Y Namkung  SM Smith  SB Lee  NV Skrypnyk  HL Kim  H Chin  RH Scheller  RW Tsien  HS Shin 《Canadian Metallurgical Quarterly》1998,95(20):12010-12015

In comparison to the well characterized role of the principal subunit of voltage-gated Ca2+ channels, the pore-forming, antagonist-binding alpha1 subunit, considerably less is understood about how beta subunits contribute to neuronal Ca2+ channel function. We studied the role of the Ca2+ channel beta3 subunit, the major Ca2+ channel beta subunit in neurons, by using a gene-targeting strategy. The beta3 deficient (beta3-/-) animals were indistinguishable from the wild type (wt) with no gross morphological or histological differences. However, in sympathetic beta3-/- neurons, the L- and N-type current was significantly reduced relative to wt. Voltage-dependent activation of P/Q-type Ca2+ channels was described by two Boltzmann components with different voltage dependence, analogous to the \"reluctant\" and \"willing\" states reported for N-type channels. The absence of the beta3 subunit was associated with a hyperpolarizing shift of the \"reluctant\" component of activation. Norepinephrine inhibited wt and beta3-/- neurons similarly but the voltage sensitive component was greater for N-type than P/Q-type Ca2+ channels. The reduction in the expression of N-type Ca2+ channels in the beta3-/- mice may be expected to impair Ca2+ entry and therefore synaptic transmission in these animals. This effect may be reversed, at least in part, by the increase in the proportion of P/Q channels activated at less depolarized voltage levels.  相似文献   

    

SC Hsu  CD Hazuka  R Roth  DL Foletti  J Heuser  RH Scheller 《Canadian Metallurgical Quarterly》1998,20(6):1111-1122

Both the sec6/8 complex and septin filaments have been implicated in directing vesicles and proteins to sites of active membrane addition in yeast. The rat brain sec6/8 complex coimmunoprecipitates with a filament composed of four mammalian septins, suggesting an interaction between these complexes. One of the septins, CDC10, displays broad subcellular and tissue distributions and is found in postmitotic neurons as well as dividing cells. Electron microscopic studies showed that the purified rat brain septins form filaments of 8.25 nm in diameter; the lengths of the filaments are multiples of 25 nm. Glutaraldehyde-fixed rat brain sec6/8 complex adopts a conformation resembling the letter \"T\" or \"Y\". The sec6/8 and septin complexes likely play an important role in trafficking vesicles and organizing proteins at the plasma membrane of neurons.  相似文献   

    

CE Sortwell  BC Blanchard  TJ Collier  JD Elsworth  JR Taylor  RH Roth  DE Redmond  JR Sladek 《Canadian Metallurgical Quarterly》1998,791(1-2):117-124

The functional regulation by serotonin (5-HT) receptors of the 5-HT-enhanced dopamine (DA) release from the rat substantia nigra (SN) was investigated using in vivo microdialysis. Exogenously administered or extracellularly enhanced 5-HT (by means of intranigral citalopram perfusion) (both 1 microM for 1 h) significantly increased nigral DA efflux to 165% and 145%, respectively. Intranigral administration of pindolol (10 microM, 3 h), a 5-HT1A/1B receptor antagonist which is clinically used in order to block 5-HT1A/1B autoreceptors, did not affect DA levels but significantly increased nigral 5-HT levels to 135%. Co-perfusion of this antagonist with 5-HT (1 microM, 1 h) did not abolish the 5-HT-induced DA release from the SN as DA was increased to 166%. Local application of the 5-HT1A/1B receptor agonist, CP 93129 (1 microM, 1 h), increased DA release from the SN to 4770% whereas 5-HT release was significantly decreased to 75%. Co-perfusion of the 5-HT1A/1B receptor antagonist, pindolol, with this agonist only partly abolished the CP 93129-induced DA release whereas the CP 93129-induced decrease in nigral 5-HT release was completely abolished. Administration of the 5-HT2A/2C receptor antagonist, ketanserin (50 microM, 3 h), significantly increased DA to 143% and 5-HT release to 363%. Co-perfusion of this antagonist with 5-HT still caused an increase in nigral DA release to 214%. Intranigral perfusion of the 5-HT4 receptor antagonist, RS 39604 (10 microM, 3 h), did not affect DA levels but significantly decreased nigral 5-HT levels to 74%. Co-perfusion of this antagonist with 5-HT was able to prevent the 5-HT-enhanced DA efflux from the SN. From this study it can be concluded that the 5-HT-enhanced (and possibly the citalopram-induced) nigral DA release is 5-HT4 receptor mediated.  相似文献   

    

LM O''Rourke  R Tooze  M Turner  DM Sandoval  RH Carter  VL Tybulewicz  DT Fearon 《Canadian Metallurgical Quarterly》1998,8(5):635-645

Germ cells are distinct from somatic cells in their immortality, totipotency, and ability to undergo meiosis. Candidates for components that guide the unique germline program are the distinctive granules observed in germ cells of many species. We show that a component of germ granules is essential for fertility in C. elegans and that its primary function is in germline proliferation. This role has been revealed by molecular and genetic analyses of pgl-1. PGL-1 is a predicted RNA-binding protein that is present on germ granules at all stages of development. Elimination of PGL-1 results in defective germ granules and sterility. Interestingly, PGL-1 function is required for fertility only at elevated temperatures, suggesting that germline development is inherently sensitive to temperature.  相似文献   

    

RM Baltrusaitis  D Coffman  J Hauser  DG Hitlin  JD Richman  JJ Russell  RH Schindler 《Canadian Metallurgical Quarterly》1986,33(3):629-638

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RH Ruiz 《Canadian Metallurgical Quarterly》1995,41(2):114-120

The diagnostic accuracy of detailed zonography using the Scanora multimodal X-ray system was compared with that of periapical radiography. The study was based on the detection of periapical bone lesions at 259 dental sites distributed evenly throughout the dentitions of 164 patients. Each site was examined by periapical radiography and zonography, in parallel. The zonograms consisted of four detailed images that could also be read as stereopairs, in either the horizontal or vertical direction. Five observers evaluated the sites for the presence or absence of periapical osteolysis or sclerosis and apical widening of the periodontal ligament space for the whole dentition, and for three dental regions. ROC analysis revealed no significant overall or regional differences between the diagnostic accuracies of the periapical and zonographic techniques, regardless of whether the zonograms were read as sets of four images (multiview) or stereoscopic images. The sensitivity of periapical radiography was 72%, that of multiview zonography 88%, and that of stereoscopic zonography 85%. Specificities were 93%, 84% and 89%, respectively. The energy imparted during detailed zonography was 0.98 mJ. It is concluded that zonography is as good as periapical radiography for the detection of periapical pathology.  相似文献   

    

RS Wallis  P Nsubuga  C Whalen  RD Mugerwa  A Okwera  D Oette  JB Jackson  JL Johnson  JJ Ellner 《Canadian Metallurgical Quarterly》1996,174(4):727-733

Macrophage activation and tumor necrosis factor-alpha (TNF-alpha) production are critical in tuberculosis immunity but may result in increased human immunodeficiency virus (HIV) expression and accelerated HIV disease progression in HIV-infected persons. Pentoxifylline inhibits expression of TNF-alpha and HIV. A double-blind, placebo-controlled study of adjunctive therapy with pentoxifylline (1800 mg/day) as a timed-release formulation was done in Ugandan HIV-infected patients with pulmonary tuberculosis. Subjects had early HIV disease (mean CD4 cell count, 380/microL) and did not receive other antiretroviral drugs. Pentoxifylline resulted in decreased plasma HIV RNA and serum beta 2-microglobulin and, in a subset of moderately anemic patients, improved blood hemoglobin levels. Trends were noted toward reduced TNF-alpha production in vitro and improved performance scores, but these did not reach statistical significance. No effect was noted on body mass, CD4 cell count, or survival. Additional studies of more potent TNF-alpha inhibitors in HIV-positive subjects with tuberculosis are warranted.  相似文献   

    

JW Cohen  AC Monheit  KM Beauregard  SB Cohen  DC Lefkowitz  DE Potter  JP Sommers  AK Taylor  RH Arnett 《Canadian Metallurgical Quarterly》1996,33(4):373-389

This article describes the Medical Expenditure Panel Survey (MEPS), the third in a series of nationally representative surveys of medical care use and expenditures sponsored by the Agency for Health Care Policy and Research. The MEPS is designed to provide extensive data on the types of health care services American use, how frequently they use them, how much is paid for the services, and who pays for them. It also will provide information on the types and costs of private health insurance available to the U.S. population. The survey is unparalleled in its degree of detail, as well as its ability to link medical care use, payments, and health insurance coverage to specific survey respondents and their families. It allows analysts to examine how individual and family characteristics, including the characteristics of their health insurance, affect medical care use and spending. This article discusses each of the MEPS components, focusing on design enhancements that have been made since the survey was last conducted nearly a decade ago.  相似文献   

    

A Aidoo  LE Lyn-Cook  RH Heflich  EO George  DA Casciano 《Canadian Metallurgical Quarterly》1993,298(3):169-178

The persistence of 6-thioguanine-resistant (TGr) T-lymphocytes was investigated in Fischer 344 rats treated with N-ethyl-N-nitrosourea (ENU) using two schedules. Male rats, aged 3 months, were given i.p. injections containing a total of 0, 50 or 100 mg ENU/kg either as a single treatment (single-dose group) or divided among 10 weekly treatments (split-dose group). At 1, 3, 5, 10, 20, 30 and 50 weeks after the single-dose treatment, and 10, 20, 30 and 50 weeks after beginning the split-dose regimen, animals were assayed for the frequency of TGr spleen lymphocytes. ENU produced significant dose- and time-dependent responses in the single- and the split-dose treatment groups. Although a few of the 50 mg/kg split-dose treatments were significantly higher than the comparative single-dose groups, the number of TGr lymphocytes produced by the two dosing regimens were generally similar. The frequency of TGr cells for control animals increased with the age of the animals. The mode of ENU administration did not greatly influence the percent cloning efficiency (%CE) of the non-selection cultures, although the %CE declined in animals over 10 months of age. To investigate the relationship between the frequency of TGr cells and the age of the animals at the time of ENU administration, additional rats aged 17 months were treated with a single dose of ENU and at 1, 5 and 10 weeks following exposure, the frequencies of TGr cells were determined from the isolated lymphocytes. No difference in mutagen sensitivity between rats treated at 3 months of age and those treated at 17 months of age was detected at the time points evaluated. The data demonstrate the persistence of ENU-induced TGr T-lymphocytes in the rat and suggest that the dose and possibly the treatment schedule, but not the age of the animal at the time of treatment, affect the response.  相似文献   

    

JP Orlowski  D Lonsdale  RH Nodar  GW Williams 《Canadian Metallurgical Quarterly》1982,13(4):226-232

Thirty-six infants identified as infant apnea syndrome (IAS) and 25 controls with a comparable age distribution were evaluated with Brainstem Auditory Evoked Potential (BAEP) testing. There was a significant predilection for leftsided BAEP abnormalities in IAS patients. Fifteen IAS patients had bilateral abnormalities, and of the 21 IAS patients with unilateral abnormalities, 17 had abnormalities on the left side (p less than 0.01 by McNemar's test). Significant differences (p less than 0.05 by analysis of covariance adjusting for age) between normal controls and IAS infants were found for peak latencies I, III, and V, and amplitude III. Linear regression analyses of the above parameters versus age in months for normal controls were constructed with 68% and 95% prediction interval bands to permit analysis of individual data points. Data points from the IAS infants with bilateral BAEP abnormalities have been plotted on these linear regression curves. No single measurement of latency or amplitude is abnormal in the majority of IAS infants, but many of the individual points fall outside of the 95% prediction curve.  相似文献