained: (1) Twelve of the 2015 pregnant women (0.6%) were seropositive for anti-HCV antibodies; (2) Seven of the twelve women (58%) seropositive for anti-HCV antibodies were also seropositive for HCV-RNA; (3) Three newborns of the seven HCV-RNA seropositive women (43%) were found to have HCV-RNA in the cord blood; (4) In the three newborns HCV-RNA had disappeared from the peripheral blood within one month after birth; (5) Two of the seven HCV-RNA seropositive women (29%) had HCV-RNA positive breast milk; (6) The possibility of infection via breast milk was shown in one infant at ten months after birth. Based on these results, it is indicated that HCV vertical transmission is possible in more than half of the HCV-RNA seropositive mothers. However, because of the disappearance of HCV from the infants' peripheral blood, further following study is needed.

Base Sequence↗

Neurogenic inflammation in nasal allergy: histochemical and pharmacological studies in guinea pigs. A review.

The role of neuropeptides in nasal allergy was examined in guinea pigs by histochemical and pharmacological study. Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like behaviors: sneezing and watery rhinorrhea, and decreased histamine content in the nasal mucosa in guinea pigs sensitized with TDI. The immunoreactivity of substance P (SP) and calcitonin gene-related peptide (CGRP) in the nerve terminals in the nasal mucosa was increased after intranasal application of TDI. We also observed a decrease in the immunoreactivity of SP and CGRP, and an increase in their mRNA expression in the trigeminal ganglion neurons. These findings indicate that exposure to TDI enhanced the biosynthesis of both SP and CGRP in the trigeminal ganglion neurons and their axonal transportation to the terminals in the nasal mucosa. In animals pretreated with capsaicin before sensitization, TDI did not induce nasal allergy-like behaviors and histamine release in the nasal mucosa. Since capsaicin depletes SP and CGRP in the sensory nerves, this finding indicates neuropeptide-mediated histamine release in the nasal mucosa. All these findings suggest that, on exposure to TDI, the antidromic release of SP and CGRP in the nasal mucosa triggers the release of histamine, resulting in the development of symptoms of nasal allergy.

Animals↗

Pharmacokinetics of a new thienodiazepine platelet activating factor receptor antagonist (E6123) in laboratory animals. Is there a metabolic polymorphism in the rhesus monkey?

1. The pharmacokinetics of E6123, a platelet activating factor receptor antagonist, were studied after i.v. and oral administration to rat, guinea-pig, dog and rhesus monkey. Plasma concentrations of E6123 were determined by h.p.l.c. with UV detection. 2. After i.v. dosing (1 mg/kg), the plasma concentration-time curves fitted a two-compartment model. The half-lives for the terminal phases (t1/2) in rat, dog, and guinea-pig showed very little inter-individual variation, but t1/2 in the monkey (n = 4) varied more than four-fold. The distribution parameters were very similar in rat, dog and monkey (Vc and Vss approx. 1.2 and 1.5 l/kg, respectively) but slightly higher values were found in the guinea-pig, which also showed the lowest plasma protein binding. 3. After oral dosing (1 mg/kg), the maximum plasma concentrations were obtained within 0.3-3.0 h in all species. The half-life for each individual animal was almost the same as that after i.v. dosing. The mean bioavailabilities of E6123 in rat, guinea-pig and dog were about 65, 95 and 81%, respectively, but the values for monkey were again highly variable (range 32-99%). 4. The high variability in the monkey was confirmed by i.v. administration to a further 10 animals. The mean half-lives for the terminal phase in extensive metabolizers (EMs) (n = 4) and poor metabolizers (PMs) (n = 10) were approx. 1 and 4 h, respectively. 5. The rank order for total body clearance of E6123 was: rat > monkey (EMs) > dog > guinea-pig > monkey (PMs).

Animals↗

Metabolic polymorphism of E6123 in rhesus monkey.

1. The metabolic polymorphism of a new thienodiazepine platelet activating factor receptor antagonist (E6123) in rhesus monkey was studied in vivo and in vitro. 2. After i.v. dosing of 14C-E6123, the levels of radioactivity in blood, plasma and red blood cells were higher in poor metabolizers (PMs) with AUC(0-24 h) values which were about 1.3-1.5 times higher than those in extensive metabolizers (EMs). 3. After i.v. dosing of 14C-E6123, radioactivity was excreted rapidly by both EMs and PMs. However, EMs excreted the radioactivity mainly in urine whereas, for PMs, radioactivity was excreted fairly equally in urine and faeces. 4. In vivo and in vitro studies demonstrated that the metabolic polymorphism of E6123 in rhesus monkey is caused by a difference in the hydrolysis of an amide side chain. 5. Our results suggested that there are two types of the enzymes which metabolize E6123 by this route in EMs, but only one type in PMs. 6. The low affinity enzyme in EMs might be the same as the enzyme in PMs, indicating that the metabolic polymorphism of E6123 in rhesus monkey could depend on the existence of a high affinity enzyme.

Animals↗

[Effect of hydronephrosis on the contralateral blood flow and glomerular volume].

We designed a following experiment to appraise the effect of unilateral hydronephrosis on the contralateral kidney using weanling rats whose kidneys were in a growing stage. Rats were divided into 4 groups. Complete unilateral (left) ureteral obstruction (CUUO) was made on the experiment rats, and these went through the following procedures on the day 3 after CUUO; 1) Group R: CUUO released, 2) Group N: left nephrectomy performed, 3) Group S: CUUO continued. Sham-operations were performed on the days 0 and 3 to the controls. Renal cortical blood flow and glomerular volume of the contralateral (right) kidneys were determined on the days 5, 7, 9, 14 and 21. Blood flow to the renal cortex per unit volume (ml/min/100 cm3; measured with Laser blood perfusion monitor) in the contralateral kidneys increased gradually in the all groups, but statistical significance was not confirmed in the observed period between any groups. Increases in total renal blood flow (wet kidney weight times renal cortical blood flow per unit volume; g x ml/min/100 cm3) were proportional to the measured wet kidney weight in the all groups. Notably in the group N, a significant increase was noted compared to the group R and the controls. Glomerular volume (GV) of the contralateral kidneys did not show significant changes on the day 3 compared to the controls. GV significantly grew up during the day 5 to the day 14 (2 to 11 days after the relief of CUUO) in the group R and then it settled to the level of the controls on the day 21.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Renal function of contralateral kidney after total or partial removal of kidney with ectopic ureter].

The effects of partial or total removal of the kidney with ectopic ureter on the contralateral kidney were evaluated using DMSA renal uptake rate on 8 patients. After partial nephrectomy on 6 cases, the affected residual kidneys showed significant decrease in DMSA renal uptake rate in 2 cases in which the extirpated kidneys had normal renal tissue in part but did not show significant change in DMSA uptake rate in 4 cases in which the extirpated kidneys were dominated mainly with dysplasia. Post-operative increase in DMSA uptake rate of the contralateral kidneys were significant in 3 of 4 patients who had the operation before they became 2 years old. In 2 of these 3 cases, pre-operative scintigram showed extremely low rate of DMSA renal uptake. Four cases aged 2 years old and over did not show post-operative increase in the uptake rate. As we have previously reported on the cases with hydronephrosis, these results suggest that 1) existence of obstruction caused by ectopic ureter inhibit the development of the contralateral kidney and 2) the growth of the kidney can resume the release of that obstruction, if the release is made while the kidneys are still in developing stage.

Child↗

[Studies on reflux nephropathy--renal tubular and glomerular damage evaluated by various urinary indices].

Measurements were performed on beta 2-microglobulin (beta 2-MG), alpha 1-microglobulin (alpha 1-MG), N-acetyl-beta-D-glucosaminidase (NAG) as indices of renal tubular damage and microalbumin as an index of renal glomerular damage in 204 cases with primary vesicoureteral reflux (VUR). Investigations were made on the relationship between each index and extent of renal cortical damage from the findings of 99mTc-dimercapto-succinic acid (DMSA) renoscintigraphy, and also on the changes of each index before and after antireflux operation. At the first examination, high values of urinary beta 2-MG, alpha 1-MG, NAG and albumin were noted in 36%, 40%, 50% and 34% of cases with VUR respectively. Almost all the cases with high indices values before the operation showed improvement in those values accompanied with disappearance of VUR after the operation. These findings suggest that renal tubular and glomerular damage were induced by the sterile reflux itself. High values of urinary indices were confirmed in 16% (beta 2-MG), 40% (alpha 1-MG), 27% (NAG) and 32% (albumin) cases after a lapse of 2 years or longer since antireflux operation or spontaneous disappearance of VUR. In some of these cases indices values showed some improvement but have not returned to normal levels, and in other cases indices were within normal limits preoperatively but turned out to be high levels during the observation period even after the disappearance of VUR. Most of these cases were accompanied with severe cortical damage of unilateral or bilateral kidneys on DMSA renoscintigraphy. Based on these findings, we suggest that overload to residual nephron, caused by reduced mass of functional nephron, is playing an important role on raising the values of various urinary indices.

Acetylglucosaminidase↗

[The effect of unilateral ureteral obstruction on the contralateral renal growth in weanling rats].

The effect of unilateral hydronephrosis on the growth of contralateral kidney were evaluated with weanling rats of which kidneys were in growing stage (body weighted between 80 g and 90 g). These rats underwent complete unilateral ureteral obstruction (CUUO) on day 0. They were divided into 3 groups and went through second operations on day 3 (CUUO-3) as follows; a) CUUO released, b) nephrectomy performed and c) CUUO continued. Sham-operation was performed on day 0 and on day 3 to the controls. Wet weights and bromodeoxy-uridine (BrdU) labeling index (L.I.) (index for cell proliferation in the uriniferous tubules) of the contralateral kidneys were measured for the evaluation. The wet weights were significantly higher in all the groups than that of the controls throughout the observation period on and after the day 3. The group that underwent nephrectomy demonstrated a sharp rise in L.I. after the day 7. In the group that was continued in CUUO, the L.I. started to rise later than its rise in nephrectomised group but the index caught up at the time when the blood flow completely disappeared in the kidneys of the ligated side. L.I. in the group of which CUUO was released became significantly higher than that of controls on the day 7 and remained its significance until the day 21 in spite of resolution of the hydronephrosis. To reveal the effect of length of obstructed term, the same trial was carried out that rats endured in CUUO for 5 days (CUUO-5) till the second operation. This turned out lower L.I. in the CUUO-5 than the CUUO-3. These results suggest that the presence of hydronephrosis made by CUUO suppress the growth (cell proliferation) of contralateral kidney and also duration of obstruction can be critical on the renal growth that shorter obstructed period turns out preferable for cell proliferation after relief of CUUO.

Animals↗

R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. I. Taxonomy, fermentation, isolation and biological properties.

New non-steroidal estrogen-receptor antagonists, R1128 A, B, C and D, were isolated from the cultured broth of Streptomyces sp. No. 1128 by solvent extraction, silica gel chromatography, reverse phase chromatography and preparative HPLC. These compounds inhibited estrogen binding to its receptor. The IC50 values of R1128 A, B, C and D for partially purified rat uterine cytosol receptor were 1.1 x 10(-7) M, 1.2 x 10(-7) M, 2.6 x 10(-7) M and 2.7 x 10(-7) M, respectively.

Animals↗

R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. III. Pharmacological properties and antitumor activities.

R1128 B (1,3,6-trihydroxy-8-n-butylanthraquinone), a new antibiotic produced by Streptomyces sp. No. 1128, inhibited estrogen binding to its receptor. The IC50 value of R1128 B for partially purified rat uterine cytosol receptor was 1.2 x 10(-7) M. However, the IC50 value of R1128 B against androgen-receptor binding was about 50-fold greater than that against estrogen-receptor binding. R1128 B was a competitive inhibitor against estrogen-receptor binding. R1128 B inhibited the growth of estrogen-responsive human mammary adenocarcinoma MCF-7 cells in soft agar. This inhibition, however, was reversed when estradiol was added to the culture medium. R1128 B showed antitumor activities against MCF-7 both xenografted to nude mice and implanted in subrenal capsule of mice (SRC assay). The potency of R1128 B was about 8-fold lower than that of tamoxifen both in vitro and in vivo.

Androgen Receptor Antagonists↗

WB2838 [3-chloro-4-(2-amino-3-chlorophenyl)-pyrrole]: non-steroidal androgen-receptor antagonist produced by a Pseudomonas.

In the course of our search for non-steroidal androgen-receptor antagonists of microbial origin, Pseudomonas sp. No. 2838 was found to produce an inhibitor of androgen binding to its receptor. This compound, named WB2838, was isolated and identified as 3-chloro-4-(2-amino-3-chlorophenyl)-pyrrole. The IC50 value of WB2838 for partially purified rat prostate cytosol receptor was 8.0 x 10(-7) M. However, the IC50 value of WB2838 against estrogen-receptor binding was about 90-fold greater than that against androgen-receptor binding. WB2838 inhibited the growth of androgen-responsive mouse mammary carcinoma SC-3 cells in the presence of 10(-8) M testosterone at IC50 value of 4.1 x 10(-7) M. This inhibition was reversed by adding 10(-5) M testosterone to the culture medium. WB2838 also showed the inhibitory activity against the growth of the ventral prostate induced by testosterone propionate in castrated immature rats. Therefore, it was concluded that WB2838 was a non-steroidal androgen-receptor antagonist.

Androgen Receptor Antagonists↗

Patient's comprehension of the medical informations presented before the invasive procedures.

The requirement of an informed consent has become a major issue even in the rural area of Japan. Particular interests were focussed on understanding of the information and the effect of pre-existing anxiety on that understanding. Nineteen neurological patients who were going to have either surgeries or invasive diagnostic procedures, agreed to cooperate with the study. Results of the study revealed the followings; (1) comprehension of medical disclosure varied widely from one patient to another, (2) assistance from co-medical staff (a registered nurse in the study) could not facilitate greater comprehension, and (3) the more anxious patients comprehended more. It seemed to remain a question as to how much adults of sound mind actually comprehended it even when the medical disclosure was presented fully and in a simple style.

Adult↗

In vivo acquired drug resistance and multidrug resistance gene (MDR1) expression in the KB carcinoma cell line xenotransplanted in nude mice.

We studied the correlation between in vivo responsiveness of KB xenografts to anticancer drugs and the expression level of the human multidrug resistance gene (MDR1) encoding P-Glycoprotein (P-Gp). We established KB xenografts (xeKB3-1 and xeKB8-5) by inoculating these in vitro lines into nude mice. The responsiveness was evaluated by an in vivo chemosensitivity assay (T/C; sensitive, < 50%). Xenograft xeKB3-1 was sensitive to vincristine (VCR) (T/C, 48%), and xeKB8-5 was resistant to VCR (T/C, 72%). We selected a VCR-resistant variant (xeKB3-1-R, T/C, 76%) by treating xeKB3-1 with VCR (1.2 mg/kg, x3) in vivo. The MDR1 expression was evaluated by a semi-quantitative assay using reverse transcription-polymerase chain reaction. A MDR1 expression pattern in xeKB3-1 and xeKB8-5 in vivo was the same as that to KB3-1 and KB8-5 in vitro. The xenograft xeKB3-1-R expressed definitive but significantly lower levels of MDR1 than xeKB8-5. These results suggest that acquired drug resistance is related to minimally enhanced expression of the P-Gp protein/MDR1 gene in KB xenografts in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Noninvasive assessment of left internal thoracic artery graft patency using transthoracic echocardiography].

To evaluate the utility of transthoracic echocardiography (TTE) for assessing the long-term patency of left internal thoracic artery (LITA) grafts, 36 patients who had coronary artery bypass grafting (CABG) were examined simultaneously for graft flow velocity by TTE and by graft angiogram. The flow velocity in the LITA graft was clearly visualized by TTE in 25 patients from the left supraclavicular echo view. On the basis of the angiogram, the sensitivity and specificity of TTE in the diagnosis of LITA graft patency were 71.4% and 100%, respectively. These 25 patients (mean follow-up time after CABG-29.6 months) were divided into 3 groups according to their preoperative diagnosis and the presence of grafts stenosis by angiogram as follows: APS(-), angina pectoris without graft stenosis in 15 cases; APS(+), angina pectoris with graft stenosis in 2 cases; OMI, old myocardial infarction without graft stenosis in 8 cases. The peak flow velocity D/S ratio and time velocity integral D/S ratio in the APS(-) group (2.48 +/- 0.73, 3.21 +/- 0.89) were significantly (p < 0.01) higher than those in the APS(+) group (0.30 +/- 0.23, 0.35 +/- 0.21) or in the OMI group (0.96 +/- 0.44, 0.87 +/- 0.51). Peak flow velocity D/(S+D) and time velocity integral D/(S+D) ratios in the APS(-) group (0.70 +/- 0.05, 0.75 +/- 0.06) were significantly (p < 0.01) higher than those in the APS(+) group (0.22 +/- 0.14, 0.25 +/- 0.11) or in the OMI group (0.46 +/- 0.17, 0.43 +/- 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗