Biomedical subjects

H Furuta

Publications and source records attributed to H Furuta.

At least 55 records · Page 3Linked to original sources

PubMed2000

A polymorphic marker in the leptin gene associated with Japanese morbid obesity.

The prevaleance of morbid obesity (body mass index of 35.0 or greater) is low in Japan (0.2-0.3%), and little systematic investigation of its cause in this population has been carried out. Leptin plays a central role in regulation of body weight; mice deficient in leptin develop marked obesity. We sought mutations in the leptin gene in 53 morbidly obese Japanese (maximum body mass index 35-60) including 46 with type 2 diabetes. Direct DNA sequencing was performed following polymerase chain reaction amplification. Apart from a silent mutation at codon 25 (CAA/CAG, glutamine) detected in eight subjects, no mutations were detected. We found a significantly higher prevalence of the variant leptin 25CAG allele among the 53 obese subjects (0.085) studied than in 132 nonobese control subjects (0.011, P<0.001). In Japanese populations mutations in the protein coding sequence of the leptin gene are unlikely to be a major cause of morbid obesity. However, the leptin 25CAG allele may be linked to morbid obesity in this population. Specifically, genetic variation located near the leptin gene may be involved in pathogenesis. The leptin polymorphism 25CAG appears to be a new genetic marker for obesity susceptibility, at least in Japanese.

Body Mass Index↗

PubMed2000

An unusual case of rhythmic movement disorder.

Rhythmic movement disorder is one of the sleep-wake transition disorders listed in the International Classification of Sleep Disorders. According to this classification, the condition commonly occurs in infants and toddlers, and persistence beyond 4 years of age is unusual. Recently, we encountered a case in which rhythmic movement disorder persisted up until the age of 12 years with spikes registering on the sleep electroencephalogram. Epileptic seizure was ruled out because of the characteristic rolling movement, absence of any other epileptic symptoms (e.g. vocalization and tonic-clonic seizure) and cessation as a result of removal of the blanket.

Child↗

PubMed2000

[The 1999 domestic state of development of anti-asthma].

According to the "Guideline for Diagnosis and Treatment of Asthma" established by the Japanese Society of Allergy in 1998, inhaled adrenergic beta 2 agonists and inhaled corticosteroids are recommended for treatment of asthma. Thereafter, the development of new drugs for the treatment of asthma has begun changing. The concepts upon which the development of investigational drugs for asthma are based include improvements of drug delivery systems (ease of use, long-acting preparations, fewer side-effects), device design and appropriate auxiliary instrumentation. Moreover, chronic asthma has come to be recognized as an inflammatory disease of airway mucosa. At present, various antiallergic compounds such as tachykinin, leucotrien, PAF antagonists and others are under investigation thanks to the identification of new chemical mediators of airway inflammation and studies have progressed to the synthesis and manufacturing of new pharmaceuticals with antagonistic action. Thus, this review classified and introduced various new investigational anti-asthma and further describes the structure-activity relationships of beta 2 agonists and inhaled corticosteroids.

Adrenergic beta-Agonists↗

PubMed2000

Induction of metallothionein mRNA expression in the mouse liver after cadmium injection as measured by the reverse transcriptase-polymerase chain reaction method.

Metallothioneins (MTs) are low molecular weight proteins that have been considered to be important metal-binding proteins in the defense against cadmium (Cd) toxicity in animals. These proteins are known to be induced by the injection of heavy metals such as Cd. Previously, we developed the RT-PCR method to measure the level of MT mRNA expression. In this study, we analyzed the time course and dose response of Cd-induced MT-I mRNA expression in the male and female mouse liver. By this method, we measured hepatic MT-I mRNA expression which reached the highest peak 6 h after subcutaneous injection of 1.1 mg/kg Cd in 9-week old male and female mice compared with those of corresponding controls (0 h). There was no statistical difference in the hepatic MT-I mRNA expression between male and female mice 6 h after the injection of this dosage. However, it is notable that the MT-I mRNA expression in male mice was much higher than that in females 6 h after injection of 0.5 mg/kg Cd. Thus, the induction of hepatic MT-I mRNA expression is dependent on the sex of the mouse, the dosage and the time course of Cd.

Animals↗

PubMed2000

Beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the hepatocyte nuclear factor-3beta gene (HNF3B) in Japanese patients with maturity-onset diabetes of the young.

Mutations in the transcription factors hepatocyte nuclear factor (HNF)-4alpha and -1alpha, insulin promoter factor-1, and HNF-1beta are the causes of four forms of maturity-onset diabetes of the young (MODY1 and 3-5, respectively). The winged-helix transcription factor HNF-3beta has been implicated in the regulation of expression of each of these MODY genes, suggesting that mutations in the HNF-3beta gene (HNF3B) may also cause MODY. We have tested this hypothesis by screening a panel of 57 unrelated Japanese subjects with a clinical diagnosis of MODY for mutations in HNF3B. This analysis revealed four frequent polymorphisms that were not associated with MODY, including one in the promoter region (-213A/G), two silent mutations in the codons for Ala 97 (291C/T) and Gly 279 (837A/G), and one in the 3'-untranslated region (1424C/T). Two rare substitutions in the 5'-untranslated region, -156C/T and -67A/C, were found in a heterozygous state in two subjects, and two subjects were heterozygous for putative missense mutations, S109N (326G > A) and A328V (983C>T). The two missense mutations were not found in 106 normal chromosomes from nondiabetic subjects. It was not possible to test for co-segregation of these mutations with diabetes and thus, it is unclear whether or not these mutations can cause MODY. The results of our study suggest that mutations in HNF3B are not a common cause of MODY in Japanese subjects.

Adult↗

PubMed2000

Nonsense mutation of islet-1 gene (Q310X) found in a type 2 diabetic patient with a strong family history.

Islet-1 (Isl-1) is one of the transcription factors that play an important role for the formation of the islet cells. We scanned the Isl-1 gene in 77 Japanese type 2 diabetic patients with a family history and found a heterozygous nonsense mutation (Q310X) in 1 diabetic patient. The mutation was not found in 180 nondiabetic subjects. This mutation is located in the putative transactivation domain and deletes 40 amino acids of the COOH-terminal lesion. The Q310X mutant exhibited a 50% reduction in activity compared with the wild-type when tested for stimulation of transcription of a human amylin promoter-linked luciferase reporter gene in betaTC3 cells. The patient was a 49-year-old nonobese man who was diagnosed as having type 2 diabetes at 32 years of age and has been treated with sulfonylureas. The mutation was found in his mother, who has type 2 diabetes, and in his 14-year-old daughter, who has normal glucose tolerance but a relatively low insulin response. This is the first reported finding of Isl-1 gene mutation in type 2 diabetes. Although Isl-1 is not a common predisposing gene for Japanese type 2 diabetes, the mutation in this gene may be a rare cause of diabetes in isolated families.

Adolescent↗

PubMed2000

Content and release of bisphenol A from polycarbonate dental products.

Bisphenol A (BPA) is an endocrine disruptor, and is used as a raw material for bisphenol A diglycidyl methacrylate and polycarbonate, that are used in the dental materials. In this study, the total and released amounts of BPA from polycarbonate-based dental materials were measured with high-pressure liquid chromatography (HPLC). The specimens used were orthodontic brackets and denture base resins in the same condition as when obtained commercially were cut into 3 x 3 x 4 mm pieces and crushed into powder. The HPLC analysis was carried out after immersion of the specimens in water or ethanol for a determined time. The total amount of BPA in the specimens was analyzed after dissolution in chloroform. The amount of BPA released after immersion in water for 1 hr was 0.01-0.4 microgram/g for the block samples and 0.14-4.22 micrograms/g for the crushed samples, while that in ethanol for 1 hr was 0.12-9.42 micrograms/g for the block samples and 0.42-22.24 micrograms/g for the crushed samples. The control of BPA in the denture preform resin was 78.9 micrograms/g and this increased to 90.2 micrograms/g after heating to form dentures and then to 250 micrograms/g with mechanical crushing. The results of this study indicate that BPA is released from polycarbonates used in dentistry, and that the thermal conditions during the manufacturing of restorations may cause polymer decomposition resulting in the formation of BPA.

Acrylic Resins↗

PubMed2000

Comparative study on semen quality of one- and two-year-old ganders during the entire reproductive season.

AIM: To evaluate the characteristics of semen produced by one- and two-years old White Italian ganders during the entire reproductive season, in order to clarify whether the young ganders are responsible for a low fertility rate in young geese. METHODS: Males were kept individually in cages under natural light. Semen was collected by dorso-abdominal massage three times a week and routine examination was performed. RESULTS: The mean ejaculate volume (2.1 and 1.6 mL, respectively) and sperm concentration (323 and 281 x 10(6)/mL, respectively) in one-year-old ganders were higher than those of two-year-old ones. The percentages viable spermatozoa of one- and two-year-old ganders were similar (91.4 and 92.3%, respectively), but the percentage of normally formed viable spermatozoa was significantly higher in the older ganders than in the younger (47.8 and 42.9%, respectively, P < 0.05). CONCLUSION: The semina from one- or two-year-old Ganders were similar in regard to volume, sperm density and sperm motility, but the percentage of normally formed viable spermatozoa, which is critical for fertilization, was significantly higher in the older ganders. It appears that the ganders are responsible for the low fertility rate in young geese.

Age Factors↗

PubMed1999

In vivo kinetics of transduced cells in peripheral T cell-directed gene therapy: role of CD8+ cells in improved immunological function in an adenosine deaminase (ADA)-SCID patient.

We previously reported successful peripheral T cell-directed gene therapy in a boy with adenosine deaminase (ADA)-SCID. In the present study, to better understand the reconstitutive effect of this gene therapy on his immunological system, we investigated the in vivo kinetics and functional subsets of T cells in PBL. Apparent immunological improvements were obtained after infusion of transduced cells at more than 4 x 108 cells/kg/therapy/3 mo. Frequency of ADAcDNA-integrated cells in PBL, ADA activity in PBL and clinical improvement showed good correlation, even though CD8+ cells gradually became predominant in PBL. On the basis that polyethylene glycol (PEG)-ADA was maintained at the same dosage as before gene therapy, we consider that his immunological improvement resulted from the gene therapy itself. Most CD3+ cells in PBL after gene therapy expressed TCRalphabeta. Analysis of TCR repertoire based on TCR V region usage revealed no expansion of limited clones in his PBL. The T cell subset cells CD8+CDw60+ and CD8+CD27+CD45RA-, which are reported to provide substantial help to B cells, were maintained throughout the gene therapy. Furthermore, his reconstituted peripheral T cells helped normal B cells to produce substantial IgG in vitro. Expression of both Th1- and Th2-type cytokine genes was induced in his reconstituted T cells at the same comparably high level as in normal subjects. Collectively, these results provide evidence of persistent and distinct functions of transduced cells in this patient's PBL after gene therapy.

Adenosine Deaminase↗

PubMed1999

Novel cyclopropapyrroloindole derivative (AT-3510) bearing methoxycarbonyl and trifluoromethyl groups.

The seco-Cl 3-methoxycarbonyl-2-trifluoromethylcyclopropapyrroloindole (MCTFCPI) derivatives dl- and/or (S)-10 carrying various acyl moieties at the N6-position were synthesized along with their prodrugs (S)-12, and their antitumor activity was evaluated. Among these derivatives, AT-3510 [(S)-12m], the novel prodrug MCTFCPI derivative carrying a 5-(7-methoxybenzofuran-2-ylcarbonyl)aminoindole-2-carb onyl group at the N6-position, was found to exhibit more excellent antitumor activity against human tumor xenografts than the clinical trial candidates carzelesin (6) and KW-2189 (7) and cisplatin.

Animals↗

PubMed1999

Molecular cloning and pharmacological characterization of a somatostatin receptor subtype in the gymnotiform fish Apteronotus albifrons.

The actions of the various forms of somatostatin (SRIF), including those of the tetradecapeptide SRIF(14), are mediated by specific receptors. In mammals, five subtypes of SRIF receptors, termed sst(1-5), have been cloned. Using a combination of reverse transcriptase-polymerase chain reaction and genomic library screening in the gymnotiform fish Apteronotus albifrons, a gene encoding the first-known nonmammalian SRIF receptor has been isolated. The deduced amino acid sequence displays 59% identity with the human sst(3) receptor protein; hence, the gene is termed "Apteronotus sst(3)." The predicted protein consists of 494 amino acid residues exhibiting a putative seven-transmembrane domain topology typical of G protein-coupled receptors. A signal corresponding to the Apteronotus sst(3) receptor was detected in brain after amplification of poly(A)(+)-RNA by reverse transcriptase-polymerase chain reaction, but not by Northern blot analysis or in situ hybridization, suggesting a low level of expression. Membranes prepared from CCL39 cells stably expressing the Apteronotus sst(3) receptor gene bound [(125)I][Leu(8),d-Trp(22), (125) I-Tyr(25)]SRIF(28) with high affinity and in a saturable manner (B(max) = 4470 fmol/mg protein; pK(D) = 10.5). SRIF(14) and various synthetic SRIF receptor agonists produced a dose-dependent inhibition of radioligand binding, with the following rank order of potency: SRIF(14) approximately SRIF(28) > BIM 23052 > octreotide > BIM 23056. Under low stringency conditions, an Apteronotus sst(3) probe hybridized to multiple DNA fragments in HindIII or EcoRI digests of A. albifrons DNA, indicating that the Apteronotus sst(3) receptor is a member of a larger family of Apteronotus SRIF receptors.

Amino Acid Sequence↗

PubMed1999

Expression of adenosine triphosphate-sensitive potassium channel subunits in female rat reproductive tissues: overlapping distribution of messenger ribonucleic acid for weak inwardly rectifying potassium channel subunit 6.1 and sulfonylurea-binding regulatory subunit 2.

OBJECTIVE: Potassium channel activation has been shown to decrease uterine tone and is a target for inhibition of uterine activity in the treatment of preterm labor. In addition, potassium channel activation also appears to be involved in oocyte maturation. The specific potassium channels responsible for these channel currents have not been identified but are known to be responsive to such agents as pinacidil and to be inhibited by glibenclamide. These findings suggest the presence of an adenosine triphosphate-sensitive potassium channel that is a complex of a weak inwardly rectifying potassium channel subunit 6.1 or 6.2 and sulfonylurea-binding regulatory subunit 1 or 2. STUDY DESIGN: The technique of reverse transcriptase-polymerase chain reaction was used to detect the presence of messenger ribonucleic acid for sulfonylurea-binding regulatory subunit 1 and 2 and weak inwardly rectifying potassium channel subunit 6.1 and 6.2 in the ovary and myometrium of the pregnant rat. In situ hybridization histochemical analysis was used to identify the specific cell types expressing each messenger ribonucleic acid. RESULTS: Reverse transcriptase-polymerase chain reaction analysis found expression of messenger ribonucleic acid for sulfonylurea-binding regulatory subunits 1 and 2B and messenger ribonucleic acid for weak inwardly rectifying potassium channel subunit 6.1 in rat myometrium and ovary during gestation. There was no evidence for expression of weak inwardly rectifying potassium channel subunit 6.2 messenger ribonucleic acid in the ovary or the myometrium of the pregnant rat. In situ hybridization histochemical examination localized expression of messenger ribonucleic acid for sulfonylurea-binding regulatory subunit 2B and messenger ribonucleic acid for weak inwardly rectifying potassium channel subunit 6.1 to uterine myocytes and granulosa cells of the corpus luteum. The cells expressing sulfonylurea-binding regulatory subunit 1 messenger ribonucleic acid could not be identified because of the scarcity of this messenger ribonucleic acid. Messenger ribonucleic acid for sulfonylurea-binding regulatory subunit 1, messenger ribonucleic acid for sulfonylurea-binding regulatory subunit 2B, and messenger ribonucleic acid for weak inwardly rectifying potassium channel subunit 6.1 were also observed in the placenta by in situ hybridization histochemical examination. CONCLUSION: The results suggest that the major adenosine triphosphate-sensitive potassium channel expressed in the myometrium and the corpus luteum during pregnancy is a complex of sulfonylurea-binding regulatory subunit 2B and weak inwardly rectifying potassium channel subunit 6.1.

ATP-Binding Cassette Transporters↗

PubMed1999

A new method of double cardiomyoplasty: "contractile muscular sling".

BACKGROUND: In several experimental studies, double cardiomyoplasty using both latissimus dorsi muscles did not provide sufficient assist to the failing heart and did not clearly show improvement compared with single cardiomyoplasty. This study demonstrated the superior efficacy of our method of double cardiomyoplasty compared with single cardiomyoplasty. METHODS: In 16 dogs, the two latissimus dorsi muscles were crossed in front of the heart and directly sutured to each other behind the heart. Control hemodynamic measurements were obtained, and acute heart failure was induced by intravenous administration of propranolol. After the hemodynamic changes with bilateral latissimus dorsi muscle assistance were measured, single cardiomyoplasty was done in the same dog, and the hemodynamic variables were measured. RESULTS: With our double cardiomyoplasty, aortic systolic pressure increased by 25% (p < 0.001); pulmonary artery systolic pressure, by 40% (p < 0.001); end-systolic elastance, by 155% (p < 0.001); and cardiac output, by 55% (p < 0.001). There were significant increases in aortic pressure, pulmonary artery pressure, end-systolic elastance, stroke volume, and cardiac output with our double cardiomyoplasty compared with single cardiomyoplasty. CONCLUSIONS: In this study, our double cardiomyoplasty provided significant hemodynamic improvement compared with single cardiomyoplasty.

Animals↗

PubMed1999

Epworth Sleepiness Scale and sleep studies in patients with obstructive sleep apnea syndrome.

Excessive daytime sleepiness (EDS) is the major symptom of patients with obstructive sleep apnea syndrome (OSAS). In this study, we examined the relationship between subjective EDS scored with the Epworth Sleepiness Scale (ESS), objective EDS measured with the multiple sleep latency test (MSLT) and sleep variables evaluated with polysomnography for patients with OSAS. Subjects were 10 patients (51.7+/-19.0 years old). The average ESS and MSLT scores were 10.6+/-5.6 and 7.7+/-5.6, respectively. There was no significant relationship between ESS and MSLT. The Multiple Sleep Latency Test had a significant negative relationship with the number of awakenings and the apnea/hypopnea index. No relationship was found between nocturnal hypoxia and either ESS or MSLT. Our findings suggest that objective EDS in OSAS is related with fragmentation of sleep, and that several patients are not aware of their EDS.

Adult↗

PubMed1999

Double-blind test on the efficacy of methylcobalamin on sleep-wake rhythm disorders.

The therapeutic effect of methylcobalamin (Met-12) on sleep-wake rhythm disorders was examined in a double-blind test. In the test group which was given a large dosage, a higher percentage of improvement was found compared to the control group with a small dosage, although the difference was not significant. The test group inconsistently showed significant improvement in both the sleep-wake cycle parameters and in clinical symptoms. The tendency was for the results to show a beneficial effect of Met-12 on rhythm disorders. However, because the percentage of improvement was low and significant improvement was inconsistent, Met-12 might be considered to have a low therapeutic potency and possible use as a booster for other treatment methods of the disorders.

Affect↗

PubMed1999

Polysomnographic and urodynamic changes in a case of obstructive sleep apnea syndrome with enuresis.

A 53-year-old female patient with obstructive sleep apnea syndrome was reported. She had complained of enuresis as well as a 15-year history of snoring, but she had no complaint of sleep and awake disturbance. Polysomnographic study showed repeated obstructive apnea and hypopnea with an apnea/hypopnea index of 52.6, and severe oxygen desaturation during sleep. On cystometography during sleep, the changing amplitude of the spike wave corresponds to the changes of respiratory efforts against a closed upper airway. The patient was treated successfully with imipramine and acetazolamide for the obstructive sleep apnea and enuresis. Apnea/hypopnea index, nocturnal oxygen desaturation, and sleep architecture were improved, and enuresis completely disappeared. Cystometrography during sleep showed that the average amplitude of the spike wave tended to be low. Percentage urinary volume during sleep compared with 24 h volume was significantly reduced. We considered that the enuresis was mainly related to increased intra-abdominal pressure produced by respiratory efforts and enhanced nocturnal urine production.

Acetazolamide↗

PubMed1999

Expression of mRNAs encoding hormone receptors in the endolymphatic sac of the rat.

The endolymphatic sac (ES) is believed to absorb the endolymphatic fluid produced by the stria vascularis and vestibular dark cells. Recent studies have implied that the function of the ES may be controlled by circulating hormones, suggesting that hormone receptors should exist there. In the present study, the expression of genes encoding receptors for aldosterone, atrial natriuretic peptide (ANP) and vasopressin in the ES was examined by reverse transcription-polymerase chain reaction (RT-PCR). Next, the cellular localization of the expression of these genes was investigated by in situ hybridization. RT-PCR indicated that aldosterone. ANP-A and vasopressin V1a receptor genes were expressed in the ES. In contrast, neither ANP-B nor vasopressin V2 receptor gene expression was detected. In situ hybridization experiments demonstrated aldosterone receptor gene expression in epithelial cells of the intermediate potion of the ES, while expression of ANP-A or V1a receptor genes was not detected. The present results suggested that aldosterone may play a specific role in the function of the ES. However, we could not conclude that ANP and vasopressin play physiological roles in the ES because receptors for these hormones were detected only by highly sensitive PCR.

Aldosterone↗

PubMed1999

[NIDDM susceptibility genes].

Non-insulin dependent diabetes mellitus (NIDDM) is a heterogeneous disorder and both genetic and nongenetic factors are associated with the development of diabetes. Until now five genes (HNF-4 alpha, glucokinase, HNF-1 alpha, IPF-1 and HNF-1 beta), whose mutation can result in MODY, insulin and insulin receptor genes, and mitochondria DNA have been reported to be responsible for diabetes. Furthermore the mutations in some genes which work for insulin secretion or action also have been reported. This review discusses our current knowledge of these NIDDM susceptibility genes.

Diabetes Mellitus, Type 2↗