DNA repair: knockouts still mutating after first round

Recent studies have investigated whether particular DNA repair pathways are involved in the somatic hypermutation mechanism that increases antibody diversity. The primary mutation mechanism still functions in mice carrying knockouts of all repair genes examined, but mismatch repair defects affect the final outcome.     

Pruritus and dermal response to insect antigens in sheep infested with Bovicola ovis

This study examined the relationships among louse density, pruritus and dermal response to insect antigens in sheep infested with Bovicola ovis. Polypay and Columbia ewes were allocated to two groups, infested and naive, and louse densities and pruritus were monitored for 15 months. Ten months after the initial infestation, all sheep were tested for hypersensitivity on the midside and ears by intradermal injection of soluble extracts of B. ovis, Stomoxys calcitrans and Musca autumnalis. The areas of skin reactions were measured at 20 min, 1, 3 and 24 h after injection and skin thickness was measured at 24 h. Louse densities on Polypays were approximately 10 times greater than on Columbias, and pruritus was correlated with louse numbers at most inspections. Most pruritic behaviour was directed to the sides of infested sheep. Wheal and flare reactions developed rapidly to all extracts in both infested and naive ewes. Reactions to louse extract were larger in infested than naive sheep at all four times after injection. In the infested Polypays, reactions to louse extract were greater than to the fly extracts, but in naive sheep there was little difference among extracts. Reactions in naive Columbias were larger than in naive Polypays at 20 min, 1 and 3 h, but had almost completely abated in both groups at 24 h. Reactions in infested Columbias were greater than in infested Polypays at 20 min, but at 24 h reactions in the Polypays were larger. Louse numbers and pruritus were correlated with wheal areas and skin thickness at 24 h, but there was little relationship with the size of reactions at earlier times. These findings are consistent with the development of a hypersensitive response to B. ovis and suggest that dermal reactions to lice may influence sheep susceptibility.     

Characteristics of apneas and hypopneas during sleep and relation to excessive daytime sleepiness

STUDY OBJECTIVES: One of the most important symptoms in patients evaluated for possible obstructive sleep apnea syndrome is excessive daytime sleepiness, but the measures of apnea severity and of sleepiness used most commonly have not generally shown strong associations. We explored whether information recorded during standard polysomnography, other than the overall rate of apneas and hypopneas per hour of sleep (AHI), might help explain the measured severity of sleepiness. DESIGN: Observational SETTING: A clinical sleep laboratory in a university hospital PATIENTS: N = 1,146 patients evaluated for suspected sleep-disordered breathing with nocturnal polysomnograms and multiple sleep latency tests. RESULTS: The AHI during supine sleep (recorded in a subgroup of n = 169 subjects), the rate of apneas (n = 1,146), and the rate of obstructive apneas (n = 1,146) were particularly useful in explaining variation in measured levels sleepiness; rates of hypopneas and central apneas were less useful (n = 1,146). In addition, the minimum recorded oxygen saturation (n = 1,097) was as important as the AHI to the level of sleepiness. CONCLUSIONS: In an attempt to explain excessive daytime sleepiness among patients evaluated for sleep-disordered breathing, additional insight is provided by observation of supine sleep during polysomnography, by emphasis on apneas rather than hypopneas, by emphasis on obstructive rather than central events, and by consideration of the minimum oxygen saturation.     

Rotational Spectrum, Structure, and Electric Dipole Moment of Bis(difluoromethyl) Ether

The rotational spectrum of bis(difluoromethyl) ether (CF2HOCF2H) has been observed and analyzed using both a conventional Stark-modulated microwave spectrometer and a pulsed molecular beam Fabry-Perot cavity microwave (FTMW) spectrometer. The lowest energy conformer studied here has a (hydrogen) syn-anti conformation. The high sensitivity of the FTMW spectrometer permits observation and analysis of the 13C, 18O, and 2H isotopomers in natural abundance. The electric dipole moment was measured for the normal species and found to be μa = 5.020(7) x 10(-30) C. m [1.505(2) D], μb = 0.19(4) x 10(-30) C. m [0.056(11) D], μc = 0.48(2) x 10(-30) C. m [0.144(7) D], and μT = 5.047(10) x 10(-30) C. m [1.513(3) D].     

Instability of tuberculin and Candida skin test reactivity in HIV-infected Ugandans. The Uganda-Case Western Reserve University Research Collaboration

Anergy testing has been used as an adjunct to tuberculin testing for assessing M. tuberculosis (MTB) infection and indications for isoniazid preventive therapy in HIV-infected persons. We examined factors associated with the stability of skin test responses to purified protein derivative (PPD) and candida antigens in a cohort of HIV-infected adults followed prospectively in a tuberculosis preventive therapy trial in Uganda. PPD-positive and anergic subjects in the placebo arms of the preventive therapy study underwent repeat skin testing and immunologic testing including measurement of MTB culture filtrate (CF)-stimulated interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) levels in whole-blood culture supernatants. Anergy was present in 27% of 4,058 HIV-infected subjects screened for the tuberculosis preventive therapy trial compared with 10% of 682 HIV-non-infected persons. On follow-up testing of enrolled subjects, 42% of 139 initially anergic subjects were no longer anergic; two thirds of these had PPD reactions >= 5 mm. Stability of anergy was associated with intercurrent opportunistic infections and AIDS-associated dermatitis at baseline. Thirty-five percent of 313 subjects with an initial positive PPD had a negative PPD test at follow-up, 26% of whom had a positive candida skin test at the same time as the negative PPD test. Baseline MTBCF-stimulated IFN-gamma levels were significantly higher among PPD-positive subjects who remained PPD-positive than in those who were falsely negative. We conclude first that anergy is unstable and second that anergy testing is unreliable in identifying HIV-infected adults who are not infected with MTB and should not be used routinely for this purpose in assessing indications for isoniazid preventive therapy.     

Dissolution of particulate hydroxyapatite in a macrophage organelle model

The optimum 14N pulse lengths in the 13C-14N rotational-echo adiabatic-passage double-resonance (REAPDOR) NMR experiment are determined from calculations and from experiments on samples of glycine and L-alanine. The REAPDOR experiment utilizes the adiabatic passages that 14N spins make between the 14N Zeeman energy levels during the application of a single, short 14N radiofrequency pulse. Use of a short 14N irradiation time of less than one-quarter of a rotor period ensures that the number of 14N spins that undergo more than one passage is minimized. This simplifies calculations describing 13C dipolar dephasing and provides better agreement between calculations and experiments. Recovery of the 13C-14N dipolar couplings and 14N quadrupolar coupling constants and asymmetry parameters is described.     

Perirhinal and postrhinal cortices of the rat: interconnectivity and connections with the entorhinal cortex

The cortical regions dorsally adjacent to the posterior rhinal sulcus in the rat can be divided into a rostral region, the perirhinal cortex, which shares features of the monkey perirhinal cortex, and a caudal region, the postrhinal cortex, which has connectional attributes similar to the monkey parahippocampal cortex. We examined the connectivity among the rat perirhinal (areas 35 and 36), postrhinal, and entorhinal cortices by placing anterograde and retrograde tracers in all three regions. There is a dorsal-to-ventral cascade of connections in the perirhinal and entorhinal cortices. Dorsal area 36 projects strongly to ventral area 36, and ventral area 36 projects strongly to area 35. The return projections are substantially weaker. The cascade continues with the perirhinal to entorhinal connections. Area 35 is more strongly interconnected with the entorhinal cortex, ventral area 36 somewhat less strongly, and dorsal area 36 projects only weakly to the entorhinal cortex. The postrhinal-to-perirhinal connections also follow this general pattern. The postrhinal cortex is more heavily connected with dorsal area 36 than with ventral area 36 and is more heavily connected with area 36 than with area 35. The rostral portion of the postrhinal cortex has the strongest connections with the perirhinal cortex. Like in the monkey, the perirhinal and postrhinal cortices have different patterns of projections to the entorhinal cortex. The perirhinal cortex is preferentially connected with the rostrolateral portion of the entorhinal cortex. The postrhinal cortex projects to a part of this same region but is also connected to caudal and redial portions of the entorhinal cortex. The perirhinal and postrhinal projections to the entorhinal cortex originate in layers III and V and terminate preferentially in layers II and III.     

The PPVT-R: validity as a quick screen of intelligence in a postacute rehabilitation setting for brain-injured adults

The utility of the Peabody Picture Vocabulary Test-Revised (PPVT-R) as a surrogate for the Wechsler Adult Intelligence Test-Revised (WAIS-R) was investigated in 61 brain-injured adult participants in a postacute rehabilitation setting. Idiographic comparison revealed substantial disagreement in clinical classification between the two instruments, and it is concluded that the PPVT-R is not a good surrogate for the WAIS-R for this purpose. In contrast, the PPVT-R was judged an adequate surrogate for the WAIS-R for the purpose of group comparison, as is common in biomedical research. Finally, contrary to prior report, the PPVT-R was demonstrated to measure more than simply Vocabulary. As such, in the absence of independent validation research, perhaps the most parsimonious conclusion regarding what the PPVT-R is measuring is that like each of the various subtests of the WAIS-R, the PPVT-R shares some of the variance of the construct termed intelligence, as well as demonstrates some unique variance that is likely comprised of error and, perhaps, a unique or different facet of intelligence.     

Relationship of Bcl-2 expression with apoptosis and proliferation in colonic graft versus host disease

OBJECTIVE: To compare hydrostatic weighing with and without head submersion and bioelectric impedance analysis (BIA) for measurement of body composition of persons who are morbidly obese. DESIGN: Body composition was determined using 3 methods: hydrostatic weighing with and without head submersion and BIA. Residual volume for the hydrostatic weighing calculation was determined by body plethysmography. SUBJECTS: Subjects were 16 morbidly obese men (142.5 kg mean body weight) and 30 morbidly obese women (125.9 kg mean body weight) living in the Salt Lake County, Utah, area. Morbid obesity was defined as 40 kg or more over ideal weight. STATISTICAL ANALYSIS: One-way, repeated-measures analysis of variance was followed by Scheffé post hoc tests; body-fat measurement method served as the repeated variable and percentage of body fat as the dependent variable. Men and women were analyzed separately. In addition, degree of agreement between the 3 methods of determining body composition was determined. A regression equation was used to calculate body density for hydrostatic weighing without head submersion. Two new BIA regression equations were developed from the data of the 16 men and 30 women. RESULTS: Values for percentage body fat from hydrostatic weighing with and without head submersion (41.8% vs 41.7%, respectively) were the same for men but differed for women (52.2% vs 49.4%, respectively, P < .0001). Values for body fat percentage measured by BIA were significantly lower for men (36.1%) and women (43.1%) (for both, P < .0001) compared with values from hydrostatic weighing methods. BIA underpredicted percentage body fat by a mean of 5.7% in men and 9.1% in women compared with the traditional hydrostatic weighing method. APPLICATIONS/CONCLUSIONS: BIA tended to underpredict the measurement of percentage body fat in male and female subjects who were morbidly obese. Hydrostatic weighing without head submersion provides an accurate, acceptable, and convenient alternative method for body composition assessment of the morbidly obese population in comparison with the traditional hydrostatic weighing method. In population screening or other settings where underwater weighing is impractical, population-specific BIA regression equations should be used because general BIA equations lead to consistent underprediction of percentage body fat compared with hydrostatic weighing.