Hematopoetic precursors respond to a unique B lymphocyte-derived factor in vivo

In this study we detected a factor that stimulates the proliferation of bone marrow-derived hematopoietic precursors in diffusion chambers implanted in mice. This factor, called diffusible colony-stimulating factor (D-CSF), was found in medium conditioned in the presence of spleen and peripheral blood cells from mice with B cell leukemia (BCL1). After the administration of D-CSF, the number of colonies formed in the plasma clot inside the chamber (CFU-DG) was increased, as were the number of hematopoietic precursors (CFU-MIX, CFU-S, CFU-C, and BFU-E) as judged by a subculture of diffusion chamber contents. Depletion of macrophages and T cells from the spleen cell suspension did not decrease the production of D-CSF, thereby indicating that it was derived from B cells. Neoplastic BCL1 cells appear to be the source because D-CSF could not be detected in medium conditioned with normal B cells. BCL1-conditioned medium (CM) did not enhance CFU-MIX, BFU-E, and CFU-C colony formation in vitro, which suggested that D-CSF is different from multi-CSF, EPA, or CSF. The addition of BCL1 CM to multi- CSF-, erythroid potentiating activity (EPA), and CSF (EL-4CM)- containing cultures had no effect on CFU-MIX, BFU-E, and CFU-C colony formation, thus indicating the absence of a synergistic or inhibitory activity. On the other hand, EL-4 CM, which stimulates CFU-MIX, BFU-E, and CFU-C in vitro, had no effect on CFU-DG in vivo. Biochemical characterization of BCL1 CM revealed that D-CSF is relatively heat stable and loses its bioactivity with protease treatments. It binds to lentil-lectin, according to gel-filtration chromatography has a relative molecular weight of approximately 43,000, and on reverse-phase high-performance liquid chromatography elutes with acetonitrile. These data also indicate that transformed B cells may serve as a source for hematopoietic regulators that act on hematopoietic precursors in vivo.     

Suppressive therapy with levothyroxinefor solitary thyroid nodules

OBJECTIVE: To evaluate the effect of treatment with TSH suppressive dose of levothyroxine in patients with benign thyroid nodules. DESIGN: Prospective randomized study. Group A (n = 20) patients received levothyroxine and group B (n = 20) patients did not. The dose of levothyroxine was adjusted to obtain an effective suppression of TSH. A clinical, analytical and morphological (with ultrasound) review was performed every 3 months. The mean +/- SD follow-up period was 10.6 +/- 2.2 months. PATIENTS: Forty euthyroid women with solitary thyroid nodule on palpation, cold on scintigraphy and cytologically benign without contraindication participated. MEASUREMENTS: At entry: biochemical and hormonal parameters, thyroid scintigraphy and thyroid ultrasonography. Every 3 months additional determinations of thyroid hormones and TSH levels were carried out, if necessary, to verify effective TSH suppression. Every 6 months thyroid ultrasound imaging was performed. RESULTS: Patients were euthyroid at entry into the study. The mean dose of levothyroxine necessary to obtain TSH suppression was 2.82 +/- 0.6 micrograms/kg/day. No significant modification in the thyroid nodule diameter (mean +/- SD 2.6 +/- 1.2 vs 2.5 +/- 1.2 cm) or in the thyroid nodule volume (10.3 +/- 11.9 vs 10.1 +/- 12.2 ml) were observed in group A. In group B the results were similar (2.8 +/- 0.9 vs 2.7 +/- 1.8 cm and 9.2 +/- 6.4 vs 9.2 +/- 9.5 ml, respectively). No differences were found in either group in the number of nodules that reduced significantly their volume (four and three, respectively). CONCLUSIONS: The suppressive therapy with levothyroxine was not effective in reducing nodule sizes in patients with solitary benign thyroid nodules.     

National health accounts data from 1996 to 2010: a systematic review

Objective

To collect, compile and evaluate publicly available national health accounts (NHA) reports produced worldwide between 1996 and 2010.

Methods

We downloaded country-generated NHA reports from the World Health Organization global health expenditure database and the Organisation for Economic Co-operation and Development (OECD) StatExtract website. We also obtained reports from Abt Associates, through contacts in individual countries and through an online search. We compiled data in the four main types used in these reports: (i) financing source; (ii) financing agent; (iii) health function; and (iv) health provider. We combined and adjusted data to conform with OECD’s first edition of A system of health accounts manual, (2000).

Findings

We identified 872 NHA reports from 117 countries containing a total of 2936 matrices for the four data types. Most countries did not provide complete health expenditure data: only 252 of the 872 reports contained data in all four types. Thirty-eight countries reported an average not-specified-by-kind value greater than 20% for all data types and years. Some countries reported substantial year-on-year changes in both the level and composition of health expenditure that were probably produced by data-generation processes. All study data are publicly available at http://vizhub.healthdata.org/nha/.

Conclusion

Data from NHA reports on health expenditure are often incomplete and, in some cases, of questionable quality. Better data would help finance ministries allocate resources to health systems, assist health ministries in allocating capital within the health sector and enable researchers to make accurate comparisons between health systems.     

Effects of autonomic denervation on canine exocrine pancreatic secretion and blood flow

The effect of autonomic denervation on the exocrine pancreatic secretion and blood flow was studied in a group of dogs. Pancreatic secretion was collected and analyzed for volume and bicarbonate by direct cannulation of the main papilla through a duodenotomy prior to and following truncal vagotomy and celiac plexus denervation. Pancreatic blood flow was determined by the radioisotope distribution method (141Ce). Truncal vagotomy causes a reduction in pancreatic secretion of volume and bicarbonate by 25-30%, while celiac denervation caused a reduction of 70% in the secretion. The mean baseline pancreatic blood flow was 0.5 ml/g pancreas/min. Truncal vagotomy did not cause any significant flow changes, while celiac denervation caused a significant increase in blood flow of 350% (to 1.75 ml/g/min). These results suggest that both the parasympathetic and the sympathetic system affect pancreatic secretion independently of their effect upon pancreatic blood flow.     

Two successful pregnancies in pyridoxine-nonresponsive homocystinuria

Two successful pregnancies are reported in a pyridoxine-nonresponsive woman who was also homozygous for the MTHFR 677C>T polymorphism. Two healthy children were delivered, although there had also been an early miscarriage of an apparently normal fetus in another pregnancy. Management of the patient's homocystine and methionine levels was maintained throughout pregnancy and, in view of the increased thromboembolic risk, anticoagulation therapy was also included in management.     

Anti-viral immune responses in a primitive lung: Characterization and expression analysis of interferon-inducible immunoproteasome subunits LMP2, LMP7 and MECL-1 in a sarcopterygian fish,the Nigerian spotted lungfish (Protopterus dolloi)

Lungfishes (Dipnoi) represent the closest ancestor of tetrapods. Dipnoi have dual breathing modes extracting oxygen from water and air. The primitive lungs of lungfishes are exposed to external antigens including viruses. To date, the immune response of lungfishes against viruses has not been investigated. During viral immune responses, cell exposure to type I interferon induces the replacement of the constitutive proteasome with LMP2, LMP7 and MECL-1 beta subunits forming the immunoproteasome and enhancing antigen presentation to MHC class I molecules. In order to study the immune defense system of the lungfish lung, we have characterized for the first time the three immunoproteasome subunits in the sarcopterygian fish, the Nigerian spotted lungfish (Protopterus dolloi). LMP2, LMP7 and MECL-1 were identified in P. dolloi and their sequences encoded predicted proteins of 216, 275 and 278 amino acids, respectively. The mRNA of these three genes was expressed in multiple tissues, including the lung, with the highest abundance observed in kidney and post-pyloric spleen. In vitro stimulation of lungfish lung and kidney primary cell cultures with PolyI:C for 4 and 12 h resulted in increased LMP2, LMP7 and MECL-1 expression in both tissues. These results suggest a central role of these genes in the activation of an antiviral immune response in lungfish. Importantly, they indicate that the primitive lung of the common ancestor of all tetrapods is capable of inducing the expression of these genes in response to viral stimulation.     

The impact of noise on the reliability of heart-rate variability and complexity analysis in trauma patients

This study focused on the impact of noise on the reliability of heart-rate variability and complexity (HRV, HRC) to discriminate between different trauma patients and to monitor individual patients. Life-saving interventions (LSIs) were chosen as an endpoint because performance of LSIs is a critical aspect of trauma patient care. Noise was modeled and simulated by modifying original R–R interval (RRI) sequences via decimation, concatenation, and division of RRIs, as well as R-wave detection using the electrocardiogram. Results showed that under increasing simulated noise, entropy and autocorrelation measures can still effectively discriminate between LSI and non-LSI patients and monitor individuals over time.     

Functional Differentiation of Mouse Visual Cortical Areas Depends upon Early Binocular Experience

The mammalian visual cortex contains multiple retinotopically defined areas that process distinct features of the visual scene. Little is known about what guides the functional differentiation of visual cortical areas during development. Recent studies in mice have revealed that visual input from the two eyes provides spatiotemporally distinct signals to primary visual cortex (V1), such that contralateral eye-dominated V1 neurons respond to higher spatial frequencies than ipsilateral eye-dominated neurons. To test whether binocular visual input drives the differentiation of visual cortical areas, we used two-photon calcium imaging to characterize the effects of juvenile monocular deprivation (MD) on the responses of neurons in V1 and two higher visual areas, LM (lateromedial) and PM (posteromedial). In adult mice of either sex, we find that MD prevents the emergence of distinct spatiotemporal tuning in V1, LM, and PM. We also find that, within each of these areas, MD reorganizes the distinct spatiotemporal tuning properties driven by the two eyes. Moreover, we find a relationship between speed tuning and ocular dominance in all three areas that MD preferentially disrupts in V1, but not in LM or PM. Together, these results reveal that balanced binocular vision during development is essential for driving the functional differentiation of visual cortical areas. The higher visual areas of mouse visual cortex may provide a useful platform for investigating the experience-dependent mechanisms that set up the specialized processing within neocortical areas during postnatal development.SIGNIFICANCE STATEMENT Little is known about the factors guiding the emergence of functionally distinct areas in the brain. Using in vivo Ca²⁺ imaging, we recorded visually evoked activity from cells in V1 and higher visual areas LM (lateromedial) and PM (posteromedial) of mice. Neurons in these areas normally display distinct spatiotemporal tuning properties. We found that depriving one eye of normal input during development prevents the functional differentiation of visual areas. Deprivation did not disrupt the degree of speed tuning, a property thought to emerge in higher visual areas. Thus, some properties of visual cortical neurons are shaped by binocular experience, while others are resistant. Our study uncovers the fundamental role of binocular experience in the formation of distinct areas in visual cortex.