Search PubMed⌕ Search

Biomedical subjects

K Iwamoto

Publications and source records attributed to K Iwamoto.

At least 109 records · Page 6Linked to original sources
PubMed1994

Evidence of a steroidogenic enzyme gene dose effect on adrenal gene expression in hereditary rabbit congenital adrenal hyperplasia.

We previously reported the gene deletion encoding cytochrome P-450 cholesterol side-chain cleavage enzyme (P-450SCC, resulting in complete elimination of the adrenal gene expression and causing congenital adrenal hyperplasia in the rabbit. Using the rabbit congenital adrenal hyperplasia model, we investigated the wild type (wt) P-450SCC gene dose effect on gene expression in three P-450SCC genotype animals [wt/wt, wt/mutant (mt), mt/mt] identified by Southern blot analysis. Northern blots using a rabbit P-450SCC cDNA probe revealed no detectable P-450SCC mRNA in individual adrenals of animals with congenital adrenal hyperplasia (mt/mt) and approximately half or slightly less than half the levels of the mRNA in the pooled adrenals of five heterozygous (wt/mt) newborn animals compared with the mRNA levels in the pooled adrenals of five homozygous normal (wt/wt) newborn animals. Identical P-450SCC mRNA levels were found individual adrenals of adult animals with regard to the P-450SCC genotype, although at a higher expression level than in the newborn animals of the same genotype. Control Northern blots using human CPY21-B cDNA and cytoplasmic actin cDNA probes confirmed the accuracy and integrity of RNA. Western immunoblotting using anti-ovine P-450SCC antibody revealed decreased P-450SCC protein in the adrenals of wt/mt animals at approximately half the level of the P-450SCC protein in the adrenals of the wt/wt animals. Baseline and ACTH-stimulated serum corticosterone (B) levels in vivo were similar between the age-matched wt/mt and wt/wt animals, whereas ACTH-stimulated B levels in adult animals were higher than those in the newborn animals irrespective of P-450SCC genotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1994

Comparative study of permeability into rat cerebrospinal fluid of the quinolones: dependency on their lipophilicities.

Pharmacokinetic behavior involved in the entry of four quinolone antibacterial agents, norfloxacin (NFLX), ciprofloxacin (CPFX), ofloxacin (OFLX) and nalidixic acid (NA), into cerebrospinal fluid (CSF) was comparatively investigated in rats. Periodically, after the bolus i.v. dose of each quinolone (10 mg/kg), aliquots of CSF were collected by cisternal puncture and blood samples were then withdrawn from the jugular vein. CSF and serum (total and unbound) levels of the drugs were determined by HPLC method. Transport parameters for three new quinolones (NFLX, CPFX, OFLX) into CSF were obtained by physiological model analysis. Serum levels of OFLX and NFLX declined bi-exponentially with time, whereas the serum levels of NA and CPFX declined in mono-exponential and tri-exponential fashion, respectively. Fractions of each quinolone unbound to serum protein (approximately 0.7 for NFLX, CPFX, and OFLX, 0.12 for NA) were almost the same at any point in time. The CSF levels of these quinolones rose quite rapidly after drug administration, and then declined, along with their serum levels. Both the CSF level and the ratio of CSF concentration to serum unbound concentration were the highest for NA, followed by OFLX, CPFX and NFLX. These values of the four quinolones were almost proportional to the apparent partition coefficient (Papp) between n-octanol and phosphate buffer (pH 7.0) values of each reported in a previous paper [Tsuji et al., Antimicrob. Agents Chemother., 32, 190 (1988)]. In the three new quinolones, OFLX had a larger value of apparent diffusional clearance between blood and CSF (PAc) than CPFX and NFLX.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Cationic technetium-99m complexes of N-substituted pyridoxal derivatives as renal function agents.

UNLABELLED: New cationic technetium-chelating agents containing a pyridinium group have been synthesized and evaluated as potential renal radiopharmaceuticals. METHODS: The pyridinium compounds used in the study are N-methyl pyridoxal chloride, N-ethyl pyridoxal chloride, N-propyl pyridoxal chloride, 1-methyl-3-hydroxy-4-formylpyridinium chloride, 1-methyl-2-formyl-3-hydroxypyridinium chloride and the Schiff's bases of N-methyl pyridoxal chloride with amino acid, amino acid ester and amino acid amide. Complexes of these chelating agents with 99mTc were prepared using a Na2S2O4 or a SnCl2 solution as a reducing agent. The purity of the 99mTc complexes was determined by paper electrophoresis in 0.1 M tris buffer. RESULTS: Electrophoresis indicates slightly positive-charged species. The log P values of these complexes showed a hydrophilic nature. Urinary excretion of the 99mTc N-alkylated pyridoxal derivatives, 99mTc-diethylenetriaminepentaacetic acid, 99mTc-mercaptoacetylglycylglycylglycine (MAG3) and 131I-O-iodohippurate were determined in mice and rats at different time intervals. In a rat model, the pyridoxal-derived 99mTc complexes are rapidly excreted in urine and provide clear renal scintigrams. Hepatobiliary excretion was negligible, reducing scan interference from the intestines. Total clearances were lower than that of 131I-hippurate and 99mTc-MAG3. CONCLUSIONS: The rate of urinary clearance of the new tracers was not significantly faster than 99mTc diethylenetriaminepentaacetic acid and the inhibitor N1-methylnicotinamide had only a minimal effect on the renal behavior. Though the new tracers have cationic properties, the pyridinium group did not contribute largely to the excretion of active transport.

Animals↗
PubMed1994

Transvaginal ultrasonographic diagnosis of bladder-wall invasion in patients with cervical cancer.

OBJECTIVE: To evaluate the use of transvaginal ultrasonography for diagnosing invasion of the bladder by cervical cancer. METHODS: Twenty-one women with stages Ib-IIIb cervical cancer underwent radical hysterectomy or staging laparotomy. All had computed tomography (CT) scans and cystoscopic examinations, and five also underwent magnetic resonance imaging (MRI). During transvaginal ultrasonography, a transvaginal transducer was inserted into the anterior fornix of the vagina and the bladder wall was studied in the sagittal plane. The moveability of the bladder wall was assessed by the ability of the bladder to slide along the uterine cervix when the probe was pushed up against the bladder from the anterior fornix. Moveability was considered to indicate an intact bladder wall. RESULTS: The accuracy of transvaginal ultrasonography was superior to that of the other methods for detecting bladder-wall invasion by cervical cancer. The accuracy was 95% for transvaginal ultrasonography, 76% for CT, 86% for cystoscopy, and 80% for MRI. CONCLUSION: Transvaginal ultrasonographic examination is useful for detecting invasion of the bladder wall by cervical cancer.

Diagnostic Imaging↗
PubMed1993

High-performance liquid chromatographic determination of nalidixic acid in rat serum, brain and cerebrospinal fluid.

A high-performance liquid chromatographic method for the determination of nalidixic acid (NA) in rat serum, brain and cerebrospinal fluid (CSF) was developed. NA in rat serum and brain homogenate was extracted and injected onto a reversed-phase column. CSF was directly analysed without extraction procedure. The limits of detection were 0.05 microgram ml-1 for serum, 0.07 microgram g-1 for brain and 0.02 microgram ml-1 for CSF, respectively. Calibration curves were linear over the concentration ranges 0.1-50 micrograms ml-1 for serum, 0.12-9 micrograms g-1 for brain and 0.05-10 micrograms ml-1 for CSF, respectively. The reproducibility of NA assay in rat biological media ranged from 1 to 4% relative standard deviations (RSD). The recoveries of NA added to serum and brain were higher than 96% with an RSD of less than 4%. The present method was found to be applicable to pharmacokinetic study of NA in rat serum, brain and CSF.

Animals↗
PubMed1993

Dependency of salivary excretion of mexiletine on the plasma concentration in rats.

The effect of steady-state plasma concentrations on the salivary excretion of mexiletine was investigated following simultaneous bolus intravenous injection of the loading dose (2.7 or 16.1 mg kg-1) and constant-rate intravenous infusion of the maintenance dose (15 or 102 micrograms min-1 kg-1) in male Wistar rats. Parotid and mandibular saliva was collected separately by stimulating salivation with a constant-rate infusion of pilocarpine (50 micrograms kg-1 min-1) in each rat. The low and high steady-state levels of mexiletine in blood plasma were attained at 0.259 +/- 0.123 and 1.616 +/- 0.475 micrograms mL-1, respectively, within the first 1-2 h after drug administration. Similarly, the two different steady-states in both parotid and mandibular saliva were attained. Although the mexiletine levels in both types of saliva were lower than that in plasma, the drug level in parotid saliva was always higher than that in mandibular saliva at any steady-state (P < 0.001 or 0.01). In parotid saliva, the high steady-state produced greater saliva to plasma drug concentration ratios (S/P ratio, 0.475 +/- 0.160) than that (0.386 +/- 0.131) at the low steady-state (P < 0.05). The S/P ratio for mandibular saliva at the high (0.204 +/- 0.060) steady-state was also greater than that at the low (0.158 +/- 0.050) steady-state (P < 0.01). These changes in the S/P ratio could not be explained by the pH for either parotid or mandibular saliva, but partially by the change in the unbound fraction of the drug which tended to be consistent with that in the ratio for both salivary glands. These findings suggest that the salivary excretion of mexiletine may be dependent on the plasma unbound concentration in rats.

Animals↗
PubMed1993

Mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene in a patient with classic salt-wasting 3 beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia.

Inherited adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency is most likely caused by a mutation of the type II 3 beta-HSD gene. Cloning and sequencing of exons I-II, III, and IV and portions of the adjacent introns, amplified by polymerase chain reaction using primers specific for the type II gene, in one male pseudohermaphrodite with salt-wasting classic 3 beta-HSD deficiency congenital adrenal hyperplasia revealed the same mutation in all nine clones of exon IV consisting of a missense mutation at codon 248 [GTC(Val)-->AAC(Asn)] followed by a frameshift mutation at codon 249 [CGA (Arg)-->TA], resulting in a stop codon TAG, and normal sequences of exon I-II and III and the adjacent portions of introns. The same codon 248 and 249 mutations were found on one clone of his mother's DNA, but two other clones revealed normal sequences. These data indicate a homozygous combined missense/frameshift mutation in exon IV of the type II 3 beta-HSD gene resulting in severe salt-wasting adrenal and gonadal 3 beta-HSD deficiency in the patient.

3-Hydroxysteroid Dehydrogenases↗
PubMed1993

Inherited congenital adrenal hyperplasia in the rabbit is caused by a deletion in the gene encoding cytochrome P450 cholesterol side-chain cleavage enzyme.

Congenital adrenal hyperplasia (CAH) comprises a family of inherited human disorders caused by a defect in cortisol biosynthesis. We previously reported absent cholesterol side-chain cleavage enzyme cytochrome P450 (P450scc) expression in rabbits affected with CAH. Further molecular studies via Southern blotting analyses, using a full-length human P450scc cDNA probe and a cloned rabbit P450scc cDNA probe, demonstrated the absence of P450scc DNA fragments in CAH animals. Reverse transcriptase-based polymerase chain reactions revealed that P450scc mRNA was not detectable in the adrenals of CAH rabbits, confirming the previous findings of absent P450scc gene expression by Northern and Western blotting. Cloning and sequencing of a 1336-basepair fragment of rabbit P450scc cDNA (85% of the coding sequence) revealed an approximately 80% identical nucleotide sequence and a 76% identical amino acid sequence compared to the human P450scc cDNA. We conclude that a large deletion mutation in the P450scc gene is most likely responsible for the absent P450scc gene expression resulting in the lethal and feminizing form of CAH in the rabbit. Further investigation of adrenal and gonadal steroidogenic enzyme gene expression in this CAH animal model will provide a greater understanding of the molecular genetics of CAH, while wild-type P450scc gene transfer experiments using CAH adrenals in vitro or in vivo will ultimately characterize the molecular basis of CAH and provide a foundation for CAH gene therapy modality.

Adrenal Hyperplasia, Congenital↗
PubMed1993

Postoperative pneumonia in elderly patients: incidence and mortality in comparison with younger patients.

To determine whether elderly patients have an increased incidence of postoperative pneumonia and/or an increased mortality, we conducted a retrospective study of 4,380 patients who underwent thoracic, abdominal or neurosurgery under general anesthesia. Thirty of these patients developed postoperative pneumonia (incidence, 0.68%). The elderly patients aged 65 years or older who underwent thoracic surgery had the highest incidence of pneumonia. Nine of the 30 patients with pneumonia died (mortality, 30%). Elderly patients did not show a higher mortality than the younger patients. The extent of pulmonary infiltrates on chest roentgenogram and the serum bilirubin level, both of which were determined at the onset of pneumonia, independently had a significant association with mortality. Our study suggests that advanced age is a risk factor for postoperative pneumonia in patients who undergo thoracic surgery.

Adult↗
PubMed1993

Postnatal development, sex-related difference and hormonal regulation of acetohexamide reductase activities in rat liver and kidney.

A variety of patterns of postnatal development were observed for acetohexamide reductase activities in microsomes and cytosols from the liver and kidney of male and female rats. Furthermore, there were pronounced sex-related differences in the activities of liver and kidney microsomes. Prepubertal and neonatal testectomies decreased markedly the activities in liver and kidney microsomes of adult male rats to the female levels. The activities in liver and kidney microsomes decreased by prepubertal testectomy and the activity in kidney microsomes decreased by neonatal testectomy were restored to control levels by testosterone propionate treatment, whereas the activity in liver microsomes decreased by neonatal testectomy was unaffected by the same treatment. Prepubertal or neonatal testectomy had no effect on the activity in liver or kidney cytosol of adult male rats. Prepubertal ovariectomy decreased the activities in liver and kidney cytosols of adult female rats and the decreased activities were restored to control levels by estradiol benzoate treatment. Based on these results, we propose that the postnatal development and sex-related difference of acetohexamide reductase activities in rat liver and kidney can be regulated by sex hormones such as testosterone propionate and estradiol benzoate.

Alcohol Oxidoreductases↗
PubMed1993

[A case of parenchymal pulmonary endometriosis with recurrent chest pain].

A 36-year-old woman was admitted to Nagasaki Citizens Hospital because of severe pleuritic chest pain associated with small amounts of hemoptysis. This episode occurred with the onset of her menses 2 months after a surgical abortion. Chest X-ray revealed a nodular shadow in the left middle lung field. ECG showed no abnormal findings. Pulmonary perfusion scintigram and arteriogram showed no evidence of pulmonary thromboembolism. Over the next 5 years she suffered 5 further episodes of chest pain without hemoptysis, in which every episode coincided with her menses and disappeared within several days after the end of the menses. Chest X-rays disclosed transient nodular shadows on 4 of 6 of the above mentioned episodes. In the earlier episodes one nodular shadow was noted in the left upper lobe S5 a. Later, it was accompanied by an additional nodular shadow in the S5b. Those shadows disappeared in accordance with the diminution of chest pain. From these findings the diagnosis of pulmonary endometriosis was confirmed. Consequently, the antigonadotropin danazol was administered for 6 months. After this, she had no recurrence of her symptoms. Catamenial hemoptysis is usually the most striking symptom of pulmonary endometriosis, which might be an important clue for its diagnosis. The case presented here was characterized by severe chest pain with paucity of hemoptysis.

Adult↗
PubMed1992

Effect of fenbufen on the pharmacokinetics of sparfloxacin in rats.

The effects of fenbufen on the serum concentrations and penetration into the brain and CSF of sparfloxacin (AT-4140), a new quinolone antibacterial agent, were investigated in rats. At designated times after a bolus iv dose of sparfloxacin 10 mg/kg with or without fenbufen 20 mg/kg, arterial blood, CSF and whole brain were simultaneously collected from each rat. Sparfloxacin concentrations were assayed by HPLC. Serum concentration of sparfloxacin declined bi-exponentially with time and was not changed by coadministered fenbufen. Binding sparfloxacin to serum protein slightly decreased after the coadministration. No elevation of sparfloxacin concentrations was observed in either brain or CSF after coadministration with fenbufen except for only a few time-points. The pharmacokinetic analysis based on the physiological model indicated that fenbufen did not affect the permeability across the blood-brain or blood-CSF barrier. These results suggest that fenbufen may be unlikely to affect the pharmacokinetics, involving the entry into the central nervous system, of sparfloxacin.

Algorithms↗
PubMed1992

Effect of fenbufen on the entry of new quinolones, norfloxacin and ofloxacin, into the central nervous system in rats.

The entry of two new quinolone antibacterial agents, norfloxacin and ofloxacin, into the central nervous system (CNS) of rats, and the effect of fenbufen on this was investigated. At various times after the administration of a bolus intravenous dose of norfloxacin or ofloxacin (10 mg kg-1) with or without fenbufen (20 mg kg-1), serum and cerebrospinal fluid (CSF) samples and whole brain were collected from the rats and the concentration of norfloxacin or ofloxacin in each sample was determined. Serum concentrations of both quinolones declined biexponentially with time and were significantly elevated by coadministration with fenbufen at the terminal phase. The fractions of these quinolones bound to serum protein were not altered by coadministration with fenbufen. Coadministered fenbufen raised the brain concentrations of both quinolones but did not affect their brain to serum unbound concentration ratios. In contrast, CSF to serum unbound concentration ratios as well as CSF concentrations of norfloxacin and ofloxacin were elevated by coadministration with fenbufen. Apparent diffusional clearances between blood and CSF of norfloxacin and ofloxacin estimated by the physiological model analysis increased by 1.9 and 2.6 times, respectively, after coadministration with fenbufen. These findings suggest that coadministered fenbufen may facilitate the entry of norfloxacin and ofloxacin into the CNS.

Animals↗
PubMed1992

Salivary excretion of mexiletine after bolus intravenous administration in rats.

Salivary excretion of mexiletine was investigated following bolus intravenous administration (10 mg kg-1) in rats. Parotid and mandibular saliva was collected separately by stimulating salivation with constant rate infusion of pilocarpine (3 mg kg-1 h-1). The mexiletine levels in blood plasma and parotid and mandibular saliva declined biexponentially with time in almost parallel fashion. Although the mexiletine levels in both types of saliva were lower than that in plasma, the drug level in parotid saliva was always higher than that in mandibular saliva. Significant correlations were observed when all data relating mexiletine concentration in plasma and saliva were included (P less than 0.001). The saliva/plasma drug concentration ratios (S/P ratios) did not vary to a large extent (0.56 +/- 0.10 for parotid saliva, 0.21 +/- 0.06 for mandibular saliva), but there was a consistent tendency for the higher plasma drug levels in the distribution phase to produce relatively high S/P ratios for both parotid and mandibular saliva. Moreover, the plasma mexiletine levels calculated by the equation of Matin et al (1974) employing the observed values for the saliva drug level, saliva pH and free fraction of mexiletine in plasma were significantly higher than the observed drug levels. Therefore, it is suggested that the salivary excretion of mexiletine could not be explained quantitatively by simple, passive secretion based on pH-partition theory.

Animals↗
PubMed1992

Pharmacokinetics of [6]-gingerol after intravenous administration in rats with acute renal or hepatic failure.

The pharmacokinetics of [6]-gingerol were investigated in rats with acute renal failure induced by bilateral nephrectomy, or those with acute hepatic failure induced by a single oral administration of carbon tetrachloride (CCl4), to clarify the contribution of the kidney and liver to the elimination process of [6]-gingerol. After bolus intravenous administration, a plasma concentration-time curve of [6]-gingerol was illustrated by a two-compartment open model. There was no significant difference in either the plasma concentration-time curve or any pharmacokinetic parameters between the control and nephrectomized rats. It is suggested, therefore, that renal excretion does not contribute at all to the disappearance of [6]-gingerol from plasma in rats. In contrast, hepatic intoxication with CCl4 elevated the plasma concentration of [6]-gingerol at the terminal phase. Its elimination half-life increased significantly, from 8.5 to 11.0 min, in CCl4-intoxicated rats. The extent of [6]-gingerol bound to serum protein was more than 90% and was affected very slightly by the CCl4-intoxication. These aspects indicate that [6]-gingerol is eliminated partly by the liver.

Acute Disease↗
PubMed1992

Response rate and cell-cycle changes due to intra-arterial infusion chemotherapy with cisplatin and bleomycin for locally recurrent uterine cervical cancer.

Intra-arterial infusion with cisplatin (CDDP) and bleomycin (BLM) was carried out in 21 patients with locally recurrent uterine cervical cancer who were previously treated with irradiation alone. Patients were treated with a bolus infusion into both internal iliac arteries of 50 mg/m2 of CDDP and 30 mg/m2 of BLM. Two to four courses of the infusion therapy were given to each patient, and the response rate, the tumor and serum drug concentrations, and the cell kinetics in tumor tissue were evaluated. The response rate (CR+PR) was 71.4% according to the WHO criteria. There was no difference, in the tumor tissue concentrations of CDDP and BLM between responders and nonresponders. Although the DNA ploidy of tumor cells was not significantly different between the two groups before treatment, both the labeling index with BrdU and the proliferation index with flow cytometry significantly increased 24 hours after treatment in responding tumors but not in nonresponding tumors. These results show that intra-arterial infusion with CDDP and BLM improves the prognosis of recurrent cervical cancer and that labeling and proliferation indices may be useful for determining the response of cervical cancer to intra-arterial chemotherapy.

Adult↗
PubMed1992

Evaluation of measurement of fetal crown-rump length from ultrasonically timed ovulation and fertilization in vitro.

To assess with accuracy the development and maturity of the fetus, we evaluated fetal growth in 46 pregnant women who had conceived subsequent to ultrasonically timed ovulation. Fetal crown-rump length (CRL) was measured at gestational ages that differed by about 1 day from those previously reported. The variance in CRL measurements at each gestational age was small, and the data were normally distributed. The CRL growth curves of this and previous studies were tested using measurements from 7 pregnancies derived from in vitro fertilization (IVF). The data from IVF pregnancies were consistent with our curve, having 1 day difference to those previously reported. The gender of the fetus did not influence the CRL during the first trimester. The results suggest that fetal growth is uniform during the first trimester.

Embryonic and Fetal Development↗