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Biomedical subjects

H Masuzaki

Publications and source records attributed to H Masuzaki.

At least 73 records · Page 4Linked to original sources
PubMed1997

Augmentation of obese (ob) gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats).

To explore the pathophysiologic roles of the obese (ob) gene product, leptin, in the development of obesity and hypertension, we examined ob gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats) at the stage of established obesity and hypertension. Expression of the ob gene was augmented in the epididymal, mesenteric, subcutaneous, and retroperitoneal white adipose tissue (WAT) from 20-week-old male obese SHR compared to their lean littermates (lean SHR). Using a radioimmunoassay for rat leptin, we also measured plasma leptin levels in 20-week-old lean and obese SHR. Plasma leptin levels in obese SHR (292.5 +/- 37.1 ng/ml) were more than 100-fold higher than those in lean SHR (2.8 +/- 1.0 ng/ml). The present study demonstrates that ob gene expression and leptin secretion are markedly augmented in obese SHR.

Animals↗
PubMed1997

Fetal redistribution of blood flow and amniotic fluid volume in growth-retarded fetuses.

Our purpose was to assess the relationship between the fetal redistribution of blood flow and the amount of amniotic fluid in appropriate-for gestational-age fetuses and growth-retarded fetuses. Blood flow velocity waveforms of the umbilical artery, descending aorta, middle cerebral artery, renal artery and uterine artery were recorded using pulsed Doppler ultrasonography in 100 appropriate-for gestational age fetuses and 39 growth-retarded fetuses. The pulsatility index (PI) values and the amount of amniotic fluid were compared between the two groups. The PI values of the umbilical artery and renal artery were significantly higher in appropriate for gestational-age-fetuses with oligohydraminos than in fetuses with an adequate amount of amniotic fluid. The PI values of the umbilical artery and renal artery were significantly higher and the PI of the middle cerebral artery was significantly lower in growth-retarded fetuses with oligohydramnios than in fetuses with an adequate amount of amniotic fluid. Furthermore, there was a significant negative correlation between the PI value of the renal artery and the vertical diameter of amniotic fluid, and between the PI value of the renal artery and the amniotic fluid index. The PI value of the renal artery was related to the amount of amniotic fluid in growth-retarded fetuses, and the same relationship was demonstrated in appropriate-for gestational age fetuses.

Amniotic Fluid↗
PubMed1997

Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity.

Leptin is an adipocyte-derived blood-borne satiety factor that acts on its cognate leptin receptor (Ob-R) in the hypothalamus, thereby regulating food intake and energy expenditure. To explore whether mutations in the Ob-R gene cause obesity in humans, we have searched for mutations in the gene for Ob-Rb, a biologically active receptor isoform, in obese Japanese subjects. We have also examined associations between such mutants and obesity in the Japanese. Genomic DNAs were used as templates in polymerase chain reaction (PCR) with primers selected to amplify exons 2 to 20 of the human Ob-Rb gene. Direct sequence analysis of the PCR products revealed 7 nucleotide sequence variants (Lys109Arg, Gln223Arg, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the Ob-Rb coding region from 17 obese Japanese subjects with a family history of obesity (BMI 39.3 +/- 8.4 kg/m2). No missense and nonsense mutations were found such as those in Zucker fatty (fa/fa) rats and Koletsky (fa[k]/ fa[k]) rats. Nucleotide substitutions occurred at relatively high frequencies at codons 109, 223, 976, and 1019 (79, 91, 100, and 85%, respectively). Allele frequency of each variant determined by PCR-RFLP and PCR-single strand conformation polymorphism analyses showed no significant differences between 47 obese (BMI 35.1 +/- 6.5 kg/m2) and 68 non-obese (BMI 21.6 +/- 2.2 kg/m2) subjects. The present study represents the first report of sequence variants of the Ob-Rb gene in the Japanese and provides evidence against either obesity-causing mutations or association of sequence variants with obesity in obese Japanese subjects.

Adolescent↗
PubMed1997

The effects of oligohydramnios and cervical cord transection on lung growth in experimental pulmonary hypoplasia in rabbits.

OBJECTIVE: Our goal was to examine the effects of oligohydramnios and cervical cord transection on fetal lung development, pulmonary surfactant, and lung mechanics in rabbits. STUDY DESIGN: The amniotic fluid was shunted into the maternal abdominal cavity in a group of 12 fetal rabbits. In another group (n = 12) high cervical cord transection was performed at day 24 of gestation. Another 12 littermates not operated on served as the control group. Fetuses were delivered on day 30 of gestation by cesarean section and immediately put to death. The body weight and wet lung and liver weights were measured. To determine the extent of fetal lung growth, we measured the size of lung acini, the number of terminal airspaces, and the diameter of alveoli. We also measured the dynamic compliance of the lung, the concentration of phosphatidylcholine, and the lecithin/sphingomyelin ratio in lung lavage fluid at birth. RESULTS: Amniotic fluid shunting produced a significant reduction in amniotic fluid volume. Amniotic shunt and cervical cord transection significantly decreased wet lung weight and fetal lung/body weight ratio compared with the control. The concentration of phosphatidylcholine and the lecithin/sphingomyelin ratio in lung fluid lavage from fetuses with amniotic shunt were significantly higher than the values for control and cord transection fetuses. Histopathologic examination of the lungs showed significant reductions in the size of acini, the number of terminal airspaces, and the diameter of alveoli in shunted and cord transection groups compared with the control group. The dynamic compliance of transection fetuses was significantly reduced compared with control and shunted fetuses. CONCLUSION: Our results indicate that oligohydramnios or cervical cord transections cause pulmonary hypoplasia. However, oligohydramnios-induced pulmonary hypoplasia is associated with increased pulmonary surfactant compared with control and cord transection fetuses.

Animals↗
PubMed1997

Expression of estrogen and progesterone receptors in endometrium and peritoneal endometriosis: an immunohistochemical and in situ hybridization study.

OBJECTIVE: To clarify the role of ovarian steroids in the development and progression of endometriosis, estrogen receptors (ERs) and progesterone receptors (PRs) were localized by immunohistochemistry, and ER messenger RNA (mRNA) was detected by in situ hybridization in the uterine endometrium and in normal and altered pelvic peritoneum. DESIGN: Retrospective and prospective study. SETTING: Nagasaki University School of Medicine, Nagasaki, Japan. PATIENT(S): A retrospective study of 61 formalin-fixed uterine endometria and normal and altered pelvic peritonea from patients suffering from various gynecologic diseases was conducted. In addition, in 22 fresh frozen tissue specimens, ER mRNA expression was evaluated prospectively. MAIN OUTCOME MEASURE(S): In formalin-fixed tissues, ER and PR were localized immunohistochemically. The results of immunohistochemical staining were scored from 0 to 4, depending on the signal intensity and frequency of positive cells. In fresh frozen specimens, ER mRNA expression was assessed by nonradioactive in situ hybridization using thymine-thymine dimerized oligonucleotide probes. RESULTS: The highest score of ERs and PRs was observed in the epithelial and stromal cells of the normal uterine endometrium at the early proliferative phase of the menstrual cycle. The ER and PR scores declined throughout the secretory phase. In typical endometriotic lesions, the ER and PR scores were constantly high independent of the menstrual cycle. The expression pattern of ER mRNA was mostly in parallel with that of ERs. In typical endometriosis, ERs and PRs were found in both glandular epithelial cells and their surrounding stromal cells. Expression of ER mRNA was found in typical endometriotic peritonea and in pelvic peritoneum with columnar epithelial cells, but not in normal pelvic peritoneum (mesothelium). Estrogen receptors and PRs were negative in mesothelium, but were positive in the nuclei of fibroblasts in the connective tissue. CONCLUSION(S): We demonstrated the expression of ERs, ER mRNA, and PRs in the columnar cells in pelvic peritonea and typical endometriosis, but not in normal mesothelium. These results suggest that endometriosis may originate from the columnar cells with ERs and PRs in the pelvic peritoneal lining.

Endometriosis↗
PubMed1997

Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans.

Leptin is a circulating hormone that is expressed abundantly and specifically in the adipose tissue. It is involved in the regulation of energy homeostasis, as well as the neuroendocrine and reproductive systems. Here, we demonstrate production of leptin by nonadipose tissue, namely, placental trophoblasts and amnion cells from uteri of pregnant women. We show that pregnant women secrete a considerable amount of leptin from the placenta into the maternal circulation as compared with nonpregnant obese women. Leptin production was also detected in a cultured human choriocarcinoma cell line, BeWo cells, and was augmented during the course of forskolin-induced differentiation of cytotrophoblasts into syncytiotrophoblasts. Plasma leptin levels were markedly elevated in patients with hydatidiform mole or choriocarcinoma and were reduced after surgical treatment or chemotherapy. Leptin is also produced by primary cultured human amnion cells and is secreted into the amniotic fluid. The present study provides evidence for leptin as a novel placenta-derived hormone in humans and suggests the physiologic and pathophysiologic significance of leptin in normal pregnancy and gestational trophoblastic neoplasms.

Adipose Tissue↗
PubMed1997

Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats: evidence for loss of its satiety effect in VMH-lesioned rats.

To explore the pathophysiological significance of the obese (ob) gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats, we examined the synthesis and secretion of leptin and its satiety effect in VMH-lesioned rats compared with those in sham-operated rats. Northern blot analysis revealed that ob gene expression is markedly augmented in the mesenteric and sc white adipose tissue, but remained unchanged in the epididymal white adipose tissue during the development of obesity in VMH-lesioned rats. Plasma leptin levels were relatively constant in sham-operated rats, but were elevated during the development of obesity in VMH-lesioned rats. In sham-operated rats, a single i.v. (1.0 mg/rat) or intracerebroventricular (2.0 micrograms/rat) injection of recombinant human leptin reduced food intake and body weight gain in sham-operated rats. By contrast, no significant effect on food intake or body weight gain was observed in VMH-lesioned rats. The present study provides evidence that VMH-lesioned rats overproduce leptin and increase its release but cannot respond to it and suggests that the loss of its satiety effect contributes to the development of obesity and the obesity-related phenotypes in VMH-lesioned rats.

Animals↗
PubMed1997

Glucocorticoid regulation of leptin synthesis and secretion in humans: elevated plasma leptin levels in Cushing's syndrome.

Leptin, the obese (ob) gene product, is an adipocyte-derived satiety factor that is involved in the regulation of food ingestion and body weight. To investigate glucocorticoid regulation of leptin synthesis and secretion in humans, we measured plasma leptin levels in patients with Cushing's syndrome with adrenal or pituitary adenoma and in patients with iatrogenic Cushing's syndrome. Plasma leptin levels in patients with Cushing's syndrome were significantly elevated compared to those in nonobese healthy subjects and obese subjects without any metabolic or endocrine diseases at a given percentage of body fat by analysis of covariance. In patients with adrenal or pituitary adenoma, after the tumor resection, plasma leptin levels were reduced, with a concurrent decrease in plasma cortisol levels. With no significant changes in body weight, plasma leptin levels were also elevated significantly in lean healthy volunteers 24 h after the administration of 1 mg dexamethasone. Dexamethasone potently induced ob gene expression and leptin secretion in the organ culture of human adipose tissue. The data demonstrate that glucocorticoids act, at least in part, directly on the adipose tissue and increase leptin synthesis and secretion in humans.

Adenoma↗
PubMed1997

Molecular screening of both the promoter and the protein coding regions in the human ob gene in Japanese obese subjects with non-insulin-dependent diabetes mellitus.

OBJECTIVE: Although the molecular mechanism of obesity has been poorly understood, recent studies indicate that leptin plays a critical role in regulating both food intake and body weight. Because obesity decreases the sensitivity to insulin, the human ob gene is presumed to be one of the candidate genes for non-insulin-dependent diabetes mellitus (NIDDM) associated with obesity. Although the protein coding region in the ob gene has been screened for mutations, the promoter region and the non-coding first exon have not yet been studied. We investigated the involvement of the human ob gene, especially mutations at the promoter region and the non-coding first exon, in the development of NIDDM associated with obesity. SUBJECTS: The study group comprised 60 Japanese obese subjects with NIDDM (body mass index (BMI) 43.6 > or = BMI > or = 26.4, 29.0+/-0.41 (mean+/-S.E.M.)) and 24 obese individuals with impaired glucose tolerance (IGT) (30 > or = BMI > or = 26.4, 27.1+/-0.22). METHODS: Mutations at both the promoter region and all three exons in the human ob gene were screened by the single-stranded conformational polymorphism analysis. When aberrantly migrated bands were recognized, the PCR-amplified DNA fragment was directly sequenced. RESULTS: In the protein coding region a silent mutation in the second exon was detected. The non-coding first exon and the about 100 bp 5'-flanking region of the gene which contains a proximal CCAAT/enhancer-binding protein site were screened, but no mutations were found. CONCLUSION: These results suggest that no mutations in either the promoter region at the about 100 bp 5'-flanking region of the gene, or in any of the three exons, are involved in the development of NIDDM or IGT associated with obesity.

Asian People↗
PubMed1997

Comparison between the single deepest pocket and amniotic fluid index in predicting fetal distress in small-for-gestational age fetuses.

BACKGROUND: The relationship between reduced amniotic fluid volume and increased risk of fetal distress in small-for-gestational age fetuses is not yet clear. Furthermore, the criteria used for the diagnosis of 'oligohydramnios' are different between the single deepest pocket method and amniotic fluid index. We investigated the relationship between the single deepest pocket and amniotic fluid index and their ability in predicting fetal distress in small-for-gestational age fetuses. METHOD: We examined 69 pregnant women with singleton pregnancy, intact membranes, birth weight below the 50% percentile - 1.5 s.d., in whom delivery occurred within seven days of the last estimation of amniotic fluid volume. Amniotic fluid volume was measured in each woman simultaneously by single deepest pocket and amniotic fluid index. Fetal distress was determined by intrapartum monitoring of fetal heart rate. RESULTS: Estimates of amniotic fluid volume measured by the two methods showed a significant correlation at 24 to 41 weeks of gestation. A cut-off value for single deepest pocket of 3.0 cm was associated with the highest accuracy in predicting fetal distress in small-for-gestational age fetuses. The rate of cesarean section among patients with single deepest pocket <3.0 cm was higher than that in amniotic fluid index <8.0 cm. CONCLUSION: Our results demonstrated that a single deepest pocket measurement of <3 cm is the most useful criterion for 'oligohydramnios' in the prediction of fetal distress.

Amniotic Fluid↗
PubMed1996

Effects of gemfibrozil administration on very low density lipoprotein receptor mRNA levels in rabbits.

To elucidate the regulation of very low density lipoprotein (VLDL) receptor gene expression, we administered to rabbits for 14 days gemfibrozil, a fabric acid derivative and a lipid lowering drug that is also included among peroxisome proliferators. VLDL receptor mRNA levels were examined by Northern blot analysis. The VLDL receptor mRNA levels in retroperitoneal adipose tissue and in gastrocnemius muscle were increased 6.9-fold and 3.7-fold, respectively, with gemfibrozil treatment, but no marked changes were observed in the heart, the organ in which VLDL receptor is most highly expressed. In the liver, VLDL receptor mRNA was not detected either before or after gemfibrozil administration. Lipoprotein lipase (LPL) and long-chain acyl coenzyme A synthetase (ACS) mRNA levels were also increased in parallel in adipose tissue. The enhanced expression of VLDL receptor mRNA may contribute to the increase of triglyceride-rich lipoprotein catabolism in peripheral tissues such as adipose tissue and muscles.

Adipose Tissue↗
PubMed1996

Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in Zucker fatty (fa/fa) rats.

We cloned the full-length rat leptin receptor (Ob-R) isoform complementary DNAs (cDNAs) and examined the gene expression in rats. We also identified a mutation in Ob-R in Zucker fatty (fa/fa) rats. Three alternatively spliced isoforms (Ob-Ra, Ob-Rb, and Ob-Re) have been identified, which are closely related to the gp130 signal-transduction component of class I cytokine receptors. Rat Ob-Ra and Ob-Rb were single transmembrane proteins, which differ in the C-terminal amino acid sequences. On the other hand, Ob-Re had no transmembrane domain and was a soluble form of the receptor. Reverse transcription-polymerase chain reaction analysis revealed that Ob-R isoform messenger RNAs (mRNAs) are expressed in a wide variety of rat tissues in tissue-specific manners. A missense mutation (an A to C conversion at nucleotide position 806) was found in the extracellular domain of all the isoforms in Zucker fatty (fa/fa) rats, which resulted in an amino acid change from Gln to Pro at + 269 (the Gln269Pro mutation). These Ob-R isoform mRNAs were present in the brain from Zucker fatty (fa/fa) rats at comparable amounts to those in their lean littermates. The present study provides new insight into the molecular mechanisms for Ob-R.

Alternative Splicing↗
PubMed1996

Development of radioimmunoassay for human leptin.

Using recombinant human leptin, we have produced an antiserum for human leptin and developed a radioimmunoassay (RIA) specific and sensitive for human leptin. We detected leptin-like immunoreactivity (-LI) in culture media of adipose tissue from subcutaneous abdominal fat in human. The plasma leptin-LI concentration in nonobese subjects (17.6 <body mass index (BMI)<23.0) was 5.6 +/- 1.3 (mean +/-SE) ng/ml, while that in obese subjects (29.0 <BMI) was 43.0 +/- 9.4 (mean +/- SE) ng/ml. In gel permeation chromatographic analyses, leptin-LI in culture media and plasma consisted of single component emerging at the elution position of recombinant human leptin. These findings indicate that leptin is secreted from the adipose tissue into the circulating blood as a large molecular form corresponding to recombinant leptin. The RIA developed in the present study will be a powerful tool to investigate the physiological and pathophysiological significance of leptin in human.

Adipose Tissue↗
PubMed1996

Augmented expression of obese (ob) gene during the process of obesity in genetically obese-hyperglycemic Wistar fatty (fa/fa) rats.

Expression of the obese (ob) gene is up-regulated in the adipose tissue in several obese rodent models. To study the regulation of the ob gene expression during the development of obesity, we examined the ob gene expression in genetically obese-hyperglycemic Wistar fatty (fa/fa) rats at several stages of obesity. The ob mRNA levels in the adipose tissue from Wistar fatty rats was unequivocally augmented and continued to rise in the process of obesity. Furthermore, the ob gene expression in this obese model was much more rapidly enhanced in the mesenteric fat than in the subcutaneous fat. Moreover, the ob gene expression was more greatly augmented in the mesenteric fat than the lipoprotein lipase gene expression. These results suggest the presence of obesity-linked and region-specific regulation of the ob gene expression.

Adipose Tissue↗
PubMed1996

A partial hydatidiform mole with 2N/3N mosaicism identified by molecular analysis.

PURPOSE: A placenta with a partial hydatidiform mole was studied using DNA polymorphic markers to determine whether it has a triploid cell line. METHOD: Parent-mole transmission of alleles at 23 polymorphic loci was traced in cells from a molar region and a normal-looking region of the placenta by polymerase chain reaction (PCR) amplification or Southern blot analysis, both followed by densitometric analysis. RESULTS: Allele patterns for 8 of the 23 loci were identical between the DNA from the molar and normal regions of the placenta, while those of the remaining 15 loci were uninformative. In the molar region, the band intensity for the paternally derived allele at each informative locus was always greater than that of the maternally derived allele, the average intensity ratio of the former to the latter being 1.5, whereas the ratio in the normal region was even. CONCLUSIONS: The results suggested that the molar region was a mixoploid consisting of diploid and triploid cells and the phenotypically normal region had a mainly diploid constitution. It is most likely that the placenta may have originated from a single diploid or triploid conceptus, followed by postzygotic gain or loss of a paternal haploid set, and that an extra paternal set contributed to hydropic changes of the placenta.

Diploidy↗
PubMed1996

Ultrasonographic prediction of lethal pulmonary hypoplasia: comparison of eight different ultrasonographic parameters.

OBJECTIVE: The aim of this study was to determine the usefulness of eight different ultrasonographic fetal parameters for predicting fetal pulmonary hypoplasia. STUDY DESIGN: Nomograms of eight different ultrasonographic fetal parameters were evaluated by studying uncomplicated single fetus pregnancies with well-established dates between 18 and 40 weeks of gestation. The eight parameters, which could reflect fetal lung mass, were as follows: thoracic circumference, thoracic area, thoracic area minus heart area, lung area, thoracic circumference/abdominal circumference ratio, thoracic area/heart area ratio, thoracic area minus heart area/thoracic area ratio and lung area/thoracic area ratio. The relative efficacy of the eight parameters was determined by studying 21 fetuses at high risk for development of lethal pulmonary hypoplasia and 30 fetuses with premature rupture of membranes within 1 week. RESULTS: The lung area (gestational age-dependent parameter) and the thoracic circumference/abdominal circumference (gestational age-independent parameter) ratio had the best diagnostic accuracy (sensitivity 81.3% and 90.5%, specificity 100% and 90.0%, positive predictive value 100% and 86.4%, negative predictive value 90.9% and 93.1%, respectively). There were significant linear relationships between lung weight and lung area and between the lung weight/body weight ratio and the thoracic circumference/abdominal circumference ratio. CONCLUSION: These data suggested that the application of lung area and the thoracic circumference/abdominal circumference ratio are clinically useful for the evaluation of fetal pulmonary hypoplasia.

Abdomen↗
PubMed1996

Hyperinsulinemia increases the risk of gestational hypertension.

OBJECTIVE: To determine whether hyperinsulinemia is related to gestational hypertension. METHODS: We measured the arterial blood pressure and the level of immunoreactive insulin (IRI) during a 75 g oral glucose tolerance test in a total of 84 pregnant women. Hyperinsulinemia was defined as a fasting IRI level > or = 9 IU/l, while gestational hypertension was defined as arterial blood pressure > or = 140/90 mmHg. RESULTS: The incidence of gestational hypertension was higher in the hyperinsulinemic group (n = 29) than in the control group (n = 55) (24.1% vs. 7.3%, respectively P < 0.05). After controlling for maternal age, parity, pre-pregnancy body mass index and the gestational age at the time of oral glucose tolerance test (OGTT), using a multiple regression model, the relative risk of developing gestational hypertension for a fasting insulin level was 1.19 (95% C.I., 1.03-1.38). CONCLUSION: Pregnant women with hyperinsulinemia are at increased risk of developing gestational hypertension.

Adult↗