Amino acid and energy interrelationships in growing beef steers: II. Effects of energy intake and metabolizable lysine supply on growth

We conducted three experiments to determine the optimal metabolizable Lys:net energy ratio for growth of beef calves. The single basal diet fed contained corn (56.1%), soybean hulls (18%), cottonseed hulls (15%), animal fat (4.25%), and corn gluten meal (5.6%). In Exp. 1, 54 steers were individually fed the basal diet at 1.5, 2.25, and 3.0 times NEm requirement; rations were top-dressed with 3.4 g of rumen-stable (RS) Met and either 0, 2, 4, 6, 8, or 12 g of RS-Lys daily. An additional 18 steers were fed the same three levels of energy and supplemented with 125 g of blood meal per steer. In Exp. 2, 68 crossbred steers were subjected to the same experimental protocol, with the exception that only the two highest levels of energy were used. Of these steers, 48 were fed individually and received the RS-Lys treatments; the remaining 20 steers received 125 g of blood meal per steer. No interaction (P > .10) was detected between level of supplemental Lys and energy intake in Exp. 1 or 2. Supplementation with RS-Lys improved (P < .01) ADG in Exp. 1, but it had no effect (P > .10) on growth in Exp. 2. The Lys requirement estimates were 44.3 and 51.3 g/d, corresponding to maximal growth rates of 1.21 and 1.64 kg/d for the 2.25 and 3.0 times maintenance treatments, respectively. Comparing the growth rates of steers fed supplemental Lys with those of steers fed blood meal in Exp. 1 and 2 revealed an ADG advantage (P < .03) with blood meal supplementation. To confirm the blood meal response, Exp. 3 used 75 crossbred steers fed the basal diet at 3.0 times NEm requirement plus either 3.4 g RS-Met, 3.4 g RS-Met and 12 g RS-Lys, or 125 g of blood meal per steer. Blood meal supplementation improved (P < .01) growth of steers over those fed supplemental Met or Met plus Lys. Although a distinct relationship between amino acid requirements and energy supply may exist, Lys and Met were not first-limiting in these experiments, or selective supplementation with undegradable protein may have provided some factor that enhanced performance beyond that detected with Lys and Met alone.     

Fluorouracil and leucovorin with or without interferon alfa-2b in advanced colorectal cancer: analysis of a prospective randomized phase III trial. Hellenic Cooperative Oncology Group

PURPOSE: To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid [FA]) and interferon alfa-2b (IFN 2b) improves responses and survival in comparison to single modulation of 5-FU with FA. PATIENTS AND METHODS: One hundred six patients with histologically confirmed advanced colorectal cancer, measurable disease, and without previous chemotherapy were prospectively randomized into two groups. Patients in group A received 5-FU 450 mg/m2 as an intravenous bolus in the midinfusion of FA weekly. FA was given at a dose of 200 mg/m2 in 500 mL 0.9% normal saline solution in 2-hour infusion. Patients in group B received exactly the same regimen plus IFN 2b 5 million units subcutaneously three times weekly. RESULTS: All patients were well balanced in both groups regarding age, sex, performance status, number, and site of metastasis. One hundred two patients were assessable. All patients have died. There was no difference in response between the two groups (7.8% v 9.8%). Median survival was 10.1 months in group A, and 7.2 months in group B (P = .00189). Median time to progression was 8.4 and 5.2 months, respectively (P = .00196). Overall, better performance status and older age had a positive impact on survival. Toxicity was the most important and catastrophic aspect of this study. Patients who received IFN 2b had significantly worse anemia, neutropenia, diarrhea, anorexia, weight loss, flu-like syndrome, and psychological reactions. CONCLUSION: Based on this final analysis, the addition of IFN 2b to the combination of 5-FU and FA enhances toxicity and contributes to decreased survival.     

Radiation down-regulates replication origin activity throughout the S phase in mammalian cells

An asynchronous culture of mammalian cells responds acutely to ionizing radiation by inhibiting the overall rate of DNA replication by approximately 50% for a period of several hours, presumably to allow time to repair DNA damage. At low and moderate doses, this S phase damage-sensing (SDS) pathway appears to function primarily at the level of individual origins of replication, with only a modest inhibition of chain elongation per se. We have shown previously that the majority of the inhibition observed in an asynchronous culture can be accounted for by late G1cells that were within 2-3 h of entering the S period at the time of irradiation and which then fail to do so. A much smaller effect was observed on the overall rate of replication in cells that had already entered the S phase. This raised the question whether origins of replication that are activated within S phase per se are inhibited in response to ionizing radiation. Here we have used a two-dimensional gel replicon mapping strategy to show that cells with an intact SDS pathway completely down-regulate initiation in both early- and late-firing rDNA origins in human cells. We also show that initiation in mid- or late-firing rDNA origins is not inhibited in cells from patients with ataxia telangiectasia, confirming the suggestion that these individuals lack the SDS pathway.     

A molecular mechanism for electrical tuning of cochlear hair cells

Cochlear frequency selectivity in lower vertebrates arises in part from electrical tuning intrinsic to the sensory hair cells. The resonant frequency is determined largely by the gating kinetics of calcium-activated potassium (BK) channels encoded by the slo gene. Alternative splicing of slo from chick cochlea generated kinetically distinct BK channels. Combination with accessory beta subunits slowed the gating kinetics of alpha splice variants but preserved relative differences between them. In situ hybridization showed that the beta subunit is preferentially expressed by low-frequency (apical) hair cells in the avian cochlea. Interaction of beta with alpha splice variants could provide the kinetic range needed for electrical tuning of cochlear hair cells.     

Colocalisation of taurine- with transmitter-immunoreactivities in the nervous system of the migratory locust

The validity of whiplash syndrome has been a source of debate in the medical literature for many years. Some authors have published articles suggesting that whiplash injuries are impossible at certain collision speeds; others have stated that the problem is psychological, or is feigned as a means to obtain secondary financial gain. These articles contradict the majority of the literature, which shows that whiplash injuries and their sequelae are a highly prevalent problem that affects a significant proportion of the population. The authors of the current literature critique reviewed the biomedical and engineering literature relating to whiplash syndrome, searching for articles that refuted the validity of whiplash injuries. Twenty articles containing nine distinct statements refuting the validity of whiplash syndrome were found that fit the inclusion criteria. The methodology described in these articles was evaluated critically to determine if the authors' observations regarding the validity of whiplash syndrome were scientifically sound. The authors of the current critique found that all of the articles contained significant methodologic flaws with regard to their respective authors' statements refuting the validity of whiplash syndrome. The most frequently found flaws were inadequate study size, nonrepresentative study sample, nonrepresentative crash conditions (for crash tests), and inappropriate study design. As a result of the current literature review, it was determined that there is no epidemiologic or scientific basis in the literature for the following statements: whiplash injuries do not lead to chronic pain, rear impact collisions that do not result in vehicle damage are unlikely to cause injury, and whiplash trauma is biomechanically comparable with common movements of daily living.