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1.
Studies of gastric morphology in North American Chiroptera (Emballonuridae, Noctilionidae, and Phyllostomatidae) 总被引:1,自引:0,他引:1
G L Forman 《Journal of mammalogy》1973,54(4):909-923
2.
Christine E. Brown Charles D. Warden Renate Starr Xutao Deng Behnam Badie Yate-Ching Yuan Stephen J. Forman Michael E. Barish 《PloS one》2013,8(10)
A major challenge for successful immunotherapy against glioma is the identification and characterization of validated targets. We have taken a bioinformatics approach towards understanding the biological context of IL-13 receptor α2 (IL13Rα2) expression in brain tumors, and its functional significance for patient survival. Querying multiple gene expression databases, we show that IL13Rα2 expression increases with glioma malignancy grade, and expression for high-grade tumors is bimodal, with approximately 58% of WHO grade IV gliomas over-expressing this receptor. By several measures, IL13Rα2 expression in patient samples and low-passage primary glioma lines most consistently correlates with the expression of signature genes defining mesenchymal subclass tumors and negatively correlates with proneural signature genes as defined by two studies. Positive associations were also noted with proliferative signature genes, whereas no consistent associations were found with either classical or neural signature genes. Probing the potential functional consequences of this mesenchymal association through IPA analysis suggests that IL13Rα2 expression is associated with activation of proinflammatory and immune pathways characteristic of mesenchymal subclass tumors. In addition, survival analyses indicate that IL13Rα2 over-expression is associated with poor patient prognosis, a single gene correlation ranking IL13Rα2 in the top ~1% of total gene expression probes with regard to survival association with WHO IV gliomas. This study better defines the functional consequences of IL13Rα2 expression by demonstrating association with mesenchymal signature gene expression and poor patient prognosis. It thus highlights the utility of IL13Rα2 as a therapeutic target, and helps define patient populations most likely to respond to immunotherapy in present and future clinical trials. 相似文献
3.
Cytotoxic T lymphocytes from mice with soluble class I Q10 molecules in their serum are not tolerant to membrane-bound Q10 总被引:2,自引:0,他引:2
D W Mann I Stroynowski L Hood J Forman 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(1):240-245
Q10 is a class I Qa-2 region-encoded molecule that is secreted by the liver and present in serum at high concentrations (about 10 to 60 micrograms/ml) in most strains of mice. The amino terminal portion of this molecule can also be expressed as an integral membrane protein by splicing the 5' end of the Q10 gene to the 3' end of H-2Ld and transfecting the hybrid gene into murine L cells. Because CTL primarily recognize polymorphic determinants controlled by the alpha 1 and alpha 2 domains of class I molecules and because the Q10d/Ld product expressed by transfected L cells includes the alpha 1 and alpha 2 domains of Q10d, we could address whether mice bearing serum Q10 were tolerant to this molecule at the CTL level. The results of these experiments demonstrate that Q10+ mice are able to generate H-2-unrestricted CTL activity against Q10d expressed on transfected L cells, and this response was not inhibitable by the addition of Q10-containing normal mouse serum. It is unlikely that this CTL activity is due to possible polymorphic differences in Q10 alleles, since semisyngeneic BALB/c (H-2d) mice, from which the Q10d hybrid gene construct was derived, are able to generate anti-Q10d effector cells. The Q10d molecule was shown to cross-react with H-2Ld, lending support to the concept that Qa genes can serve as donors for polymorphic sequences found in H-2K, -D, and -L. That mice can generate anti-Q10 CTL activity suggests that this soluble class I protein does not act as a toleragen for these cells. The implications of these findings for an understanding of self-tolerance are discussed. 相似文献
4.
The D region of the H-2
d
haplotype contains five class I genes: H-2D
d
, D2
d
, D3
d
, D4
d
and H-2L
d
. Although previous studies have suggested the presence of D-end encoded class I molecules in addition to H-2Dd and H-2Ld, segregation of genes encoding such molecules has not been demonstrated. In this report we have used cãtotoxic T lymphocytes (CTL) to examine the D region of the H-2
d
haplotype for the presence of additional class I molecules. CTL generated in (C3H × B6.K1)F1 (K
k
D
k
, K
b
D
b
) mice against the hybrid class I gene product Q10d/Ld expressed on L cells cross-react with H-2Ld but not H-2Dd molecules, as determined by lysis of transfected cells expressing H-2Ld but not H-2Dd. Although H-2Ld-specific monoclonal antibodies (mAb) completely inhibit H-2Ld-specific CTL from killing B10.A(3R) (K
b
D
d
L
d
) target cells, only partial inhibition of anti-Q10 CTL-mediated lysis was observed, suggesting the presence of an additional D-end molecule as a target for these latter CTL. To identify the region containing the gene encoding the Q10 cross-reactive molecule, we show that anti-Q10 CTL lyse target cells from a D-region recombinant strain B10.RQDB, which has H-2D
d
, D2
d
, D3
d
, D4
d
, and H-2D
b
but not the H-2L
d
H-2
d
, and H-2L
d
(including D2
d
, D3
d
, and D4
d
, lacks this anti-Q10 CTL target molecule. Together, these data demonstrate that a class I gene mapping between H-2D
d
and H-2L
d
encodes an antigen recognozed by anti-Q10 CTL. A likely candidate for this gene is D2
d
, D3
d
or D4
d
. 相似文献
5.
A G-band karyotypic analysis was carried out in individual species groups of three Callitrichid primate genera: Cebuella, Callithrix, and Leontopithecus. Within Callithrix, the karyotypes of the morphologically distinct and geographically isolated morphotypes C. jacchus jacchus and C. jacchus penicillata were identical. Within the lion tamarin genus, Leontopithecus, the karyotypes of the three morphotypes (L. rosalia rosalia, L. rosalia chrysomelas and L. rosalia chrysopygus) were also indistinguishable from one another. These results are consistent with the taxonomic designation of subspecies rank to the different morphotypes. A comparison of type specimens among the three Callitrichid genera showed that their phyletic radiation has been paralleled by a limited number of chromosome rearrangements and a relatively high amount of karyotypic invariance. A fusion/fission event has been postulated to account for the difference in diploid number between Cebuella (2n = 44) and the other species (2n = 46). The karyotype of Callithrix jacchus was found to be more directly derived from Cebuella than was that of Leontopithecus. These findings differ from the previous proposition that Leontopithecus might have diverged from a common Callitrichid ancestor before the emergence of the genus Callithrix. 相似文献
6.
7.
Effect of the expression of a hepatocyte-specific MHC molecule in transgenic mice on T cell tolerance 总被引:2,自引:0,他引:2
S L Jones-Youngblood K Wieties J Forman R E Hammer 《Journal of immunology (Baltimore, Md. : 1950)》1990,144(4):1187-1195
A hybrid murine class I gene, Q10/L, was injected into C3H/HeJ fertilized ova to produce transgenic (TG) mice. This fusion gene contained 414 bp of Q10 promoter sequences which was sufficient to direct liver-specific expression in two lines of animals. Animals from these lines did not have Q10/L mRNA in 10 nonhepatic tissues examined including thymus, spleen, and bone marrow. The ontogeny of Q10/Ld expression in both liver and yolk sac paralleled expression of endogenous Q10. Analysis of liver cells from these lines by flow cytometry and immunofluorescence demonstrated the presence of the Q10/L Ag solely on hepatocytes. TG animals showed no signs of hepatic disease as evidenced by an absence of cellular infiltrates in the liver and a normal profile of serum enzymes that are elevated in association with hepatic disease. When spleen cells from TG animals were cocultured with splenocytes that express Ag cross-reactive with Q10/L, CTL were generated that recognized and lysed L cells which express Q10/L. However, the extent of lysis was less than that generated from non-TG control littermates. That these cross-reactive T cells were physiologically significant was demonstrated by adoptive transfer of in vivo primed T cell enriched spleen cells which produced a mononuclear infiltration of the liver of TG recipients. However, inoculation of Q10/L L cells or splenocytes expressing Q10/L cross-reactive Ag into TG mice did not induce cellular infiltration or overt hepatic disease. Whereas inoculation of normal C3H mice with these cells led to priming of Q10/L reactive CTL, anti-Q10/L CTL could not be primed in TG mice. This suggests that Ag expression solely on hepatocytes can lead to inactivation of specific CTL clones and thus account for the observed in vivo tolerance. 相似文献
8.
P. M. Webb T. Knight S. Greaves A. Wilson D. G. Newell J. Elder D. Forman 《BMJ (Clinical research ed.)》1994,308(6931):750-753
OBJECTIVES--To relate the prevalence of infection with Helicobacter pylori in adults to their living conditions in childhood to identify risk factors for infection. DESIGN--Prevalence study of IgG antibodies to H pylori (> 10 micrograms IgG/ml, determined by enzyme linked immunosorbent assay (ELISA)) and reported living conditions and other socioeconomic factors in childhood. SETTING--Three factories in Stoke on Trent. SUBJECTS--471 male volunteers aged 18 to 65 years. MAIN OUTCOME MEASURES--Seroprevalence and variables in childhood. RESULTS--Seroprevalence of H pylori increased with age (22/74 (29.7%) at < 30 years v 29/46 (63%) at 55-65 years; P < 0.001 for trend) and was related to manual occupation (14/65 (21.5%) for non-manual v 162/406 (39.9%) for manual; P = 0.003). After data were adjusted for age and occupation subjects from large families, whose childhood homes were crowded or who regularly shared a bed in childhood, were significantly more likely to be seropositive (adjusted odds ratio (95% confidence interval) 2.15 (1.41 to 3.30) for crowding and 2.13 (1.38 to 3.30) for sharing a bed), but there was no relation with possession of a bathroom, inside toilet, refrigerator, or household pets in childhood. CONCLUSIONS--Close person to person contact in childhood is an important determinant of seroprevalence of H pylori in adulthood, suggesting that the infection is transmitted directly from one person to another and may be commonly acquired in early life. 相似文献
9.
Two satellite DNAs, designated CapA and CapB, were isolated from the neotropical primate,Cebus apella. The satellites exhibit nonoverlapping distributions onC. apella chromosomes. CapA is a major component of interstitial regions of constitutive heterochromatin, a very large block of heterochromatin comprising most of the long arm of chromosome 11, and some telomeres. The CapA monomer has a length of about 1500 bp and appears recently to have undergone an amplification episode in theC. apella genome. CapA-like sequences are probably present in members of the family Cebidae (to whichC. apella belongs), but not in members of the family Callitrichidae (marmosets). CapB sequences can be detected at the centromeres of manyC. apella chromosomes, and similar sequences are present in all neotropical primates. The 342 bp CapB monomer shares 60%–64% sequence identity with several alpha satellite sequences of human origin. Because of its structure, sequence, and location, it appears that CapB is the New World primate homolog of Old World primate alpha satellite DNA. 相似文献
10.
In eight nulliparous women with severe primary dysmenorrhoea, intrauterine pressure was recorded on the first day of menstruation before and after administration of diflunisal 1000 mg. Uterine activity was significantly decreased in all patients but abolished in none. Seven women experienced almost complete relief of pain. To four of the patients, including the one who did not become pain-free after diflunisal, nifedipine 30 mg was also given. Uterine activity was abolished in all, but the patient not responding to diflunisal had persistent pains. It is suggested that diflunisal may be used for treatment of pain in primary dysmenorrhoea. Addition of nifedipine can produce a further decrease in uterine activity, but whether combined therapy may offer therapeutic advantages remains to be established. 相似文献