Erythropoietin, an autocrine regulator? Serum-free production of erythropoietin by cloned erythroid cell lines

Production of lymphoid and myeloid growth regulatory factors by hematopoietic cells is well documented. On the other hand, the major site of production of erythropoietin (Epo), which regulates physiologic red blood cell development, is thought to be the kidney. Here we report the isolation of multiple erythroleukemia cell lines that produce erythropoietic factors and present extensive biological, immunologic, and biochemical evidence to document that the active agent is Epo. The erythropoietic activity was neutralized by Epo antiserum and exhibited physical properties indistinguishable from those of human and sheep Epo. Positive lines produced between 0.1 and 1.5 U/mL of Epo, which stimulated erythropoiesis in vivo and in vitro in nine biological assays. Twenty sublines derived from single cells were inducible for hemoglobin and spectrin synthesis. All the sublines produced Epo. Production of the hormone continued when the cells were seeded in the absence of serum. Our finding that multiple independent isolates produce Epo raises the possibility that Epo production by erythroid precursors may play a role in normal erythropoiesis or, alternatively, that Epo gene activation may be a relatively common occurrence that contributes to, or is associated with, certain forms of virus-induced leukemias.     

Alcohol-Related Fracture Admissions: A Retrospective Observational Study

IntroductionIn April 2011 the NI public health agency estimated that alcohol misuse generates overall annual healthcare costs of £122.2m. There is currently a paucity of data regarding the burden of alcohol-related fractures on the provinces Trauma and Orthopaedic service.ResultsAlcohol related fractures accounted for 6.1% of all acute fractures admissions in the 12 month period. 73% were male, with a bimodal age distribution. The majority of patients were classed as social drinkers; however a significant proportion (23.1%) were alcohol dependent. 62.5% of patients were smokers at the time of admission. 95% of patients suffered a single injury which was commonly secondary to a simple mechanical fall (53.8%). The majority of patients sustained lower limb injuries, with 30.8% of these being ankle fractures.ConclusionIn conclusion, our study has identified that alcohol-related trauma creates a significant financial burden on the NHS. It is likely that the incidence of alcohol related fracture is higher than documented in this study. We advocate the assessment of patients using the AUDIT-C score to assess for at risk drinking behaviour in those presenting with an alcohol related fracture.     

IL 6 expression in transferred NIH3T3 cells by retrovirus vector

ＩＬ６ｅｘｐｒｅｓｓｉｏｎｉｎｔｒａｎｓｆｅｒｒｅｄＮＩＨ３Ｔ３ｃｅｌｓｂｙｒｅｔｒｏｖｉｒｕｓｖｅｃｔｏｒＸＩＡＯＢｉｎｇ１，ＪＩＡＮＧＢｏ２，ＺＨＯＵＤｉａｎＹｕａｎ２ａｎｄＺＨＡＮＧＷａｎＤａｉ２１ＤｅｐａｒｔｍｅｎｔｏｆＤｉｇｅｓｔｉｏｎ...     

A positive Tinel sign as predictor of pain relief or sensory recovery after decompression of chronic tibial nerve compression in patients with diabetic neuropathy

Predictive ability of a positive Tinel sign over the tibial nerve in the tarsal was evaluated as a prognostic sign in determining sensory outcomes after distal tibial neurolysis in diabetics with chronic nerve compression at this location. Outcomes were evaluated with a visual analog score (VAS) for pain and measurements of the cutaneous pressure threshold/two-point discrimination. A multicenter prospective study enrolled 628 patients who had a positive Tinel sign. Of these patients, 465 (74%) had VAS >5. Each patient had a release of the tarsal tunnel and a neurolysis of the medial and lateral plantar and calcaneal tunnels. Subsequent, contralateral, identical surgery was done in 211 of the patients (152 of which had a VAS >5). Mean VAS score decreased from 8.5 to 2.0 (p <0.001) at 6 months, and remained at this level for 3.5 years. Sensibility improved from a loss of protective sensation to recovery of some two-point discrimination during this same time period. It is concluded that a positive Tinel sign over the tibial nerve at the tarsal tunnel in a diabetic patient with chronic nerve compression at this location predicts significant relief of pain and improvement in plantar sensibility.     

Pulsed radiofrequency electromagnetic field therapy: a potential novel treatment of plantar fasciitis

Plantar fasciitis is a common cause of heel pain, and although treatments are usually conservative, they can take up to 2 years to achieve resolution. A double-blind, multicenter, randomized, placebo-controlled study was used to evaluate a small, wearable, extended-use pulsed radiofrequency electromagnetic field (PRFE) device as a treatment of plantar fasciitis. A total of 70 subjects diagnosed with plantar fasciitis were enrolled in the present study. The subjects were randomly assigned a placebo or active PRFE device. The subjects were instructed to wear the PRFE device overnight, record their morning and evening pain using a 0- to 10-point visual analog scale (VAS), and log any medication use. The primary outcome measure for the present study was morning pain, a hallmark of plantar fasciitis. The study group using the active PRFE device showed progressive decline in morning pain. The day 7 AM-VAS score was 40% lower than the day 1 AM-VAS score. The control group, in comparison, showed a 7% decline. A significantly different decline was demonstrated between the 2 groups (p = .03). The PM-VAS scores declined by 30% in the study group and 19% in the control group, although the difference was not significant. Medication use in the study group also showed a trend downward, but the use in the control group remained consistent with the day 1 levels. PRFE therapy worn on a nightly basis appears to offer a simple, drug-free, noninvasive therapy to reduce the pain associated with plantar fasciitis.     

ROUTINE CLINICAL BIOCHEMISTRY TESTS COLLECTED FROM PATIENTS DYING IN HOSPITAL

SUMMARY A study conducted of the collection of samples from patients dying in hospital and the results of their analysis found that samples are often collected unnecessarily from patients dying in hospital, and are collected more often from women than from men.     

Mutational screening of ACVR1 gene in Brazilian fibrodysplasia ossificans progressiva patients

Carvalho DR, Navarro MMM, Martins BJAF, Coelho KEFA, Mello WD, Takata RI, Speck‐Martins CE. Mutational screening of ACVR1 gene in Brazilian fibrodysplasia ossificans progressiva patients. Fibrodysplasia ossificans progressiva (FOP) is a severe genetic disorder reported worldwide. A specific heterozygous mutation (c.617G> A; p.R206H) in the activin A type I receptor gene (ACVR1) is regarded as the genetic cause of FOP in all classically affected individuals worldwide. However, a few patients with FOP variants harbor distinct mutations in ACVR1. We screened a group of FOP Brazilian population for mutations in ACVR1. Of 16 patients with a classic FOP phenotype (10 males and 6 females, age range of 3–42 years), all had the classic mutation (p.R206H). One 21‐year‐old woman with a variant FOP phenotype had the previously reported c.983G> A mutation (p.G328E). Our study contributes to the understanding of the predominant FOP phenotype and genotype and suggests that variant FOP phenotypes are associated with specific mutations in ACVR1 gene.     

High-level secretion of tumor necrosis factor-alpha contributes to hematopoietic failure in hairy cell leukemia [see comments]

Hairy cell leukemia (HCL) is frequently associated with severe pancytopenia. The authors detected high levels of tumor necrosis factor (TNF)-alpha in the bone marrow serum of patients with HCL and found anti-TNF-alpha neutralizing monoclonal antibodies (MoAbs) to be able to enhance hematopoiesis of HCL patients in in vitro colony assays. As potent producers of TNF-alpha, hairy cells could be identified, thus implicating the malignant population in the pathogenesis of hematopoietic failure due to inappropriate secretion of this cytokine.