Normalization of serum lactic dehydrogenase in β-thalassemia patients following bone marrow transplantation

Serum lactic dehydrogenase (LDH) levels are mildly elevated in β-thalassemia major due to ineffective erythropoiesis. We reviewed the charts of 15 consecutive thalassemic children who underwent allogeneic, T-cell-depleted bone marrow transplantation (BMT) in our department during the last 3 years. Eleven patients had successful engraftment and are alive and well without evidence of disease, according to physical examinations, blood counts, and polymerase chain reaction (PCR) tests, with a median follow-up of 2 years. Two patients died due to transplantation-related complications, and two rejected the graft and received their backup autologous marrow. The LDH levels in the transplanted patients gradually decreased from an average of 952 ± 155 IU/L 10 days pre-transplant (N = 300–620) to 426 ± 56 IU/L at the day of transplantation, and stayed at approximately the same level post-transplant (489 ± 55 IU/L). By contrast, the LDH levels reverted to the pre-transplant value in those patients who rejected their marrow. The significance of this clinical observation for the pathophysiologic mechanism of intramedullary hemolysis and ineffective erythropoiesis in β-thalassemia major is discussed. © 1996 Wiley-Liss, Inc.     

Enhanced Survival and Neurite Network Formation of Human Umbilical Cord Blood Neuronal Progenitors in Three-Dimensional Collagen Constructs

Umbilical cord blood (CB) stem cells have been proposed for cell-based therapeutic applications for diverse diseases of the CNS. We hypothesized that tissue-engineering strategies may extend the efficacy of these approaches by improving the long-term viability and function of stem cell-derived neuronal progenitors. To test our hypothesis, we explored the survival and differentiation of human CB-derived neuronal progenitors (HUCBNP) in a three-dimensional (3D) collagen construct. In contrast to two-dimensional culture conditions, the cells survived in 3D for an extended period of time of more than 2 months. Under 3D conditions, HUCBNP underwent spontaneous neuronal differentiation, which was further enhanced by treatment with neuronal conditioned medium (CM) and nerve growth factor (NGF). Neurite outgrowth, quantified by assessing the fractal dimension (D _f) of the complex neuronal networks, was significantly enhanced under 3D conditions in the presence of CM/NGF, concomitant with a reduced expression of the early neuronal marker nestin (1.9-fold), and increased levels of mature neuronal markers such as MAP-2 (3.6-fold), β-tubulin (1.5-fold), and neuronal specific enolase (6.6-fold) and the appearance of the synaptic marker synaptophysin. To assess the feasibility for clinical usage, HUCBNP were also isolated from frozen CB samples and cultured under 3D conditions. The data indicate the essential complete preservation of neurotrophic (survival) and neurotropic (neurite outgrowth) properties. In conclusion, 3D culture conditions are proposed as an essential step for both maintenance of CB neuronal progenitors in vitro and for investigating specific features of neuronal differentiation towards future use in regenerative therapy.     

Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells

Beta-cell replacement is considered to be the most promising approach for treatment of type 1 diabetes. Its application on a large scale is hindered by a shortage of cells for transplantation. Activation of insulin expression, storage, and regulated secretion in stem/progenitor cells offers novel ways to overcome this shortage. We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells. FH cells possess a considerable replication capacity, and this was further extended by introduction of the gene for the catalytic subunit of human telomerase. Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose. When transplanted into hyperglycemic immunodeficient mice, the cells restored and maintained euglycemia for prolonged periods. Quantitation of human C-peptide in the mouse serum confirmed that the glycemia was normalized by the transplanted human cells. This approach offers the potential of a novel source of cells for transplantation into patients with type 1 diabetes.     

Pituitary Society Delphi Survey: An international perspective on endocrine management of patients undergoing transsphenoidal surgery for pituitary adenomas

Pituitary - In adults and children, transsphenoidal surgery (TSS) represents the cornerstone of management for most large or functioning sellar lesions with the exception of prolactinomas....     

Identification of FDA-Approved Drugs and Bioactives that Protect Hair Cells in the Zebrafish (Danio rerio) Lateral Line and Mouse (Mus musculus) Utricle

The hair cells of the larval zebrafish lateral line provide a useful preparation in which to study hair cell death and to screen for genes and small molecules that modulate hair cell toxicity. We recently reported preliminary results from screening a small-molecule library for compounds that inhibit aminoglycoside-induced hair cell death. To potentially reduce the time required for development of drugs and drug combinations that can be clinically useful, we screened a library of 1,040 FDA-approved drugs and bioactive compounds (NINDS Custom Collection II). Seven compounds that protect against neomycin-induced hair cell death were identified. Four of the seven drugs inhibited aminoglycoside uptake, based on Texas-Red-conjugated gentamicin uptake. The activities of two of the remaining three drugs were evaluated using an in vitro adult mouse utricle preparation. One drug, 9-amino-1,2,3,4-tetrahydroacridine (tacrine) demonstrated conserved protective effects in the mouse utricle. These results demonstrate that the zebrafish lateral line can be used to screen successfully for drugs within a library of FDA-approved drugs and bioactives that inhibit hair cell death in the mammalian inner ear and identify tacrine as a promising protective drug for future studies.     

The Effect of Hypercholesterolemia on Rotator Cuff Disease

Background  

The causes of rotator cuff tendon rupture are multifactorial and still unclear. Intrinsic and extrinsic factors have been implicated as predisposing risk factors for rotator cuff rupture. Previous studies have suggested a relationship between elevated serum lipid profiles and tendon ruptures, although not rotator cuff tears specifically.     

Glucocorticoid Regulation of Clock Gene Expression in the Mammalian Limbic Forebrain

The cyclical expression of the clock protein PERIOD2 (PER2) in select regions of the limbic forebrain is contingent upon the rhythmic secretion of the adrenal glucocorticoid, corticosterone. Daily rhythmic PER2 expression in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) and the central nucleus of the amygdala (CEA) is abolished with the removal of the adrenal glands but restored with rhythmic hormone replacement via the drinking water at a time corresponding to the endogenous peak of circulating glucocorticoids. Here, we investigated the effects of serial or acute systemic injections of corticosterone on the expression of PER2 in the BNSTov and CEA of both adrenalectomized (ADX) and intact rats. We sought to determine whether there is a temporal window of corticosterone sensitivity by delivering the hormone at a time corresponding to trough levels of circulating glucocorticoids, at lights on. We found that daily morning injections of corticosterone induced PER2 expression in the BNSTov and CEA of ADX rats, with levels peaking 1 h after injection. In intact rats, daily morning injections significantly upregulated the expression of PER2 in the BNSTov and CEA 1 h after injection and dampened the evening peak, while a single injection abolished the rhythm of PER2 expression in the CEA but had no effect on PER2 in the BNSTov. Our findings suggest that despite the potential masking effect of signals from the light-entrained master clock, daytime chronic and acute corticosterone administration can alter the rhythmic expression of PER2 in the BNSTov and CEA, and that the response is region-specific and dependent on the duration of treatment.     

The Impact of Advances in Instrumentation and Techniques of Colonoscopy from 1988 to 2008 on Inpatient Colonoscopy Performance at a High Volume Endoscopy Unit in the United States: Significantly Shorter Procedure Time,Higher Completion Rate,Performance on Sicker Inpatients,and Near Disappearance of Flexible Sigmoidoscopy

Background and Aims  

Colonoscopy instrumentation and technique have improved from 1988 to 2008. We analyze whether these improvements have resulted in improved colonoscopy performance.