Bidirectional Relationships Between Weight Change and Sleep Apnea in a Behavioral Weight Loss Intervention

Objective

To examine the bidirectional relationship between weight change and obstructive sleep apnea (OSA) in the context of a behavioral weight loss intervention.

Inhaled metaproterenol is superior to inhaled cromolyn in protecting against cold-air-induced bronchospasm

Eucapneic hyperventilation of cold air (EHCA) provokes bronchospasm in asthmatics. Although inhaled cromolyn powder and sympathomimetic solutions have attenuated the bronchospasm induced by EHCA, comparison of both drugs in solution has not been performed. We performed a prospective double-blind study comparing cromolyn solution, metaproterenol solution, and placebo (normal saline) given prior to EHCA. Eight asthmatics defined by a 20% reduction in forced expiratory volume in 1s (FEV1) after EHCA consented to the study. Patients were tested on 3 separate occasions at a similar time of day. Each session began with a determination of FEV1 followed by a randomized double-blind treatment. A repeat FEV1 (pre-EHCA) was performed 20 min after drug inhalation. Twelve minutes of EHCA was performed consisting of 4 min of tidal breathing, 4 min of eucapneic hyperventilation (60-70% of the predicted MVV) and a final 4 min of tidal breathing. FEV1 was performed immediately, 5 min, and 10 min after EHCA. The lowest value was defined as the post-EHCA FEV1. The pre-EHCA FEV1 was significantly larger after metaproterenol pretreatment compared to the pre-EHCA FEV1 following cromolyn (p = 0.01) and saline (p = 0.04). Metaproterenol pretreatment had a significant protective effect in comparison to placebo pretreatment (p less than 0.01). No other paired comparisons (cromolyn vs. placebo, cromolyn vs. metaproterenol) achieved statistical significance at a 0.05 level. In conclusion, metaproterenol is superior to cromolyn in protecting against cold-air-induced bronchospasm.     

Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice

Motor incoordination, immune deficiencies, and an increased risk of cancer are the characteristic features of the hereditary disease ataxia-telangiectasia (A-T), which is caused by mutations in the ATM gene. Through gene targeting, we have generated a line of Atm mutant mice, Atm(y/y) mice. In contrast to other Atm mutant mice, Atm(y/y) mice show a lower incidence of thymic lymphoma and survive beyond a few months of age. Atm(y/y) mice exhibit deficits in motor learning indicative of cerebellar dysfunction. Even though we found no gross cerebellar degeneration in older Atm(y/y) animals, ectopic and abnormally differentiated Purkinje cells were apparent in mutant mice of all ages. These findings establish that some neuropathological abnormalities seen in A-T patients also are present in Atm mutant mice. In addition, we report a previously unrecognized effect of Atm deficiency on development or maintenance of CD4(+)8(+) thymocytes. We discuss these findings in the context of the hypothesis that abnormal development of Purkinje cells and lymphocytes contributes to the pathogenesis of A-T.     

Gene transfer to primary normal and malignant human hemopoietic progenitors using recombinant retroviruses

To study the feasibility of using retroviruses for gene transfer into human hemopoietic cells, various cell types were exposed to virus carrying the gene for neomycin resistance (neor). In preliminary studies using K562 cells as targets, we found that high viral titer and co-cultivation with viral producer cells rather than incubation in medium exposed to viral producer cells were important variables for achieving high frequencies of G418 resistant (G418r) colonies. The maximum frequency of G418r K562 colonies after co-cultivation with cells producing a neor virus titer of 4 X 10(6) cfu/mL was 60%. When primary human progenitors from normal marrow, fetal liver, or chronic myelogenous leukemia blood were exposed to high titer viral stocks, both with and without helper virus, under conditions optimized for K562 cells, maximum frequencies of G418r colonies were 3% to 16% for granulocyte macrophage progenitors and 2% to 6% for primitive erythroid progenitors. The presence of the neor gene in both G418r K562 and primary hemopoietic colonies was verified by Southern blot. Expression of the neor gene was shown by RNA spot blot. These data demonstrate efficient transfer and expression of the neor gene in both K562 cells and primary human hemopoietic cells from normal and leukemic individuals.     

Interspike interval analysis of retinal ganglion cell receptive fields

The interspike interval (ISI) preceding a retinal spike has a strong influence on whether retinal spikes will drive postsynaptic responses in the lateral geniculate nucleus (LGN). This ISI-based filtering of retinal spikes could, in principle, be used as a mechanism for processing visual information en route from retina to cortex; however, this form of processing has not been previously explored. Using a white noise stimulus and reverse correlation analysis, we compared the receptive fields associated with retinal spikes over a range of ISIs (0-120 ms). Results showed that, although the location and sign of retinal ganglion cell receptive fields are invariant to ISI, the size and amplitude of receptive fields vary with ISI. These results support the notion that ISI-based filtering of retinal spikes can serve as a mechanism for shaping receptive fields.     

Inhibition of day-12 spleen colony-forming units by a monoclonal antibody to the murine macrophage/monocyte colony-stimulating factor receptor

Primitive hematopoietic stem cells differentiate into committed progenitors that are thought to selectively express hematopoietic growth factor receptor(s), thereby acquiring hematopoietic growth factor responsiveness. To assess whether hematopoietic stem cells express hematopoietic growth factor receptors, the progenitor activity of bone marrow (BM) fractions, isolated by expression of receptors for macrophage/monocyte colony-stimulating factor (M-CSF), were examined. Recovery of day-12 spleen colony-forming units (CFU-S) is diminished in both M-CSF receptor-positive (M-CSFR+) and M-CSFR- fractions, indicating antibody inhibition of day-12 CFU-S. Incubation of BM cells with antibody without fractionation inhibits 50% to 60% of day-12 CFU- S. This inhibition is specific (control antibodies have no effect) and reversible by removal of bound antibody at low pH. Incubating BM cells with control or antireceptor antibody does not affect day-8 CFU-S, which are predominantly erythroid. Treating sublethally irradiated mice with antibody inhibits endogenous day-12 CFU-S. These results indicate that some early progenitors express M-CSFRs, and blocking M-CSFRs inhibits the ability of these progenitors to form colonies, possibly because of inactivation caused by prolonged receptor blockade.     

Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes

We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common.