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121.
Paloma E Coco R Martínez-Mir A Vilageliu L Balcells S Gonzàlez-Duarte R 《Human mutation》2002,20(6):476-476
Genotype-phenotype correlations highlighted the function of ABCA4 in retinitis pigmentosa (RP),cone-rod dystrophy (CRD) and Stargardt/Fundus Flavimaculatus disease (STGD/FFM). Initial screening of ABCA4 variants showed a correlation between the type of mutation and the severity of the disease. In the present study we have undertaken mutational and haplotype analysis of ABCA4 in three mixed pedigrees segregating different retinal dystrophies. In family I, we have shown cosegregation of different ABCA4 alleles with CRD (homozygosity for L1940P) and three subtypes of STGD/FFM. The first, a mild form, consisting on fundus flavimaculatus-like distribution of flecks, but good visual acuity and absence of dark choroid, was found to cosegregate with alleles R1097C and F553L; the second, a conventional Stargardt phenotype was associated to alleles L1940P/R1097C and the third, displaying severely reduced visual acuity and dark choroid (named FFM), was associated to L1940P/F553L. In family II, segregating STGD and RP phenotypes, while the involvement of ABCA4 in STGD seems clear this is not the case for RP. Finally, in family III, also segregating STGD and RP, ABCA4 fails to explain either phenotype. Our data highlight the wide allelic heterogeneity involving this gene and support the genetic variability (beyond ABCA4) of mixed STGD/RP pedigrees. 相似文献
122.
T. Angelone E. Filice A. M. Quintieri S. Imbrogno A. Recchia E. Pulerà C. Mannarino D. Pellegrino M. C. Cerra 《Acta physiologica (Oxford, England)》2008,193(3):229-239
Aims: Using a model of isolated and Langendorff‐perfused rat heart we analysed whether activation of β3‐adrenergic receptors (β3‐ARs) influences ventricular lusitropic performance. We also focused on the NOS/NO/cGMP/PKG cascade as the signal transduction mechanism. Methods: Hearts were treated with increasing concentrations (from 10?12 to 10?6 m ) of BRL37344, a selective β3‐AR agonist, and cardiac performance was evaluated by analysing both lusitropic parameters and coronary motility. Cardiac preparations were also perfused with BRL37344 in the presence of either isoproterenol (ISO) or nadolol, or pertussis toxin (PTx), or selective inhibitors of the NOS/NO/cGMP/PKG pathway. Results: BRL37344 caused a significant concentration‐dependent reduction in (LVdP/dt)min, a decrease in half time relaxation significant starting from 10?12 m , and an increase in (LVdP/dt)max/(LVdP/dt)min ratio (T/?t). BRL37344 abolished the ISO‐mediated positive lusitropism. β3‐AR‐dependent effects on relaxation were insensitive to β1/β2‐AR inhibition by nadolol (100 nm ), and were abolished by Gi/o protein inhibition by PTx (0.01 nm ). NO scavenging by haemoglobin (10 μm ), and nitric oxide synthase (NOS) inhibition by NG‐monomethyl‐l ‐arginine (10 μm ) revealed the involvement of NO signalling in BRL37344 response. Pre‐treatment with inhibitors of either soluble guanylate cyclase (ODQ; 10 μm ) or PKG (KT5823; 100 nm ) abolished β3‐AR‐dependent negative lusitropism. In contrast, anantin (10 nm ), an inhibitor of particulate guanylate cyclase, did not modify the effect of BRL37344 on relaxation. Conclusion: Taken together, our findings provide functional evidence for β3‐AR modulation of ventricular relaxation in the rat heart which involves PTx‐sensitive inhibitory Gi protein and occurs via an NO‐cGMP‐PKG cascade. Whether the effects of β3‐AR stimulation on lusitropism are beneficial or detrimental remains to be established. 相似文献
123.
Spring M Stahl-Hennig C Stolte N Bischofberger N Heeney J ten Haaft P Tenner-Ràcz K Ràcz P Lorenzen D Hunsmann G Dittmer U 《Virology》2001,279(1):221-232
Losing the decisive virus-specific functions of both CD4(+) and CD8(+) T lymphocytes in the first weeks after immunodeficiency virus infection ultimately leads to AIDS. The SIV/rhesus monkey model for AIDS was used to demonstrate that a 4-week chemotherapeutic reduction of viral load during acute SIV infection of macaques allowed the development of a competent immune response able to control virus replication after discontinuation of treatment in two of five monkeys. Increasing SIV-specific CD4(+) T-helper-cell proliferation was found in all macaques several weeks after treatment, independent of their viral load. However, only macaques with low viral loads showed persistent T-cell reactivity of lymph node cells. In contrast to animals with higher viral loads, T-helper-cell counts and memory T-helper cells did not decline in the two macaques controlling viral replication. Lymphocyte apoptosis was consistently low in all treated macaques. In contrast, high CD8(+) lymphocyte death but only slightly increased CD4(+) lymphocyte apoptosis were observed during the first weeks after infection in untreated control animals, indicating that early apoptotic death of virus-specific CTL could be an important factor for disease development. Antiretroviral treatment early after infection obviously retained virus-specific and competent T lymphocytes, whereby a virus-specific immune response could develop in two animals able to control the viral replication after cessation of treatment. 相似文献
124.
Amills M Sulas C Sànchez A Bertoni G Zanoni R Obexer-Ruff G 《Molecular immunology》2005,42(3):375-379
The major histocompatibility class II DQ molecules are dimeric glycoproteins involved in antigen presentation to CD4(+) T cells. In the current work, we have performed the molecular analysis of the goat Cahi-DQA1 gene. Sequencing of the Cahi-DQA1 cDNA revealed a single 768bp open reading frame. The alignment of this sequence with its bovine and ovine DQA1 counterparts revealed a remarkable degree of nucleotide identity (92-93% for the most similar bovine and ovine sequences). Moreover, we amplified a region including the 3'-end of intron 1, exon 2 and the 5'-end of intron 2. We identified seven Cahi-DQA1 alleles that likely correspond to four different allelic lineages. The alignment of these seven Cahi-DQA1 alleles revealed the existence of 23 amino acid polymorphic sites, seven of which (alpha(10), alpha(55), alpha(56), alpha(68), alpha(69), alpha(71) and alpha(76)) are highly polymorphic with at least three amino acid substitutions. Ten of the 23 polymorphic amino acid sites were included in the peptide binding region and consequently they might play a crucial role in immunological processes modulating disease pathogenesis. 相似文献
125.
Establishment of the paternal methylation imprint of the human H19 and MEST/PEG1 genes during spermatogenesis 总被引:9,自引:0,他引:9
Kerjean A Dupont JM Vasseur C Le Tessier D Cuisset L Pàldi A Jouannet P Jeanpierre M 《Human molecular genetics》2000,9(14):2183-2187
Parental-specific epigenetic modifications are imprinted on a subset of genes in the mammalian genome during germ cell maturation. However, the precise timing of their establishment remains to be determined. Methylation of CpG dinucleotides has been shown to be a part of the parental imprint. We have examined how the methylation pattern characteristic of the paternal allele in germ cells are established during human spermatogenesis. Two representative imprinted genes, H19 and MEST/PEG1, were studied. The experiments were performed using the bisulphite sequencing method on microdissected individual cells at different stages of male germ cell differentiation. We show that both genes are unmethylated in fetal spermatogonia, suggesting that all pre-existing methylation imprints are already erased by this stage. The MEST/PEG1 gene remains unmethylated at all subsequent post-pubertal stages of spermatogenesis, including mature spermatozoa. The methylation of H19 typical of the paternal allele first appears in a subset of adult spermatogonia and then is maintained in spermatocytes, spermatids and mature spermatozoa. Our results suggest that the methylation imprint inherited from the parents is first erased in the male germ line at an early fetal stage. The paternal-specific imprint is re-established only later, during spermatogonial differentiation in the adult testis. 相似文献
126.
Wade NA Zielinski MA Butsashvili M McNutt LA Warren BL Glaros R Cheku B Pulver W Pass K Fox K Novello AC Birkhead GS 《Journal of acquired immune deficiency syndromes (1999)》2004,36(5):1075-1082
BACKGROUND: Perinatal HIV transmission has declined significantly in New York State (NYS) since implementation of a 3-part regimen of zidovudine prophylaxis in the antenatal, intrapartum, and newborn periods. This study describes the factors associated with perinatal transmission in NYS from 1997 to 2000, the first 4 years of NYS's comprehensive program in which all HIV-exposed newborns were identified through universal HIV testing of newborns. METHODS: This population-based observational study included all HIV-exposed newborns whose infection status was known and their mothers identified in NYS through the universal Newborn HIV Screening Program (NSP) from February 1997 to December 2000. Antepartum, intrapartum, newborn, and pediatric medical records of HIV-positive mothers/infants were reviewed for history of prenatal care, antiretroviral therapy (ART), and infant infection status. Risks associated with perinatal HIV transmission were examined. RESULTS: Perinatal HIV transmission declined significantly from 11.0% in 1997 to 3.7% in 2000 (P < 0.05). Prenatal ART was associated with a decline in perinatal HIV transmission both for monotherapy (5.8%, relative risk [RR] = 0.3, 95% confidence interval: 0.2%-0.5%) and combination therapy [2.4%, RR = 0.1, 95% confidence interval: 0.1%-0.2%) compared with no prenatal antiretroviral prophylaxis (P < 0.05). CONCLUSIONS: Public health policies to improve access to care for pregnant women and advances in clinical care, including receipt of appropriate preventive therapies, have contributed to declines in perinatal HIV transmission in NYS. 相似文献
127.
E. Zanette L. Bozzao C. Buttinelli A. Mariottini S. Pappatà G. L. Lenzi 《Acta neurochirurgica》1987,89(1-2):43-47
Summary Tumour growth essentially requires fibrin formation and fibrinopeptide A (FPA) is liberated into the circulation on fibrin formation. In the present study, a possible elevation of serum FPA level was examined in patients with metastatic brain tumour. A significant elevation of serum FPA level was shown in all 6 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. It was extremely high in 2 patients with rapidly growing tumour. However, such a significant elevation was not shown in 3 cancer patients without brain metastasis or in 1 patient with a huge meningioma. This suggests the possibility that the presence of metastatic brain tumour could be detected by measuring FPA in blood drawn form the internal jugular vein. This also suggests the tendency that elevation of serum FPA is higher in patients with more rapidly growing tumour.Infusion of urokinase into the internal carotid artery resulted in an elevation of serum fibrinopeptide B (1)15–42 (FPB) in 5 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. This suggests that urokinase could induce fibrinolysis in the tumour tissue, though this remains in conclusive because of the lack of complete controls. 相似文献
128.
Jackie J. H. Chuong MD Dr. Rosemarie L. Fisher MD Roberta L. B. Chuong MSN Howard M. Spiro MD 《Digestive diseases and sciences》1986,31(11):1178-1184
In 1958 the Yale freshman class gave blood samples as part of a study intended to determine the predictive value of plasma pepsinogen (PP) for the subsequent development of duodenal ulcer (DU). We report a long-term follow-up of this cohort. A selfadministered questionnaire designed to ascertain information about the development of peptic ulcers, and the presence of risk factors was mailed to 861 subjects with active addresses. A second questionnaire was mailed to each respondent's physician(s) to verify the diagnosis of DU. Completed questionnaires were returned, after three mailings, by 604 (70%) of the subjects. They reported 18 documented DUs, 15 since 1958, for an incidence of 1.1/1000 person years. Only smoking (P<0.05) and undergraduate physical inactivity (P<0.01) were identified as risk factors for DU. Family history; blood type; blood antigen secretor status; ingestion of coffee, alcohol, milk, salicylates, soda, or tea; and COPD were not identified as risk factors for DU. Patients with DU had higher mean PP values than those who did not (391.6±99.6 vs 346.6±106.7, mean ±sd) but this was not statistically significant (P>0.05). The predictive value of an elevated PP(>450) for the development of DU was 7.9%, but a low or normal PP predicted the absence of a DU in 97.5% of subjects over a 22-year span. We conclude that in a selected population followed for 22 years there is a low incidence of DU, supporting the general belief that duodenal ulcer is declining, that smoking and undergraduate physical inactivity are risk factors for duodenal ulcer, and that a low or normal PP may be useful as a predictor for a low susceptibility to duodenal ulcer disease.Dr. J. Chuong acknowledges the support of the Robert Wood Johnson Clinical Scholar Program, and the Daland Fellowship in Clinical Medicine of the American Philosophical Society. 相似文献
129.
130.
Lineage relationship of chronic lymphocytic leukemia and hairy cell leukemia: studies with TPA 总被引:2,自引:0,他引:2
F Caligaris-Cappio G Janossy D Campana M Chilosi L Bergui R Foà D Delia M C Giubellino P Preda M Gobbi 《Leukemia research》1984,8(4):567-578
The tumor promoting agent TPA (phorbol ester; 1.6 X 10(-8)M) was used to induce the differentiation in vitro of B-chronic lymphocytic leukemia (B-CLL) cells from 14 untreated patients. The uninduced phenotype was SIg+, Mrbc+, RFT-1+, RFA-4-, FMC7-. After 72 h incubation with TPA, B-CLL cells became RFA-4+, FMC7+ and lost the capability of Mrbc rosetting. Large proportions of the "induced" cells also showed morphological and ultrastructural changes, such as undulating membranes and bleblike protusions and became strongly positive for tartrate resistant acid phosphatase (TRAP+) and also contained cytoplasmic immunoglobulins. These features are very similar to the features of hairy cell leukemia (HCL). These observations confirm previous clinical findings that B-CLL and HCL are related disorders of the B lineage. The development of "hairy" features in induced B-CLL and in HCL seems to be a malignancy-associated feature because the Mrbc+ normal B cells (B-CLL-equivalent cells) isolated from tonsil also develop TRAP positivity but no membrane aberrations. 相似文献