Mitotic and meiotic detection of radiation-induced translocations in mouse stem cell spermatogonia using fluorescencein situ hybridization

The efficiency of two methods of detection of translocations induced in mouse stem cell spermatogonia by X-ray doses of 2, 5 and 7 Gy was compared: classical multivalent analysis at diakinesis-metaphase I of meiosis and observation via fluorescencein situ hybridization analysis of mitotic or meiotic stages. Specific DNA libraries for chromosomes 1, 11 and 13 were used. The results obtained indicate that (a) chromosomes 1, 11 and 13 are more involved in multivalent formation than expected on the basis of DNA content and (b) if the mitotic FISH analysis data are corrected for the observed over-representation, the frequencies of induced translocations are similar to those recorded in the classical multivalent studies, suggesting equal scoring efficiencies in both systems.     

Eosinophil chemotaxis and anterior uveitis from topical dimaprit and nordimaprit

Topical application of the H2-histamine receptor agonist, dimaprit (S-[4-N,N-dimethylaminopropyl]isothiourea), produced eosinophil chemotaxis into the anterior segment of rabbit eyes only when an H2-antagonist was co-administered. Nordimaprit (S-[4-N,N-dimethylaminoethyl]isothiourea), a structural homologue of dimaprit that lacked activity at histamine receptors, produced eosinophil chemotaxis whether or not an H2-antagonist was co-administered. Onset of eosinophil chemotaxis began after 2 or more days of treatment, and was accompanied by corneal edema, opacification, and ocular inflammation. There was no concurrent eosinophilia in the peripheral blood or in the conjunctiva. The response occurred in pigmented and albino rabbit eyes, and was facilitated by prior co-administration of proparacaine eye drops. Another dimaprit homologue without activity at histamine receptors, homodimaprit (S-[4-N,N-dimethylaminobutyl]isothiourea), did not produce eosinophil chemotaxis when applied topically, nor did the H2-agonists impromidine, histamine, or 4-methylhistamine, whether co-administered with an H2-antagonist or not. It was concluded that dimaprit and nordimaprit produced a selective eosinophil chemotaxis unrelated to H1- and H2-histamine receptor activity. However, the H2-agonist activity of dimaprit appeared to inhibit this response unless neutralized by an H2-antagonist. Topical application of dimaprit with an H2-antagonist or nordimaprit alone may allow large numbers of non-degranulated eosinophils, free of other cell types, to be harvested from the aqueous humor.     

Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.     

Human Herpesvirus 6 in Bronchalveolar Lavage Fluid after Lung Transplantation: A Risk Factor for Bronchiolitis Obliterans Syndrome?

Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term survival after lung transplantation. Previous studies suggested respiratory viral tract infections are associated with the development of BOS. To identify the impact of virus detection in bronchoalveolar lavage (BAL) fluid, we analyzed BAL samples from 87 consecutive lung transplant recipients for human herpesvirus (HHV)-6, Epstein-Barr virus, Herpes simplex virus 1/2, Cytomegalovirus, respiratory syncytical virus and adenovirus by PCR. Acute rejection, BOS and death were recorded for a mean follow-up time of 3.27 +/- 0.47 years. Results of PCR analysis and other potential risk factors were entered into a Cox regression analysis of BOS predictors and death. Only acute rejection was a distinct risk factor for BOS of all stages, death and death from BOS. HHV-6 was detected in 20 patients. Univariate and multivariate analysis revealed that HHV-6 was associated with an increased risk to develop BOS > orb = stage 1 and death, separate from the risk attributable to acute rejection. Identification of HHV-6 DNA in BAL fluid is a potential risk factor for BOS. Our results warrant further studies to elucidate a possible causal link between HHV-6 and BOS.     

Expression of the protein related to Dan and Cerberus gene--prdc--During eye, pharyngeal arch, somite, and swim bladder development in zebrafish.

The protein related to Dan and Cerberus, or PRDC, is a secreted glycoprotein, which belongs to the DAN subfamily of bone morphogenetic protein (BMP) antagonists. In zebrafish, prdc is expressed initially around 17 hours postfertilization in the developing eyes and the first two pharyngeal arches. Expression in the eye starts in the outer layers of the optic cup. Later, prdc expression domains are juxtaposed at the edges of the optic cup surrounding the choroid fissure, then gradually becoming restricted to a small site in the ventral marginal zone. Prdc expression in the arch mesenchyme expands stepwise to the remaining posterior arches. Prdc is also detectable in the ventral part of the somites and the mesenchyme of the swim bladder. The relatively late appearance during development is a unique feature of Prdc among BMP antagonists. Moreover, the complexity of the prdc expression pattern suggests possible roles in eye development, pharyngeal arch remodeling, somitogenesis, and swim bladder organogenesis.     

Reflex tear ascorbate in Hong Kong Chinese subjects: method comparison and biological variation.

BACKGROUND: Tear ascorbate is important for corneal health. A rapid and simple method for measurement of ascorbate in tears is needed, and adequate knowledge of physiological variation of tear ascorbate is important to facilitate comparative studies of the effect of, for example, contact lens wear and environmental conditions and stresses. However, there are currently no data on physiological variation of tear ascorbate. This study validated a simple and speedy method for tear ascorbate and investigated between-eye and between-day variation in tear ascorbate in healthy young adults. METHODS: Yawn-induced reflex tears were collected from 32 healthy Hong Kong Chinese subjects and measured by both high-performance liquid chromatography (HPLC) and by an enzyme-linked colorimetric method known as FRASC (total ferric reducing (antioxidant) activity and ascorbate concentration measurement). For between-eye variation, yawn reflex tears were collected from each eye of the same 32 healthy subjects, and ascorbate was measured using HPLC; in a separate experiment for between-day variation, tears were collected on two separate days from 14 subjects, and ascorbate was measured by FRASC. RESULTS: Both HPLC and FRASC showed high precision, and results obtained using FRASC were not statistically different from those using HPLC; mean +/- SD were, respectively, 18.5 +/- 4.4 microM and 18.5 +/- 4.8 microM for HPLC and FRASC methods (p = 0.943). No significant between-eye difference in tear ascorbate was found (p = 0.386), and no significant between-day variation was found overall: mean +/- SD ascorbate was 20.0 +/- 6.2 microM on day 1 and 19.3 +/- 6.8 microM on day 2 (p = 0.772). However, between-day variation was large in seven of 14 subjects. CONCLUSION: FRASC is an acceptable alternative to HPLC for measurement of tear ascorbate. Tears for ascorbate investigation can be collected from either eye or, if necessary, from both eyes and pooled. However, tear ascorbate may vary widely from day to day in the same individual. The reasons for this variation require further study but may relate to differences in ascorbate supply or demand within the precorneal tear layer.     

Skin Cancer Risk Associated with Immunosuppressive Therapy in Organ Transplant Recipients

The aim of this review is to summarise the available literature regarding the epidemiology and proposed mechanisms of skin cancer development in organ transplant recipients who are receiving lifelong treatment with immunosuppressive therapy and to review the different strategies for managing complications in this group of patients. Organ transplantation is complicated by an increased incidence of certain cancers, of which non-Hodgkin's lymphoma, Kaposi's sarcoma and squamous cell carcinoma are the most common. The most important risk factor for these cancers is immunosuppressive therapy. The relative importance of different immunosuppressive therapy regimens in relation to the development of skin cancer is still unclear. Immunosuppression per se may play the most important role, but other mechanisms, which are independent of host immunity and which may be different for the various agents used, may also be of importance for the increased risk of cancer. Apart from immunosuppressive therapy, exposure to sunlight and infection with human papillomaviruses are believed to be the most important risk factors for the development of cutaneous squamous cell carcinoma in organ transplant recipients. Human papillomaviruses, no doubt, benefit considerably from immunosuppression, as is indicated by the large number of warts found in these patients, but many questions remain unanswered about their significance in cutaneous oncogenesis. The E6 protein from a range of cutaneous human papillomavirus types effectively inhibits apoptosis in response to ultraviolet light damage. It is, therefore, conceivable that the development of skin cancer in organ transplant recipients is the result of a complex interplay between exposure to ultraviolet radiation, human papillomavirus infection and genetic predisposition. Measures for protection from the sun are important for reducing the risk of skin cancer in organ transplant recipients. Regular surveillance of patients with skin problems and easy access to a dermatologist for these patients is advised. Changing the immunosuppressive regimen from azathioprine to cyclosporin or vice versa does not seem to relieve the skin problems. Tapering the immunosuppressive therapy to the lowest possible dose may be of some advantage. Oral retinoids, e.g. acitretin, have some effect in reducing the number of keratotic skin lesions and in the prevention of skin cancer in organ transplant recipients. Resurfacing the back of the hand can be a successful treatment for patients with multiple skin cancers on the back of the hand and can be used prophylactically in patients with severely actinically damaged skin.     

肝素酶和碱性成纤维细胞生长因子与非小细胞肺癌转移和预后的关系

目的 探讨肝素酶(heparanase)和碱性成纤维细胞生长因子(bFGF)在人非小细胞肺癌(NSCLC)组织中表达的临床意义及其与肺癌转移和预后的关系。方法 采用免疫组织化学、原位杂交和Western blot方法,检测115例人NSCLC石蜡切片和45例新鲜肺癌及对应癌旁正常组织中肝素酶和bFGF的表达情况。采用χ^2检验、t检验、生存曲线和Cox比例风险回归等方法分析肝素酶和bFGF分别表达及共表达的意义。结果 免疫组织化学染色证实肝素酶(91／115)和bFGF(89／115)主要表达在癌细胞质和(或)细胞膜中,在正常肺泡上皮和支气管上皮中则呈阴性表达。Western blot也证实肝素酶在肺癌中的表达明显增高(P=0．041)。统计分析结果显示：肝素酶和bFGF的表达具有明显的一致性(P：0．0001),二者单独表达和共表达均与肺癌的分期、血管侵袭、淋巴结转移、微血管密度和预后有关,其中,二者共表达时与分期和微血管密度的相关性更显著;另外,bFGF还与肺癌的分化程度有关。多因素分析结果显示,肺癌的分化程度、血管浸润、淋巴结转移和bFGF的表达可以作为判断肺癌预后的危险因素,但肝素酶不是影响预后的独立因素。结论 肝素酶和bFGF均与肺癌的转移、血管生成和预后密切相关。