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101.
Elliott AM Graham JM Curry CJ Pal T Rimoin DL Lachman RS 《American journal of medical genetics》2002,113(4):351-361
Dolichospondylic dysplasia (DD) is a rare skeletal dysplasia primarily characterized by tall vertebral bodies and disproportionate short stature. Radiographic manifestations include tall vertebral bodies and gracile bones of the hands. Patients usually have eye and ear findings in addition to borderline mental retardation; however, tall vertebral bodies and slender tubular bones are also seen in the 3-M syndrome. Patients with the 3-M syndrome have a characteristic face with a triangular shape, frontal bossing, a flattened malar region, full eyebrows, a short nose with a bulbous tip, upturned nares, and full lips. We present two unrelated patients who share a distinct phenotype and have tall vertebral bodies, overtubulation of long bones, and short tubular bones of the hands and feet. We discuss the overlapping and distinguishing features between DD and the 3-M syndrome. Patient 1 was a 13-year-old female, and patient 2 was an unrelated adult female. These patients had normocephaly and short stature. They shared a common phenotype consisting of mild malar hypoplasia, a narrowed nasal body with a fleshy tip, full lips, and normal intelligence. In addition, they showed mild hand and foot abnormalities. These two patients lack many of the typical clinical features of both DD and the 3-M syndrome. They share a common phenotype and likely represent a distinct disorder. The spectrum of disorders with tall vertebral bodies as a key feature may include different entities that may be further defined with the characterization of the molecular defect(s). 相似文献
102.
Peebles RS Sheller JR Collins RD Jarzecka AK Mitchell DB Parker RA Graham BS 《Journal of medical virology》2001,63(2):178-188
Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined murine models of allergen-sensitization and RSV infection to explore the interaction of allergic and virus-induced airway inflammation and its impact on airway hyperresponsiveness (AHR). We found that RSV infection during ova-sensitization (OVA/RSV) increased and prolonged AHR compared to mice only RSV-infected (RSV) or ova-sensitized (OVA). AHR is known to be associated with an increase in Type 2 cytokines (IL-4, IL-5, and IL-13) in allergen-sensitized mice. Therefore, we hypothesized that RSV-induced enhancement of AHR was a result of potentiating the Type 2 cytokine profile promoted by ova-sensitization. Surprisingly, we found that Type 2 cytokines induced by ova-sensitization were not increased by RSV infection despite the increase in AHR, and in some cases were diminished. RNAse protection assay revealed no difference in IL-4 and IL-5 mRNA levels between the OVA and OVA/RSV groups, and IL-13 mRNA was significantly decreased in the OVA/RSV mice compared to the OVA group. Flow cytometric analysis of Type 2 cytokines demonstrated the same frequency of IL-4 and IL-5 production in lung-derived T lymphocytes from the OVA/RSV and OVA groups. Direct cytokine ELISA measurements of lung supernatant showed the level of IL-13 was significantly decreased in the OVA/RSV group compared to OVA mice, while there was no difference in either IL-4 or IL-5 between these two groups. These data indicate that the enhanced and prolonged AHR caused by the interaction of allergic airway inflammation and virus-induced immune responses is a complex process that can not be explained simply by augmented production of Type 2 cytokines. 相似文献
103.
Cook Graham P.; Meyer Kerstin B.; Neuberger Michael S.; Pettersson Sven 《International immunology》1995,7(1):89-95
The activity of the IgH (Eµ) enhancer in the T lymphocytelineage has been investigated using both transgenic mice andtransfection studies. Thymocyte fractionation experiments indicatethat a transgene consisting of the bacterial chloramphenicolacetyl transferase (CAT) gene, linked to Eµ and the SV40early promoter (Eµ–CAT), is expressed only in thymocyteswith a mature medullary phenotype and not in immature cells.Transfection of this same construct into two thymoma cell linesrepresenting different stages of thymocyte development mimicsthe pattern of activity observed in vivo. Further transfectionexperiments suggest that this pattern of expression might beattributed to the differential activity of the E2E3 and octanucleotidemotifs of Eµ during development. In contrast, an Ig transgene(linked to Eµ and an Ig V promoter) is expressed in themajority of thymocytes. We envisage that the different patternsof expression of the two transgenes reflect interactions betweentheir respective promoters and the factors which are bound toEµ at different stages of thymocyte development. Althoughdiffering in their pattern of expression within the thymus,the two transgenes share the property of extinction in peripheralT lymphocytes. These results indicate that the expression ofEµ-linked transgenes in the thymus cannot simply be explainedby activation of the enhancer in a lymphoid progenitor cellprior to B/T lineage divergence. Rather, the enhancer (or componentsof it) must be independently activated (and inactivated) duringT lymphocyte development. Furthermore, this activity is consistentwith the developmental timing of Ig DH–JH rearrangementsin these cells. 相似文献
104.
105.
Characterization of a Helicobacter pylori neutrophil-activating protein. 总被引:25,自引:0,他引:25 下载免费PDF全文
D J Evans Jr D G Evans T Takemura H Nakano H C Lampert D Y Graham D N Granger P R Kvietys 《Infection and immunity》1995,63(6):2213-2220
Helicobacter pylori-associated gastritis is mainly an inflammatory cell response. In earlier work we showed that activation of human neutrophils by a cell-free water extract of H. pylori is characterized by increased expression of neutrophil CD11b/CD18 and increased adhesiveness to endothelial cells. The work reported here indicates that the neutrophil-activating factor is a 150,000-molecular-weight protein (150K protein). Neutrophil proadhesive activity copurified with this protein, which is a polymer of identical 15K subunits. Specific antibody, prepared against the purified 15K subunit, neutralized the proadhesive activity of the pure protein and of water extracts obtained from different strains of H. pylori. The gene (napA) for this protein (termed HP-NAP, for H. pylori neutrophil-activating protein) was detected, by PCR amplification, in all of the H. pylori isolates tested; however, there was considerable strain variation in the level of expression of HP-NAP activity in vitro. HP-NAP could play an important role in the gastric inflammatory response to H. pylori infection. 相似文献
106.
Interphase cytogenetics using biotin and digoxigenin labelled probes II: Simultaneous differential detection of human and papilloma virus nucleic acids in individual nuclei. 总被引:1,自引:8,他引:1 下载免费PDF全文
C S Herrington J Burns A K Graham B Bhatt J O McGee 《Journal of clinical pathology》1989,42(6):601-606
A method was developed for the simultaneous detection of viral and human DNA in contrasting colours in routine formalin fixed, paraffin wax embedded biopsy specimens. This was achieved by non-isotopic in situ hybridisation (NISH) with a biotinylated Y chromosome probe and digoxigenin labelled probe for human papilloma virus type 6 (HPV 6). The tissues studied were peripheral lymphocytes, tonsil, and penile warts. The hybridisation signals produced by biotinylated probes were visualised in red using streptavidin peroxidase and those produced by digoxigenin labelled probes as a blue/black colour using anti-digoxigenin alkaline phosphatase. In lymphocytes and tonsil 95-100% of cells had a detectable Y chromosome; in warts only 60-70% of infected keratinocytes near the skin surface had a demonstrable Y chromosome. This suggests that this chromosome is lost or occluded in cell maturation. In simultaneous double hybridisation with both probes, HPV and Y sequences were demonstrable within the same nucleus in penile warts. This technique permits the simultaneous differential detection of two nuclei acid sequences in interphase nuclei and will have application in analysis of putative dual HPV infections and in determining the intranuclear spatial relations between nucleic acids in interphase nuclei. 相似文献
107.
Much has been written about social worker/general-practitioner collaboration, particularly about conflict of roles, differing functions, avenues of accountability, and problems of distributing scarce resources.
We suggest that if the two professions are to work more comfortably together, then it is imperative that both also share the despair, hopelessness, anxiety, and anger that are the occupational hazards of each. We suggest ways in which doctors and social workers can look at the pain their patients are suffering to the benefit of the patient and their own working relationship.
相似文献108.
W C Graham D R Hill G N Woodruff M A Sambrook A R Crossman 《Neuroscience letters》1991,131(1):129-134
Cholecystokinin (CCK) receptors were visualized autoradiographically using [125I]Bolton Hunter CCK8 ([125I]BHCCK8) in the fore- and midbrain of 3 monkeys rendered hemi-parkinsonian by unilateral intra-carotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). More specifically, CCK-A receptors were detected using [3H]MK-329 (devazepide), a peripheral-type (CCK-A) receptor antagonist. In the substantia nigra pars compacta, ipsilateral to the toxin infusion, where dopamine D2 receptors (labelled with [3H]sulpiride) were lost, there was a decrease in the binding of both [125I]BHCCK8 and [3H]MK-329. Binding of the two CCK ligands was also reduced in the ipsilateral nucleus accumbens and most medial part of the caudate nucleus, whereas 3H-sulpiride binding was increased in the lateral caudate nucleus and putamen. These results indicate that CCK-A receptors may be located on dopaminergic cells within the substantia nigra, which are lost in the parkinsonian brain, and may also be present on dopaminergic terminals within restricted regions of nigral/ventral tegmental area projection sites. 相似文献
109.
Boosting with poxviruses enhances Mycobacterium bovis BCG efficacy against tuberculosis in guinea pigs 下载免费PDF全文
Williams A Goonetilleke NP McShane H Clark SO Hatch G Gilbert SC Hill AV 《Infection and immunity》2005,73(6):3814-3816
Tuberculosis is rising in the developing world due to poor health care, human immunodeficiency virus type 1 infection, and the low protective efficacy of the Mycobacterium bovis BCG vaccine. A new vaccination strategy that could protect adults in the developing world from tuberculosis could have a huge impact on public health. We show that BCG boosted by poxviruses expressing antigen 85A induced unprecedented 100% protection of guinea pigs from high-dose aerosol challenge with Mycobacterium tuberculosis, suggesting a strategy for enhancing and prolonging the efficacy of BCG. 相似文献
110.
F A el-Zaatari S A Naser D C Markesich D C Kalter L Engstand D Y Graham 《Journal of clinical microbiology》1996,34(9):2240-2245
Cell wall-defective bacteria which later reverted to acid-fast bacilli have been isolated from sarcoid tissue. These have not been conclusively shown to be mycobacteria. Specific PCR assays were applied to identify mycobacterial nucleic acids in these cultured isolates and in fresh specimens obtained from patients with sarcoidosis. Positive amplification and hybridization were observed with Mycobacterium avium complex- and/or Mycobacterium paratuberculosis-specific probes in five of the six cultured isolates and two fresh skin biopsy samples and one cerebrospinal fluid specimen. There was no amplification or hybridization with Mycobacterium tuberculosis or M. avium subsp. silvaticum probes, respectively. Patients' sera were also tested for antibody reactivities by immunoblotting with M. paratuberculosis recombinant clones expressing the 36,000-molecular-weight antigen (36K antigen) (p36) and the 65K heat shock protein (PTB65K). All seven sarcoidosis, four of six tuberculosis, and all six leprosy patient serum specimens showed strong reactivity with p36 antigen. In contrast, 13 of 38 controls showed only weak reactivity with p36 (P = 0.002 for controls versus sarcoidosis samples). Similarly, PTB65K reacted with high intensity with sera from 5 of 5 sarcoidosis, 5 of 6 tuberculosis, and 5 of 6 leprosy patients, compared with its low-intensity reaction with 5 of 22 controls (P = 0.001 for controls versus sarcoidosis samples). This study demonstrates the isolation and/or identification of M. paratuberculosis or a closely related M. avium complex strain from sarcoid skin lesions and cerebrospinal fluid. Furthermore, the reactivity of antibodies in sarcoid patient sera against p36 and PTB65K antigens was comparable to the reactivity of sera obtained from patients with known mycobacterial disease. Collectively, these data provide further support for the theory of the mycobacterial etiology of sarcoidosis. 相似文献