Chromosomal localization of ARSB,the gene for human N-acetylgalactosamine-4-sulphatase

Summary A deficiency of N-acetylgalactosamine-4-sulphatase (G4S, gene symbol ARSB), results in the accumulation of undegraded substrate and the lysosomal storage disorder, Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI). In situ hybridization using an ³H-labelled human G4S genomic DNA fragment to human metaphase chromosomes localized ARSB to chromosome 5q13–5q14. This location is consistent with, an refines, previous chromosomal assignments based on the expression of human G4S in somatic cell hybrids.     

Feeding Response of Rats to No-Fat and High-Fat Cakes

The nutritional effects of high-fat diets have been extensively studied in laboratory animals, but as yet few experiments have examined the feeding response of animals to newly developed fat substitutes. The present study used commercially available no-fat (0% fat, 92% carbohydrate) and high-fat (41% fat, 54% carbohydrate) cake to determine the effects of fat substitutes on food preference and caloric intake in rats. The first experiment showed that nondeprived rats found the high-fat and no-fat cakes equally palatable and highly preferred to lab chow. Food deprived rats, however, preferred the high-fat cake to the no-fat cake, which may be related to its higher caloric density. In the second experiment, rats fed high-fat cake, in addition to chow, for 30 days consumed more calories and gained more weight than did rats fed no-fat cake and chow. The no-fat cake group, however, overate and gained more weight than chow-only controls. The hyperphagic response to the no-fat cake can be attributed to its carbohydrate content, moisture, and high palatability. Thus, removing fat from the cake reduced, but did not eliminate, its obesity-promoting effect. Obviously, low-fat foods must be consumed in moderation if used for weight control.     

Pharmacological Inhibition of AMP-Deaminase in Rat Cardiac Myocytes

Because mutation of AMP deaminase 1 gene leading to reduced AMP deaminase activity may result in protection of cardiac function in patients with heart disease, inhibitors of AMP deaminase (AMPD) may have therapeutic applications. This study evaluated the effect of a specific inhibitor of AMP deaminase 3-[2-(3-carboxy-4-bromo-5,6,7,8-tetrahydronaphthyl)ethyl]-3,6,7,8-tetrahydroimidazo [4,5-d][1,3]diazepin-8-ol (AMPDI) on the isolated human enzyme and on nucleotide catabolism in rat cardiomyocytes. AMPDI effectively inhibited isolated human AMPD with an IC ₅₀ = 0.5 μ M. AMPDI was much less effective with isolated cardiomyocytes (IC ₅₀ = 0.5 mM). AMPDI is a very effective inhibitor of AMPD that despite lower efficiency in the cell system examined could be useful for in vivo studies.     

Broad Salinity Tolerance as a Refuge from Predation in the Harmful Raphidophyte Alga Heterosigma akashiwo (Raphidophyceae)

The ability of harmful algal species to form dense, nearly monospecific blooms remains an ecological and evolutionary puzzle. We hypothesized that predation interacts with estuarine salinity gradients to promote blooms of Heterosigma akashiwo (Y. Hada) Y. Hada ex Y. Hara et M. Chihara, a cosmopolitan toxic raphidophyte. Specifically, H. akashiwo's broad salinity tolerance appears to provide a refuge from predation that enhances the net growth of H. akashiwo populations through several mechanisms. (1) Contrasting salinity tolerance of predators and prey. Estuarine H. akashiwo isolates from the west coast of North America grew rapidly at salinities as low as six, and distributed throughout experimental salinity gradients to salinities as low as three. In contrast, survival of most protistan predator species was restricted to salinities >15. (2) H. akashiwo physiological and behavioral plasticity. Acclimation to low salinity enhanced H. akashiwo's ability to accumulate and grow in low salinity waters. In addition, the presence of a ciliate predator altered H. akashiwo swimming behavior, promoting accumulation in low‐salinity surface layers inhospitable to the ciliate. (3) Negative effects of low salinity on predation processes. Ciliate predation rates decreased sharply at salinities <25 and, for one species, H. akashiwo toxicity increased at low salinities. Taken together, these behaviors and responses imply that blooms can readily initiate in low salinity waters where H. akashiwo would experience decreased predation pressure while maintaining near‐maximal growth rates. The salinity structure of a typical estuary would provide this HAB species a unique refuge from predation. Broad salinity tolerance in raphidophytes may have evolved in part as a response to selective pressures associated with predation.     

Fine map of the Gct1 spontaneous ovarian granulosa cell tumor locus

The spontaneous development of juvenile-onset, ovarian granulosa cell (GC) tumors in the SWR/Bm (SWR) inbred mouse strain is a model for juvenile-type GC tumors that appear in infants and young girls. GC tumor susceptibility is supported by multiple Granulosa cell tumor (Gct) loci, but the Gct1 locus on Chr 4 derived from SWR strain background is fundamental for GC tumor development and uniquely responsive to the androgenic precursor dehydroepiandrosterone (DHEA). To resolve the location of Gct1 independently from other susceptibility loci, Gct1 was isolated in a congenic strain that replaces the distal segment of Chr 4 in SWR mice with a 47 × 10⁶-bp genomic segment from the Castaneus/Ei (CAST) strain. SWR females homozygous for the CAST donor segment were confirmed to be resistant to DHEA- and testosterone-induced GC tumorigenesis, indicating successful exchange of CAST alleles (Gct1 ^CA ) for SWR alleles (Gct1 ^SW ) at this tumor susceptibility locus. A series of nested, overlapping, congenic sublines was created to fine-map Gct1 based on GC tumor susceptibility under the influence of pubertal DHEA treatment. Twelve informative lines have resolved the Gct1 locus to a 1.31 × 10⁶-bp interval on mouse Chr 4, a region orthologous to human Chr 1p36.22.     

Medical and Household Characteristics Associated with Methicillin Resistant Staphylococcus aureus Nasal Carriage among Patients Admitted to a Rural Tertiary Care Hospital

Background

Methicillin resistant Staphylococcus aureus (MRSA) poses a threat to patient safety and public health. Understanding how MRSA is acquired is important for prevention efforts. This study investigates risk factors for MRSA nasal carriage among patients at an eastern North Carolina hospital in 2011.

Methods

Using a case-control design, hospitalized patients ages 18 – 65 years were enrolled between July 25, 2011 and December 15, 2011 at Vidant Medical Center, a tertiary care hospital that screens all admitted patients for nasal MRSA carriage. Cases, defined as MRSA nasal carriers, were age and gender matched to controls, non-MRSA carriers. In-hospital interviews were conducted, and medical records were reviewed to obtain information on medical and household exposures. Multivariable conditional logistic regression was used to derive odds ratio (OR) estimates of association between MRSA carriage and medical and household exposures.

Results

In total, 117 cases and 119 controls were recruited to participate. Risk factors for MRSA carriage included having household members who took antibiotics or were hospitalized (OR: 3.27; 95% Confidence Interval (CI): 1.24–8.57) and prior hospitalization with a positive MRSA screen (OR: 3.21; 95% CI: 1.12–9.23). A lower proportion of cases than controls were previously hospitalized without a past positive MRSA screen (OR: 0.40; 95% CI: 0.19–0.87).

Conclusion

These findings suggest that household exposures are important determinants of MRSA nasal carriage in hospitalized patients screened at admission.     

Hydroxyurea Use and Hospitalization Trends in a Comprehensive Pediatric Sickle Cell Program

Background

A decline in hospitalizations and pain episodes among those with sickle cell disease (SCD) who take hydroxyurea (HU) has been shown when compared to pre-HU patterns but paradoxically, when compared to those who have never been treated, HU recipients often have more frequent hospitalizations. This analysis evaluates the impact of increasing usage of HU on trends in hospitalizations and blood transfusions within a large SCD treatment program.

Methods

Eligibility was restricted to patients with Hb SS or Hb Sβ⁰-thalassemia who were 2–18 years old between 2006–2010 and received care at St. Jude Children''s Research Hospital (N = 508). Hospitalizations and blood transfusions were calculated for each of the years under study for those exposed and never exposed to HU. Differences in number of hospitalizations before and after HU initiation were compared.

Results

The proportion of patients receiving HU increased by 4% per year on average. In the HU exposed group, a modest decline in mean per-patient hospitalizations and per-patient hospital days occurred, while those never exposed to HU trended toward a slight increase over time. Rates of blood transfusions declined among those on HU but not in patients never exposed to HU. Patients on HU had a median of one fewer hospital admission in the year after initiation of HU, compared to the year prior. Two deaths occurred in the patient population, both of whom were not exposed to HU.

Conclusions

Increasing usage of HU was concurrent with decreased hospitalization rates and blood transfusions. Our results support the utility of HU on decreasing hospitalizations and transfusions for patients with SCD outside of the clinical trial setting.