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Biomedical subjects

K Arai

Publications and source records attributed to K Arai.

At least 91 records · Page 5Linked to original sources
PubMed2001

Ghrelin and growth hormone (GH) secretagogue receptor (GHSR) mRNA expression in human pituitary adenomas.

OBJECTIVE: The level of growth hormone (GH), growth hormone secretogogue (GHS) and GHS receptor (GHSR) messenger ribonucleic acid (mRNA) expression has been reported as being higher in GH-producing pituitary adenomas than in other types of pituitary adenomas. Recently, ghrelin, an endogenous ligand specific for GHSR, was isolated. Therefore, we attempted to clarify whether ghrelin mRNA is expressed in various types of human pituitary adenoma by competitive reverse transcription-polymerase chain reaction (RT-PCR). We also examined the relationship between the levels of ghrelin or GHSR mRNA and hormonal and tumour characteristics in patients with pituitary adenomas. PATIENTS: Pituitary adenoma tissue was obtained at surgery from 13 patients with acromegaly, 4 with prolactinomas, 5 with gonadotrophin (Gn)-producing adenomas, 4 with non-functioning adenomas, 2 with ACTH-producing adenomas and 2 with TSH-producing adenomas. METHODS: The expression levels of human ghrelin mRNA and GHSR mRNA were quantified using a competitive RT-PCR method. RESULTS: Ghrelin mRNA was detected in all pituitary adenoma tissues examined, with the highest mean level detected in non-functioning adenomas, a moderate level in GH-producing adenomas and Gn-producing adenomas, and the lowest level in prolactinomas. The level of ghrelin mRNA expression in GH-producing adenomas correlated negatively with the size of the adenoma (n = 13) (r = - 0.756, P = 0.0028). Furthermore, the mean level of ghrelin mRNA expression in high-grade (III and IV of Hardy classification) GH-producing adenomas was significantly lower than that in low-grade (I and II) GH-producing adenomas (P = 0.0016). GHSR mRNA was also detected in all pituitary adenomas with the highest mean level in GH-producing adenomas, a moderate level in nonfunctioning adenoma, and the lowest level in prolactinoma and Gn-producing adenomas. CONCLUSIONS: Ghrelin mRNA, in addition to GHSR mRNA, is expressed in various types of pituitary adenoma with different levels of expression in each type. Our findings suggest that ghrelin produced in pituitary adenoma may play some role in the mechanism underlying the development of adenoma cells through autocrine and/or paracrine pathways.

Adenoma↗
PubMed2001

Higher expression of K-ras is associated with parathyroid hormone-related protein-induced hypercalcaemia in renal cell carcinoma.

OBJECTIVES: To determine whether the K-ras oncogene is associated with parathyroid hormone-related protein (PTHrP) production in renal cell carcinoma (RCC) and whether the serum value of PTHrP is related to the patients' survival. PATIENTS AND METHODS: The serum levels of PTHrP and corrected serum calcium levels were analysed in 51 consecutive patients (29 men and 22 women, mean age 63.7 years, range 33-82) with newly diagnosed RCC. Matched pairs were analysed of the mRNA levels of K-ras and PTHrP in tumour and in corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. RESULTS: Seven patients had elevated serum PTHrP values at the diagnosis of RCC. The mRNA expression of K-ras and PTHrP were detected in both tumour and non-tumour tissues, with K-ras mRNA levels being higher in the former than the latter (P < 0.05), and correlated with tumour stage (P < 0.05). There were no differences in PTHrP mRNA levels between the tissues. Furthermore, the mRNA levels of K-ras and PTHrP in seven tumours from patients with high serum values of PTHrP were higher than in tumours from those with normal values (both P < 0.01). The expression of mRNAs of K-ras and PTHrP was positively correlated (r = 0.771, P < 0.001). In seven patients with high serum PTHrP values the mRNA levels of PTHrP correlated with serum values of PTHrP and calcium (r = 0.875, P < 0.01 and r = 0.762, P < 0.05, respectively). Kaplan-Meier plots of survival rate in patients with elevated or normal serum PTHrP showed that high serum PTHrP was associated with a shorter overall survival (P < 0.05). The Cox proportional hazards model showed that serum PTHrP was an independent predictor of overall survival (P < 0.05). CONCLUSIONS: These findings suggest that K-ras may be associated with PTHrP-induced hypercalcaemia and that PTHrP levels may reflect the aggressiveness of tumour cells through the K-ras oncogene in RCC.

Adult↗
PubMed2001

Overexpression of RhoA mRNA is associated with advanced stage in testicular germ cell tumour.

OBJECTIVE: To clarify the role of Rho small GTP-binding protein (Rho) in the progression of testicular germ cell tumour (GCT), by examining the expression levels of mRNAs of Rho genes in testicular GCT. PATIENTS AND METHODS: The mRNA levels of the RhoA, RhoB and RhoC genes were analysed in the surgical specimens of testicular GCT tissues from 45 consecutive Japanese patients, and in the corresponding unaffected tissue originating from the same patient, using reverse transcription-polymerase chain reaction. The expression levels in tumour tissues were compared with those in unaffected tissues and the relationship between their expression levels in tumours and tumour stage evaluated. The expression levels of mRNAs of the Rho genes were also evaluated between tumours with seminoma only, and mixed tumours with seminoma and nonseminoma. RESULTS: The mRNA levels of RhoA were greater in tumour tissues than in unaffected tissues of the resected testis (P < 0.01); the mRNAs of RhoB and RhoC were not detected in either tissue. The increase in RhoA mRNA levels was related to tumour stage (P < 0.05). The mRNA levels of RhoA in seminomatous and nonseminomatous areas where both were present were higher than those in tumours with seminoma only (P < 0.05). CONCLUSIONS: These results suggest that RhoA is involved in testicular germinal epithelial carcinogenesis and progression in testicular GCT, indicating that RhoA may be a useful prognostic marker for progression in testicular GCT.

Adolescent↗
PubMed2001

Intrahepatic amino acid and glucose metabolism in a D-galactosamine-induced rat liver failure model.

A better understanding of the hepatic metabolic pathways affected by fulminant hepatic failure (FHF) would help develop nutritional support and other nonsurgical medical therapies for FHF. We used an isolated perfused liver system in combination with a mass-balance model of hepatic intermediary metabolism to generate a comprehensive map of metabolic alterations in the liver in FHF. To induce FHF, rats were fasted for 36 hours, during which they received 2 D-galactosamine injections. The livers were then perfused for 60 minutes via the portal vein with amino acid-supplemented Eagle minimal essential medium containing 3% wt/vol bovine serum albumin and oxygenated with 95% O(2)/5% CO(2). Control rats were fasted for 36 hours with no other treatment before perfusion. FHF rat livers exhibited reduced amino acid uptake, a switch from gluconeogenesis to glycolysis, and a decrease in urea synthesis, but no change in ammonia consumption compared with normal fasted rat livers. Mass-balance analysis showed that hepatic glucose synthesis was inhibited as a result of a reduction in amino acid entry into the tricarboxylic acid cycle by anaplerosis. Furthermore, FHF inhibited intrahepatic aspartate synthesis, which resulted in a 50% reduction in urea cycle flux. Urea synthesis by conversion of exogenous arginine to ornithine was unchanged. Ammonia removal was quantitatively maintained by glutamine synthesis from glutamate and a decrease in the conversion of glutamate to alpha-ketoglutarate. Mass-balance analysis of hepatic metabolism will be useful in characterizing changes during FHF, and in elucidating the effects of nutritional supplements and other treatments on hepatic function.

Amino Acids↗
PubMed2001

Arthroscopic diagnosis and treatment of dorsal wrist ganglion.

Thirty-seven patients with dorsal wrist ganglia underwent arthroscopic resection. The mean follow-up was 20 months, and no complications were encountered. The ganglia were classified into three types according to their arthroscopic appearance. This classification helps to determine the amount of dorsal capsular resection required.

Adolescent↗
PubMed2001

One-bone forearm formation using vascularized fibula graft for massive bone defect of the forearm with infection: case report.

Massive long-bone defects of greater than 6 cm are difficult to treat with conventional bone grafts, and other methods are sometimes recommended, such as vascularized bone grafts or bone transport using the Ilizarov external fixator. The combination of local infection with a massive bone defect exacerbates the problem, and provides an even more negative prognosis. The authors treated a large bone defect of the forearm with local infection, using a one-bone forearm formation with a large vascularized fibula graft. They attached an adequate amount of muscle fascia to the vascularized fibula, which was useful not only for coverage of the skin defect, but also for treatment of the local infection. Twenty months after surgery, elbow and hand functions were maintained, and the patient had no disturbance of hand function in daily activities, although rotation of the forearm was sacrificed.

Bone Wires↗
PubMed2001

Contribution of endogenous inhibin to the decline of the secondary surge of follicle-stimulating hormone in the rat.

The involvement of inhibin in the decline of the secondary surge of follicle-stimulating hormone (FSH) was investigated in the rat. After ovariectomy or treatment with inhibin antiserum conducted at 2300 hours during pro-oestrus, plasma concentrations of FSH were maintained at high levels compared with control rats. However, plasma FSH started to decline at 0500 hours during oestrus in both the groups. The same treatments conducted during metoestrus markedly increased plasma FSH after 24 h (twofold compared with the treatments during pro-oestrus), suggesting that the treatments sufficiently depleted circulating inhibin. To examine whether the decline of plasma FSH occurred through a transcriptional mechanism or through a translational mechanism, FSH-beta mRNA expression and the pituitary concentration of FSH were measured. Neither ovariectomy nor inhibin immunization conducted during the night of pro-oestrus, affected the pituitary concentration of FSH after 24 h, whereas a noticeable increase was observed after the treatments conducted during metoestrus. In both stages, both ovariectomy and inhibin immunization significantly increased FSH-beta mRNA expression compared with control rats. In contrast with the pituitary concentration of FSH, the effect of inhibin immunization on FSH-beta mRNA expression was not different between the stages. The present data demonstrate the involvement of inhibin in the decline of the secondary surge of FSH, and suggest that a factor or factors other than inhibin may also be responsible for the fall in FSH. Changes in the pituitary concentration of FSH and FSH-beta mRNA expression suggest that post-transcriptional mechanisms may be involved in the suppression of FSH secretion during oestrus.

Animals↗
PubMed2001

Role of intraoperative insulin monitoring in surgical management of insulinoma.

BACKGROUND AND PURPOSE: Precise localization and surgical excision is the therapeutic strategy for insulinomas. However, it is often difficult to localize the insulinomas, because of their small size. Surgeons may not localize and remove all of them together, particularly in patients with multiple insulinomas. We reviewed our experience to confirm the efficacy of blood glucose and intraoperative immunoreactive insulin (IRI) monitoring for surgical management of insulinomas. PATIENTS AND METHODS: Thirty-nine patients with insulinoma were surgically treated in our department. Perioperative blood glucose monitoring was performed in 14 patients, intraoperative quick IRI assay of the peripheral blood in 10 patients, and assay of a portal sample in 4 patients by an IMX analyzer. RESULTS: Rebound response of blood glucose to insulinoma removal was not always noted (8/14; 57%). Seven of ten patients showed a decrease of peripheral serum IRI levels within 15 minutes after removal of the insulinoma. The other two patients showed a rebound response of peripheral blood glucose or portal IRI. All the patients who had intraoperative monitoring of peripheral blood and peripheral and portal IRI had no recurrent insulinoma syndrome after surgical removal of their insulinomas. CONCLUSION: Combined monitoring of peripheral blood glucose and peripheral and portal IRI are helpful in the surgical management of insulinomas, as they can indicate that no insulinoma remains.

Adolescent↗
PubMed2001

Recruitment of nonexpanded polyglutamine proteins to intranuclear aggregates in neuronal intranuclear hyaline inclusion disease.

Recruitment of polyglutamine-containing proteins into nuclear inclusions (NIs) was investigated in neuronal intranuclear hyaline inclusion disease (NIHID). Some polyglutamine-containing proteins, ataxin-2, ataxin-3, and TATA box binding protein (TBP), as well as unidentified proteins with expanded polyglutamine tracts were recruited into NIs with different frequencies. Ataxin-3 was incorporated into most of the NIs and disappeared from its normal cytoplasmic localization, whereas only a small fraction of NIs contained ataxin-2 and TBP. The consistent presence of ataxin-3 in NIs could reflect a biological feature of wild-type ataxin-3, which is translocated into the nucleus under pathological conditions and participates in the formation of aggregates. Ataxin-2 also accumulated in the nucleus, but was not necessarily incorporated into NIs, suggesting that transport of these cytoplasmic proteins into the nucleus and their recruitment into NIs are not wholly explained by an interaction with a polyglutamine stretch and must be regulated in part by other mechanisms. The prevalence of ubiquitin-immunopositive NIs was inversely correlated to neuronal loss in all cases examined. This correlation could be explained if NI formation is a protective mechanism involving the ubiquitin-proteasome pathway. This hypothesis is supported by the finding that the polyglutamine epitope in the center of NIs was surrounded by ubiquitin.

Adult↗
PubMed2001

Some Lactobacillus L-lactate dehydrogenases exhibit comparable catalytic activities for pyruvate and oxaloacetate.

The nonallosteric and allosteric L-lactate dehydrogenases of Lactobacillus pentosus and L. casei, respectively, exhibited broad substrate specificities, giving virtually the same maximal reaction velocity and substrate K(m) values for pyruvate and oxaloacetate. Replacement of Pro101 with Asn reduced the activity of the L. pentosus enzyme toward these alternative substrates to a greater extent than the activity toward pyruvate.

Amino Acid Sequence↗
PubMed2001

Nicotine infusion alters leptin and uncoupling protein 1 mRNA expression in adipose tissues of rats.

We attempted to clarify whether leptin and uncoupling protein 1 (UCP1) are involved in the action of nicotine on the energy balance. Male Wistar rats were infused subcutaneously with nicotine (12 mg x kg(-1) x day(-1)) for 4 or 14 days. At the end of the 4-day period, the plasma concentrations of leptin of the nicotine-treated and pair-fed rats were lower than those of the freely fed rats, although the levels of leptin mRNA expression in various white adipose tissues did not differ among the three groups. At the end of the 14-day nicotine infusion period, plasma concentrations of leptin were higher, and leptin mRNA expression in the omentum and epididymal and retroperitoneal adipose tissues was stronger in the nicotine-treated rats than in the pair-fed and freely fed rats. UCP1 mRNA expression in the brown adipose tissue of nicotine-treated was stronger than that of the pair-fed rats. These results suggest that continuous nicotine infusion differentially affects the synthesis and secretion of leptin according to the duration of infusion and stimulates UCP1 mRNA expression, probably in a manner independent of leptin.

Adipose Tissue↗
PubMed2001

Relationship of electrochemical oxidation of catechins on their antioxidant activity in microsomal lipid peroxidation.

The oxidation potentials of catechins were measured by employing flow-through column electrolysis. The oxidation potentials of catechins were shown to depend on their structures. At the same time, the antioxidant activity of catechins on NADPH-dependent lipid peroxidation in rat liver microsomes was evaluated. Catechins showed a 50% inhibition of lipid peroxidation in the concentration range of 10-51 microM. Among those studied, galloylated catechins exhibited stronger antioxidant activities than those of nongalloylated catechins. A quantitative relationship has been obtained to describe the antioxidant activity of catechins: log IC50 (microM)= 1.56+2.49E1/2 (V)-0.29 logP (r=0.907), where IC50 represents the concentration for 50% inhibition of lipid peroxidation, E1/2 represents the half-wave potential of the first oxidation wave, and P represents the octanol/water partition coefficient. This relationship suggested two important characteristics determining catechin antioxidant activity, namely the ease of oxidation and the lipophilicity.

Animals↗
PubMed2001

[Assay in high throughput screening].

HTS (High Throughput Screening) has been put into practice in recent years. HTS is aiming to discover lead compounds for medicinal drugs. High efficiency must be achieved in all the processes including sample preparation, assay procedure, automation and data management. This review will focus on the aspects concerned with the assay technology and the efficiency in HTS. One of the major trends in HTS is assay miniaturization using high-density microplates with 384 and 1536 wells. This allows us to increase the throughput and to decrease the cost. The so-called "mix and measure" or "homogeneous" assay system, which has no separation steps such as washing or filtration, is effective for this purpose. The homogeneous assays, such as scintillation proximity assay (SPA), fluorescence energy transfer (HTRF, LANCE) and fluorescence polarization (FP), are frequently used. The reporter gene assay or the cell proliferation assay can be adapted for the homogeneous assay using high-density plates. In addition, HTS measuring the intracellular Ca2+ influx is also possible using a CCD Imager. The assay quality as well as the efficiency is also important especially in HTS. The Z'-factor provides a good tool for evaluating the quality of assays.

Biological Assay↗
PubMed2001

Short term hypercholesterolemia alters N(G)-nitro-L-arginine- and indomethacin-resistant endothelium-dependent relaxation by acetylcholine in rabbit renal artery.

The tension of isolated rings was measured isometrically to compare the N(G)-nitro-L-arginine- and indomethacin-resistant relaxation by acetylcholine (ACh) in the renal artery from normal rabbits and short term hypercholesterolemia rabbits (0.5% cholesterol chow for 5 weeks). ACh-induced relaxation in the renal artery precontracted with phenylephrine was not influenced by cholesterol-enriched chow. However, in comparison with artery from normal rabbits, the N(G)-nitro-L-arginine- and indomethacin-resistant endothelium-dependent relaxation by ACh was significantly enhanced by the chow. The resistant part of ACh-induced relaxation was significantly inhibited when the artery was treated with tetraethylammonium or SKF 525a. Results suggest that short term hypercholesterolemia modulates endothelium-derived hyperpolarizing factor-mediated relaxation in rabbit renal artery.

Acetylcholine↗
PubMed2001

Deterioration of spatial learning performances in lipopolysaccharide-treated mice.

It is well demonstrated that acute or chronic stress leads to reduction of learning ability. Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, induces profound physiological and behavioral changes, including fever, decrease in food motivation, and decrease in social behavior. These changes might be interpreted as an acute stress reaction to the LPS. In the present study, therefore, we investigated the effects of LPS (400-800 microg/kg, i.p.) on spatial learning performances using C57BL/6J male mice. In the Morris water-maze task, spatial learning performances were examined in six trials of training for two consecutive days. LPS-treated mice took a longer time to reach the hidden platform than control mice (F(1,60)=4.80801, P<0.05 at 600 microg/kg). In addition, injection of LPS decreased the percent of correct choices in the Y-maze test (P<0.05 at 800 microg/kg). LPS, however, did not alter the body weight, grip tone, motor activity or swimming speed. Taken together, these results indicate that LPS treatment specifically impaired spatial learning performances.

Animals↗