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111.
PrP accumulation in the brains of mice infected with scrapie takes several different forms: amyloid plaques, widespread accumulation
in neuropile, and perineuronal deposits. PrP is also sometimes detected within microglia and in or around astrocytes. There
are dramatic and reproducible differences between scrapie strains in the relative prominence of these changes and their distribution
in the brain. Depending on the scrapie strain, PrP pathology is targeted precisely to particular brain areas, often showing
a clear association with identifiable groups of neurons. These results suggest that PrP changes are primarily associated with
neurons, and that different scrapie strains recognize and selectively replicate in different populations of neurons. Immunostaining
at the ultrastructural level demonstrates an association of PrP with neurite plasmalemma, around amyloid plaques, and in areas
of widespread neuropile and perineuronal accumulation. It is probable that PrP is encoded by theSinc gene, which controls the incubation period of scrapie in mice. Studies using the intraocular infection route show that theSinc gene controls the onset rather than the rate of replication, suggesting that PrP may be involved in cell-to-cell spread of
infection. The accumulation of PrP at the surface of neurons is consistent with such a role. 相似文献
112.
Refixation of xylem sap CO2 in Populus deltoides 总被引:1,自引:0,他引:1
Vascular plants have respiring tissues which are perfused by the transpiration stream, allowing solubilization of respiratory CO2 in the xylem sap. The transpiration stream could provide a conduit for the internal delivery of respiratory CO2 to leaves. Trees have large amounts of respiring tissues in the root systems and stems, and may have elevated levels of CO2 in the xylem sap which could be delivered to and refixed by the leaves. Xylem sap from the shoots of three Populus deltoides trees had mean dissolved inorganic carbon concentrations (CO2+H2CO3+HCO?3) ranging from 0. 5 to 0. 9 mM. When excised leaves were allowed to transpire 1 mM[14C]NaHCO3, 99. 6% of the label was fixed in the light. Seventy-seven percent of the label was fixed in major veins and the remainder was fixed in the minor veins. Autoradiography confirmed that label was confined to the vasculature. In the dark, approximately 80% of the transpired label escaped the leaf, the remainder was fixed in the major veins, slightly elevating dark respiration measurements. This indicates that the vascular tissue in P. deltoides leaves is supplied with a carbon source distinct from the atmospheric source fixed by interveinal lamina. However, the contribution of CO2 delivered to the leaves in the transpiration stream and fixed in the veins was only 0. 5% of atmospheric CO2 uptake. In the light 90% of the label was found in sugar, starch and protein, a pattern similar to that found for atmospheric uptake of[14C]CO2. Compared with leaves labelled in the light, leaves labelled in the dark had more label in organic acid, amino acid and protein and less label in sugar and starch. After a 5-s pulse the majority of the label fed to petioles in both the light and the dark was found in malate. The majority of the label was found in malate at 120 s in the dark; only 2% of the label was found in phosphorylated compounds at 120 s. The proportion of label found in phosphorylated compounds increased from 17% at 5 s to 80% at 120 s in the light. This suggests that CO2 delivered to leaves in the light via the transpiration stream is fixed in the veins, a small portion through dark fixation into malate, the remainder by C-3 photosynthesis. 相似文献
113.
Joan Silk Jenny Short Jeffrey Roberts Jill Kusnitz 《International journal of primatology》1993,14(1):95-104
We describe some of the sources of variation in gestation length among rhesus macaques. the data were obtained from the timed-mating breeding program at the California Regional Primate Research Center (CRPRC). Information about approximately 700 pregnancies that resulted in spontaneous vaginal deliveries of liveborn young is presented. The average length of these pregnancies was 166.5 days. In this population, older females with higher parities had significantly longer pregnancies and significantly heavier infants than other females did. Other factors, including infant sex, month of conception, maternal reproductive history, and paternal identity, had no consistent effect upon gestation length. 相似文献
114.
A chemically reactive analog of the phytotropin N-1-naphthylphthalamic acid (NPA) was synthesized and evaluated as a site-directed irreversible ligand for the NPA receptor. The NPA analog (5-isothiocyanato-N-1-naphthylphthalamic acid; NCS-NPA) was synthesized in two steps. Pretreatment of etiolated Helianthus hypocotyl segments with NCS-NPA at concentrations in excess of 1 M resulted in a dose-dependent inhibition of basipetal [14C]IAA transport. Net uptake of IAA by hypocotyl segments was stimulated by NCS-NPA at concentrations of 1 M or greater. NCS-NPA inhibited the saturable binding of [3H]NPA in Helianthus microsomes in a dose-dependent fashion with 50% inhibition occurring at NCS-NPA concentrations of 3 to 10 nM. The binding affinity of [3H]NPA in microsomes pretreated with NCS-NPA followed by extensive washing was substantially reduced. These results demonstrate that NCS-NPA is a site-directed irreversible ligand for the NPA receptor and suggest that it may be of use in the purification and characterization of this biologically important receptor.Abbreviations ANPA
5-amino-naphthylphthalamic acid
- IAA
indole-3-acetic acid
- NCS-NPA
5-isothiocyanato-N-1-naphthylphthalamic acid
- NPA
N-1-naphthylphthalamic acid
- TLC
thin-layer chromatography 相似文献
115.
Cyclic AMP (cAMP) elevation causes diverse types of cultured cells to round partially and develop arborized cell processes. Renal glomerular mesangial cells are smooth, muscle-like cells and in culture contain abundant actin microfilament cables that insert into substratum focal contacts. cAMP elevation causes adhesion loss, microfilament cable fragmentation, and shape change in cultured mesangial cells. We investigated the roles of the classical vitronectin (αVβ3 integrin) and fibronectin (α5β1 integrin) receptors in these changes. Mesangial cells on vitronectin-rich substrata contained microfilament cables that terminated in focal contacts that stained with antibodies to vitronectin receptor. cAMP elevation caused loss of focal contact and associated vitronectin receptor. Both fibronectin and its receptor stained in a fibrillary pattern at the cell surface under control conditions but appeared aggregated along the cell processes after cAMP elevation. This suggested that cAMP elevation caused loss of adhesion mediated by vitronectin receptor but not by fibronectin receptor. We plated cells onto fibronectin-coated slides to test the effect of ligand immobilization on the cellular response to cAMP. On fibronectin-coated slides fibronectin receptor was observed in peripheral focal contacts where actin filaments terminated, as seen with vitronectin receptor on vitronectin-coated substrata, and in abundant linear arrays distributed along microfilaments as well. Substratum contacts mediated by fibronectin receptor along the length of actin filaments have been termed fibronexus contacts. After cAMP elevation, microfilaments fragmented and fibronectin receptor disappeared from peripheral focal contacts, but the more central contacts along residual microfilament fragments appeared intact. Also, substratum adhesion was maintained after cAMP elevation on fibronectin—but not on vitronectincoated surfaces. Although other types of extracellular matrix receptors may also be involved, our observations suggest that cAMP regulates adhesion at focal contacts but not at fibronexus-type extracellular matrix contacts. © 1993 Wiley-Liss, Inc. 相似文献
116.
Lapita is a distinctive ceramic style that first appeared in the Bismarck Archipelago about 3600 B.P. and over the next few centuries spread throughout island Melanesia. For many prehistorians the distribution of Lapita sherds identifies the expansion of Austronesian-speaking populations through Oceania. This article addresses the Lapita language question by exploring the implications of the relationship among gamma globulin (Gm) genetics, paleoenvironments, malaria, natural selection, and prehistoric settlement patterns. Archeological sites with Lapita ceramics are consistently located in coastal lowlands, which in some parts of Oceania would have been malarious areas. Drawing on recent evidence that Austronesian-speaking populations in Near Oceania possess a genetic advantage over Non-Austronesian speakers with regard to malaria, we contend that Austronesian speakers have been able to occupy—on a permanent basis—malarious coastal lowlands that were detrimental to Non-Austronesian speakers. It follows, therefore, that the inhabitants of those Lapita sites spoke one or more of the Austronesian languages. 相似文献
117.
Gerard D. Schellenberg Haydeh Payami Ellen M. Wijsman Harry T. Orr Katrina A. B. Goddard Leojean Anderson Ellen Nemens June A. White M. Elisa Alonso Melvyn J. Ball Jeffrey Kaye John C. Morris Helena Chui A. Dessa Sadovnick Leonard L. Heston George M. Martin Thomas D. Bird 《American journal of human genetics》1993,53(3):619-628
Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analyses were used, in 49 families with a mean age at onset ≥60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependent penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score ≤ –2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P < .02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset ≥60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. 相似文献
118.
Jeffrey S. Chamberlain Michael Boehnke Thomas S. Frank Sam Kiousis Junxhe Xu Sun-Wei Guo Elizabeth R. Hauser Robert A. Norum Elizabeth A. Helmbold Dorene S. Markel Sima M. Keshavarzi C. Eugene Jackson Kathleen Calzone Judy Garber Francis S. Collins Barbara L. Weber 《American journal of human genetics》1993,52(4):792-798
Previous studies have demonstrated linkage between early-onset breast cancer and ovarian cancer and genetic markers on chromosome 17q21. These markers define the location of a gene (BRCA1) which appears to be inherited as an autosomal dominant susceptibility allele. We analyzed five families with multiple affected individuals for evidence of linkage to the BRCA1 region. Two of the five families appear to be linked to BRCA1. One apparently linked family contains critical recombinants, suggesting that the gene is proximal to the marker D17S579 (Mfd188). These findings are consistent with the maximum-likelihood position estimated by the Breast Cancer Linkage Consortium and with recombination events detected in other linked families. Linkage analysis was greatly aided by PCR-based analysis of paraffin-embedded normal breast tissue from deceased family members, demonstrating the feasibility and importance of this approach. One of the two families with evidence of linkage between breast cancer and genetic markers flanking BRCA1 represents the first such family of African-American descent to be reported in detail. 相似文献
119.
Jeffrey C. Geesin Laura J. Brown Joel S. Gordon Richard A. Berg 《Experimental cell research》1993,206(2)
Ascorbic acid has been shown to stimulate collagen synthesis in monolayer cultures of human dermal fibroblasts. In the present studies, we examined whether the presence of a collagen matrix influences this response of dermal fibroblasts to ascorbic acid. Fibroblasts and collagen were mixed and allowed to gel and contract for 6 days to form a matrix prior to determining the concentration and time dependence for ascorbic acid to affect collagen synthesis by fibroblasts within the matrix. Collagen synthesis was stimulated at levels at or above 10 μM ascorbic acid and was maximal after 2 days of treatment. This concentration and time dependence is similar to that of cells grown in monolayer cultures. The effects of transforming growth factor-β (TGF-β) and fibroblast growth factor (FGF) were also examined in this model. TGF-β increased and FGF inhibited collagen synthesis in the gels, as has been shown for cells in monolayer cultures. The effects of potential inhibitors of lipid peroxidation induced by ascorbic acid were also examined in these matrices and compared to previous results obtained in monolayer cultures. Propyl gallate, cobalt chloride, α,α-dipyridyl, and α-tocopherol inhibited the ascorbic acid-mediated stimulation of collagen synthesis while mannitol had no effect. Natural retinoids inhibited total protein synthesis without the specific effect on collagen synthesis that was seen in monolayer cultures. These results indicate that ascorbic acid stimulates collagen synthesis in fibroblasts grown in a collagen matrix in a manner similar to that found in monolayer cultures. In contracting collagen gels, however, the magnitude of the effect is less and retinoids do not specifically inhibit collagen synthesis. 相似文献
120.
Doing what the patient orders: maintaining integrity in the doctor-patient relationship 总被引:3,自引:0,他引:3
Blustein J 《Bioethics》1993,7(4):289-314
No profession has undergone as much scrutiny in the past several decades as that of medicine. Indeed, one might well argue that no profession has ever undergone so much change in so short a time. An essential part of this change has been the growing insistence that competent, adult patients have the right to decide about the course of their own medical treatment. However, the familiar and widely accepted principle of patient self-determination entails a corollary that has received little attention in the growing literature on the ethics of physician-patient relations: if patients are to direct the course of their own medical treatment, then physicians are at least sometimes to be guided in their actions on behalf of patients by values that are not, and may even be incompatible with, their own values. Unless it is supposed that it would be best if physicians were simply to accommodate any and all patient requests, a possibility I consider and reject in this paper, there are bound to be numerous instances of legitimate moral conflict between the preferences of physicians and patients. In this paper, I examine the implications of this sort of moral conflict from the standpoint of the integrity of the physician....I have also considered the common practice of patient referral from the standpoint of physician integrity, and asked whether a physician who refuses to treat a patient as a matter of conscience can consistently refer the patient to another physician for the same treatment.... 相似文献