Spleen size in chronic renal failure.

To investigate the cause of clinically detectable splenomegaly, which is common in patients receiving regular haemodialysis, splenic volume was assessed by isotopic scanning using intravenously injected technetium-99m microspheres in 34 controls and 149 patients with chronic renal failure. Of the patients, 16 had never received dialysis, 10 were undergoing continuous peritoneal dialysis, 94 were undergoing regular haemodialysis, and 29 had undergone successful renal transplantation more than nine months previously. Mean splenic volume was increased only in the patients who were receiving haemodialysis. Splenic enlargement was probably not due to iron overload as it occurred in all patients who had received haemodialysis, 14 of whom had not received intravenous iron. No patient had had hepatitis. Splenic enlargement was probably related to the process of haemodialysis itself and may have been due either to red cell damage produced by haemodialysis or to an immunological reaction induced by a component of haemodialysis, possibly ethylene oxide.     

Tempo and mode of concerted evolution in the L1 repeat family of mice

A 300-bp DNA sequence has been determined for 30 (10 from each of three species of mice) random isolates of a subset of the long interspersed repeat family L1. From these data we conclude that members of the L1 family are evolving in concert at the DNA sequence level in Mus domesticus, Mus caroli, and Mus platythrix. The mechanism responsible for this phenomenon may be either duplicative transposition, gene conversion, or a combination of the two. The amount of intraspecies divergence averages 4.4%, although between species base substitutions accumulate at the rate of approximately 0.85%/Myr to a maximum divergence of 9.1% between M. platythrix and both M. domesticus and M. caroli. Parsimony analysis reveals that the M. platythrix L1 family has evolved into a distinct clade in the 10-12 Myr since M. platythrix last shared a common ancestor with M. domesticus and M. caroli. The parsimony tree also provides a means to derive the average half-life of L1 sequences in the genome. The rates of gain and loss of individual copies of L1 were estimated to be approximately equal, such that approximately one-half of them turn over every 3.3 Myr.      

LARaLink 2.0: a comprehensive aid to basic and clinical cytogenetic research

LARaLink 2.0 (Loci Analysis for Rearrangement Link) is an enabling web technology that permits the rapid retrieval of clinical cytogenetic and molecular data. New data mining capabilities have been incorporated into version 2.0, building upon LARaLink 1.0, to extend the utility of the system for applications in both the clinical and basic sciences. These include access to the Chromosomal Variation in Man database and the GEO database. Together these new resources enhance the user's ability to associate genotype with phenotype to identify potential gene candidates. Unlimited access for researchers exploring disease-gene relationships and for clinicians extending practice in patient care is available at LARaLink.bioinformatics.wayne.edu:8080/ unigene.     

Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue disease

Modifications occurring on autoantigens during cell death have been proposed to have a role in the initiation of autoimmune diseases. Patients suffering from mixed connective tissue disease (MCTD) produce autoantibodies directed to U1 small nuclear ribonucleoprotein (snRNP), and antibodies against a 70 kDa protein component, the U1-70K (70K) protein, are the most prominent. During apoptosis, 70K is cleaved by caspase-3 to a 40 kDa product, which remains associated with the complex. Autoantibodies preferentially recognizing the apoptotic form of 70K have been described previously, and an apoptosis-specific epitope on 70K has been identified. This study shows that 29 of 53 (54%) MCTD sera preferentially recognize the apoptotic form of 70K over intact 70K. Moreover, we show that antibodies directed to an apoptosis-specific epitope on 70K are more specifically associated with MCTD than other anti-70K antibodies, suggesting that apoptotic 70K is a better antigen for the detection of these antibodies in MCTD patients. Longitudinal analysis of 12 MCTD patients showed in several patients that early sera are relatively enriched with antibodies recognizing an apoptosis-specific epitope, and that the levels of these apoptosis-specific antibodies decrease in time. These findings indicate that the early detection of apoptotic 70K is of considerable interest for anti-U1 snRNP-positive patients.     

Effects of thymoquinone on liver miRNAs and oxidative stress in Ehrlich acid mouse solid tumor model

We investigated the effects of thymoquinone (TQ) on the expression of liver microRNAs (miRNAs), liver histopathology and oxidative stress in Ehrlich acid solid tumor model induced mice. We used 24 male BALB/c mice divided randomly into three groups. Control (C) group mice were injected intraperitoneally (i.p.) with 0.5 ml saline for four weeks. Tumor (T) group mice were injected i.p. with 0.5 ml saline for four weeks, then Ehrlich acid tumor cells were injected subcutaneously into the neck to induce solid tumor formation. TQ (T + Tq) group mice injected i.p. with 10 mg/kg TQ for four weeks, then Ehrlich acid tumor cells were injected subcutaneously into the neck of the mice in this group to induce solid tumor formation. At the end of the study, liver from all groups were removed for histopathological and miRNAs analysis, and oxidative stress measurement. We found that the expression of miR-206b-3p was up-regulated and the oxidative stress and necrosis increased in the liver tissue of mice with Ehrlich acid solid tumor. TQ application decreased the oxidative stress, prevented necrosis, increased regeneration and down-regulated the expression of miR-206b-3p in the liver tissue.     

Workload of general practitioners before and after the new contract.

OBJECTIVE--To assess changes in general practitioners'' workload associated with the new contract introduced in April 1990. DESIGN--Weekly workload diary completed during four weeks in February-March 1990 and during the same period in 1991. SETTING--Sheffield, United Kingdom. SUBJECTS--All 300 general practitioners on Sheffield Family Health Services Authority list as principals in 1990 and 1991. MAIN OUTCOME MEASURES--Mean number of hours worked per week, number of patients seen each week, and mean time spent per patient. RESULTS--181 (60%) general practitioners responded in 1990 and 163 (54%) in 1991. Of these, 18 (10%) were not working in 1990 and 14 (7%) in 1991. General medical service work increased during a "normal working week" from a mean of 38.6 hours a week in 1990 to 40.6 hours in 1991, and non-general medical service work decreased from 5.4 hours a week to 4.5 hours. Hours spent on call were similar before and after the contract. For the 99 general practitioners who responded in both years, time spent on general medical service duties increased significantly (40.5 h in 1990 v 42.5 h [corrected] in 1991; p = 0.033), mainly due to more time being spent in clinics. Significantly more patients were being seen in clinics (9 v 14; p = 0.001); the average time spent per patient remained at about 8 1/2 minutes during surgeries and 16 minutes for a home visit, and rose from 13 to 14 minutes for patients seen in clinics. The time spent on practice administration fell but not significantly. CONCLUSION--Since the new contract there has been a significant increase in general medical services work, mainly due to more patients being seen in clinics, with no reduction in the time spent per patient.