Parallel neurodegenerative phenotypes in sporadic Parkinson's disease fibroblasts and midbrain dopamine neurons.

Understanding the mechanisms causing Parkinson's disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls. Additionally, significant alterations in alpha synuclein expression and electrical activity were also noted in the PD DA neurons. Interestingly, although the fibroblast and neuronal phenotypes were similar to each other, they differed in their nature and scale. Furthermore, statistical analysis revealed potential novel associations between various clinical measures of the PD subjects and the different fibroblast and neuronal data. In essence, these findings encapsulate spontaneous, in-tandem, disease-related phenotypes in both sporadic PD fibroblasts and iPSC-based DA neurons, from the same patient, and generates an innovative model to investigate PD mechanisms with a view towards rational disease stratification and precision treatments.

Parallel Neurodegenerative Phenotypes in Sporadic Parkinson's Disease Fibroblasts and Midbrain Dopamine Neurons.

Understanding the mechanisms causing Parkinson's disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls. Additionally, significant alterations in alpha synuclein expression and electrical activity were also noted in the PD DA neurons. Interestingly, although the fibroblast and neuronal phenotypes were similar to each other, they also differed in their nature and scale. Furthermore, statistical analysis revealed novel associations between various clinical measures of the PD subjects and the different fibroblast and neuronal data. In essence, these findings encapsulate spontaneous, in-tandem, disease-related phenotypes in both sporadic PD fibroblasts and iPSC-based DA neurons, from the same patient, and generates an innovative model to investigate PD mechanisms with a view towards rational disease stratification and precision treatments.

Immunosensors in medical diagnostics--major hurdles to commercial success.

In the last few years the format of commercial immunoassays has dramatically changed. Automated instruments running up to 180 samples per hour and dry strip or film immunochemistry products are now available. These changes have been precipitated by the need for immunoassays that require less time and skill to perform. To date, no immunosensor technology has been successfully commercialized although a few are purported to be on the brink of being released for sale. Here, B. Manning and T. Maley evaluate the major factors affecting the success of immunosensors.

Acute myocardial infarction resulting from the migration of a Greenfield filter.

A paraplegic patient who underwent the placement of Greenfield filters to prevent pulmonary emboli had one of the filters migrate proximally to the junction of the inferior vena cava and right atrium, then into the right atrium a few months later. This resulted in an acute myocardial infarction by apparently causing an intimal dissection of the posterior descending artery. Treatment, follow-up and causes of filter migration are discussed.

Disc embolization from a Beall mitral valve prosthesis.

Although embolization of the disc from a Beall valve is rare, several reports in the literature have identified patients suffering this complication. This report details the clinical and radiologic course of a patient with an embolized disc from a Model 103 Beall mitral valve prosthesis. The patient lived approximately 39 hours without the disc prior to surgical correction. Depending on the cardiac reserve and the amount of pannus formation, patients may live long enough to allow surgical correction of this complication.

Effect of methylprednisolone on predicted myocardial infarction size in man.

Therapeutic manipulations designed to conserve myocardium in patients with acute myocardial infarction appear to improve prognosis. To assess the role of glucocorticoids given in pharmacologic dosage in the early treatment of patients with acute myocardial infarction, serial serum creatine phosphokinase (CPK) were obtained every 1-2 hours in 39 consecutive patients admitted with acute myocardial infarction. Determination of completed infarction size (ISc) was made using all available CPK values (range 70-160 hours). Predicted infarct size (ILp) was based on early data following the rise in CPK from baseline values: projected CPK values were obtained over a 160 hour period using a curve fitting procedure based upon nonlinear Gauss-Newton stepwise iterations. In 13 uncomplicated control patients ISp was 43.2 +/- 11.6 (mean +/- SE) CPK-gram-equivalents (CPK-q-eq), based on data from the first 7 hours following the rise in serum CPK, while ISc was 44.7 +/- 11.4 CPK-geq (r = .99, n = 13). In 7 additional control patients whose hospitals courses were complicated by clinical extension ISp was 71.8 +/- 18.0 CPK-g-eq while ISc was 118.6 +/- 31.0 CPK-g-eq (p less than .03). In 19 patients treated with 3 grams of methylprednisolone 7-14 hours following the rise in serum CPK from baseline, data from early CPK determinations (7 hours) indicated an ISp of 118.5 +/- 24.1 CPK-g-eq while total CPK data indicate an ISc of 89.6 +/- 13.2 CPK-g-Eq (p less than .04). The exponential clearance of CPK (kd) was approximated in the controls (kd = .00095 +/- .00007 min-1) and glucocorticoid treated patients (kd = .00099 +/- .00006 min-1) and found to be similar. Thus, administration of a pharmacologic dose of methylprednisolone 7-14 hours following rise in serum CPK from baseline in a group of patients with acute myocardial infarctions has resulted in salvage of myocardium.