Butting by calves, Bos taurus, and rate of milk flow

During nursing, the young of many ungulates butt at their dams' udder, which has been hypothesized to reflect difficulty obtaining milk. We investigated the effect of manipulating milk flow rate on the butting behaviour of domestic calves sucking milk from an artificial teat. The lowest rate of butting during nutritive sucking occurred with the fastest flow rate, and the highest rate of butting occurred with the slowest flow rate. When milk flow rate was changed during a meal, calves butted more following a decrease in flow rate than following an increase in flow rate. Butting rates were consistent and relatively low with a constant flow of milk. Regardless of flow rate, calves butted more at the beginning of their meal compared with the middle and end. Overall, the highest butting rate occurred when milk flow stopped, either at the end of the meal or when milk flow during the meal was stopped repeatedly for 30-s periods. We conclude that calves are sensitive to variations in milk flow rate and that butting rate changes accordingly. The occurrence of butting by young ungulates during nursing thus may indicate either a stoppage of milk flow or a decrease in milk flow rate, and thus may help identify periods of nonnutritive sucking during nursing. (c) 1998 The Association for the Study of Animal Behaviour.     

Tourette''s syndrome: [I-123]beta-CIT SPECT correlates of vocal tic severity

Frostbite injuries have traditionally been treated with expectant observation. With the exception of early blister aspiration tissues are allowed to demarcate before definitive debridement is accomplished. Triple-phase bone scanning has been used to define the extent of fatally damaged tissues in an attempt to allow for early debridement and wound closure. We suggest extending this technology to assess injury and direct debridement in patients for whom early aggressive salvage attempts are indicated. We present two cases in which triple-phase scanning was used to direct early debridement for aggressive limb salvage with flap reconstruction. Bone, ligament, tendon, and nerve were preserved and covered with vascularized tissue before the onset of frank necrosis. Postoperative scans reveal revascularization of these tissues. An algorithm incorporating triple-phase scanning for the evaluation and treatment of frostbite is presented.     

Resonance Raman spectral properties and stability of manganese protoporphyrin IX cytochrome b5

The structure and stability of cytochrome b5 reconstituted with manganese protoporphyrin IX instead of iron protoporphyrin IX has been investigated by resonance Raman spectroscopy and stopped-flow visible spectroscopy. The resonance Raman spectrum of MnIII cytochrome b5 was consistent with a high-spin hexacoordinate MnIII protoporphyrin IX structure that converted to a high-spin pentacoordinate structure at higher laser power. The resonance Raman spectrum of MnII cytochrome b5 indicated a high-spin pentacoordinate structure which was independent of laser power. Studies of the binding of MnIII protoporphyrin IX to apocytochrome b5 indicated that the MnIII-containing porphyrin bound much less tightly to the protein than did heme. Although the second-order rate constant at 20 degrees C for the association of heme with apocytochrome b5 (4.5 x 10(7) M(-1) s(-1)) was estimated to be only 1 order of magnitude higher than that with Mn protoporphyrin IX (3.3 x 10(6) M(-1) s(-1)), the dissociation of manganese substituted cytochrome b5 into the apoprotein and free Mn protoporphyrin IX occurs with a first-order rate constant of 1.2 x 10(-2) s(-1) at 20 degrees C while the dissociation of heme from cytochrome b5 at room temperature occurs 3 orders of magnitude more slowly with a first-order rate constant of 1.67 x 10(-5) s(-1) [Vergeres, G., Chen, D. Y., Wu, F.F., & Waskell, L. (1993) Arch. Biochem. Biophys. 305, 231-241]. The equilibrium dissociation constant for manganese-substituted cytochrome b5 increased with temperature from 4 nM at 20 degrees C to 14 nM at 37 degrees C. These results suggest that, in the reconstituted cytochrome P450 metabolizing system, especially in studies done with low protein concentrations (0.1 microM), and at elevated temperatures (37 degrees C), as much as 30% of the manganese-substituted cytochrome b5 may dissociate to free Mn-protoporphyrin IX and apocytochrome b5.     

T cells reactive to a single immunodominant self-restricted allopeptide induce skin graft rejection in mice

Alloreactive T lymphocytes can respond to foreign MHC complexed with foreign peptides through the direct pathway of allorecognition and can additionally recognize allopeptides expressed in the context of recipient (self) MHC through the indirect pathway. To better elucidate how indirect pathway-responsive CD4(+) T cells mediate allograft rejection, we isolated and characterized a TH1 T cell line from BALB/c recipients of B10.A skin that responds to a defined immunodominant, self-restricted allopeptide, I-Abetak58-71. When transferred into BALB/c severe combined immunodeficiency recipients of B10.A skin allografts, this cell line specifically induced a form of skin graft rejection characterized by the presence of TH1 cytokines, macrophage infiltration, and extensive fibrosis. Recall immune responses and immunofluorescence of the rejecting skin revealed only the presence of the peptide-specific T cells within the recipient animals, with no evidence of a direct pathway alloresponse. These studies demonstrate that T cells reactive to a single self-restricted allopeptide can mediate a form of allogeneic skin graft rejection that exhibits characteristics of a chronic, fibrosing process.     

Cytotoxic activities of Mannich bases of chalcones and related compounds

Various Mannich bases of chalcones and related compounds displayed significant cytotoxicity toward murine P388 and L1210 leukemia cells as well as a number of human tumor cell lines. The most promising lead molecule was 21 that had the highest activity toward L1210 and human tumor cells. In addition, 21 exerted preferential toxicity to human tumor lines compared to transformed human T-lymphocytes. Other compounds of interest were 38, with a huge differential in cytotoxicity between P388 and L1210 cells, and 42, with a high therapeutic index when cytotoxicity to P388 cells and Molt 4/C8 T-lymphocytes were compared. In general, the Mannich bases were more cytotoxic than the corresponding chalcones toward L1210 but not P388 cells. A ClusCor analysis of the data obtained from the in vitro human tumor screen revealed that the mode of action of certain groups of compounds was similar. For some groups of compounds, cytotoxicity was correlated with the sigma, pi, or molar refractivity constants in the aryl ring attached to the olefinic group. In addition, the IC50 values in all three screens correlated with the redox potentials of a number of Mannich bases. X-ray crystallography and molecular modeling of representative compounds revealed various structural features which were considered to contribute to cytotoxicity. While a representative compound 15 was stable and unreactive toward glutathione (GSH) in buffer, the Mannich bases 15, 18, and 21 reacted with GSH in the presence of the pi isozyme of glutathione S-transferase, suggesting that thiol alkylation may be one mechanism by which cytotoxicity was exerted in vitro. Representative compounds were shown to be nonmutagenic in an intrachromosomal recombination assay in yeast, devoid of antimicrobial properties and possessing anticonvulsant and neurotoxic properties. Thus Mannich bases of chalcones represent a new group of cytotoxic agents of which 21 in particular serves as an useful prototypic molecule.     

Retrospective and prospective analyses of the treatment of overanticoagulated patients

STUDY OBJECTIVE: To compare withholding warfarin therapy with low-dose (2.5 mg) oral vitamin K therapy in excessively anticoagulated patients without bleeding complications. DESIGN: Prospective and retrospective studies. SETTING: Anticoagulation clinic at a Veterans Affairs institution. PATIENTS: Twenty-eight men were matched according to initial international normalized ratio (INR) and INR goal ranges. INTERVENTIONS: The retrospective arm of the study consisted of chart reviews of overanticoagulated patients whose warfarin doses were held until therapeutic INR values were reached. The prospective arm included overanticoagulated patients who were administered a single 2.5-mg dose of oral vitamin K. MEASUREMENTS AND MAIN RESULTS: Mean days to therapeutic INR values were 2.3+/-0.6 and 1.4+/-0.6 (p=0.001), and mean reduction in INR 1 day after treatment intervention was 1.32+/-0.79 and 3.46+/-1.31 (p<001) U for the withholding and vitamin K groups, respectively. CONCLUSION: Compared with withholding the warfarin dose, administration of 2.5 mg of oral vitamin K to excessively anticoagulated patients receiving warfarin significantly reduced the time required to reach a therapeutic INR as well as final INR.     

Biodistribution of 125I-labeled des(1-3) insulin-like growth factor I in tumor-bearing nude mice and its in vitro catabolism

Insulin-like growth factor I (IGF-I) is a potent mitogen for many tumor cell lines, and IGF-I receptors are overexpressed in many tumors. Specific IGF-binding proteins (IGFBPs) modulate the interaction of IGF and its receptors. Consequently, radiolabeled IGF-I has been considered for tumor imaging. In the present study, we investigated the biodistribution of 125I-labeled des(1-3)IGF-I, a truncated analogue of IGF-I, in tumor-bearing nude mice. Additional studies included its catabolism by tumor cells in vitro and its binding to serum IGFBPs in vivo in nude mice. We also compared groups that were and were not injected with unlabeled peptide analogue. Our data showed that 125I-labeled des(1-3)IGF-I catabolized very fast, with a rapid appearance of nonprecipitable iodine, when incubated at 37 degrees C, but it was not catabolized at 4 degrees C incubation. 125I-labeled des(1-3)IGF-I was bound to serum-binding proteins, mainly in a complex with a molecular weight of M(r) 150,000. The uptake of radioactivity in normal tissues decreased quickly with time, particularly in the kidneys. In mice receiving higher doses of des(1-3)IGF-I, the radioactivity in all normal tissues was lower than in the mice with no carrier-added des(1-3)IGF-I, except in the stomach and spleen. These data suggest that 125I-labeled des(1-3)IGF-I is rapidly internalized after binding to the IGF receptor and is rapidly catabolized with release of breakdown products. Lower specific activity of 125I-labeled des(1-3)IGF-I resulted in altered biodistribution, including faster blood clearance and higher tumor uptake, by decreasing the formation of complexes with IGFBPs.     

Physical development of children under conditions of formation of a new social structure of the population

The relaxing effects of local heat-air exposures (TAE) on man (60 male students aged 19-21 years) were studied using a specially designed device which may control temperatures and time on an individual basis depending on the examinees' sensation of a positive emotion. On study days and under examination stress. TAE was shown to reduce situation-induced anxiety, to increase the duration and variability of R-R intervals on ECG, to make EEG right-frontal delta- and theta-indices lower and EEG right occipital and frontal alpha-index higher. The range of visual accommodation increased. The findings suggest that the proposed graded local heat-air exposure procedure is an effective tool of relaxation and prevention of negative effects of emotional stress.