Serum macrophage migration inhibitory factor (MIF) levels after allogeneic hematopoietic stem cell transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72178/1/j.1751-553X.2007.01016.x.pd

Severe brain atrophy after long-term survival seen in siblings with familial amyotrophic lateral sclerosis and a mutation in the optineurin gene: a case series

<p>Abstract</p> <p>Introduction</p> <p>Previous studies have shown widespread multisystem degeneration in patients with sporadic amyotrophic lateral sclerosis who develop a total locked-in state and survive under mechanical ventilation for a prolonged period of time. However, the disease progressions reported in these studies were several years after disease onset. There have been no reports of long-term follow-up with brain imaging of patients with familial amyotrophic lateral sclerosis at an advanced stage of the disease. We report the cases of siblings with amyotrophic lateral sclerosis with homozygous deletions of the exon 5 mutation of the gene encoding optineurin, in whom brain computed tomography scans were followed up for more than 20 years.</p> <p>Case presentation</p> <p>The patients were a Japanese brother and sister. The elder sister was 33 years of age at the onset of disease, which began with muscle weakness of her left lower limb. Two years later she required mechanical ventilation. She became bedridden at the age of 34, and died at the age of 57. A computed tomography scan of her brain at the age of 36 revealed no abnormality. Atrophy of her brain gradually progressed. Ten years after the onset of mechanical ventilation, atrophy of her whole brain, including the cerebral cortex, brain stem and cerebellum, markedly progressed. Her younger brother was 36 years of age at the onset of disease, which presented as muscle weakness of his left upper limb. One year later, he showed dysphagia and dysarthria, and tracheostomy ventilation was performed. He became bedridden at the age of 37 and died at the age of 55. There were no abnormal intracranial findings on brain computed tomography scans obtained at the age of 37 years. At the age of 48 years, computed tomography scans showed marked brain atrophy with ventricular dilatation. Subsequently, atrophy of the whole brain rapidly progressed as in his elder sister.</p> <p>Conclusion</p> <p>We conclude that a homozygous deletion-type mutation in the optineurin gene may be associated with widespread multisystem degeneration in amyotrophic lateral sclerosis.</p

Gene Expression Signature of Fibroblast Serum Response Predicts Human Cancer Progression: Similarities between Tumors and Wounds

Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are unclear. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. The genes comprising this fibroblast common serum response are coordinately regulated in many human tumors, allowing us to identify tumors with gene expression signatures suggestive of active wounds. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. The molecular features that define this wound-like phenotype are evident at an early clinical stage, persist during treatment, and predict increased risk of metastasis and death in breast, lung, and gastric carcinomas. Thus, the transcriptional signature of the response of fibroblasts to serum provides a possible link between cancer progression and wound healing, as well as a powerful predictor of the clinical course in several common carcinomas

Macrophage Migration Inhibitory Factor Activates Hypoxia-Inducible Factor in a p53-Dependent Manner

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Serum macrophage migration inhibitory factor reflects adrenal function in the hypothalamo-pituitary-adrenal axis of septic patients: an observational study

<p>Abstract</p> <p>Background</p> <p>The hypothalamo-pituitary-adrenal (HPA) axis modulates the inflammatory response during sepsis. Macrophage migration inhibitory factor (MIF), which counteracts the anti-inflammatory activity of glucocorticoid (GC), is one of the mediators of the development of inflammation. An inflammatory imbalance involving GC and MIF might be the cause or result of adrenal insufficiency. Our objective was to clarify the relationship between serum MIF and adrenal function in the HPA axis of sepsis patients using the adrenocorticotropic hormone (ACTH) stimulation test.</p> <p>Methods</p> <p>An observational study was performed in a university intensive care unit over a two-year period. Of 64 consecutive sepsis patients, 41 were enrolled. The enrolled patients underwent an ACTH stimulation test within 24 h of the diagnosis of severe sepsis or septic shock. Clinical and laboratory parameters, including serum MIF and cortisol, were measured.</p> <p>Results</p> <p>Based on their responses to the ACTH stimulation test, the patients were divided into a normal adrenal response (NAR) group (n = 22) and an adrenal insufficiency (AI) group (n = 19). The AI group had significantly more septic shock patients and higher prothrombin time ratios, serum MIF, and baseline cortisol than did the NAR group (<it>P </it>< 0.05). Serum MIF correlated significantly with the SOFA (Sequential Organ Failure Assessment) score, prothrombin time ratio, and delta max cortisol, which is maximum increment of serum cortisol concentration after ACTH stimulation test (rs = 0.414, 0.355, and -0.49, respectively, <it>P </it>< 0.05). Serum MIF also correlated significantly with the delta max cortisol/albumin ratio (rs = -0.501, <it>P </it>= 0.001). Receiver operating characteristic curve analysis identified the threshold serum MIF concentration (19.5 ng/mL, <it>P </it>= 0.01) that segregated patients into the NAR and AI groups.</p> <p>Conclusions</p> <p>The inverse correlation between serum MIF and delta max cortisol or the delta max cortisol/albumin ratio suggests that high serum MIF reflects an insufficient adrenal response in the HPA axis. Serum MIF could be a valuable clinical marker of adrenal insufficiency in sepsis patients.</p