Diaphragmatic fatigue following voluntary hyperpnea

A significant relationship between sex ratio and litter size at birth was observed in the young of guinea-pigs caged singly from 8 weeks of age and during their first pregnancy; a male was present only at or around oestrus. Small litters (1-2 young) had significantly more males than did large litters (4-5 young). Such a relationship was not apparent in animals housed communally, whether young or older or in their second pregnancy. Litters in late pregnancy (day 63) or at delivery were significantly smaller than at mid-pregnancy (day 35). A significant negative relationship was found between litter size and bodymass at birth and to at least 63 days of age. Growth rates during the period of lactation were lower in animals born in large litters. The possible adaptive significance of a plastic relationship between litter size and sex ratio is considered together with the physiological mechanism that might be involved.     

Electrical maturation of the murine oocyte: an increase in calcium current coincides with acquisition of meiotic competence

We have used the whole-cell recording technique to compare three stages of primary and secondary oocytes from F1 hybrid mice (C57BL/6J x SJL/J): neonatal germinal vesicle (NGV) stage primary oocytes from 10- to 20-day-old, prepubescent mice; mature germinal vesicle (MGV) stage primary oocytes from 12-week-old, post-pubescent, superovulated mice; first polar body (FPB) stage secondary oocytes from 12-week-old, post-pubescent mice during the normal oestrus cycle or following superovulation. NGV, MGV and FPB oocytes all exhibit two voltage-dependent currents: an inward, rapidly activating/inactivating current, and an outward, slowly activating/non-inactivating current. In 1.5 mmol/l external Ca the average peak inward current is -2.9, -12.4 and -13.8 microA/cm2 in NGV, MGV and FPB oocytes, respectively. In 20 mmol/l Ca these currents increase and the reversal potential shifts to the right. The outward current decreases slightly with growth and development: at 40 mV test potentials, NGV oocytes have average outward currents of 8.9 microA/cm2, and MGV and FPB oocytes have currents of 5.0 and 5.5 microA/cm2, respectively. Thus, MGV oocytes express FPB current patterns. The reversal potentials, kinetics and pharmacology of the currents indicate that Ca channels carry the inward current and K channels carry the outward current. During growth in vivo a gradual depolarisation accompanies maturation. Resting potentials ranged from -45 to -30 mV in NGV oocytes to -35 to -17 mV in MGV oocytes to -20 mV to -3 mV in FPB oocytes. These data suggest that a selective increase occurs in the number of Ca channels during oocyte growth. This increase precedes nuclear maturation and coincides with the acquisition of meiotic competence.     

Evaluation of the aortic root by MRI: insights from patients with homozygous familial hypercholesterolemia

Hepatitis C chronically infects approximately 1.5% of Americans and is the most common clinical problem facing hepatologists. Since the virus was initially described in 1989, development of an effective therapy has been challenging. Although several different therapeutic agents have been used, no therapy has been shown to reliably eradicate the virus. Interferon-alpha, a cytokine with immunostimulatory and anti-viral properties, has become the therapy of choice for patients with chronic hepatitis C infection. Trials assessing the efficacy of interferon-alpha have characterized host and viral factors predictive of responses to treatment. A thorough understanding of these predictive factors is requisite to providing cost-effective therapeutic decisions for the patient with chronic hepatitis C infection.     

Studies on lymphocyte subpopulations and the effect of age on immune competence in turkeys

We characterized the lymphocyte subpopulations and investigated the effect of age on cellular and humoral immunity, development of lymphoid organs, and the relative proportions of CD4+ and CD8+ cells in turkeys. The mitogenic responses of peripheral T cells were poorly developed at hatch but developed rapidly after hatch and reached adult levels by 2 weeks-of-age. The average percentage of CD4+ cells was 45, 29.8, and 26.3 in the thymi, peripheral blood, and spleens, respectively, in turkeys. The mean percentage of CD8+ cells in the thymi, peripheral blood, and spleens of turkeys was 53.8, 13.6, and 15.5, respectively. Age did not influence the relative proportions of CD4+ and CD8+ T cells in the spleens and peripheral blood of turkeys. The mean percentages of IgM+ cells in the bursae and spleens were 78.5 and 26.8, respectively. Day-old turkeys did not develop detectable antibodies to either thymus dependent or independent antigens. However, 2 week or older turkeys showed good humoral responses. Inoculation of BSA at hatch induced tolerance, whereas injection of SRBC did not. Analysis of relative organ weights of turkey lymphoid organs showed that spleens and thymi developed rapidly during the first week-of-age.     

Protein adsorption onto poly(ether urethane ureas) containing Methacrol 2138F: a surface-active amphiphilic additive

Surface characterization and protein adsorption studies were carried out on a series of additive dispersed and additive coated poly(ether urethane ureas), PEUUs, to characterize early events in the blood compatibility of these materials. A hypothesis that is based on surface hydrophilicity, surface flexibility, and adsorption media has been developed to understand the modulated adsorption of plasma proteins by PEUU additives. Electron spectroscopy for chemical analysis (ESCA) and contact angle analysis were performed on two PEUU formulation as well as on PEUU formulations modified with Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate (DM)][3/1]) or acrylate or methacrylate polymer or copolymer analogs of Methacrol 2138F. Methacrol 2138F is a commercially used amphiphilic copolymethacrylate. ESCA showed that the PEUUs loaded with Methacrol 2138F or with its hydrophilic component, homopoly (DIPAM) (h-(DIPAM)), had a higher percentage of nitrogen at their surfaces than did the base PEUUs. Contact angle analysis also showed that the air side of PEUU formulations loaded with Methacrol 2138F were more hydrophobic than was the air side of base PEUUs when films were cast from dimethylacetamide. However, during contact angle testing, the air side of PEUU films loaded with Methacrol 2138F rapidly became more hydrophilic than did the air side of the base PEUU films. A radioimmunoassay and whole or diluted human plasma were also used to characterize the presence of the proteins fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin, on the surface of the same PEUUs as analyzed by ESCA and contact angle. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F, with a copolyacrylate analog of Methacrol 2138F (co(diisopropylaminoethyl acrylate [DIPAA]/decyl acrylate [DA]) [3/1]), or with the hydrophilic polyacrylate or polymethacrylate component analogs of Methacrol 2138F (h-DIPAM or h-DIPAA) adsorbed significantly lower amounts of the proteins than did either the base PEUU formulations or the homopoly(decyl methacrylate) (h-DM) or homopoly(decyl acrylate) (h-DA) coated or loaded PEUUs.     

The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity

A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts.     

Monoclonal antibodies to bovine growth hormone potentiate hormonal activity in vivo by enhancing growth hormone binding to hepatic somatogenic receptors

Administration of GH complexed with monoclonal antibodies (MABs) potentiates the in vivo actions of the hormone. In particular, growth and serum IGF-I concentrations of GH-treated hypophysectomized rats are increased by concomitant injection of anti-GH MABs. Among 37 anti-bovine GH (bGH) MABs, we selected one MAB with the most potentiating effects to investigate the mechanisms responsible for this phenomenon. Hypophysectomized rats were killed 18 h after a single s.c. injection of bGH (100 micrograms/rat), alone or complexed with increasing doses of MAB (4, 40, 400 micrograms/rat; MAB:bGH molar ratio: 0.005, 0.05, 0.5). IGF-I was measured by radioimmunoassay in acid-extracted sera and livers, whereas liver IGF-I mRNA was quantified by Northern blot hybridization. The in vivo occupancy of liver somatogenic (GH) receptors was derived from the determinations of total and free 125I-labelled bGH binding to liver homogenates treated with 4 mol MgCl2/l or water. Injection of MAB-bGH complexes enhanced body weight gain and raised serum IGF-I, liver IGF-I and liver IGF-I mRNA more than bGH alone (1.6-, 6-, 10- and 7-fold increases at the highest dose of MAB, compared with bGH alone; P < 0.001). These potentiating effects of the MAB were dose-dependent and significant potentiation of the growth response was already observed with the lowest dose of MAB. In vivo occupancy of liver GH receptors was markedly higher 18 h after injection of MAB-bGH complexes than after bGH alone, and this effect was also dose-dependent (receptor occupancy of 28%, 37% and 83% after 4, 40 and 400 micrograms of MAB respectively compared with 6% after bGH alone; P < 0.05, 0.05 and 0.001 respectively). In contrast, the in vitro binding of 125I-labelled bGH to liver homogenates was decreased in the presence of high doses of MAB. We conclude that low amounts of MABs complexed with bGH potentiate the stimulation by the hormone of liver IGF-I synthesis and secretion in a dose-dependent manner. These effects are mediated, at least in part, through changes in hormone-receptor interaction in vivo, leading to enhanced and/or prolonged binding of bGH to its somatogenic receptors.