Biomedical subjects

H Nakata

Publications and source records attributed to H Nakata.

At least 19 recordsLinked to original sources

PubMed2006

Reverse white-coat effect as an independent risk for left ventricular concentric hypertrophy in patients with treated essential hypertension.

Recent studies have shown that the converse phenomenon of white-coat hypertension called 'reverse white-coat hypertension' or 'masked hypertension' is associated with poor cardiovascular prognosis. We assessed the hypothesis that this phenomenon may specifically influence left ventricular (LV) structure in treated hypertensive patients. A total of 272 outpatients (mean age, 65 years) with chronically treated essential hypertension and without remarkable white-coat effect were enrolled. Patients were classified into two groups according to office and daytime ambulatory systolic blood pressure (SBP); that is subjects without (Group 1: office SBP > or =daytime SBP, n=149) and with reverse white-coat effect (Group 2: office SBP<daytime SBP, n=123). LV mass index and relative wall thickness were echocardiographically determined. In all subjects, LV mass index and relative wall thickness were positively correlated with daytime and 24-h SBP, but not with office SBP. In addition, these two indices were inversely correlated with office--daytime SBP difference. LV mass index (136+/-31 and 115+/-28 g/m(2), mean+/-s.d.) and relative wall thickness (0.49+/-0.09 and 0.46+/-0.07) were significantly greater in Group 2 than in Group 1. As for LV geometric patterns, Group 2 had a significantly higher rate of concentric hypertrophy compared with Group 1 (48 and 28%). Multivariate analyses revealed that the presence of reverse white-coat effect was a predictor for LV concentric hypertrophy, independent of age, sex, hypertension duration, antihypertensive treatment and ambulatory blood pressure levels. Our findings demonstrate that reverse white-coat effect is an independent risk factor for LV hypertrophy, especially concentric hypertrophy, in treated hypertensive patients.

Aged↗

PubMed2006

[New method for localization of the small ground-glass opacity lesion in resected lung].

A small lesion showing ground-glass opacity (GGO) by preoperative computed tomography (CT) is sometimes difficult to detect after lobectomy when it locates in the central part of the lobe. In order to facilitate to identify the lesion for marking pathological specimen, we developed a new method using CT. After surgery, the resected pulmonary lobe was expanded with airflow through the bronchial stump and the target lesion was examined with CT. The laser beam of the CT on the surface of the lung is used as a guiding line for cutting. Through the application of this method for 2 clinical cases, it was found to be possible to exactly identify the GGO lesion from the surface of the resected lung enabling to visualize a fresh surface of the lesion like a CT image with minimal destruction of the structure.

Aged↗

PubMed2005

Changes in the centrifugal gating effect on somatosensory evoked potentials depending on the level of contractile force.

In this study, we investigated the somatosensory evoked potentials (SEPs) during the preparatory period of self-initiated plantar flexion at different force levels of muscle contraction and elucidated the mechanism behind the centrifugal gating effect on somatosensory information processing. We recorded SEPs following stimulation of the tibial nerve at the popliteal fossa during the preparatory period of a 20% maximal voluntary contraction (MVC) and 50% MVC. The preparatory period was divided into two sub-periods based on the components of movement-related cortical potentials, the negative slope (NS sub-period) and the Bereitschaftspotential (BP sub-period). The subjects were instructed to concentrate on the movement and not to pay attention to the continuous electrical stimulation. Pre-movement SEPs were averaged separately during the two sub-periods under each MVC condition. The mean amplitudes of BP and NS were larger during the 50% MVC than the 20% MVC. As for the components of SEPs, during the NS sub-period the amplitude of P30 under the 50% MVC and N40 under both conditions were significantly smaller than that in the stationary sequence, and N40 amplitude was significantly smaller during the 50% MVC than the 20% MVC. During the BP sub-period, the amplitude of P30 and N40 during the 50% MVC was significantly smaller than during the stationary sequence, while it was not significantly different between the 20% and 50% MVCs. In conclusion, the extent of the centrifugal gating effect on SEPs was dependent on the activities of motor-related areas, which generated the NS and BP.

Adult↗

PubMed2004

Facilitation of A[delta]-fiber-mediated acute pain by repetitive transcranial magnetic stimulation.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex modulates acute and chronic pain perception. The authors previously showed that rTMS over the primary motor cortex (M1) inhibited capsaicin-induced acute pain ascending through C-fibers. OBJECTIVE: To investigate the effects of 1-Hz rTMS over M1 on acute experimentally induced pain mediated by Adelta-fibers (i.e., another type of acute pain). METHODS: The authors examined whether rTMS over M1 affected laser evoked potentials (LEPs) in 13 normal subjects using thulium: yttrium-aluminum-garnet laser stimulation. Subjective pain-rating scores and LEPs obtained under three different conditions--rTMS, realistic sham stimulation, and a control condition with no stimulation--were compared. RESULTS: The authors found that 1-Hz rTMS over M1 significantly aggravated the subjective pain and enhanced the N2-P2 amplitudes compared with the sham or control sessions. Because the pain-rating scores and the N2-P2 amplitudes correlated positively, the N2-P2 amplitudes in the present study can be regarded as the cortical correlate of subjective pain. CONCLUSIONS: Together with the authors' previous study on C-fiber pain, this facilitatory effect of repetitive transcranial magnetic stimulation on Adelta-fiber-mediated further strengthens the notion of a relationship between repetitive transcranial magnetic stimulation over M1 and pain perception.

Acute Disease↗

PubMed2004

Identification of protein phosphatase 2C and confirmation of other protein phosphatases in the ocular lenses.

The reversible phosphorylation of proteins plays essential roles in regulating various cellular events, and is regulated by the opposing actions of protein kinases and protein phosphatases. Protein kinases in the lens system have been well studied, but very little is known about lens protein phosphatases. Protein phosphatases can be divided several families, such as protein phosphatase types 1, 2A, 2B and 2C (PP1, PP2A, PP2B and PP2C) and protein tyrosine phosphatases (PTP). In this study we evaluated what kinds of protein phosphatases are present in the lens by using various specific substrates and inhibitors. Samples were prepared from lenses of 17-day-old chick embryos, and fractionated by high-resolution gel permeation column chromatography, then the fractions were assayed for phosphatase activities. The results with 32P-labeled glycogen phosphorylase A, okadaic acid and inhibitor-1, which are a specific substrate and inhibitors of PP1 and/or PP2A, showed that PP1activities were present in the 500-, 115- and 45-kDa fractions of the lens protein. The 115-kDa fraction also contained PP2A activity. By using a phosphothreonine-containing peptide as a substrate, three peaks of phosphatase activities were found at around 115, 55 and 35 kDa. Based on their response to various phosphatase inhibitors and their metal dependency, the fractions of 115 and 35 kDa were concluded to contain PP2A, while the 55-kDa fraction contained PP2C. Immunoblot using specific antibodies against PP1, PP2A and PP2C confirmed that each fraction above contained corresponding protein phosphatases as proteins. When a phosphotyrosine-containing peptide substrate was examined at pH 7.4, we observed a major peak at 500 kDa, which was presumed to contain receptor-like PTP(s). On the other hand, at pH 5.5, we observed a peak of 18 kDa, which was confirmed to contain a low-molecular-weight PTP. These protein phosphatases have recently been suggested to be involved in stress response and apoptosis. Their physiological roles in the lens are of much interest.

Animals↗

PubMed2004

Pool of dust particles over the Asian continent: balloon-borne optical particle counter and ground-based lidar measurements at Dunhuang, China.

Measurements of aerosols were made in 2001 and 2002 at Dunhuang (40 degrees 00'N, 94 degrees 30'E), China to understand the nature of atmospheric particles over the desert areas in the Asian continent. Balloon-borne measurements with an optical particle counter suggested that particle size and concentration had noticeable peaks in super micron size range not only in the boundary mixing layer but also in the free troposphere. Super-micron particle concentration largely decreased in the mid tropopause (from 5 to 10 km; above sea level, a.s.l.). Lidar measurements made during August 2002 at Dunhuang suggested the possibility that mixing of dust particles occurred from near the ground to about 6 km even under calm weather conditions, and a large depolarization ratio of particulate matter was found in the aerosol layer. The top of the aerosol layer was found at heights of nearly 6 km (a.s.l.). It is strongly suggested that nonspherical dust particles (Kosa particles) frequently diffused in the free atmosphere over the Taklamakan desert through small-scale turbulences and are possible sources of dust particles of weak Kosa events that have been identified in the free troposphere not only in spring but also in summer over Japanese archipelago. Electron microscopic experiments of the particles collected in the free troposphere confirmed that coarse and nonspherical particles observed by the mineral particle were major components of coarse mode (diameter larger than 1 microm) below about 5 km over Dunhuang, China.

Aerosols↗

PubMed2004

Identification of protein phosphatase 2C and confirmation of other protein phosphatases in the ocular lenses.

The reversible phosphorylation of proteins plays essential roles in regulating various cellular events, and is regulated by the opposing actions of protein kinases and protein phosphatases. Protein kinases in the lens system have been well studied, but very little is known about lens protein phosphatases. Protein phosphatases can be divided several families, such as protein phosphatase types 1, 2A, 2B and 2C (PP1, PP2A, PP2B and PP2C) and protein tyrosine phosphatases (PTP). In this study we evaluated what kinds of protein phosphatases are present in the lens by using various specific substrates and inhibitors. Samples were prepared from lenses of 17-day-old chick embryos, and fractionated by high-resolution gel permeation column chromatography, then the fractions were assayed for phosphatase activities. The results with 32P-labeled glycogen phosphorylase A, okadaic acid and inhibitor-1, which are a specific substrate and inhibitors of PP1 and/or PP2A, showed that PP1 activities were present in the 500-, 115- and 45-kDa fractions of the lens protein. The 115-kDa fraction also contained PP2A activity. By using a phosphothreonine-containing peptide as a substrate, three peaks of phosphatase activities were found at around 115, 55 and 35 kDa. Based on their response to various phosphatase inhibitors and their metal dependency, the fractions of 115 and 35 kDa were concluded to contain PP2A, while the 55-kDa fraction contained PP2C. Immunoblot using specific antibodies against PP1, PP2A and PP2C confirmed that each fraction above contained corresponding protein phosphatases as proteins. When a phosphotyrosine-containing peptide substrate was examined at pH 7.4, we observed a major peak at 500 kDa, which was presumed to contain receptor-like PTP(s). On the other hand, at pH 5.5, we observed a peak of 18 kDa, which was confirmed to contain a low-molecular-weight PTP. These protein phosphatases have recently been suggested to be involved in stress response and apoptosis. Their physiological roles in the lens are of much interest.

Animals↗

PubMed2003

Global pollution monitoring of PCBs and organochlorine pesticides using skipjack tuna as a bioindicator.

Concentrations of organochlorines (OCs) representing persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyl trichloroethane and its metabolites (DDTs), chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs), and hexachlorobenzene (HCB), were determined in the liver of skipjack tuna (Katsuwonus pelamis) collected from the offshore waters of various regions in the world (offshore waters around Japan, Taiwan, Philippines, Indonesia, Seychelles, and Brazil, and the Japan Sea, the East China Sea, the South China Sea, the Bay of Bengal, and the North Pacific Ocean). OCs were detected in livers of all of the skipjack tuna collected from the locations surveyed, supporting the thesis that there is widespread contamination of persistent OCs in the marine environment. Within a location, no significant relationship between growth-stage (body length and weight) and OC concentrations (lipid weight basis) was observed, and the OC residue levels were rather uniform among the individuals. Interestingly, the distribution of OC concentrations in skipjack tuna was similar to those in surface seawaters from which they were taken. These results suggest that OC concentrations in skipjack tuna could reflect the pollution levels in seawater from which they are collected and that this species is a suitable bioindicator for monitoring the global distribution of OCs in offshore waters and the open ocean. Concentrations of PCBs and CHLs in skipjack tuna were higher in offshore waters around Japan (up to 1100 and 250 ng/g lipid wt, respectively), suggesting the presence of sources of PCBs and CHLs in Japan. High concentrations of DDTs and HCHs were observed in samples from the Japan Sea, the East China Sea, the South China Sea, and the Bay of Bengal (up to 1300 and 22 ng/g lipid wt, respectively). This result suggests recent use of technical DDT and HCH for agricultural and/or public health purposes in Russia, China, India, and some other developing Asian countries. Relatively high concentrations of PCBs, CHLs, HCHs, and HCB were also observed in samples collected from some locations in the middle of the Pacific Ocean, indicating the expansion of OC contamination on a global scale. Considering these facts, continuous studies monitoring these compounds in offshore waters and the open seas, using skipjack tuna as a bioindicator, are needed to further understand the future trend of contamination.

Animals↗

PubMed2003

Carbon dioxide insufflation for chronic subdural haematoma: a simple addition to burr-hole irrigation and closed-system drainage.

Burr-hole irrigation with closed-system drainage is a common surgical method used for chronic subdural haematoma. However, the subdural space with air that entered during surgery sometimes remains for a prolonged period after surgery and may hamper uncomplicated healing of the subdural space. We combined a simple procedure, insufflation of carbon dioxide (CO2) into the subdural space through a drainage catheter, with conventional burr-hole irrigation and closed-system drainage. By this additional procedure, both the subdural space and the gas within the space decreased rapidly, and the subdural drain could be removed within 24 h. By promoting obliteration of the subdural space, this simple combined technique may contribute to early recovery and discharge of patients, and to a reduction in the recurrence rate of the disease.

Aged↗

PubMed2003

Impaired interleukin-1beta converting enzyme (ICE) activity in patients with pulmonary tuberculosis.

We measured the activity of IL-1beta converting enzyme (ICE) of monocytes from pulmonary tuberculosis (PTB) patients. Peripheral blood mononuclear cells (PBMCs) and serum were collected from PTB patients (n = 16) and healthy subjects (n = 6). Serum IL-18 levels were significantly higher in PTB patients (515.9 +/- 326.5 pg/ml) than in controls (108.7 +/- 65.2 pg/ml) (P < 0.01), but gradually decreased with tuberculosis therapy. ICE activity was significantly lower in TB patients (65.3 +/- 34.4 vs. 142.2 +/- 75.6 U/mg) (P < 0.05). Serum IL-18 levels inversely correlated with ICE activity (P < 0.05). Altered ICE activity may explain why there is reduced IFN-gamma production from PBMCs; however, serum IL-18 is probably not regulated by ICE in monocytes in TB patients.

Caspase 1↗

PubMed2002

Growth-dependent and species-specific accumulation of polychlorinated biphenyls (PCBs) in tidal flat organisms collected from the Ariake Sea, Japan.

The growth-related as well as species-specific accumulation of polychlorinated biphenyls (PCBs) was studied for tidal flat organisms collected from the Ariake Sea, western Japan. Elevated concentrations of PCBs were found in omnivore fishes, followed in decreasing order by crabs, herbivore fishes, and mussels. This revealed that trophic levels play an important role in PCB accumulation in these organisms. Age- and body length-dependent accumulations of PCBs were observed in herbivorous mudskippers, although a large range of concentrations was found in similar growth stage of fishes. High correlations have been found between concentrations and body length rather than age, which may indicate that the growth rate, which is strongly influenced by the feeding rate of diets, seems to be the predominant factor in determining PCB accumulation. Besides, based on PCB levels in eggs and the whole body in herbivore fishes, the transfer rate of PCBs was estimated to be approximately 10% of female body burdens. Comparison of PCB compositions between eggs and whole body suggests the selective transfer of lower-chlorinated congeners to eggs, which may be due to their instantaneous periods to achieve steady state between egg and whole body lipids. The relationship between BSAFs (biota-sediment accumulation factors) in organisms and log Kow revealed that omnivore mudskipper significantly accumulated PCBs in their body, which might be due to their greater feeding rate and/or higher trophic status in the tidal flat environment.

Animals↗

PubMed2002

Organochlorine pesticides and polychlorinated biphenyl residues in foodstuffs and human tissues from china: status of contamination, historical trend, and human dietary exposure.

Concentrations of persistent organochlorine pesticides such as DDTs, hexachlorocyclohexanes (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs), were determined in a wide variety of foodstuffs and human tissues collected from Shanghai and its vicinity in China in 2000-2001. Among the organochlorines analyzed, DDT and its metabolites were prominent compounds in most of the foodstuffs. In particular, mussels contained noticeable residues of DDTs (34,000 ng/g lipid weight), which are one to three orders greater than those reported levels in bivalves from other Asian countries. Concentrations of HCHs, CHLs, HCB, and PCBs in foodstuffs were generally low, suggesting small amounts of inputs into the environment. Temporal trends examined by comparing the results of previous studies of organochlorine levels in Chinese foodstuffs in 1970s and 1992 revealed a greater amounts of declines of DDTs and HCHs residues and the average daily intakes during the past 30 years. In contrast, very high concentrations of DDTs and HCHs were detected in human tissues from Shanghai, with the maximum values as high as 19,000 ng/g lipid weight (mean: 7,600 ng/g) and 17,000 ng/g (mean: 7,400 ng/g), respectively. Considering that foodstuffs are a main source of human exposure to contaminants, the greater concentrations of DDTs and HCHs in Chinese people might be due to past extensive usage of these compounds as agricultural pesticides. Continuous monitoring and epidemiological studies of organochlorine pesticides in humans are warranted in China. To our knowledge, this is the first report to present the residue levels of persistent organochlorine pesticides and PCBs in human tissues of China.

Aged↗

PubMed2002

Evaluation of mitogen-induced responses in marine mammal and human lymphocytes by in-vitro exposure of butyltins and non-ortho coplanar PCBs.

The effects of exposure to butyltin compounds (BTs: tributyltin; TBT, dibutyltin; DBT and monobutyltin; MBT) and non-ortho coplanar PCBs (IUPAC 77, 126 and 169) on marine mammals and human lymphocyte were evaluated. Peripheral blood mononuclear cells (PBMCs) isolated from Dall's porpoises (Phocoenoides dalli), bottlenose dolphins (Tursiops truncatus), a California sealion (Zalophus californianus), a larga seal (Phocoa largha) and humans (Homo sapiens) were exposed at varying concentrations of BTs and coplanar PCBs. Concanavalin A (Con A)-stimulated mitogenesis found significantly suppressed (P<0.01) when the cells were exposed at 300 nM (89 ng/ml) of TBT and 330 nM of DBT (77 ng/ml), while MBT showed little cytotoxicity at treatment levels of up to 3,600 nM (620 ng/ml). BTs concentrations in the liver of Dall's porpoises from Japanese coastal waters ranged between 81-450 ng/g for TBT and 200-1,100 ng/g (wet wt.) for DBTs, which is greater than the cytotoxic levels registered in this study. In contrast, non-ortho coplanar PCBs did not suppress cell proliferation at concentrations of up to 30 nM (10 ng/ml). The residue levels of coplanar PCBs in the blubber of Dall's porpoises were 0.12-1.3 ng/g, which were one order of lower than those levels that do cell proliferation. When cells were exposed to a mixture of TBT/DBTand coplanar PCBs, the proliferation was significantly reduced to 33 nM DBT plus 34 nM CB-77 and 33 nM DBT plus 28 nM CB-169 mixtures, respectively. The investigations relating the contaminant-induced immunosuppression in marine mammals have been focused on persistent organochlorines such as PCBs. pesticides and dioxin compounds. However, this study suggested the possibility of BTs could also pose a serious threat to the immune functions in free-ranging marine mammals and humans.

Animals↗

PubMed2002

Type III hyperlipoproteinema with apolipoprotein E2/2 genotype in Japan.

Limited information is available concerning type III hyperlipoproteinemia (HLP) in the Asian population. Therefore, clinical and biochemical characteristics of type III HLP were examined in 16 Japanese patients. Mean plasma triglyceride (TG) and total cholesterol (chol) levels were 381 mg/dl and 253 mg/dl, respectively, and the mean very low density lipoprotein (VLDL)-chol/plasma TG ratio was 0.27, which were lower than those reported in Western countries. Eighty percent of the patients had high plasma remnant-like particles (RLP)-chol levels above 50 mg/dl and a high RLP-chol/plasma TG ratio above 0.1. Twelve patients (75.0%) were obese. Seven patients (43.8%) had type 2 diabetes mellitus and four patients (25.0%) had impaired glucose tolerance. Six patients (37.5%) had coronary heart disease (CHD), but none had peripheral vascular disease or xanthomas. TG-rich lipoproteins from type III HLP patients with diabetes mellitus stimulated cholesteryl ester synthesis by human macrophages significantly (p < 0.001) more than those from type III HLP patients without diabetes mellitus. In conclusion, the Japanese type III HLP patients had lower plasma TG and total chol levels and a lower VLDL-chol/plasma TG ratio, but CHD was more common. The patients were characterized by a high frequency of obesity and/or glucose intolerance. The TG-rich lipoproteins from type III HLP patients with diabetes mellitus were more atherogenic.

Adult↗

PubMed2002

[The usefulness of induction chemotherapy in cases with tumors showing border-line pathological aspects between thymoma and thymic carcinoma].

We present 2 surgically treated cases with thymoma classified as Masaoka stage III and IV a (type B 3 thymoma), which showed the border-line pathological aspects between the thymoma and thymic carcinoma. Induction chemotherapy [CAV-PVP (cyclophosphamide, adriamycin, vincristine sulfate, etoposide) therapy in one case and ADOC (adriamycin, cisplatin, vincristine sulfate, cyclophosphamide) therapy in another case] preluded their surgical resection resulted in reduction of the tumor's size moderately or severely. After achievement of induction chemotherapy, these tumors were resected with the midsternotomy approach, along with resection of the right upper lobe and the left brachiocephalic vein replacing the expanded pdytetrafluoroethylene (ePTFE) graft following mediastinal lymphnodes dissection in one case and leaving the tumor tissue around the pulmonary trunk in another case. Postoperative irradiation of 40 Gy in one case and 60 Gy in another case were performed in the mediastinal regions. From pathological aspects especially in second case, though the specimen by preoperative needle biopsy stained positive for bcl-2 and strong immunoreactivity (20%) for MIB-1, specimens excised operatively after induction chemotherapy showed negative staining for bcl-2 and little staining (lower than 5%) for MIB-1. This fact indicates that the induction chemotherapy makes the tumor less malignant, in other words, from the face of thymic carcinoma to the face of thymoma. Induction chemotherapy performed for the purpose of reducing the tumor size was very advantage in these 2 cases with type B 3 thymoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Seroepidemiological survey of distemper virus infection in the Caspian Sea and in Lake Baikal.

Forty Caspian seals were surveyed seroepidemiologically between 1993 and 1998 around the times of mass mortality that occurred in 1997 in the Caspian Sea and seven Baikal seals were also surveyed in 1998. Virus neutralizing tests and ELISA clearly suggested that distemper virus epidemic was caused in Caspian seals before the spring of 1997 and that CDV infection continued to occur in Lake Baikal in recent years.

Animals↗

PubMed2001

Heteromeric association creates a P2Y-like adenosine receptor.

Adenosine and its endogenous precursor ATP are main components of the purinergic system that modulates cellular and tissue functions via specific adenosine and ATP receptors (P1 and P2 receptors), respectively. Although adenosine inhibits excitability and ATP functions as an excitatory transmitter in the central nervous system, little is known about the ability of P1 and P2 receptors to form new functional structures such as a heteromer to control the complex purinergic cascade. Here we have shown that G(i/o) protein-coupled A1 adenosine receptor (A1R) and Gq protein-coupled P2Y1 receptor (P2Y1R) coimmunoprecipitate in cotransfected HEK293T cells, suggesting the oligomeric association between distinct G protein-coupled P1 and P2 receptors. A1R and P2Y2 receptor, but not A1R and dopamine D2 receptor, also were found to coimmunoprecipitate in cotransfected cells. A1R agonist and antagonist binding to cell membranes were reduced by coexpression of A1R and P2Y1R, whereas a potent P2Y1R agonist adenosine 5'-O-(2-thiotriphosphate) (ADPbetaS) revealed a significant potency to A1R binding only in the cotransfected cell membranes. Moreover, the A1R/P2Y1R coexpressed cells showed an ADPbetaS-dependent reduction of forskolin-evoked cAMP accumulation that was sensitive to pertussis toxin and A1R antagonist, indicating that ADPbetaS binds A1R and inhibits adenylyl cyclase activity via G(i/o) proteins. Also, a high degree of A1R and P2Y1R colocalization was demonstrated in cotransfected cells by double immunofluorescence experiments with confocal laser microscopy. These results suggest that oligomeric association of A1R with P2Y1R generates A1R with P2Y1R-like agonistic pharmacology and provides a molecular mechanism for an increased diversity of purine signaling.

Adenosine↗

PubMed2001

A novel regulator of G-protein signaling bearing GAP activity for Galphai and Galphaq in megakaryocytes.

The regulator of G-protein signaling (RGS) negatively regulates the alpha subunit of G proteins by accelerating their intrinsic guanosine triphosphatase (GTPase) activity. Here are reported the isolation and characterization of a novel mouse RGS, termed RGS18, which is a new member of RGS subfamily B. Northern blot analysis showed that RGS18 messenger RNA was detected predominantly in spleen and hematopoietic cells, and immunohistochemical studies demonstrated that RGS18 was expressed in megakaryocytes, platelets, granulocytes/monocytes, and, weakly, in hematopoietic stem cells, but not in lymphocytes or erythrocytes. Although various subcellular localizations of RGS have been reported, RGS18 was found to be localized in cytoplasm in megakaryocytes. In vitro binding assays of RGS18 with megakaryocyte cell lysates with or without AlF(4)(-) treatment demonstrated that RGS18 specifically binds to 2 alpha subunits of the G protein, Galphai and Galphaq. Furthermore, RGS18 clearly exhibited GTPase-activating protein (GAP) activity for Galphai and Galphaq but not for Galphas or Galpha12. In addition, chemokine stromal-derived factor 1 (SDF-1), which has been reported to stimulate megakaryocyte colony formation in the presence of thrombopoietin, affected the binding of RGS18 to Galphai but not to Galphaq. Therefore, the newly isolated RGS18 turned out to be a new member of the RGS family bearing GAP activity for Galphai, which might be stimulated by SDF-1 in megakaryocytes, as well as for Galphaq. Thus, RGS18 may play an important role in proliferation, differentiation, and/or migration of megakaryocytes.

Aluminum Compounds↗