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Biomedical subjects

T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 163 records · Page 9Linked to original sources
PubMed1995

Detection of CYP1A1 gene polymorphism using designed RFLP and distributions of CYP1A1 genotypes in Japanese.

Isoleucine (Ile)-valine (Val) polymorphism, which is caused by a point mutation from A to G in exon 7, is reported to be associated with an elevated risk of lung cancer among Japanese. Because CYP1A1 catalyzes bioactivation of environmental procarcinogens, such as benzo[a]pyrene, it is very important to study the clinical meaning of Ile-Val polymorphism using an epidemiological study. In an epidemiological study, easy, economical, rapid and reliable identification of the CYP1A1 genotype is necessary. The present study shows that the new method, designed restriction fragment length polymorphism (designed RFLP), can detect Ile-Val polymorphism of CYP1A1. The Ile-Val polymorphism detected using this new method was consistent with that found by the allele-specific PCR amplifications (ASA) method in six cases tested. This new method detected Ile-Val polymorphism of CYP1A1 using 240 healthy Japanese who lived in the northern Kyusyu region. The frequency of the genotypes was as follows: Ile/Ile 159 (66.2%); Ile/Val, 65 (27.1%); Val/Val, 16 (6.7%). The frequency of the Ile gene was 0.798 and that of the Val gene, 0.202. There was no difference in Ile-Val polymorphism based on sex or age. Racial differences influenced the distribution of this polymorphism, but Japanese regional differences did not. Since this new method, designed RFLP, is rapid, reliable and suitable for large-scale screening of polymorphisms, it may be used routinely to detect Ile-Val polymorphism of CYP1A1. Furthermore, it will help to evaluate the relationship between CYP1A1 polymorphism and individual sensitivity to xenobiotics that may affect the incidence of lung cancer.

Adult↗
PubMed1995

Distribution of various nickel compounds in rat organs after oral administration.

In this study, eight kinds of nickel (Ni) compounds were orally administered to Wistar male rats and the distribution of each compound was investigated 24 h after the administration. The Ni compounds used in this experiment were nickel metal [Ni-M], nickel oxide (green) [NiO(G)], nickel oxide (black) [NiO(B)], nickel subsulfide [Ni3S2], nickel sulfide [NiS], nickel sulfate [NiSO4], nickel chloride [NiCl2], and nickel nitrate [Ni(NO3)2]. The solubilities of the nickel compounds in saline solution were in the following order; [Ni(NO3)2 > NiCl2 > NiSO4] >> [NiS > Ni3S2] > [NiO(B) > Ni-M > NiO(G)]. The Ni level in the visceral organs was higher in the rats given soluble Ni compounds; Ni(NO3)2, NiCl2, NiSO4, than that in the rats receiving other compounds. In the rats to which soluble Ni compounds were administered, 80-90% of the recovered Ni amounts in the examined organs was detected in the kidneys. On the other hand, the Ni concentration in organs administered scarcely soluble Ni compounds; NiO(B), NiO(G), and Ni-M were very low. The estimated absorbed fraction of each Ni compounds was increased with the increase of the solubility. These results suggest that the kinetic behavior of Ni compounds administered orally is closely related with the solubility of Ni compounds, and that the solubility of Ni compounds is one of the important factors for determining the health effect of Ni compounds.

Absorption↗
PubMed1995

Inborn errors of aldosterone biosynthesis in humans.

Corticosterone methyl oxidase (CMO) type I and type II deficiencies are inborn errors at the penultimate and ultimate steps in the biosynthesis of aldosterone in humans. Recently, steroid 18-hydroxylase (P450C18), or aldosterone synthase (P450aldo), was shown to be a multifunctional enzyme catalyzing these two steps of aldosterone biosynthesis, i.e., the conversion of corticosterone to 18-hydroxycorticosterone and the subsequent conversion of 18-hydroxycorticosterone to aldosterone. This observation suggests that CMO I and CMO II deficiencies are derived from two different mutations in the P450C18 gene (CYP11B2). To elucidate whether or not this is the case, we performed molecular genetic studies on CYP11B2 of both types of patients. Nucleotide sequence analysis has indicated that the gene of CMO I deficient patients is completely inactivated by a frameshift to form a stop codon due to a 5-bp nucleotide deletion in exon 1. Sequence analysis of CYP11B2 of CMO II deficient patients has revealed two point mutations, CGG-->TGG (Arg181-->Trp) in exon 3 and GTG-->GCG (Val386-->Ala) in exon 7. CYP11B1, the gene for steroid 11 beta-hydroxylase (P45011 beta) which was previously postulated to be the target for CMO II deficiency, is not impaired in these two types of patients. Expression studies using the corresponding mutant cDNAs have shown that CMO I deficient patients are null mutants with a complete lack of P450C18 whereas CMO II deficient patients are leaky mutants with an altered P450C18 activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Hyperplasia, Congenital↗
PubMed1995

Vascular affinity of trandolapril.

This article discusses the pharmacologic basis on which trandolapril exhibits a more potent and longer-lasting antihypertensive effect than its chemical prototype enalapril. Our studies have shown that 1) trandolapril and its active metabolite trandolaprilat are more lipophilic than enalapril and its active diacid enalaprilat; 2) trandolaprilat is three times more potent than enalaprilat in vitro; and 3) trandolapril is 10 times more effective and longer-acting than enalapril in lowering the blood pressure of spontaneously hypertensive rats. The long duration of action of trandolapril can be attributed to its long-lasting inhibition of the vascular tissue angiotensin converting enzyme (ACE). The long action onto the vascular tissue ACE may be due to the high lipophilicity of trandolapril which may increase its tissue penetration and its elimination half-life from the tissue, and the unique nature of the vascular tissue which, unlike the other tissues, does not respond to trandolapril with the induction of de novo ACE that may counteract the ACE inhibition. These data imply that trandolapril is a potent ACE inhibitor with distinctively long action, which might be a result of its vascular tissue affinity and the lack of any ACE inducing ability of the vascular tissue.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Sensitivity and specificity of mass screening for gastric cancer using the measurment of serum pepsinogens.

The aim of this study was to estimate the validity of mass screening for gastric cancer using serum pepsinogens (PG test). The study subjects were 4876 workers aged from 40 to 61 years old. Sera were obtained at the time of the health checkup and serum pepsinogen levels (PG I and PG II) were measured at the same time. PG I < 50 ng/ml and PG I/PG II ratio < 3.0 were adopted as the criteria for a positive result for the PG test. PG test-positive subjects were examined, in principle, by endoscopy. Furthermore, all subjects were followed up for a year to check for occurrence of gastric cancer. Among the total subjects, 911 (18.7%) were positive for the PG test and 650 (71.4%) among the positive subjects underwent further examinations, which revealed 11 cases of gastric cancer. Seven gastric cancer cases were diagnosed during the follow-up period within one year after the PG test. When the results of one years's follow-up from the time of screening were defined as the gold standard, the sensitivity and specificity of the PG test were estimated at 66.7% and 81.5%, respectively. The authors conclude that the validity of the PG test as a mass screening method may be comparable to that of X-ray screening, if optimum criteria of a positive test are selected.

Adult↗
PubMed1995

Spontaneous rhabdomyosarcomas in aged Mastomys (Praomys coucha).

Two spontaneous tumours in the hind leg of 2 aged Mastomys were diagnosed as poorly differentiated rhabdomyosarcomas. In both cases, the neoplastic cells had no evidence of cross-striation, but had a positive reaction for muscle-specific proteins. This is the second report of rhabdomyosarcomas in Mastomys, and the first described in detail.

Animals↗
PubMed1995

Serum hepatocyte growth factor levels in liver diseases: clinical implications.

Although recent studies have shown that hepatocyte growth factor (HGF) is a potent mitogen in vivo, the significance of serum HGF in liver diseases remains unclear. To clarify clinical significance of serum HGF in liver diseases, serum HGF was measured in 127 patients with liver diseases and in 200 healthy individuals, using a highly sensitive immunoradiometric assay (IRMA). This assay is specific for HGF and is sensitive enough to detect 0.1 ng/mL of HGF. Mean values for serum HGF in acute hepatitis (AH), chronic hepatitis (CH), liver cirrhosis (LC), hepatocellular carcinoma (HCC), primary biliary cirrhosis (PBC), fulminant hepatic failure (FHF), and normal controls were 0.45, 0.40, 1.05, 1.06, 0.44, 16.40, and 0.27 ng/mL, respectively. Serum HGF levels in these diseases were significantly increased compared with those in the controls (P < .001), and exhibited a positive correlation with total bilirubin, indocyanine green (ICG) test (R15), asparate aminotransferase (AST), and a negative correlation with albumin and prothrombin time (P < .001). Cirrhotic patients with modified Child class C had higher levels of serum HGF than those graded as modified Child class A or B (P < .001). In CH, serum HGF levels were significantly related to the histological activity index (HAI) score (P < .002). Seven patients with HCC who underwent transcatheter arterial embolization (TAE) exhibited a gradual increase in serum HGF levels up to day 4 after treatment; these higher levels were maintained until day 7, although AST reached a peak on day 2 and then decreased gradually.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Inaccuracy and inefficiency of urinary sediment analysis.

When the efficiency of urine sediment analysis was studied: we found that: (1) In tests of repeatability, counts of red blood cells, white blood cells, and epithelial cells, but not of casts, showed high precision, even when they were conducted by relatively inexperienced technologists; (2) Correlation of counts of red blood cells, white blood cells, and epithelial cells was good for results obtained by an expert technologist and those obtained by relatively inexperienced technologists, but the correlation was low in the case of casts, perhaps because of their low incidence in urine sediment; (3) Hematuria and leukocyturia were often detected in specimens positive for occult blood, albumin, or both; (4) Most casts were hyaline, which are physiologic in nature. Pathologic casts such as granular casts, were found in specimens containing red and white blood cells; (5) Although urine sediment analysis was frequently requested by clinicians, most analyses showed negative results; (6) Microscopic sediment analysis requires considerable time, labor, and experience, and is more sensitive than tape tests. The results of our study indicate that there are advantages to the present method for analyzing urine sediment, but that its efficiency is doubtful.

Humans↗
PubMed1994

Cloning and structural characterization of the human endothelial nitric-oxide-synthase gene.

Nitric oxide accounts for the activity of endothelium-derived relaxing factor, which seems to have an important role in vasodilation and inhibition of platelet aggregation. In endothelial cells, one isoform of nitric-oxide synthase is constitutively expressed. Analysis of the cDNA encoding the human endothelial nitric-oxide synthase revealed that the mRNA is 4.1 kb in size and that the translated protein consists of 1203 amino acids. We have cloned a genomic DNA encoding the human endothelial nitric-oxide synthase and analyzed the entire nucleotide sequence of the gene. The gene consists of 26 exons with a total size of 21 kb. The 5' flanking region of the gene lacks TATA boxes, but it contains putative Sp1-binding sites in (G+C)-rich regions. Of particular interest is the fact that a shear-stress-responsive element is located at position -985, which probably regulates the nitric-oxide-synthase gene in response to fluid mechanical forces at the transcriptional level in the vascular endothelium. Two minisatellite sequences are detectable in introns 2 and 8; a 32-bp consensus sequence repeats 38 times and a 57-bp consensus sequence repeats ten times. We found polymorphisms of the BamHI fragment containing the former minisatellite sequence in genomic DNA from pedigree family members. Furthermore, five tandem repeats of a 27-bp core consensus sequence and 35 repeats of a dinucleotide (CA) are located in introns 4 and 13, respectively. These repeat sequences will probably provide genetic markers for gene mapping and linkage analysis of inherited diseases including cardiovascular diseases.

Amino Acid Oxidoreductases↗
PubMed1994

Effects of the anabolic steroid nandrolone phenylpropionate on craniofacial growth in rats.

Primary testosterone and its derivatives are anabolic steroids used in the treatment of osteoporosis and Turner syndrome. They also enhance fast-twitch muscle weight in female rats. The present study examines the effect of an anabolic steroid on craniofacial growth and development in rats. Five-week-old female Sprague-Dawley rats (125) were divided into experimental and control groups. The experimental group was injected subcutaneously with 1 mg nandrolone phenylpropionate in the interscapular region on alternate days, whereas those in the control group were injected with a vehicle, arachis oil. Rats were sacrificed at 60 and 120 days of age. Cephalometric analysis of soft X-ray cephalograms showed that chronic administration of the anabolic steroid, nandrolone phenylpropionate, resulted in: (1) about a 20% increase in body weight, (2) an increase in total skull length, (3) elongation of the maxillary and mandibular incisors, (4) an increase in the depth of the antegonial notch, and (5) downward-forward growth of the viscerocranium against the neurocranium. These results suggest that nandrolone phenylpropionate may accelerate craniofacial growth and/or induce high functional activity of the masticatory muscles in female rats.

Anabolic Agents↗
PubMed1994

Aryl hydrocarbon hydroxylase activity in human lung tissue: in relation to cigarette smoking and lung cancer.

In order to investigate the relationship between aryl hydrocarbon hydroxylase (AHH) activity and smoking or lung cancer, AHH activities in fresh lungs (normal tissue, tumorous tissue, and surrounding tissue of tumor) obtained from lung cancer patients and non-lung cancer patients were measured. There were no differences in lung AHH activity in the lung lobes. In the non-lung cancer patients, AHH activities ranged from 0.13 to 2.37 (pmol 3 hydroxybenzo[a]pyrene/20 min/mg protein), and whereas in the normal tissues of the lung cancer patients they ranged from 0.19 to 5.05. Lung AHH activities showed normal distribution, and a large variation (26 times) was observed in normal tissues in the lung cancer patients. In most cases, AHH activities in the tumorous tissues and the surrounding tissue of the tumor were lower than those in the normal tissues of the lung cancer patients. In the non-lung cancer group, the means of AHH activity of the nonsmoker subgroup (NN) and the smoker subgroup (SN) were 0.62 and 0.96, respectively. On the other hand, in the lung cancer group the means of AHH activity of the nonsmoker subgroup (NC) and smoker subgroup (SC) were 0.85 and 1.05, respectively. Statistically significant differences were observed between NN and SN, NN and NC, and NN and SC. These results suggest that human lung AHH activity was increased by cigarette smoke as in rodent lungs, and the distribution of basal AHH activity in lung tissue of the nonsmokers group in the lung cancer patients shifted toward high levels compared to the nonsmokers group in the non-lung cancer group. The effect of the histological cell types of the lung cancer on the AHH activity was not observed in this study.

Adenocarcinoma↗
PubMed1994

Peptide synthesis with halophenylalanines by thermolysin.

Thermolysin was able to catalyze enantioselective peptide synthesis with non-natural amino acids, halophenylalanines. However, the reactivity of thermolysin was considerably influenced by the kind and position of halogen substituents on these analogues. The manner of the recognition of the amino component by the enzyme was different from that of the carboxyl component in the synthesis of peptides with non-natural phenylalanine analogues. The phenomena observed are discussed, based on the kinetic parameters obtained.

Amino Acid Sequence↗
PubMed1994

Efficiency of serum copper/zinc ratio for differential diagnosis of patients with and without lung cancer.

We examined serum copper (Cu), serum zinc (Zn), and the serum copper/zinc ratio (Cu/Zn) in 162 patients. All of them were seen to have an abnormal shadow in the chest X-ray films, that is, 109 patients with lung cancer (LC) and 53 patients with no lung cancer (NLC). The mean Cu and Cu/Zn in LC patients were significantly higher than those in NLC patients (p < 0.05). In LC patients, Cu and Cu/Zn were higher and Zn was lower in advanced tumors than early ones. There was a significantly clear relation between Cu or Cu/Zn and the tumor (T) stages. When the relative risk (RR) of LC was estimated, it was seen that the higher Cu and Cu/Zn became, the higher RR became. Furthermore, we showed the sensitivity of the receiver operator characteristic of the test (ROC) curve for Cu, Cu/Zn, and carcinoembryonic antigen (CEA) to diagnose LC, as explained in a paragraph of methods. The determinations of Cu, Zn, and Cu/Zn are simple and inexpensive. They also appear to have a great diagnostic value in determining the local invasion of LC and as a screening test in the high-risk patients for LC.

Adult↗
PubMed1994

Pulmonary elimination of methyl tertiary-butyl ether after intraperitoneal administration in mice.

The pulmonary elimination after intraperitoneal administration at three different doses (50, 100, and 500 mg/kg) of methyl tertiary-butyl ether (MTBE) was studied using mice. There were two exponential curves with an initial rapid decrease of the elimination ratio followed by a slow decrease at the doses of 100 mg/kg and 500 mg/kg. The calculated half-lives of the two elimination curves obtained by the least squares method were approximately 45 min and 80 min. The pulmonary elimination ratios at the three different doses were from 23.2% to 69.0%. Most of the excreted MTBE was eliminated within 3 h. It is suggested in this paper that MTBE in exhaled air can be used as a biological exposure index for the exposure assessment of MTBE.

Animals↗
PubMed1994

An attempt to treat intractable skin ulcers with autologous dermal graft.

Five patients with a total of seven chronic intractable skin ulcers and impaired peripheral blood circulation were treated with autologous dermal grafts which did not contain any epidermal component. These ulcers were refractory to conventional therapy. Results from the dermal grafting were variable, with four of the ulcers (in two patients) healing 1-8 months after 1-5 graftings. These findings suggest the possibility that dermal grafting may be a simple yet effective treatment for deep, super-infected skin ulcers in which tendons and bones have become exposed. Dermal grafting may also provide an additional method by which to treat chronic skin ulcers which do not respond to conventional surgical therapy and where amputation of affected extremities is being considered.

Adult↗
PubMed1994

A cis-acting element and a trans-acting factor involved in the wound-induced expression of a horseradish peroxidase gene.

The mechanisms that control the wound-induced expression of the prxC2 gene for horseradish peroxidase (HRP) have been investigated. Analysis of the regulatory properties of 5'-deleted promoters showed that a positive element involved in the response to wounding was located between -307 and -99 bp from the site of initiation of translation. In in vitro binding assays of tobacco nuclear proteins and DNA fragments of prxC2 promoter, the binding site was the Box 1 from -296 to -283 containing the CACGTG motif. To identify the functional role of Box 1, the prxC2 promoter that has been digested from the 5' end to -289 with a disrupted Box 1 was fused to a reporter gene for beta-glucuronidase (GUS). No induction of GUS activity was observed in transgenic tobacco plants with the prxC2 (-289)/GUS construct. These data indicated that the expression of prxC2 in response to wounding required the Box 1 sequence from -296 to -283. Furthermore, a tobacco cDNA expression library was screened and a cDNA clone for a protein, designated TFHP-1, that bound specifically to the Box 1 sequence was identified. The putative TFHP-1 protein contains a basic region and leucine zipper (bZip) motif and a helix-loop-helix (HLH) motif. The mRNA for TFHP-1 was abundant in roots and stems, and it was not induced by wounding in leaves. In tobacco protoplasts, antisense TFHP-1 suppressed the expression of prxC2(-529)/GUS.

Amino Acid Sequence↗