The use of fiber concentrations for ration formulation

Dairy cattle require fibrous feedstuffs in the diet. However, defining the fiber requirements requires knowledge of many interacting components within the diet as well as how the feed is allocated and processed. To meet the demands of high producing dairy cows for energy, diets consist of large quantities of concentrates and high quality forages containing relatively low amounts of fiber. However, to maintain normal rumen function and milk fat percentage, a large portion of the fiber needs to come from forage. Current National Research Council recommendations are a minimum of 25 to 28% dietary neutral detergent fiber, 75% of which is supplied from forage. Chemical measures of fiber alone are not adequate for ration balancing; fiber varies in its effectiveness at stimulating chewing. This variation is greater when feeds contain high amounts of by-products in place of forages. The effectiveness in stimulation of chewing of fiber is variable as the particle size and retention times of indigestible and digestible fiber vary. Currently, little information exists about the fiber requirements of the cow from immediately postcalving until peak lactation. Early lactation cows are clearly more limited by physical fill than are cows in mid and late lactation. Rations based on nonforage fiber sources (> 45% neutral detergent fiber on a dry matter basis) are being evaluated for early lactation cows. Information is needed to determine the variation in the amount of fermentation acids produced, chewing activity, and amount of saliva secreted as these all contribute to the physical effectiveness of fiber.     

Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCalpha-inhibitory activity

In a continuation of our search for potential tumor inhibitors from plants, it was found that the CH2Cl2-MeOH (1:1) extracts from Digitalis purpurea and Penstemon linarioides both showed PKCalpha-inhibitory bioactivity. Bioassay-directed fractionation of the extract from D. purpurea yielded the new, weakly active phenylethanoid glycoside 2-(3-hydroxy-4-methoxy-phenyl)-ethyl-O-(alpha-L-rhamnosyl)-(1-->3) -O- (alpha-L-rhamnosyl)-(1-->6)-4-O-E-feruloyl-beta-D-glucopy ran oside (1) together with the four known compounds calceolarioside A (2), calceolarioside B (3), forsythiaside (4), and plantainoside D (5). The extract from P. linarioides yielded the three known glycosides leucosceptoside A (6), acteoside (7), and poliumoside (8), together with the iridoid plantarenaloside (9). All of the isolated compounds, except compound 9, showed inhibitory activity against PKCalpha with IC50 values (in microM) of 125 (1), 0.6 (2), 4.6 (3), 1.9 (4), 14.8 (5), 19.0 (6), 9.3 (7), and 24.4 (8).     

Antigen loss variants of a murine renal cell carcinoma: implications for tumor vaccination

Chronic graft-versus-host disease (GvHD) in mice is a model resembling glomerulonephritis in human systemic lupus erythematosus. In the present study congenic mouse strains were used to investigate the pathogenetic role of (1) donor T cell subset chimerism and (2) donor thymocytes in this model. In GvHD employing minor lymphocyte-stimulating-1 (Mls-1)-compatible donors and recipients, full-blown immune complex glomerulonephritis was associated with a low-donor CD8(+) T cell chimerism. Injection of lymphocytes from Mls-1-negative donors (Mls-1(b)) into Mls-1-positive recipients (Mls-1(a)) induces a type of GvHD characterized by rapid self-limitation accompanied by the immediate inhibition of donor T cell chimerism and the absence of glomerulonephritis. However, omission of thymocytes from the donor inoculate does result in glomerular depositions containing immunoglobulins. These results suggest that donor CD8(+) T cell chimerism is associated with attenuation of immune complex glomerulonephritis, whereas Mls-1-incompatible donor T cell precursors prevent the disease.     

Myocardial uptake and redistribution of 99mTc-N-NOET in dogs with either sustained coronary low flow or transient coronary occlusion: comparison with 201Tl and myocardial blood flow

BACKGROUND: 99mTc-N-NOET (NOET) is a new myocardial perfusion imaging agent that redistributes over time. We sought to better define the redistribution kinetics of NOET using open-chest canine models of sustained low coronary flow (protocol 1) and transient coronary occlusion followed by reflow (protocol 2). METHODS AND RESULTS: In protocol 1 (n=10), NOET and 201Tl were injected during low flow in the left anterior descending coronary artery (LAD) that was sustained for 2 hours. Protocol 2 dogs (n=6) were injected with NOET during 20 minutes of LAD occlusion followed by 2 hours of reflow. In both protocols, serial NOET planar images were acquired, and myocardial flow and 2-hour tracer activities were determined by gamma-well counting. Defect resolution was observed on images in both protocols. Initial defect count ratios, reflecting flow disparity at injection (0.66+/-0.03 and 0.57+/-0.04, respectively), increased over 2 hours (0.73+/-0.02 and 0.75+/-0.04, respectively; P<.001 versus initial). Quantitative imaging showed that NOET redistribution resulted from greater clearance from normal areas versus low-flow or transiently occluded areas. In protocol 1, 2-hour NOET and 201Tl stenotic-to-normal tissue activity ratios were similar (0.76+/-0.06 versus 0.73+/-0.04, P=NS) and higher than injection flow ratios (0.52+/-0.06 and 0.56+/-0.07, respectively, P<.001), consistent with tracer redistribution. In protocol 2, NOET redistributed to an even greater extent (injection flow ratio, 0.27+/-0.04; 2-hour tissue activity ratio, 0.84+/-0.03, P<.001). CONCLUSIONS: NOET is the first 99mTc-labeled myocardial imaging agent with kinetics similar to 201Tl in experimental models, permitting redistribution imaging. NOET appears to be a promising agent for assessing patients with coronary artery disease.     

Selective expansion of activated V delta 4+ cells during experimental infection of mice with Leishmania major

Previous work from this laboratory has revealed that infection of mice with Leishmania major leads to an expansion of gamma delta+ T cells in the spleen. Further examination of the gamma delta+ T cells expanding in infected mice has shown that the majority of these cells in the spleen, lymph nodes, blood and liver expressed the V delta 4 gene segment. Cell cycle analysis, using propidium iodide incorporation, demonstrated that while only 1% of alpha beta+ T cells in the spleen were in either S + G2/M phase, up to 10% of the gamma delta+ T cells were in cycling phase 8 weeks after infection. Comparison of the state of activation of the two populations in different organs after infection, confirmed that gamma delta+ T cells are actively dividing in lymph nodes, liver and blood, but not in the thymus or among intraepithelial lymphocytes. Examination of the expression of different activation markers on the surface of gamma delta+ T cells in the spleen of both normal and chronically infected BALB/c mice by FACS analysis, revealed increased expression of LFA-1, CD25, CD44, 4F2, CD28 and the heat-stable antigen, whereas Thy-1 and CD5 decreased. Collectively, these results suggest an oligoclonal expansion and activation of gamma delta+ T cells in response to L. major infection.     

MR imaging of the anal sphincter in multiparous women using an endoanal coil: correlation with in vitro anatomy and appearances in fecal incontinence

OBJECTIVE: The aim of this study was to correlate the components of the normal female anal sphincter seen on high-resolution MR images with the in vitro anatomy and to describe the change in appearances of these components in multiparous women with fecal incontinence. SUBJECTS AND METHODS: Ten asymptomatic female volunteers (32-72 years old; mean, 54 years old) and 22 women with fecal incontinence were studied. In six patients (26-68 years old; mean, 49 years old) fecal incontinence began immediately after childbirth; in the remaining 16 patients (45-77 years old; mean, 58 years old) fecal incontinence developed 15- 30 years after childbirth. In the latter group of patients, terminal motor latencies of the pudendal nerve were measured. Imaging was done on a 0.5-T Picker Asset unit and on a 1.0-T Picker HPQ unit. A saddle geometry endoanal receiver coil was used for all imaging. T1-weighted spin-echo (720-820/20 [range of TR/TE]), T2-weighted spin-echo (2500/80 [TR/TE]), fast spin-echo (4500/96 [TR/ effective TE]), and short inversion time inversion recovery (2500/80 [TR/TE]; inversion time, 107 msec) MR images were obtained in transverse, coronal oblique, and sagittal planes. Images were assessed for integrity of the sphincter components. A nonpaired separate-variance t test was used to compare thickness of individual muscle components between patients with delayed-onset fecal incontinence and asymptomatic age-matched volunteers. Degree of muscle atrophy was correlated with degree of delay in the terminal motor latency of the pudendal nerve. RESULTS: The high resolution obtained with an endoanal coil allowed differentiation of the various muscle components of the anal sphincter complex. The internal sphincter was seen as a ring of homogeneously high signal intensity with a low-signal-intensity rim that was rich in collagen and contained neurovascular bundles. The external anal sphincter, which had low signal intensity on T1- and T2-weighted images, was shown as three components: subcutaneous, superficial, and deep. In six patients who had fecal incontinence that began immediately after childbirth, endoanal MR imaging revealed the site and extent of a tear. All tears were confirmed at surgery. In the 16 patients who had fecal incontinence that began several years after childbirth, atrophy of the external sphincter was revealed in all cases in the superficial and deep components. The internal sphincter remained normal. However, we found that the degree of atrophy of individual components of the external sphincter did not correlate with the degree of delay in pudendal nerve conduction. CONCLUSION: MR imaging with an endoanal coil reveals the integrity and bulk of individual muscle components of the anal sphincter in multiparous women with fecal incontinence.     

Cumulative impact of sustained economic hardship on physical, cognitive, psychological, and social functioning

BACKGROUND: Although the relation between low income and poor health is well established, most previous research has measured income at only one time. METHODS: We used income information collected in 1965, 1974, and 1983 from a representative sample of adults in Alameda County, California, to examine the cumulative effect of economic hardship (defined as a total household income of less than 200 percent of the federal poverty level) on participants who were alive in 1994. RESULTS: Because of missing information, analyses were based on between 1081 and 1124 participants (median age, 65 years in 1994). After adjustment for age and sex, there were significant graded associations between the number of times income was less than 200 percent of the poverty level (range, 0 to 3) and all measures of functioning examined except social isolation. As compared with subjects without economic hardship, those with economic hardship in 1965, 1974, and 1983 were much more likely to have difficulties with independent activities of daily living (such as cooking, shopping, and managing money) (odds ratio, 3.38; 95 percent confidence interval, 1.49 to 7.64), activities of daily living (such as walking, eating, dressing, and using the toilet) (odds ratio, 3.79; 95 percent confidence interval, 1.32 to 9.81), and clinical depression (odds ratio, 3.24; 95 percent confidence interval, 1.32 to 7.89) in 1994. We found little evidence of reverse causation -- that is, that episodes of illness might have caused subsequent economic hardship. CONCLUSIONS: Sustained economic hardship leads to poorer physical, psychological, and cognitive functioning.     

Core fucosylation of high-mannose-type oligosaccharides in GlcNAc transferase I-deficient (Lec1) CHO cells

During studies on the fucosylation of endogenous proteins in parental (Pro5) and N-acetyl-D-glucosamine (GlcNAc) transferase I-deficient (Lec1) Chinese hamster ovary (CHO) cells, we observed that Lec1 cells incorporate approximately 10-fold less [3H]fucose into macromolecules than Pro5 cells. Interestingly, most of the labelled oligosaccharides from both cell types could be released from the macromolecules by digestion with peptide N-glycosidase F (PNGase F). This was unexpected for Lec1 cells because they do not synthesize complex- or hybrid-type N-glycans. Structural analyses of the fucosylated oligosaccharides from Lec1 cells showed the fucose to be in an alpha 1,6 linkage to the core GlcNAc of relatively small oligomannose N-glycans (Man4GlcNAc2 and Man5GlcNAc2, where Man is D-mannose). Comparing the sizes of oligomannose N-glycans from Pro5 and Lec1 cells demonstrated a much higher proportion of the small (Man4GlcNAc2 and Man5GlcNAc2) oligomannose species in Lec1 cells. These results suggest that the core alpha 1,6 fucosyltransferase will fucosylate small (Man4-Man5GlcNAc2), but not large (Man8-Man9GlcNAc2) oligomannose N-glycans.