Fluid and carbohydrate replacement during intermittent exercise

The reticular formation of the brainstem contains premotor systems for various musculomotor systems. In this paper, the bulbar premotor systems for jaw and tongue movements, head and neck movements, locomotion, and respiration and vocalization in birds are reviewed and compared to premotor systems in mammals. Roughly, the bulbar reticular formation can be subdivided in three longitudinal zones: a dorsolateral (RPcdl) and a ventromedial (RPcvm) parvocellular zone and a gigantocellular zone (RGc). RPcdl contains premotor neurons for the jaw and neck system, RPcvm for the jaw, tongue and neck system, and RGc for the tongue and locomotory system. RPcdl receives input from the descending sensory trigeminal system, parts of RPcvm and RGc from vestibular nuclei, whereas the tectum has a projection to the contralateral RGc. RPcdl and RPcvm receive substantial telencephalic input through the occipitomesencephalic tract. The bulbar part of the respiratory system consists of a series of cell groups in the ventrolateral reticular formation and has connections with motor centers of the vocalization system. The similarities and differences between the avian and mammalian situation are discussed. Musculomotor systems participate in various activities. It is argued that a premotor system should possess sufficient flexibility to control the participation of a motor system in the different activities. This flexibility may permit the occurrence of learning processes in terms of refining basically existing motor patterns. The emergence of new and more complex motor patterns as in vocalization requires the involvement of hierarchically higher brain centers.     

LaNiO3 and Cu3Ge contacts to YBa2Cu3O7-x films

Metallization of high-T_c superconductors using low resistivity metal oxides and Cu-Ge alloys has been investigated on high quality pulsed laser deposited epitaxial YBa₂Cu₃O_7-x (YBCO) films. Epitaxial LaNiO₃ (LNO) thin films have been grown on YBCO films at 700°C using pulsed laser deposition. The specific resistivity of LNO was measured to be 50 μΩ-cm at 300K which decreases to 19 μΩ-cm at 100K indicating good metallicity of the LNO films. The contact resistance of LNO-YBCO thin film interface was found to be reasonably low (of the order of 10^-4Ω-cm² at 77K) which suggests that the interface formed between the two films is quite clean and LNO can emerge as a promising metal electrode-material to YBCO films. A preliminary investigation related to the compatibility of Cu₃Ge alloy as a contact metallization material to YBCO films is discussed. The usage of other oxide based low resistivity materials such as SrRuO₃ (SRO) and SrVO₃ (SVO) for metallization of high-T_c YBCO superconductor films is also discussed.     

Investigation of protein folding by mass spectrometry

Bone repair by regeneration as we know it continues to undergo changes, with advances approaching that may change our treatment of patients with craniofacial deformities and skeletal defects. Perhaps by the turn of the century, patients born with asymmetric deformities due to lack of growth will be treated early in life by skeletal stretching, and then later in life by skeletal distraction that is followed by use of accelerating factors to assist the healing processes. All of these available modalities are part of the regeneration of new bone formation. The future of such changes is very interesting, and our ability to help our patients will be maximized. We may even look back 25 years from now at bone grafting and find it to be obsolete and crude. It is hoped that with the new modalities being developed, we will not deviate from the use of a bone grafting procedure, which is the workhorse of the craniofacial surgeon. Bone grafting is used by all surgeons working on the craniofacial skeleton despite the problems of unpredictability of healing and an inability to calculate what percentage of the original graft will survive. The transplantation issue will be solved. The problems with donor site morbidity will continue. The use of inorganic bone substitutes will continue to have its limitation, particularly in type II wounds, which we as plastic surgeons see in the craniofacial region. As we redefine our approach to skeletal repair, we may look back and find solutions to some of the major problems we have had. The rapid stretch of soft tissue after facial advancement or structural alteration that is accompanied by a relapse due to the elastic recoil of the soft tissue could be eliminated by gradual distraction. The bone will undergo better functional adaptation when it has a gradual change in structure based on adjustment and molding in a gradual fashion. The problem of donor site morbidity and a prediction formula for bone could be resolved with new bone formation in situ by mineralization of the area under repair. Bone healing enhancers are here to stay and their clinical application will produce a far-reaching better final outcome (Fig. 11).     

Formation of topoisomerase II alpha complexes with nascent DNA is related to VM-26-induced cytotoxicity

Several clinically active anticancer drugs are known to interfere with DNA topoisomerase II activity. However, the importance of the individual alpha (170 kDa) and beta (180 kDa) isozymes as targets of topoisomerase II-active drugs is not clear. To address this question, human CCRF-CEM leukemia cells were incubated with bromodeoxyuridine, and either the nascent DNA or bulk DNA not undergoing replication was purified by immunoprecipitation with an anti-bromodeoxyuridine antibody. The topoisomerase II isozymes that coprecipitated with either the nascent DNA or bulk DNA were analyzed by Western blotting. The alpha isozyme formed complexes with nascent DNA in cells pretreated with either VM-26 or mitoxantrone, while the beta isozyme was only bound to bulk DNA. At moderately cytotoxic concentrations, VM-26 enhanced the binding of topoisomerase II alpha to nascent DNA at least 5.2-fold compared to bulk DNA. However, in VM-26 resistant CEM/VM-1 cells incubated with equitoxic concentrations of VM-26, topoisomerase II alpha complex formation with nascent DNA was decreased at least 5.5-fold compared to bulk DNA. Drug-induced binding of topoisomerase II beta with bulk DNA in CEM/VM-1 cells did not correlate with cytotoxicity. Collectively, these results indicate that the formation of VM-26 stabilized complexes of topoisomerase II alpha with nascent DNA are critical to the development of cytotoxicity, and that resistance of CEM/VM-1 cells to VM-26 is related to impaired formation of these complexes. The results also provide indirect evidence that topoisomerase II alpha is involved in DNA, replication.     

Cytotoxic activity and mechanism of action of 5-Aza-2'-deoxycytidine in human CML cells

We investigated the cytotoxic activity and some aspects of the mode of action of 5-aza-2'-deoxycytidine (Aza-dC) in 21 primary cultures of leukemic cells freshly obtained from patients with chronic myeloid leukemia (CML) in blast crisis. The cytotoxic potency of Aza-dC was comparable or even greater than that of 1-beta-D-arabinofuranosylcytosine (Ara-C) in most cases, suggesting that this drug has potential in the therapy of blast crisis of CML. Drug incorporation into DNA was evaluated by exposing leukemic cells simultaneously to 3H-Aza-dC at the concentration of 0.1 micrograms/ml and 14C-thymidine (TdR) used as internal standard. Incorporation of Aza-dC into DNA was detectable in all cases. In 17 samples we evaluated the DNA integrity of leukemic cells exposed to Aza-dC using alkaline elution techniques. The drug caused a detectable amount of DNA alkali labile sites (ALS). DNA-ALS increased in cells exposed to Aza-dC concentrations from 0.1 to 1 microgram/ml but did not further increase at 10 micrograms/ml. A plateau in the levels of DNA-ALS was also seen in human K562 cells exposed to increasing concentrations of Aza-dC from 5 to 10 micrograms/ml, whereas in these cells Aza-dC incorporation into DNA increased with increasing Aza-dC concentrations. Therefore, DNA-ALS caused by Aza-dC are not simply the result of the chemical decomposition of azacytosine molecules incorporated into DNA, but are presumably the result of a saturable DNA repair mechanism (e.g., glycosylases) leading to formation of the apyrimidinic sites.     

Prognostic features of teratomas with malignant transformation: a clinicopathological study of 21 cases

PURPOSE: Teratomas with malignant transformation comprise up to 6% of metastatic teratomas. The prognosis of patients with these tumors can vary considerably. We delineate factors that may be related to prognosis in a cohort of men with teratoma with malignant transformation. MATERIALS AND METHODS: We analyzed pathological features, treatment, response, recurrence, time to recurrence, subsequent followup and survival for 21 patients (median age 28 years) diagnosed with teratoma with malignant transformation during a 7-year period at our institution. RESULTS: Malignant nongerm cell elements were present in the primary tumor in 11 cases (52%). Of 18 patients with testicular primaries 17 (94%) presented with metastatic disease. Despite aggressive treatment with surgery and chemotherapy 17 of 21 cases (81%) recurred (median time 6 months). Overall, 5 patients (24%) died of disease (median survival 23 months), 5 (24%) are alive with metastases (median followup 41 months) and 11 (52%) have no evidence of disease (median followup 50 months). Progression/recurrence was substantially greater for 2 of 2 cases with a mediastinal origin, 3 of 4 with rhabdomyosarcomatous differentiation and 5 of 6 with neural differentiation compared with the remainder of the cohort (p < 0.05). CONCLUSIONS: Teratomas with malignant transformation are usually metastatic at presentation, have a high recurrence rate and are more aggressive than teratomas without malignant transformation. Prognosis is especially poor for mediastinal teratomas with malignant transformation and for those with neural or rhabdomyosarcomatous differentiation. Complete surgical resection of residual or recurrent disease appears to offer the best chance for prolonged survival.     

Laminin directs growth cone navigation via two temporally and functionally distinct calcium signals

During development, growth cones navigate to their targets via numerous interactions with molecular guidance cues, yet the mechanisms of how growth cones translate guidance information into navigational decisions are poorly understood. We have examined the role of intracellular Ca2+ in laminin (LN)-mediated growth cone navigation in vitro, using chick dorsal root ganglion neurons. Subsequent to contacting LN-coated beads with filopodia, growth cones displayed a series of stereotypic changes in behavior, including turning toward LN-coated beads and a phase of increased rates of outgrowth after a pause at LN-coated beads. A pharmacological approach indicated that LN-mediated growth cone turning required an influx of extracellular Ca2+, likely in filopodia with LN contact, and activation of calmodulin (CaM). Surprisingly, fluorescent Ca2+ imaging revealed no LN-induced rise in intracellular Ca2+ in filopodia attached to their parent growth cone. However, isolation of filopodia by laser-assisted transection unmasked a rapid, LN-specific rise in intracellular Ca2+ (+73 +/- 11 nM). Additionally, a second, sustained rise in intracellular Ca2+ (+62 +/- 8 nM) occurred in growth cones, with a distinct delay 28 +/- 3 min after growth cone filopodia contacted LN-coated beads. This delayed, sustained Ca2+ signal paralleled the phase of increased rates of outgrowth, and both events were sensitive to the inhibition of Ca2+/CaM-dependent protein kinase II (CaM-kinase II) with 2 microM KN-62. We propose that LN-mediated growth cone guidance can be attributed, in part, to two temporally and functionally distinct Ca2+ signals linked by a signaling cascade composed of CaM and CaM-kinase II.     

Factors affecting the performance of simulated large herringbone and parallel milking parlors

A simulation model of double-16 and double-20 herringbone and parallel milking parlors and double-32 and double-40 parallel milking parlors was used to examine the effects of size, design, operating characteristics of the milking system, management strategies, and milk yield on parlor performance. Analysis of factorial experiments indicated that smaller parlors were more efficient. Turns per hour and milk per stall per hour for double-16, -20, -32, and -40 parallel parlors were 5.87, 5.91, 5.21, and 5.00 turns/h and 56.19, 56.46, 49.66, and 47.94 kg/h, respectively. A wider pulsation ratio (60:40 to 70:30) increased performance measures about 4%, and increased vacuum pressure (46.6 to 50.8 kPa) increased performance measures > 6%. Parallel parlors outperformed herring-bones by nearly 8%. Abbreviated milking procedures resulted in a > 6% increase in performance measures over standard milking procedures. Performance response was significantly diminished when the amount of milking labor exceeded deficit amounts (20 to 32 units per milker) for abbreviated milking procedures or standard amounts (13.3 to 16 units per milker) for standard milking procedures. When milk yield increased, turns per hour decreased, but milk per stall per hour increased.