Effect of dietary fat content and composition during pregnancy on fetal hepatic HMG CoA reductase activities and lipids in rats

The effects of diets containing 20% (wt/wt) safflower, olive or palm oil or 5% (wt/wt) safflower oil when fed throughout gestation on hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and on plasma and liver lipids were studied in fetal rats at d 21 of gestation. Hepatic total and active HMG CoA reductase activity, plasma free cholesterol and liver triglyceride and phospholipid 18:2(n-6) levels were higher in fetuses of rats fed 20% than in those of rats fed 5% safflower oil. Fetuses of rats fed olive oil had higher active HMG CoA reductase levels than fetuses of rats fed 20% safflower or palm oil; their total reductase activity was similar to that of the safflower oil group and higher than that for the palm oil group. Fetal liver and plasma cholesterol and triglyceride, as well as liver phospholipid concentrations, were not altered by the type of oil fed. The diets containing safflower oil resulted in higher 18:2(n-6) and lower 18:1 levels in fetal liver phospholipid and triglycerides than did the diets containing palm or olive oil. These studies demonstrate that fetal liver HMG CoA reductase activity is influenced by the maternal diet fat content and composition although the effect of specific fatty acids is unknown.     

The effect of first metatarsophalangeal joint arthrodesis on the first ray and the medial longitudinal arch: a radiographic study.

The purpose of this study was to examine the effect of first metatarsophalangeal arthrodesis on the sagittal plane orientation of the first ray and the medial longitudinal arch. Lateral weightbearing radiographs of 48 patients (54 feet) having undergone the procedure were retrospectively reviewed. Patients were separated into three groups based on their preoperative diagnosis: hallux rigidus, hallux valgus, or rheumatoid forefoot deformity. First metatarsal declination, talometatarsal, talar declination, calcaneal inclination, and talocalcaneal angles were measured on pre- and postoperative radiographs. Multivariate analysis of variance determined that there was a significant postoperative change (p < .001) in angular measurements, particularly in the first metatarsal declination, talometatarsal, and talocalcaneal angles. There was also a significant difference (p < .01) in the angular measurements between the hallux rigidus group and the other two groups. However, the amount of change from pre- to postoperatively did not vary significantly between the groups. A calculation of Pearson correlation coefficients found no significant correlation between the hallux dorsiflexion angle and changes in angular measurements. The radiographic changes found in this study support Hicks' windlass model: fixed dorsiflexion of the hallux causes plantarflexion of the first ray and an increase in the medial longitudinal arch.     

Effects of ethmoidal nerve stimulation on respiration-related neurones in the dorsal medulla of the cat

Stimulation of the nasal mucosa produces a number of respiratory reflexes the afferent limb of which is provided by the ethmoidal nerve, a branch of the trigeminal nerve. In the cat this nerve terminates within the trigeminal nucleus. It has no direct projection to brainstem respiratory centres. This study examines the response of respiratory-related neurones in the nucleus of the solitary tract (NTS) to ethmoidal stimulation. It demonstrates that these neurones show both excitatory and inhibitory responses to ethmoidal stimulation. Thus, the NTS appears to be involved in respiratory reflexes initiated by stimulation of the nasal mucosa.     

Characterization of HLA DR3/DQ2 transgenic mice: a potential humanized animal model for autoimmune disease studies

Linkage studies indicate close associations of certain HLA alleles with autoimmune diseases. To better understand how specific HLA alleles are related to disease pathogenesis, we have generated an HLA DR3/DQ2 transgenic mouse utilizing a 550-kb yeast artificial chromosome (YAC) construct containing the complete DRalpha, DRbeta1, DRbeta3, DQalpha, and DQbeta regions. The transgenic mouse (4D1/C2D) in an I-Abeta(o) background appears healthy with no signs of autoimmune diseases. Lymphoid tissues as well as CD4(+) T cells develop normally. Characterization of the transgene expression demonstrates that approximately 90% of B cells express high levels of DR3 and 50-70% of B cells express DQ2. CD11c(+) dendritic cells express high levels of DR and DQ. Approximately 12-18% of resting T cells are positive for DR expression, and further up-regulation to 40-50% expression is seen upon activation with anti-CD3/anti-CD28 mAb. These results suggest that the transgenic construct confers a high fidelity to the normal human temporal and spatial expression profile. Analysis of T cell receptor repertoire in transgenic mice confirms that DR3/DQ2 are able to mediate thymic selection. Furthermore, transgenic mice respond to a DR3-restricted antigen, demonstrating antigen processing and presentation by antigen-presenting cells (APC). Purified T cells from ovalbumin (OVA)-immunized 4D1 mice respond to human APC co-cultured with OVA, suggesting appropriate antigen/DR3 or DQ2 recognition by murine T cells. Immunoglobulin isotype switching is also observed, indicating functional T-B cognate interactions. Thus, the DR3/DQ2 transgenic mouse has normal lymphoid development and functionality that are mediated by HLA transgenes and can be used to investigate HLA-associated immunological questions.     

ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications

This study was undertaken in order to compare the interphase and metaphase cytogenetics of 28 patients with ETV6/RUNX1 positive acute lymphoblastic leukemia, at diagnosis and relapse. The median time to relapse was 26 months. The significant fusion positive population heterogeneity revealed at interphase by a commercial probe for ETV6/RUNX1 fusion has not been described before. Six diagnostic samples had a single abnormal population; others had up to five each, which differed in the numbers of RUNX1 signals, and in the retention or loss of the second ETV6 signal. In contrast, the number of fusion signals was more constant. At relapse, there were fewer populations; the largest or unique clone was sometimes a re-emergence of a minor, diagnostic one, with a retained copy of ETV6 and the most RUNX1 signals. Abnormal, fusion negative clones were identified in bone marrow samples at extra-medullary relapse. Variant three or four-way translocations, which involved chromosomes 12 and 21, were prominent among the complex rearrangements revealed by metaphase FISH. The frequency of their occurrence at diagnosis and reappearance at relapse, sometimes accompanied by minor clonal evolution, was another new observation. Other recurrent cytogenetic features included a second copy of the fusion signal in six cases, partial duplication of the long arm of the X chromosome in two cases, and trisomy 10 in three cases. In comparing our data with previously reported cases, a picture is beginning to emerge of certain diagnostic features, which may provide circumstantial evidence of an increased risk of relapse.