The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome

Patients with X-linked lymphoproliferative syndrome (XLP) experience excessive T cell proliferation after primary Epstein-Barr virus (EBV) infection, due to mutations in the signalling lymphocyte activation molecule (SLAM) associated protein (SAP) molecule. We examined the impact of dysfunctional proliferative control on the extent of CD8+ T cell differentiation in XLP patients who recovered from primary EBV infection. Although these young patients have normal numbers of lytic and latent EBV-epitope-specific CD8+ T cells, they were extremely differentiated as defined by loss of CCR7 and CD27, low telomerase activity and very short telomeres. This was not a direct effect arising from the loss of SAP, but was due to excessive T cell stimulation due to this defect. Thus, transduction of XLP CD8+ T cells with the catalytic component of telomerase (hTERT), but not SAP, prevented telomere loss and considerably extended proliferative lifespan in vitro. These results indicate that excessive proliferation in CD8+ T cells in XLP patients may lead to end-stage differentiation and loss of functional EBV-specific CD8+ T cells through replicative senescence. This may contribute to the defective immunity found in XLP patients who survive acute EBV infection who develop EBV-related B cell lymphomas before the fourth decade of life.     

Nasal mucosal expression of nitric oxide synthases in patients with allergic rhinitis and its relation to asthma.

BACKGROUND: Nitric oxide (NO) has contradictory roles in the pathophysiology of allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large amounts produced by inducible NOS (iNOS) are proinflammatory. OBJECTIVE: To investigate the difference in constitutive endothelial NOS (eNOS) and iNOS expression in nonallergic and allergic mucosa and the possible relation of this to the coexistence of asthma in seasonal AR. METHODS: Seventeen patients (10 women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy specimens were obtained in all. Levels of eNOS and iNOS expressed as immunohistochemical scores (HSCOREs) were determined immunohistochemically from the specimens. RESULTS: The mean +/- SD HSCOREs for eNOS in patients with seasonal AR were not significantly different from those of the nonallergic controls (1.85 +/- 0.78 vs 1.63 +/- 0.54; P = .12). On the other hand, the mean +/- SD HSCOREs for iNOS were significantly higher in patients with seasonal AR (1.75 +/- 0.75 vs 0.71 +/- 0.6; P = .004). Furthermore, although eNOS expression was not different between seasonal AR patients with and without asthma, the mean +/- SD HSCOREs for iNOS were significantly higher in the patients with asthma (1.93 +/- 0.78 vs 1.65 +/- 0.55; P = .01). CONCLUSION: Increased expression of iNOS might have a role in the development of allergic inflammation in upper and lower airways and in comorbidity of AR and asthma.     

Data clustering and other archive retrieval strategies for teleradiology and picture archiving and communication systems

A key advantage in the conversion from film-based to digital radiology is the possibility of a long-term on line electronic archival of patient studies. The popular approach based on optical disk jukeboxes for the long-term archive and magnetic disk storage for data caching is not economically attractive because of the cost of both the jukebox and the medium. Strategies for extending the archival system design with a tape jukebox have been studied. The proposed strategy calls for the use of high-ratio lossy compression together with low-cost tape storage to make long-term on line archiving more affordable. An intelligent prefetching algorithm based on hospital information system and radiologic information system triggers, which in turn are augmented by manual case preparation, can effectively overcome the longer latency of ad hoc retrievals. This longer latency is caused by both system-level bottlenecks and the sequential access constraint of the tape drive. Strategies for image clustering and tape allocation by patient classification also enhance retrieval efficiency. This archival design using image compression, prefetching, and clustering could be implemented in many of the existing teleradiology and picture archiving and communication systems.     

Immunohistochemical analysis of survivin expression in thyroid follicular adenoma and carcinoma.

Survivin is one of the 8 members of human inhibitor of apoptosis , which is differentially expressed in cancerous/transformed cells versus normal differentiated tissues. This retrospective study of thyroid histologic samples aimed to assess the clinical usefulness of survivin immunostaining for discrimination between follicular adenoma and carcinoma of thyroid. Immunohistochemical staining for survivin was performed on 41 lesions from patients who had undergone surgery for either follicular adenoma or carcinoma of thyroid. Survivin expression was significantly (P < 0.005) higher in the cases that received a diagnosis of carcinoma in comparison with follicular adenomas cases. Odds ratio of follicular carcinoma for survivin expression was 21.375 (95% CI: 3.283 to 139.177). Our results showed potential value of survivin in discrimination between follicular thyroid adenoma and follicular thyroid carcinoma. We conclude that survivin is a potential candidate for further investigation in the proper histologic diagnosis of thyroid cancers.     

Whole blood real-time quantitative PCR for cytomegalovirus infection follow-up in transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) remains a major opportunistic agent among transplant recipients. While detection of CMV pp65-lower matrix protein (pp65Ag) is still widely used for monitoring CMV infection, real-time PCR assays have been recently developed for routine quantitation of CMV DNA. However, correlations are lacking between results of pp65Ag and quantitative PCR assays and there is no consensus yet as to the more appropriate blood compartment (whole blood (WB), leukocytes, plasma) to be tested with PCR assays. OBJECTIVES: The aims of the study were to determine, in a population of transplant recipients: (i) the correlation between pp65Ag and CMV quantitative real-time PCR in our setting and (ii) the utility of plasma CMV DNA quantitation in comparison to WB quantitation. METHODS: In 170 blood samples (from 61 solid organ or bone marrow transplant recipients) with pp65Ag results, CMV quantitation was performed in WB and plasma using an in-house real-time quantitative PCR. RESULTS: Real-time PCR and pp65Ag results in WB were correlated: thresholds of 10 and 50(+) cells/200,000 cells were equivalent to 3.3 log(10)copies/mL (2,000 copies/mL) and 3.8 log(10)copies/mL (6,300 copies/mL), respectively. When WB viral load was >or=3.6 log(10)copies/mL, the risk to have a negative plasma CMV DNA result was 相似文献   

Differences in adsorption of serum proteins and production of IL-1ra by human monocytes incubated in different tissue culture microtiter plates

In vitro cell culture models can be of great value in order to further analyze the regulatory mechanisms underlying the inappropriate function of the immune system in diseases such as autoimmunity and cancer. Cell culture conditions have to be well controlled in a way that they mirror the in vivo situation. The objective of this study was to compare tissue culture microtiter plates from different manufacturers with respect to their ability to support monokine production by human monocytes cultured in human serum. Tissue culture ware, made of polystyrene, undergoes treatment by the manufacturers to make the surface more suitable for culture of adherent cell populations. It is possible that quality differences in this treatment can lead to variations in protein binding properties and thereby influence the adherence and functional properties of monocytes. We measured spontaneous interleukin-1 receptor antagonist (IL-1ra) production by peripheral blood monocytes, cultured in human serum, in five different microtiter plates made for adherent cell culture. Culture in plates from two of the five manufacturers resulted in significantly lower amounts of secreted IL-1ra. IL-1ra release by human monocytes can be induced by adherent IgG cross-linking membrane receptors for the Fc part of IgG (FcgammaR). We found that reduced IL-1ra production coincided with a reduced capacity for binding of serum IgG in one case. Furthermore, this brand of microtiter plate also displayed the lowest level of adsorption of human albumin. We conclude that the protein adsorption properties of the plastic tissue culture ware have to be taken into consideration when assessing monokine production by human monocytes in vitro.     

Prevalence and treatment of Pediculus humanus capitis with 1% permethrin and 0.4% d-phenothrin in Turkey

Pediculosis humanus capitis (head lice) is an important public health problem among school children. In our study, 20,612 schoolchildren (10,367 boys, 10,245 girls) were examined for Pediculus humanus capitis in 36 elementary schools between December 1996 and February 1998 in Ankara, Turkey. The prevalence of pediculosis capitis infestation was found to be 3.4% (701/20,612). Of these, 382 students were treated with application of 1% permethrin cream rinse, and 184 students with 0.4% d-phenothrin shampoo. On day 14 of the controlled trial, the success rates were 93.7% in the 1% permethrin cream rinse group and 75.5% in the 0.4% d-phenothrin shampoo group. The 1% permethrin cream rinse was also significantly more active in pediculicidal efficacy when compared to the 0.4% d-phenothrin shampoo (p<0.001). As a result, these findings demonstrate that pediculosis capitis still remains a widespread health problem.     

Genotype characterization and phylogenetic analysis of hepatitis B virus isolates from Iranian patients

Hepatitis B virus (HBV) is one of the major causative agents of acute and chronic liver disease worldwide and is believed to be responsible for a million deaths annually. Eight genotypes of HBV, A to H, have been described on the basis of similarity of the complete genomes sequence. Although, it is reported that the predominant HBV genotype in the Mediterranean area and the middle east is genotype D, there are no reports on HBV genotypes prevalent in Iran. In this study, the C and S regions of HBV from 26 chronic hepatitis B Iranian patients were amplified and sequenced. Phylogenetic analysis revealed that all Iranian HBV isolates sequences were classified into genotype D with bootstrap values of 100%, 73%, and 100% (1,000 replicates each) for S, C, and preS2 regions, respectively. The mean percent intra-distance of S and C regions were 0.8% and 2.3%, respectively. The mean percent inter-distance of S and C regions between Iranians and genotype D isolates were 1.7% and 3.0%, respectively, and the range of mean percent nucleotide distance of S and C regions between Iranians and the other reference isolates were 7.9%-17.5% and 4.8%-14.7%, respectively. Thirteen out of 23 HBV C region sequences showed nucleotide "A" at position 1896 (precore mutant) in C region. Nucleotide 1858 showed presence of "T" in all isolates. No insertion or deletion was found in both regions. SimPlot and BootScanning analyses did not show any recombination between Iranian isolates and other genotypes in both regions.     

Daily running promotes spatial learning and memory in rats.

Previous studies on exercise have shown that physical activity improves learning and memory. Present study was performed to determine the effects of acute, chronic and continuous exercise with different periods on spatial learning and memory recorded as the latency and length of swim path in the Morris water maze testing in subsequent 8 days. Four rat groups were included as follows: (1) group C, controls which did not exercise; (2) group A, 30 days treadmill running before and 8 days during the Morris water maze testing period; (3) group B, 30 days exercise before the Morris water maze testing period only; (4) group D, 8 days exercise only during the Morris water maze testing period. The results showed that chronic (30 days) and continuous (during 8 days of Morris water maze testing days) treadmill training produced a significant enhancement in spatial learning and memory which was indicated by decreases in path length and latency to reach the platform in the Morris water maze test (p<0.05). The benefits in these tests were lost in 3 days, if the daily running session was abandoned. In group D with acute treadmill running (8 days exercise only) the difference between the group A disappeared in 1 week and benefit seemed to be obtained in comparison with the controls without running program. In conclusion the chronic and daily running exercises promoted learning and memory in Morris water maze, but the benefits were lost in few days without daily running sessions in adult rats.     

The role of prolactin and testosterone in mediating seasonal differences in the self-grooming behavior of male meadow voles, Microtus pennsylvanicus

Self-grooming in response to the odors of conspecifics is a form of olfactory communication among meadow voles. The amount of time meadow voles spend self-grooming when they encounter the odors of conspecifics varies seasonally, with males targeting the odors of reproductively active females only during the breeding season. Other odor related behaviors in male voles such as odor preferences for conspecifics and the attractiveness of their odors to conspecifics vary seasonally as well. For male meadow voles, these behaviors are mediated by seasonal variations in testosterone (T) and prolactin (PRL) titers. The objective of this study was to determine whether seasonal differences in the amount of time male meadow voles self-groom in response to odors of conspecifics are mediated by seasonal rhythms in their circulating T and PRL titers. We tested the hypothesis that high titers of both T and PRL are necessary for reproductively active (long-photoperiod; LP) males and sufficient for reproductively quiescent (short-photoperiod; SP) male voles to spend more time self-grooming in response to odors of LP females than to those of other conspecifics. Results of this study demonstrate that high titers of PRL and T are necessary for LP male meadow vole to self-groom more in response to odors of LP females as compared to those of other conspecifics, but were not sufficient to induce SP males to preferentially self-groom to odors of LP females. The endocrine control of self-grooming by LP males appears to depend upon high titers of both PRL and T, which matches the endocrine mediation of other odor related behaviors in male voles. In contrast, the endocrine tissues that underlie self-grooming in SP male meadow voles appear to be refractory to the effects of LP-equivalent titers of PRL and T.