Bayesian analysis of twinning and ovulation rates using a multiple-trait threshold model and Gibbs sampling

The Multiple-Trait Gibbs Sampler for Animal Models programs were extended to allow analysis of ordered categorical data using a Bayesian threshold model. The algorithm is based on data augmentation, where a value on the unobserved underlying normally distributed variable (liability) is generated in each round of iteration for each categorical observation. The programs allow analysis of several continuous and ordered categorical traits. Categorical traits can have any number of response levels. Models can be different for each trait. The programs were used to analyze twinning and ovulation rates from a herd of cattle selected for twinning rate at the U.S. Meat Animal Research Center. Data included number of calves born at each parturition for the lifetime of a cow and number of eggs ovulated for several estrous cycles before first breeding as heifers. A total of 6,411 calvings was recorded for 2,087 cows with 83.2% single and 16.8% multiple births. A total of 19,849 ovulations was recorded for 2,332 heifers with 85.2% single and 14.8% multiple ovulations. Mean posterior estimates of heritability and fraction of variance accounted for by permanent environmental effects (PE) were .128 and .103 for twinning rate and .168 and .079 for ovulation rate. Mean posterior estimate of genetic correlation was .808, and correlation of PE effects was .517. Use of a threshold model could allow for more rapid genetic improvement of the twinning herd through improved identification and selection of genetically superior animals because of higher heritability on the underlying scale.     

Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy

Retrograde transport from the Golgi to the ER is an essential process. Resident ER proteins that escape the ER and proteins that cycle between the Golgi and the ER must be retrieved. The interdependence of anterograde and retrograde vesicle trafficking makes the dissection of both processes difficult in vivo. We have developed an in vitro system that measures the retrieval of a soluble reporter protein, the precursor of the yeast pheromone alpha-factor fused to a retrieval signal (HDEL) at its COOH terminus (Dean, N., and H.R.B Pelham. 1990. J. Cell Biol. 111:369-377). Retrieval depends on the HDEL sequence; the alpha-factor precursor, naturally lacking this sequence, is not retrieved. A full cycle of anterograde and retrograde transport requires a simple set of purified cytosolic proteins, including Sec18p, the Lma1p complex, Uso1p, coatomer, and Arf1p. Among the membrane-bound v-SNAP receptor (v-SNARE) proteins, Bos1p is required only for forward transport, Sec22p only for retrograde trafficking, and Bet1p is implicated in both avenues of transport. Putative retrograde carriers (COPI vesicles) generated from Golgi-enriched membranes contain v-SNAREs as well as Emp47p as cargo.     

Impact of a children's health insurance program on newly enrolled children

CONTEXT: Although there is considerable interest in decreasing the number of US children who do not have health insurance, there is little information on the effect that health insurance has on children and their families. OBJECTIVE: To determine the impact of children's health insurance programs on access to health care and on other aspects of the lives of the children and their families. DESIGN: A before-after design with a control group. The families of newly enrolled children were interviewed by telephone using an identical survey instrument at baseline, at 6 months, and at 12 months after enrollment into the program. A second group of families of newly enrolled children were interviewed 12 months after the initial interviews to form a comparison sample. SETTING: The 29 counties of western Pennsylvania, an area with a population of 4.1 million people. SUBJECTS: A total of 887 families of newly enrolled children were randomly selected to be interviewed; 88.3% agreed to participate. Of these, 659 (84%) responded to all 3 interviews. The study population consists of 1031 newly enrolled children. The children were further classified into those who were continuously enrolled in the programs. The 330 comparison families had 460 newly enrolled children. MAIN OUTCOME MEASURES: The following access measures were examined: whether the child had a usual source of medical or dental care; the number of physician visits, emergency department visits, and dentist visits; and whether the child had experienced unmet need, delayed care, or both for 6 types of care. Other indicators were restrictions on the child's usual activities and the impact of being insured or uninsured on the families. RESULTS: Access to health care services after enrollment in the program improved: at 12 months after enrollment, 99% of the children had a regular source of medical care, and 85% had a regular dentist, up from 89% and 60%, respectively, at baseline. The proportion of children reporting any unmet need or delayed care in the past 6 months decreased from 57% at baseline to 16% at 12 months. The proportion of children seeing a physician increased from 59% to 64%, while the proportion visiting an emergency department decreased from 22% to 17%. Since the comparison children were similar to the newly enrolled children at enrollment into the insurance programs, these findings can be attributed to the program. Restrictions on childhood activities because of lack of health insurance were eliminated. Parents reported that having health insurance reduced the amount of family stress, enabled children to get the care they needed, and eased family burdens. CONCLUSIONS: Extending health insurance to uninsured children had a major positive impact on children and their families. In western Pennsylvania, health insurance did not lead to excessive utilization but to more appropriate utilization.     

Dysregulation through the NF-kappaB enhancer and TATA box of the human immunodeficiency virus type 1 subtype E promoter

The global diversity of human immunodeficiency virus type 1 (HIV-1) genotypes, termed subtypes A to J, is considerable and growing. However, relatively few studies have provided evidence for an associated phenotypic divergence. Recently, we demonstrated subtype-specific functional differences within the long terminal repeat (LTR) region of expanding subtypes (M. A. Montano, V. A. Novitsky, J. T. Blackard, N. L. Cho, D. A. Katzenstein, and M. Essex, J. Virol. 71:8657-8665, 1997). Notably, all HIV-1E isolates were observed to contain a defective upstream NF-kappaB site and a unique TATA-TAR region. In this study, we demonstrate that tumor necrosis factor alpha (TNF-alpha) stimulation of the HIV-1E LTR was also impaired, consistent with a defective upstream NF-kappaB site. Furthermore, repair of the upstream NF-kappaB site within HIV-1E partially restored TNF-alpha responsiveness. We also show, in gel shift assays, that oligonucleotides spanning the HIV-1E TATA box displayed a reduced efficiency in the assembly of the TBP-TFIIB-TATA complex, relative to an HIV-1B TATA oligonucleotide. In transfection assays, the HIV-1E TATA, when changed to the canonical HIV-1B TATA sequence (ATAAAA-->ATATAA) unexpectedly reduces both heterologous HIV-1B Tat and cognate HIV-1E Tat activation of an HIV-1E LTR-driven reporter gene. However, Tat activation, irrespective of subtype, could be rescued by introducing a cognate HIV-1B TAR. Collectively, these observations suggest that the expanding HIV-1E genotype has likely evolved an alternative promoter configuration with altered NF-kappaB and TATA regulatory signals in contradistinction with HIV-1B.     

The role of dopaminergic and serotonergic mechanisms in the development of swimming ability of young rats

Neonatal swimming behavior was studied after a single subcutaneous injection of L-dopa methyl ester (50 mg/kg; 200 mg/kg) apomorphine (0.1 mg/kg; 1.0 mg/kg), DL-amphetamine (0.5 mg/kg; 10 mg/kg), haloperidol (0.5 mg/kg; 1.0 mg/kg), L-tryptophan (50 mg/kg; 100 mg/kg), methysergide (1.0 mg/kg; 5.0 mg/kg) as well as intraventricular injection of 100 microgram 6-OHDA. 1-, 3-, 5- and 7-day-old rats were placed into a temperature-controlled aquarium (37 degrees C) and the pattern of motor coordination, latency time to swimming (LTS) and the number of foreleg strokes for 10 s (FS) were measured. When compared to the physiological saline-injected controls, rats that received L-dopa showed a striking increase of FS at all ages but the most striking improvement of motor coordination was found in newborn rats. On day 1 both doses of DL-amphetamine induced increases in FS and improvement of motor coordination, whereas apomorphine failed to show any effect at this age. On days 3, 5 and 7 low doses of DL-amphetamine and apomorphine increased the FS. However, high doses resulted in a decrement in swimming performance. Haloperidol impaired swimming on day 1 but produced a significant increase of FS on days 5 and 7. Neonatal injection of 6-OHDA delayed development of motor coordination, reduced FS and increased LTS. On days 3, 5 and 7 high doses of L-tryptophan elicited an increase of FS, while high doses of methysergide caused significant impairment of performance. It is suggested that the brain rapidly converts the administered L-dopa to dopamine during the first week of life and there appears to be a strong dependent relationship between the pattern of motor coordination and the amount of available dopamine in the developing brain.     

Field experinence of the molluscicide "Frescon" in the control of fascioliasis (author''s transl)

The desipramine-sensitive uptake (neuronal uptake) of 14C-bretylium and 14C-bethanidine into the rabbit aortic adventitial layer from 3 X 10(-6) M solutions increased with time during a 20 min incubation. For both compounds a neuronal uptake of 50 pmol/50 mg wet weight adventitia was associated with 10% block of the contractile response to field stimulation at 16 Hz and 150 pmol/50 mg with 60% block. The concentration of blocking agents inside the neuron at 50% blockade was calculated to be 260 X 10(-6) M, an 87-fold increase over the medium. The bretylium in the neuron decreased by 50% during 20 min washout, and bethanidine by 29%. Desipramine when added to the bath 20 min following the addition of the blocking agents led to a loss of bretylium but not of bethanidine from the adventitia. Desipramine had little or no effect on the uptake, washout or disposition of either blocking agent in the media-intimal layers. The data indicate that bretylium has a greater propensity than bethanidine to be lost from the neurons; however, it appears to be recycled back through the membrane via the amine pump more readily than bethanidine. The fact that conservative calculations indicate that the neuronal membrane slowly established a concentration of the blocking agents within the neuron that is known to produce rapid local anesthesia when topically applied to adrenergic nerve trunks and which approaches a concentration needed to inhibit sensory endings suggests that local anesthesia may play a role in the mechanism of neuron blockade.     

Treating Pseudomonas cepacia meningitis with trimethoprim-sulfamethoxazole

An infant with neonatal meningitis caused by Pseudomonas cepacia responded promptly to treatment with trimethoprim-sulfamethoxazole (Bactrim) after other abtibiotics had failed. Pseudomonas cepacia has proven to be resistant to most of the commonly used antibiotics.