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91.
Molecular dissection of the Prader-Willi/Angelman syndrome region (15q11-13) by YAC cloning and FISH analysis. 总被引:21,自引:0,他引:21
A Kuwano A Mutirangura B Dittrich K Buiting B Horsthemke S Saitoh N Niikawa S A Ledbetter F Greenberg A C Chinault 《Human molecular genetics》1992,1(6):417-425
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation disorders associated with deletions of proximal 15q (q11-q13) of different parental origin. Yeast artificial chromosome (YAC) clones were isolated for 9 previously mapped DNA probes from this region, and for one newly derived marker, LS6-1 (D15S113). A YAC contig of 1-1.5 Mb encompassing four markers (ML34, IR4-3R, PW71, and TD189-1) was constructed. Multi-color fluorescence in situ hybridization (FISH) analysis of interphase nuclei was combined with YAC contig information to provide the following order of markers: cen-IR39-ML34-IR4-3R-PW71-TD189-1-LS6++ +-1-TD3-21-GABRB3-IR10-1-CMW1-tel. FISH analysis was performed on 8 cases of PWS and 3 cases of AS, including 5 patients with normal karyotypes. All eleven patients were deleted for YACs in the interval from IR4-3R to GABRB3. On the proximal side of the deletion interval, 10/10 breakpoints fell within a single ML34 YAC of 370 kb. On the distal side, 8/9 breakpoints fell within a single IR10-1 YAC of 200 kb. These results indicate a striking consistency in the location of the proximal and distal breakpoints in PWS and AS patients. FISH analysis on a previously reported case of familial AS confirmed a submicroscopic deletion including YACs corresponding to LS6-1, TD3-21 and GABRB3 and supports the separation of the PWS and AS critical regions. Since these three YACs do not overlap each other, the minimum size of the AS critical region is > or = 650 kb. 相似文献
92.
93.
Addressing the need for updated teaching hospital facilities is one of the most significant issues that an academic medical center faces. The authors describe the process they underwent in deciding to build a new facility at the Medical University of South Carolina (MUSC). Initial issues included whether or not the teaching hospital would continue to play a role in clinical education and whether to replace or renovate the existing facility. Once the decision to build was reached, MUSC had to choose between an on-campus or distant site for the new hospital and determine what the function of the old hospital would be. The authors examine these questions and discuss the factors involved in different stages of decision making, in order to provide the academic medicine community guidance in negotiating similar situations. Open communication within MUSC and with the greater community was a key component of the success of the enterprise to date. The authors argue that decisions concerning site, size, and focus of the hospital must be made by developing university-wide and community consensus among many different constituencies. The most important elements in the success at MUSC were having unified leadership, incorporating constituent input, engaging an external consultant, remaining unfazed by unanticipated challenges, and adhering to a realistic, aggressive timetable. The authors share their strategies for identifying and successfully managing these complex and potentially divisive aspects of building a new teaching hospital. 相似文献
94.
Li W Jin K Nagayama T He X Chang J Minami M Graham SH Simon RP Greenberg DA 《Neuroscience》2000,96(1):161-168
Calcium is an important mediator of programmed cell death induced by transient cerebral ischemia, and calcium-binding proteins have been implicated in calcium-regulated signal transduction. Apoptosis-linked gene 2 is a calcium-binding protein required for cell death induced by different apoptotic stimuli. By Western blot analysis, we found that apoptosis-linked gene 2 protein was expressed in normal brains, and that expression increased in ischemic brains after 20 or 90 min of transient focal cerebral ischemia. Immunocytochemistry showed increased apoptosis-linked gene 2 protein expression in frontal cortex, a region where neurons underwent ischemic stress but still survived, after 20 or 90 min of focal cerebral ischemia. Apoptosis-linked gene 2 protein was also up-regulated in the ischemic border-zone of parietal cortex 24h after 20 min of focal ischemia, and was remarkably over-expressed in the caudate-putamen and parietal cortex, (where cells are destined to die) 24h after 90 min of ischemia. The expression pattern of apoptosis-linked gene 2 protein was similar to that of deoxyribonucleic acid damage detected by Klenow labeling assay.Our results suggest that apoptosis-linked gene 2 may be involved in the regulation of cell death after transient focal cerebral ischemia. 相似文献
95.
Edith A. Burns Raymond Fleming David A. Wagstaff James S. Goodwin Robert Hirschman Jordan J. Greenberg 《Journal of Applied Biobehavioral Research》2002,7(2):65-74
Few investigations have looked at behavioral stress outcomes in Alzheimer's caregivers. This study documented concentration deficits to examine behavioral outcomes of stress in 33 Alzheimer's Disease (AD) caregivers and in 33 age-, sex-, and race-matched controls. As hypothesized, caregivers showed less persistence than controls in solving problems from a standard test of problem-solving ability. In addition, caregivers tended to make more errors than controls on a standard proofreading task ( p < .09). In AD caregivers, cognitive deficits (represented by lower scores on problem-solving and concentration tasks) may be representative of a broader deficit in concentration that impairs the ability of caregivers to provide for their own needs and the needs of the family member for whom they are caring. 相似文献
96.
Relative frequency of rotavirus subgroups 1 and 2 in Venezuelan children with gastroenteritis as assayed with monoclonal antibodies. 总被引:2,自引:12,他引:2
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L White I Perez M Perez G Urbina H Greenberg A Kapikian J Flores 《Journal of clinical microbiology》1984,19(4):516-520
Monoclonal antibodies recently developed against the 42,000-dalton protein of two rotavirus strains were used in an enzyme-linked immunosorbent assay to determine the subgroup specificity of 252 specimens collected during a 45-month period from Venezuelan children with rotavirus gastroenteritis. Subgroup 2 rotavirus was shed by 85% of the children, whereas only 14% shed subgroup 1 rotavirus (one-half of them in a 3-month period). No differences were found in the occurrence of fever and vomiting between children shedding either rotavirus subgroup, but it appeared that the syndrome tended to last longer in children shedding subgroup 2 rotavirus. The monoclonal subgrouping enzyme-linked immunosorbent assay seemed to be more sensitive than an immune adherence hemagglutination assay, an enzyme-linked immunosorbent assay with polyclonal antibodies, or the electrophoretic analysis of RNA extracted from the virus. Overall, 99% of the specimens could be subgrouped by this assay. 相似文献
97.
S L Marles C R Greenberg T V Persaud E P Shuckett A E Chudley 《American journal of medical genetics》1992,42(6):793-799
We report on 6 (3 male, 3 female) Manitoba Indian children with hypertelorism and variable combinations of unilateral eye malformations, aberrant anterolateral scalp hairline, and nasal and anal anomalies. These children belong to 4 related families. The parents and 7 other sibs are clinically unaffected. The family histories are otherwise unremarkable. The presence of 2 major malformations in sibs and related individuals (with unaffected parents) suggests that this is a newly described pleiotropic autosomal recessive syndrome. The differential diagnosis includes cryptophthalmos syndrome and several other related malformation syndromes. Although multifactorial determination cannot be excluded, the inbred, isolated population and distribution make autosomal recessive inheritance more likely. 相似文献
98.
Summary Axons have generally been represented as straight cylinders. It is not at all uncommon for anatomists to take single cross-sections of an axonal bundle, and from the axonal diameter compute expected conduction velocities. This assumes that each cross-section represents a slice through a perfect cylinder. We have examined the three-dimensional geometry of 98 central and peripheral unmyelinated axons, using computer-assisted serial electron microscopy. These reconstructions reveal that virtually all unmyelinated axons have highly irregular axial shapes consisting of periodic varicosities. The varicosities were, without exception, filled with membranous organelles frequently including mitochondria, and have obligatory volumes similar to that described in other neurites. The mitochondria make contact with microtubules, while the other membraneous organelles were frequently found free floating in the cytoplasm. We conclude that unmyelinated axons are fundamentally varicose structures created by the presence of organelles, and that an axon's calibre is dynamic in both space and time.These irregular axonal geometries raise serious doubts about standard two dimensional morphometric analysis and suggest that electrical properties may be more heterogeneous than expected from single section data. These results also suggest that the total number of microtubules contained in an axon, rather than its single section diameter, may prove to be a more accurate predictor of properties such as conduction velocity. Finally, these results offer an explanation for a number of pathological changes that have been described in unmyelinated axons. 相似文献
99.
Lacking sympathetic innervation, the skin of A. carolinensis, an iguanid lizard, darkens within minutes in response to circulating melanocyte stimulating hormone (MSH) or beta adrenergic agonists such as epinephrine (EPI). This change is produced by dispersion of melanin from a perinculear position within dermal melanophores into superficial dendritic processes. These melanophores possess alpha-2 and beta-2 adrenergic as well as MSH receptors except in a patch of skin behind the eye, the eyespot, which lacks alpha receptors. Activation of beta or MSH receptors leads to stimulation of adenyl cyclase whereas alpha stimulation inhibits the enzyme to override the others. In a series of trials, injection of saline or propranolol was followed after 30 minutes by saline, EPI, or MSH. Propranolol inhibited chromatophore response to EPI. It also, unexpectedly, retarded the response to MSH, increasing latency to eyespot formation and body color change as well as the duration of darkening for both. Alteration of MSH response by a beta blocker could be explained by linkage of both adrenergic receptors and the MSH receptor to a common adenyl cyclase molecule to form a functional unit in the membrane of the melanophore. 相似文献
100.
A role for hyaluronan in macrophage accumulation and collagen deposition after bleomycin-induced lung injury 总被引:6,自引:0,他引:6
Savani RC Hou G Liu P Wang C Simons E Grimm PC Stern R Greenberg AH DeLisser HM Khalil N 《American journal of respiratory cell and molecular biology》2000,23(4):475-484
Elevated concentrations of hyaluronan (HA) are associated with the accumulation of macrophages in the lung after injury. We have investigated the role of HA in the inflammatory and fibrotic responses to lung injury using the intratracheal instillation of bleomycin in rats as a model. After bleomycin-induced lung injury, both HA content in bronchoalveolar lavage (BAL) and staining for HA in macrophages accumulating in injured areas of the lung were maximal at 4 d. Increased HA in BAL correlated with increased locomotion of isolated alveolar macrophages. HA-binding peptide was able to specifically block macrophage motility in vitro. Importantly, systemic administration of HA-binding peptide to rats before injury not only decreased alveolar macrophage motility and accumulation in the lung, but also reduced lung collagen alpha (I) messenger RNA and hydroxyproline contents. We propose a model in which HA plays a critical role in the inflammatory response and fibrotic consequences of acute lung injury. 相似文献