Early assessment of renal resistance index after kidney transplant can help predict long-term renal function.

BACKGROUND: Color Doppler ultrasonography of intrarenal arterial resistance index (RI), performed early after kidney transplant, has proven to reliably predict short-term allograft function. The aim of this study was to assess whether it could also predict long-term renal function. METHODS: We retrospectively analysed 76 kidney transplant patients who underwent RI assessment within 1 month after the transplant, subdivided into two groups according to RI values, lower (group A) or higher (group B) than its median value (0.635). RESULTS: Compared with group A subjects, the patients of group B were older at the time of transplant (42 +/- 9 vs 35 +/- 8 years; P = 0.001), the donor age was also older (41 +/- 16 vs 33 +/- 13 years; P = 0.02) and had a slightly higher proteinuria (0.54 +/- 0.5 vs 0.32 +/- 0.2 g/24 h; P = 0.02). Serum creatinine, ciclosporin or tacrolimus trough level, arterial blood pressure, number of human leukocyte antigen (HLA) mismatches, anti-hypertensive medications and incidence of delayed graft function were not significantly different between the two groups. By univariate analysis, RI turned out to directly correlate with the recipient age, donor age and daily proteinuria (P = 0.007, P = 0.0007 and P = 0.02, respectively). Multivariate analysis showed that only donor and recipient age maintained their independent predictive value on RI. Kaplan-Meier analysis, considering a serum creatinine increase >50% as the endpoint of the study, showed a statistically significant different graft survival in the two groups (log-rank test = 5.489; P = 0.01). The univariate relative risk of deterioration of graft function among patients with higher RI was 3.77. Proteinuria and recipient age increased the risk as well. CONCLUSIONS: Our data seem to suggest that early determination of RI can help predict long-term graft function in kidney transplant recipients.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Alteration of acylphosphatase levels in familial Alzheimer''s disease fibroblasts with presenilin gene mutations

Acylphosphatase (ATPase), an enzyme that modulates the activity of Ca²⁺-ATPase by hydrolysing its phosphorylated moiety, has been found to be significantly higher in cultured skin fibroblasts from donors affected by early onset familial Alzheimer's disease (EOFAD) with PS-1 and PS-2 gene mutations. Of the two known isoenzymes of acylphosphatase, only the erythrocyte one accounts for the total increase in activity. No relevant alteration was observed in phosphotyrosine phosphatase activity (PTPase), in Ca²⁺-ATPase and Na⁺,K⁺-ATPase activities of the same cells as compared to age-matched controls. This finding could suggest a possible explanation for the calcium-dependent biochemical alterations previously described in Alzheimer's disease fibroblasts.     

Births of normal daughters after MicroSort sperm separation and intrauterine insemination, in-vitro fertilization, or intracytoplasmic sperm injection

The world's first deliveries of normal babies after use of flow cytometric separated human sperm cells (MicroSort) for preconception gender selection are reported. Offspring were of the desired female gender in 92.9% of the pregnancies. Most of these pregnancies and births were achieved after simple intrauterine insemination.      

Detecting pre-ovulatory luteinizing hormone surges in urine

The study objectives were to determine (i) if pre-ovulatory luteinizing hormone (LH) surges, undetected in urine by two immunoradiometric assays (IRMA), were detectable by an ultrasensitive immunofluorometric assay (IFMA) and (ii) the influence of creatinine adjustment on the detection and timing of the urinary LH surges. Daily urine specimens were contributed by healthy 25-36 year old volunteers during 14 ovulatory menstrual cycles for an epidemiological study conducted in 1983-1985. Specimens were selected as having been previously assayed by two IRMA without consistently detecting LH surges. These urine specimens were remeasured using an IFMA and adjusted for creatinine concentration. IFMA measurements revealed unambiguous LH surges in all cycles. Adjusting IRMA urinary LH values for creatinine concentrations revealed previously undetected LH surges in four of eight cycles. Creatinine adjustment also altered the timing of IRMA and IFMA LH surges by 1-5 days. These results demonstrate an IFMA that detects pre- ovulatory LH surges in unpreserved, frozen urine from cycles where such surges were previously undetectable. Further, creatinine adjustment can markedly affect detection and timing of the onset and peak of the urinary LH surge. While our analysis suggests that this adjustment improves the validity of the LH measure, this requires further investigation.      

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

Effect of phosphatidylserine on free radical susceptibility in human diploid fibroblasts

Summary We studied the effect of phosphatidylserine (PdtSER) on oxygen metabolite toxicity in skin fibroblast cell lines from apparently normal subjects. Fibroblast damage was produced by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by xanthineoxidase (Xo). In order to quantify cell damage, we measured lactate dehydrogenase (LDH) activity in culture medium and cell viability in fibroblast cultures, with and without preincubation for 4 days with PdtSER 13 M, after Xo incubation. We found a significant increase of LDH activity in culture medium of cells without preincubation with PdtSER. No significant increase of LDH activity was observed in the same cell lines after preincubation with PdtSER.     

松花粉和松针提取物在亲脂性体外模型系统中抗氧化能力和机制的研究

目的:对松花粉和松针提取物在亲脂性抗氧化模型系统中的抗氧化能力和机制进行研究。方法:采用铜诱导的LDL氧化反应模型和Rose Bengal反应模型分别进行评价。结果:松花粉乙醇提取液具有较好的自由基链式反应阻断剂的作用,有效地推迟人血浆中低密度脂蛋白(LDL)氧化生成共轭二烯。松针乙醇提取液对LDL的保护作用优于松花粉。在Rose Bengal系统中,松花粉以清除自由基和螯合铜的两种机制抑制脂质过氧化反应的发生,而松针主要作为自由基清除剂发挥抗氧化作用。结论:松花粉和松针在两个亲脂性体外模型中均发挥很好的抗氧化能力,而抗氧化机制不尽相同。