Biomedical subjects

K Hosoda

Publications and source records attributed to K Hosoda.

At least 55 records · Page 3Linked to original sources

PubMed1999

Thyrotropin decreases leptin production in rat adipocytes.

Leptin, which is secreted from adipocytes, has a role in the regulation of appetite and energy expenditure. The thyrotropin receptor (TSH-R) was recently found in adipocytes. We examined the effects of TSH on leptin production and lipolysis in rat epididymal adipocytes. TSH decreased the concentration of leptin in the medium time (approximately 24 hours)- and dose (approximately 10(-7) mol/L)-dependently (half-maximal inhibition [IC50] approximately 10(-9) mol/L). TSH also decreased the ob mRNA level approximately 55% in adipocytes. We confirmed the presence of TSH-R mRNA in the adipocytes by reverse transcription-polymerase chain reaction (RT-PCR). TSH stimulated glycerol release dose-dependently (IC50 approximately 10(-8) mol/L) in adipocytes. This TSH-induced glycerol release was further enhanced by adenosine deaminase (ADA). In summary, TSH reduced leptin production and stimulated lipolysis in rat epididymal adipocytes. Although the pathophysiological relevance of the regulation of leptin production and lipolysis by TSH is unknown, we speculate that TSH may affect the regulation of appetite and energy expenditure in pathophysiological states.

Adipocytes↗

PubMed1999

Effect of clot removal and surgical manipulation on regional cerebral blood flow and delayed vasospasm in early aneurysm surgery for subarachnoid hemorrhage.

BACKGROUND: Effect of clot removal and surgical manipulation on cerebral blood flow (CBF) and delayed vasospasm was studied in early aneurysm surgery for subarachnoid hemorrhage (SAH). METHODS: Thirty-two patients in this study fulfilled the following criteria: ruptured anterior communicating aneurysms, computed tomography (CT) within 2 days and unilateral pterional approach within 3 days after the ictus, bilaterally symmetrical clots without intracerebral hematoma, no postoperative complication, and CBF studies with single photon emission computed tomography (SPECT) with 123I-IMP. RESULTS: Postoperative regional hypoperfusion due to brain retraction was frequently recognized on 123I-IMP-SPECT without infarction. The regional CBF (rCBF) showed a continuous fall during the first 4 weeks after the ictus, followed by improvement. The rCBF in the vicinity of the surgical route was significantly lower, especially in the acute stage (Day 3-7). A significant association between decrease of cisternal blood after surgery and the degree of local vasospasm and local CBF values during spasm stage was observed in the interhemispheric cisterns, A2 and medial frontal cortex, but not in the sylvian fissure or insular cisterns, M1 or M2, and frontal watershed and temporal cortex. CONCLUSIONS: The present study provides evidence for the effectiveness of direct clot removal by early surgery for SAH on local vasospasm and CBF reduction. However, a potential improvement in local CBF with clot removal could be masked by brain retraction, which was demonstrated to affect rCBF adversely. Therefore, it is critical to perform brain retraction as gently as possible.

Adult↗

PubMed1999

The use of an external-internal shunt in the treatment of extracranial internal carotid artery saccular aneurysms: technical case report.

BACKGROUND: Extracranial internal carotid artery aneurysms (EICAA) are rare lesions. Resection and grafting is the preferred method of management. However, the details of shunt use in surgery for this type of aneurysm has been described in few articles. We describe an external-internal shunt with intra-aneurysmal trans-orifice insertion. CASE REPORT: A 55-year-old woman presented with a 5-year history of a progressively enlarging pulsatile neck mass. An examination revealed no neurological deficit. Right carotid angiogram showed a saccular EICAA involving the ICA distal to the bifurcation, with kinking of the internal carotid artery (ICA). The dome of the EICAA extended from the upper border of C4 to the midportion of C2 and the maximum diameter was 4 cm. RESULTS: Using the shunt technique, we successfully removed the aneurysm and reconstructed the ICA. The end-to-end anastomosis was easy because the shunt was involved only in the distal free end of the ICA, but not in the proximal free end of the ICA. CONCLUSION: This technique could be an option for the treatment of EICCA when a shunt is needed to maintain the cerebral circulation.

Anastomosis, Surgical↗

PubMed1999

Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor gamma.

1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma. 3. cDNA of rat PPAR gamma 1 and gamma 2 were cloned and gene regulation of PPAR gamma in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPAR gamma mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-alpha, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPAR gamma expression. 5. Thiazolidinediones dose-dependently recovered TNF-alpha-induced down-regulation of PPAR gamma mRNA expression. 6. The modulation of PPAR gamma expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPAR gamma gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.

Adipose Tissue↗

PubMed1999

New members of uncoupling protein family implicated in energy metabolism.

1. The regulation of energy metabolism involves food intake and energy expenditure. Mitochondrial uncoupling proteins (UCP) are implicated in energy expenditure. 2. cDNA of a homologue of UCP highly expressed in rat skeletal muscle, UCP-3, is isolated and sequenced. Rat UCP-2 cDNA is also isolated and sequenced. 3. Rat UCP-3 cDNA probe hybridized two bands, a major band at 2.5 kb and a minor band at 2.8 kb in rat tissues. The mRNA was expressed at the highest level in the skeletal muscle, and moderately in the interscapular brown adipose tissue (BAT). Only weak signals were detected in the epididymal white adipose tissue (WAT) and the heart. Rat UCP-2 cDNA probe hybridized a 1.7 kb band detected widely in the whole body, especially abundant in the lung and the spleen. In contrast to the UCP-3 gene expression, the UCP-2 gene expression was expressed at substantial levels in the WAT and only at slight levels in the skeletal muscle and BAT. 4. The UCP-3 gene expression is augmented two-fold in the gastrocnemius muscle from rats fed a high-fat diet (P < 0.05). The UCP-3 mRNA levels remained unchanged in the interscapular BAT, and epididymal WAT. The levels of the UCP-2 gene expression are augmented significantly in the epididymal WAT (1.6-fold; P < 0.05), while no significant increase is observed in the gastrocnemius muscle and interscapular BAT.

Adipose Tissue↗

PubMed1999

Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes.

Leptin acts as an adipocyte-derived blood-borne satiety factor that can increase glucose metabolism. To elucidate the therapeutic implications of leptin for obesity-associated diabetes, we crossed transgenic skinny mice overexpressing leptin (Tg/+), which we have developed recently, and lethal yellow KKAy mice (Ay/+), a genetic model for obesity-diabetes syndrome, and examined the metabolic phenotypes of F1 animals. At 6 weeks of age, plasma leptin concentrations in Tg/+ mice with the Ay allele (Tg/+:Ay/+) were significantly higher than those in Ay/+ mice. Although no significant differences in body weight were noted among Tg/+:Ay/+ mice, Ay/+ mice, and their wild-type lean littermates (+/+), glucose and insulin tolerance tests revealed increased glucose tolerance and insulin sensitivity in Tg/+:Ay/+ compared with Ay/+ mice. However, at 12 weeks of age, when plasma leptin concentrations in Ay/+ mice were comparable to those in Tg/+:Ay/+ mice, Tg/+:Ay/+ mice developed obesity-diabetes syndrome similar to that of Ay/+ mice. Body weights of 12-week-old Tg/+:Ay/+ and Ay/+ mice were reduced to those of +/+ mice by a 3-week food restriction; when plasma leptin concentrations remained high in Tg/+:Ay/+ mice but were markedly reduced in Ay/+ and +/+ mice, glucose tolerance and insulin sensitivity in Tg/+:Ay/+ mice were markedly improved as compared with Ay/+ and +/+ mice. The present study demonstrates that hyperleptinemia can delay the onset of impaired glucose metabolism and accelerate the recovery from diabetes during caloric restriction in Tg/+:Ay/+ mice, thereby suggesting the potential usefulness of leptin in combination with a long-term caloric restriction for the treatment of obesity-associated diabetes.

Aging↗

PubMed1999

Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion.

Leptin is an adipocyte-derived blood-borne satiety factor that acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. We have demonstrated that the hypothalamic arcuate nucleus (Arc) is a primary site of the satiety effect of leptin (Neurosci Lett 224:149-152, 1997). To explore the hypothalamic pathway of sympathetic activation of leptin, we examined the effects of a single intravenous or intracerebroventricular injection of recombinant human leptin on catecholamine secretion in rats. We also examined the effects of direct microinjection of leptin into the ventromedial hypothalamus (VMH), Arc, paraventricular nucleus (PVN), and dorsomedial hypothalamus (DMH) in rats. To further assess whether sympathetic activation of leptin is mediated via the VMH, we also examined the effects of a single intravenous injection of leptin in VMH-lesioned rats. A single injection of leptin (0.25-1.0 mg i.v./rat or 0.5-2.0 pg i.c.v./rat) increased plasma norepinephrine (NE) and epinephrine (EPI) concentrations in a dose-dependent manner. Plasma NE and EPI concentrations were increased significantly when leptin was injected directly into the VMH but were unchanged when injected into the Arc, PVN, and DMH. Plasma NE and EPI concentrations were unchanged in VMH-lesioned rats that received a single intravenous injection of leptin. The present study provides evidence that a leptin-induced increase in catecholamine secretion is mediated primarily via the VMH and suggests the presence of distinct hypothalamic pathways mediating the satiety effect and sympathetic activation of leptin.

Animals↗

PubMed1999

Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin.

Excess of body fat, or obesity, is a major health problem and confers a higher risk of cardiovascular and metabolic disorders such as diabetes, hypertension, and coronary heart disease. Leptin is an adipocyte-derived satiety factor that plays an important role in the regulation of energy homeostasis, and its synthesis and secretion are markedly increased in obese subjects. To explore the metabolic consequences of an increased amount of leptin on a long-term basis in vivo, we generated transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. Overexpression of leptin in the liver has resulted in complete disappearance of white and brown adipose tissue for a long period of time in mice. Transgenic skinny mice exhibit increased glucose metabolism accompanied by the activation of insulin signaling in the skeletal muscle and liver. They also show small-sized livers with a marked decrease in glycogen and lipid storage. The phenotypes are in striking contrast to those of recently reported animal models of lipoatrophic diabetes and patients with lipoatrophic diabetes with reduced amount of leptin. The present study provides evidence that leptin is an adipocyte-derived antidiabetic hormone in vivo and suggests its pathophysiologic and therapeutic implications in diabetes.

Animals↗

PubMed1998

Structure-function studies of human leptin.

To elucidate the structural requirement of human leptin for its functions, the wild-type, mutant-type, C-terminal deletion, and N-terminal deletion were expressed in Escherichia coli and purified in soluble forms. These leptin analogs were intracerebroventrically injected into C57BL/6J ob/ob mice, and their in vivo biological activities were evaluated. The mutant-type leptin lacking a C-terminal disulfide bond reduced food intake at doses of more than 15 pmol/mouse, which was as effective as the wild-type leptin. C-terminal deletion without the loop structure, also significantly, but to a lesser extent, reduced food intake at doses of more than 90 pmol/mouse. However, N-terminal deletions showed no effect on food intake. We also evaluated the effects of the leptin analogs on radiolabeled leptin binding to its receptor in the choroid plexus using autoradiography. An excess of unlabeled mutant-type leptin as well as wild-type leptin led to complete inhibition of binding. C-terminal deletions led to weak inhibitory activity, whereas N-terminal deletions caused no inhibitory activity. These results clearly demonstrate that the N-terminal region of leptin is essential for both its biological and receptor binding activities. The amino acid sequence of the C-terminal loop structure is also important for enhancing these actions, whereas the C-terminal disulfide bond is not needed.

Animals↗

PubMed1998

A heterogeneity in serum osteocalcin N-terminal fragments in Paget's disease: a comparison with other biochemical indices in pre- and postmenopause.

An osteocalcin (OC) nitrogen (N)-terminal sandwich enzyme immunoassay that employs anit-N-20 (amino acids 1-20) polyclonal and monoclonal antibodies has been developed. This assay has demonstrated the existence of a heterogeneity in the OC N-terminal fragments observed in the serum of a patient with Paget's disease and a normal child. The elevation of the serum OC N-terminal value that occurs in Paget's disease was considered to be comparable to the serum alkaline phosphatase (ALP) elevations that also occur. The size of the peaks corresponding to N-terminal OC fragments in Paget's serum decreased 3 months after bisphosphonate treatment. Serum levels of OC N-terminals, and other biochemical indices, were determined for 67 premenopausal and 181 postmenopausal Japanese women. Serum OC N-terminal levels increased significantly (41.2%) in postmenopausal women compared with age-matched premenopausal women. These results strongly suggest that serum OC N-terminal levels reflect bone turnover rates when bone resorption is dominant.

Adolescent↗

PubMed1998

Mutational analysis of the endothelin-B receptor gene in Japanese Hirschsprung's disease.

BACKGROUND/PURPOSE: Hirschsprung's disease (HD, HSCR) is one of the most common diseases in the field of pediatric surgery. It is well known that the aganglionic bowel is primarily a causative factor of dismotility of distal narrow segment. Recent studies have shown that mutations in endothelin-B receptor (EDNRB), endothelin-3, RET, glial cell line-derived neurotrophic factor (GDNF) genes are responsible for the occurrence of congenital aganglionosis. Here, the authors describe two new mutations of the EDNRB gene in Japanese patients with HD. RESULTS: One patient had a heterozygous point mutation at the splice donor site of intron 3, leading to premature termination of translation of EDNRB mRNA. Another patient has a heterozygous missense mutation (N1041) in exon 1, but the same mutation was found in two of 50 normal individuals, so the mutation may be a noncausative polymorphism of the EDNRB gene. CONCLUSION: These results provide further evidence that a spectrum of different mutations within the EDNRB gene are responsible for HD.

Base Sequence↗

PubMed1998

The significance of the Trp 64 Arg mutation of the beta3-adrenergic receptor gene in impaired glucose tolerance, non-insulin-dependent diabetes mellitus, and insulin resistance in Japanese subjects.

It has been reported that the Trp 64 Arg mutation of the human beta3-adrenergic receptor (beta3-AR) gene is related to an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and features of insulin resistance and weight gain in morbidly obese patients. However, such findings have not been consistent in varying ethnic populations. In the present study, we investigated the frequency of the Trp 64 Arg mutation of the human beta3-AR gene in Japanese control subjects (n = 253) and in NIDDM (n = 314) and impaired glucose tolerance (IGT) patients (n = 100). We compared the frequency of the mutation with the body-mass index (BMI) in these groups and with the metabolic clearance rate (MCR) of glucose in the NIDDM patients. A Trp 64 Arg mutation was observed in 36.7%, 31.6%, and 37.0% of the control, NIDDM, and IGT subjects, respectively. The frequency of the homozygotes for the mutation was 4.3%, 4.8%, and 3.0%, respectively. Neither the genotype frequency (Trp/Arg, Arg/Arg) nor the frequency of the mutated allele was significantly different among the three groups. The BMI of the subjects with the mutation was not significantly higher than that of the subjects without the mutation in each group. Furthermore, the allele frequency (A) was not different among the subjects with different BMIs (BMI < 22.0, 22.0 < or = BMI < or = 26.4, BMI > 26.4) in each group. In a separate group of NIDDM patients, the MCR of the subjects with intermediate BMIs (22.0 < or = BMI < or = 26.4) with the mutation tended to be lower than that of those without the mutation. In addition, the MCR of the subjects with the mutation in this group was significantly lower compared with that of those with a BMI less than 22. These results indicate that the Trp 64 Arg mutation of the beta3-AR gene may not contribute to the development of NIDDM or be a determinant of obesity in the Japanese population. However, the mutation may contribute to insulin resistance in NIDDM patients with an intermediate BMI.

Adult↗

PubMed1998

Influence of degree of carotid artery stenosis and collateral pathways and effect of carotid endarterectomy on cerebral vasoreactivity.

OBJECTIVE: The goal was to determine the influence of the degree of internal carotid artery (ICA) stenosis and collateral pathways on cerebral vasoreactivity (CVR). The effect of carotid endarterectomy on CVR is also presented. METHODS: For 36 patients with unilateral ICA stenosis of at least 70%, regional cerebral blood flow (rCBF) and regional CVR (rCVR) were investigated before and after carotid endarterectomy, with resting and acetazolamide-challenge single photon emission computed tomographic scans. The degree of ICA stenosis and the status of the collateral pathways (sizes of the A1 segment and the posterior communicating artery) were evaluated by angiography. RESULTS: Thirteen patients were classified as Type N/N (normal rCBF and normal rCVR), 5 as Type R/N (reduced rCBF and normal rCVR), 6 as Type N/R (normal rCBF and reduced rCVR), and 12 as Type R/R (reduced rCBF and reduced rCVR). The degree of ICA stenosis correlated with rCVR status. The size of the A1 segment was a second-rank factor and was less effective in affecting rCVR. The size of the posterior communicating artery was not associated with rCVR. The predictive value of reduced rCVR for postoperative improvement (100%) was significantly higher than that of reduced rCBF (50%). CONCLUSION: The present results indicate that the degree of ICA stenosis is a more significant determinant of CVR than are the collateral pathways in patients with carotid artery stenosis. The high predictive rate of reduced rCVR for postoperative improvement implies that acetazolamide-challenge single photon emission computed tomographic scanning might be useful in selecting patients with asymptomatic ICA stenosis who might benefit from carotid endarterectomy.

Acetazolamide↗

PubMed1998

Treatment of subdural effusion with hydrocephalus after ruptured intracranial aneurysm clipping.

OBJECTIVE: This study was conducted to determine whether a ventriculoperitoneal shunt alone was effective in treating subdural effusion with hydrocephalus. METHODS: Using only a ventriculoperitoneal shunt, we successfully treated eight patients who had subdural effusion with hydrocephalus after ruptured intracranial aneurysmal clipping, despite ventricular deformity and midline shift. RESULTS: For all of the patients, both the subdural effusion and ventriculomegaly subsided and clinical symptoms lessened after surgery. CONCLUSION: Ventriculoperitoneal shunting alone is an effective and satisfactory procedure; no subdural peritoneal shunt is needed for patients with subdural effusion accompanied by hydrocephalus. To-and-fro communication between the subdural effusion and ventricles is considered to be present in these patients. When selecting the treatment for subdural effusion, it is important to consider whether hydrocephalus (disturbance of cerebrospinal fluid circulation) is present.

Adult↗

PubMed1998

Augmented placental production of leptin in preeclampsia: possible involvement of placental hypoxia.

Preeclampsia (PE) is a hypertensive disorder, which develops in late pregnancy and is usually associated with placental hypoxia and dysfunction. We have recently demonstrated that leptin is a novel placenta-derived hormone in humans and suggested its significance in human pregnancy (see Ref. 19). To explore the changes in the leptin production in placenta in PE, we measured the plasma leptin level and placental leptin messenger RNA expression in pregnant women with PE. Plasma leptin levels in preeclamptic women were elevated significantly, compared with gestational age- and body mass index-matched normal pregnant women (P < 0.0001). Plasma leptin levels in the severe PE group were significantly higher than those in the mild PE group (P < 0.0001). Plasma leptin levels in preeclamptic women were reduced, soon after the placental delivery, to those expected for their body mass indices. Northern blot analysis revealed that leptin messenger RNA levels are increased in the placentas from preeclamptic women, compared with normal pregnant women. Leptin secretion was increased significantly in a human trophoblastic cell line (BeWo cells) cultured under hypoxic conditions (5% O2), compared with those cultured under standard conditions (20% O2; P < 0.01). The present study demonstrated that placental production of leptin is augmented in severe PE, probably because of placental hypoxia, thereby suggesting the possible significance of leptin as a marker of placental hypoxia in severe PE.

Adult↗

PubMed1998

Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice.

Neural crest cells arise in the dorsal aspect of the neural tube and migrate extensively to differentiate into a variety of neural and non-neural tissues. While interactions between neural crest cells and their local environments are required for the proper development of these tissues, little information is available about the molecular nature of the cell-cell interactions in cephalic neural crest development. Here we demonstrate that mice deficient for one type of endothelin receptor, ETA, mimic the human conditions collectively termed CATCH 22 or velocardiofacial syndrome, which include severe craniofacial deformities and defects in the cardiovascular outflow tract. We show that ETA receptor mRNA is expressed by the neural crest-derived ectomesenchymal cells of pharyngeal arches and cardiac outflow tissues, whereas ET-1 ligand mRNA is expressed by arch epithelium, paraxial mesoderm-derived arch core and the arch vessel endothelium. This suggests that paracrine interaction between neural crest-derived cells and both ectoderm and mesoderm is essential in forming the skeleton and connective tissue of the head. Further, we find that pharyngeal arch expression of goosecoid is absent in ETA receptor-deficient mice, placing the transcription factor as one of the possible downstream signals triggered by activation of the ETA receptor. These observations define a novel genetic pathway for inductive communication between cephalic neural crest cells and their environmental counterparts.

Animals↗

PubMed1998

Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes.

Uncoupling protein (UCP) 3 and UCP2, mitochondrial carrier proteins dissipating electrochemical gradient across the mitochondrial inner membrane, have been implicated in the regulation of energy metabolism. The UCP3 gene is expressed abundantly in the skeletal muscle, while the UCP2 gene is detected in the white adipose tissue (WAT) with diffuse localization throughout the body. Uncoupling of electron transport and ATP synthesis has been reported to increase glucose uptake, suggesting that UCP may be involved in glucose metabolism. Thiazolidinediones (TZDs), which are insulin-sensitizing agents for NIDDM, have been reported to increase energy expenditure. To elucidate the pathophysiologic significance of UCP3 and UCP2 in the effect of TZDs on glucose metabolism and energy expenditure, we examined their basal mRNA levels in the WAT, brown adipose tissue (BAT), and skeletal muscle from Wistar fatty rats, a rat model of NIDDM and obesity with leptin receptor defect, and investigated expression of the genes encoding UCP3 and UCP2 in Wistar fatty rats and in Wistar lean rats with 2-week oral administration of 3 mg x kg(-1) x day(-1) pioglitazone, a TZD derivative. Basal UCP3 mRNA levels were significantly lower (38 +/- 8, 45 +/- 13, and 76 +/- 6%) in the retroperitoneal WAT, BAT, and skeletal muscle from Wistar fatty rats than in those from Wistar lean rats, while basal UCP2 mRNA levels were significantly higher by 2.1-, 1.8-, and 2.5-fold in the subcutaneous WAT, retroperitoneal WAT, and BAT from Wistar fatty rats, respectively, than in those from Wistar lean rats. In pioglitazone-treated Wistar fatty rats, UCP3 mRNA levels were significantly increased by 2.1-, 2.0-, and 1.6-fold in the epididymal WAT, retroperitoneal WAT, and BAT, respectively, as compared with those in nontreated fatty rats. In pioglitazone-treated lean rats, UCP3 mRNA levels were significantly increased by 1.3-fold in the BAT as compared with those in nontreated lean rats. No significant change of UCP2 mRNA levels was observed in pioglitazone-treated fatty and lean rats. In addition, to examine the direct effect of TZDs on adipocytes, we examined the regulation of UCP3 and UCP2 gene expression using the primary culture of rat mature adipocytes from Sprague-Dawley rats. In rat cultured mature adipocytes, UCP3 mRNA levels were increased in a dose-responsive manner by 10(-5) to 10(-4) mol/l pioglitazone, while there was no significant change of UCP2 mRNA levels. These results clearly demonstrate that UCP3 gene expression is upregulated by TZDs in the WAT and BAT in Wistar fatty rats, an obese model with leptin receptor defect, and that adipose UCP3 gene expression is increased in response to TZDs in vitro. The present study suggests the involvement of UCP3 in the effects of TZDs on energy and glucose metabolism.

Adipocytes↗

PubMed1998

[Usefulness of multiple burr-hole operation for child Moyamoya disease].

Excellent results of multiple burr-hole operation (MBHO) for child moyamoya disease are reported in this study. Three patients of moyamoya disease had MBHO. After MBHO, transient, ischemic attacks disappeared in a patient despite progressing stenosis of the major cerebral arteries, and remarkable neurological improvement was recognized in a patient who had encephaloduroarteriosynangiosis. Another patient slowly improved and became able to go to junior high school. N-isopropyl-p-[123I] iodoamphetamine (IMPSPECT) findings also improved in all patients. There was no mortality or morbidity, and no new neurological deficits or bleedings developed during the follow up period. The authors recommend the MBHO as the surgical treatment of choice for not only adult but also child moyamoya disease because of its safety and effectiveness, and also report the usefulness of MBHO for the patients who have already received other bypass operations.

Adolescent↗