Short-term effects of thyroid hormones on the Na/H antiport in L-6 myoblasts: high molecular specificity for 3,3',5-triiodo-L-thyronine

The thyroid hormones L-T3 and L-T4 were shown to activate the Na/H antiport in L-6 cells from rat skeletal muscle by a rapid, nongenomic mechanism. Under pH equilibrium conditions, a significant rise in the intracellular pH, measured by the fluorescent pH indicator 2',7'-bis-(carboxyethyl)-5(6)-carboxyfluorescein was observed after the addition of physiological concentrations (10(-10) M) of either L-T3 or L-T4, but with different time courses. L-T3 at all concentrations increased the pH after a delay of 2 min, whereas L-T4 showed a concentration-dependent lag time, going from 11 min at 10(-11) M down to 5 min for a hormone concentration of 10(-6) M. The effect of L-T4 was blocked in the presence of the 5'-deiodinase inhibitor 6-n-propyl-2-thiouracil, suggesting that the difference in lag time between L-T3 and L-T4 was due to the 5'-deiodination process that transforms L-T4 into the bioactive L-T3. In short term studies (<5 min), a high molecular specificity for L-T3 was found, as L-T4, rT3, the D-isomer of T3, and the deaminated analogues were ineffective at physiological concentrations. In analogy with the results found at equilibrium, intracellular pH recovery from an acid load and set-point were increased after 2 min for L-T3 (10(-9) M) and after 10 min for L-T4 (10(-9) M). The effect of the hormones on the intracellular pH was completely blocked by the specific antiport inhibitor 5-(ethyl-N-isopropyl)amiloride. These findings suggest that thyroid hormones may play an active role in the recovery from muscular acidosis through direct stimulation of the Na/H antiport.     

Artificial neural networks in cancer research

Current therapy does not cure the majority of patients with B cell non-Hodgkin's lymphoma (NHL) and further intensification does not benefit the patient. Therefore, new approaches are necessary. Immunotherapy has become again a major interest as a new treatment modality for B cell lymphoma since the discovery that the lymphoma specific Id can be presented to antigen-specific T cells. Vaccination of the tumour-bearing host is one of the major strategies to induce a T cell mediated anti-tumour immunity in vivo. For B cell lymphomas the lymphoma specific Id can be used as a tumour-specific antigen to stimulate T cells. Alternatively, the malignant B cells can be modified to become efficient antigen presenting cells (APCs) and present peptides from their own tumour-specific antigens to the autologous T cells. Currently explored and future vaccination strategies for B cell lymphoma will be discussed here.     

Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity

Activation of the Cdc2.cyclin B kinase is a pivotal step of mitotic initiation. This step is mediated principally by the dephosphorylation of residues threonine 14 (Thr14) and tyrosine 15 (Tyr15) on the Cdc2 catalytic subunit. In several organisms homologs of the Wee1 kinase have been shown to be the major activity responsible for phosphorylating the Tyr15 inhibitory site. A membrane-bound kinase capable of phosphorylating residue Thr14, the Myt1 kinase, has been identified in the frog Xenopus laevis and more recently in human. In this study, we have examined the substrate specificity and cell cycle regulation of the human Myt1 kinase. We find that human Myt1 phosphorylates and inactivates Cdc2-containing cyclin complexes but not complexes containing Cdk2 or Cdk4. Analysis of endogenous Myt1 demonstrates that it remains membrane-bound throughout the cell cycle, but its kinase activity decreased during M phase arrest, when Myt1 became hyperphosphorylated. Further, Cdc2. cyclin B1 was capable of phosphorylating Myt1 in vitro, but this phosphorylation did not affect Myt1 kinase activity. These findings suggest that human Myt1 is negatively regulated by an M phase-activated kinase and that Myt1 inhibits mitosis due to its specificity for Cdc2.cyclin complexes.     

Effects of fat supplementation and immature alfalfa to concentrate ratio on plasma progesterone, energy balance and reproductive traits of dairy cattle

Forty-six multiparous Holstein cows were assigned at 5 d postpartum to a completely randomized design employing a 2 x 3 factorial arrangement of treatments. Factors were 0 and 5% added prilled long-chain fatty acids (DM basis) and three forage to concentrate ratios (45:55, 64:36, 84:16). Diets consisted of immature alfalfa silage and a concentrate of shelled corn and soybean meal with or without fat replacing a portion of the corn. Mean plasma concentration of cholesterol was higher for cows fed 5% vs. 0% fat and increased over the first 100 d in milk for all animals regardless of treatment. There were no differences in reproductive performance due to either of the main effects. Mean plasma progesterone was higher due to fat treatment in the mid to late luteal phase of the second postpartum cycle as well as the metestrous to early luteal phase and mid to late luteal phase of the third cycle. Even though progesterone concentrations were higher in cows fed 5% fat during the luteal phase after breeding, the conception rates at this service were not different from those fed 0% fat. The biological significance of increased plasma progesterone concentration was not identified with any postpartum reproductive trait measured in this trial.     

Dry bean tannins: A review of nutritional implications

Tannins are one of several antinutritional factors present in dry beans and are located mainly in the seed coat or testa. The tannin content of dry beans ranges from 0.0 to 2.0% depending on the bean species and color of the seed coat. Many high tannin bean varieties are of lower nutritional quality than low tannin varieties of beans. Naturally occurring food legume tannins are reported to interact with proteins (both enzyme and nonenzyme proteins) to form tannin-protein complexes resulting in inactivation of digestive enzymes and protein insolubility. Both in vitro and in vivo studies indicate that bean tannins decrease protein digestibility, either by inactivating digestive enzymes or by reducing the susceptibility of the substrate proteins after forming complexes with tannins and absorbed ionizable iron. Other deleterious effects of tannins include a lowered feed efficiency and growth depression in experimental animals. The antinutritional activity of bean tannins can be reduced by processing (1 or a combination of 2 or more methods), for example dehulling, soaking, cooking and germination. Genetic selection also may help in breeding varieties low in tannins. Potential chemical treatments such as use of tannin complexing agents are discussed. Presented at the AOCS Meeting, Dallas, Texas, April 1984.     

Efficacy of ultraviolet light for reducing Escherichia coli O157:H7 in unpasteurized apple cider

This study examined the efficacy of UV light for reducing Escherichia coli O157:H7 in unpasteurized cider. Cider containing a mixture of acid-resistant E. coli O157:H7 (6.3 log CFU/ml) was treated using a thin-film UV disinfection unit at 254 nm. Dosages ranged from 9,402 to 61,005 microW-s/cm2. Treatment significantly reduced E. coli O157:H7 (P < or = 0.0001). Mean reduction for all treated samples was 3.81 log CFU/ml. Reduction was also affected by the level of background microflora in cider. Results indicate that UV light is effective for reducing this pathogen in cider. However, with the dosages used in this experiment, additional reduction measures are necessary to achieve the required 5-log reduction.     

Probiotic effects of feeding heat-killed Lactobacillus acidophilus and Lactobacillus casei to Candida albicans-colonized immunodeficient mice

Probiotic bacteria can protect immunodeficient mice from orogastric candidiasis but cause some pathology of their own. Severely immunodeficient patients may be at risk if fed viable probiotics, so this study evaluated the probiotic potential of nonviable probiotic bacteria to protect immunodeficient mice from Candida albicans infections. Heat-killed probiotic bacteria were fed to gnotobiotic bg/bg-nu/nu and bg/bg-nu/+ mice to ascertain if they could protect the mice from mucosal and systemic candidiasis. Both heat-killed Lactobacillus acidophilus (HKLA) and heat-killed Lactobacillus casei (HKLC), in comparison to control mice not fed the probiotic bacteria but challenged (oral) with C. albicans, suppressed the severity of orogastric candidiasis in bg/bg-nu/nu mice at 2 weeks after colonization with C. albicans, inhibited disseminated candidiasis in C. albicans-colonized bg/bg-nu/+ mice at 4 weeks after colonization, and suppressed the number of viable C. albicans in the alimentary tract. HKLA, but not HKLC, treatment inhibited disseminated candidiasis in bg/bg-nu/nu mice at 2 weeks after oral challenge and enhanced the proliferative responses of splenocytes from C. albicans-colonized bg/bg-nu/+ mice to C. albicans antigens. Neither HKLA nor HKLC were able to prolong the survival of gnotobiotic bg/bg-nu/nu mice after oral challenge with C. albicans. These results demonstrate that heat-killed lactobacilli can induce some (limited) protection (probiotic effect) against candidiasis in mice.