The effect of warm-up on responses to intense exercise.

The purpose of this study was to determine if prior physical activity (warm-up) affected physiological responses to intense exercise. Eight highly trained collegiate swimmers performed a paced 365.8-m (440 yds) intense swim (mean +/- SE, 94.4 +/- 3.3% VO2max) 5 min after the following warm-up conditions: trial N, no warm-up; trial S, an intensity-specific interval set (4 x 45.7 m with one-min rest intervals at the intense swim pace); trial M, a mild-intensity, long-duration swim (1371.6 m at 64.7 +/- 3.3% VO2max); and trial MS, a mild-intensity, long-duration swim (1188.7 m at the same pace as trial M) followed by the intensity-specific interval set (trial S). When comparing trial N with trials M and MS, stroke distance (m/stroke) was significantly (p less than 0.05) lower during the last 91.4 m of the intense, paced swim and 3-, 5-, 8- and 10-min recovery blood lactate levels and one-minute recovery heart rates were significantly elevated (p less than 0.05). There was no significant difference (p greater than 0.05) in stroke distance during the final 91.4 m of the intense swim between trials S and N. There were no significant differences for any variables between trials M and MS. These results suggest that a warm-up consisting of mild-intensity, long-duration exercise was beneficial compared to no warm-up and that intensity-specific exercise was not a vital component of warm-up. Although performance was not directly measured, these data demonstrate the benefit of warm-up.     

Stable micro-dystrophin gene transfer using an integrating adeno-retroviral hybrid vector ameliorates the dystrophic pathology in mdx mouse muscle

The ability to transfer the dystrophin gene stably to the skeletal muscle of DMD patients is a major confounding issue in establishing an effective gene therapy for this disease. To overcome this problem, we have examined the ability of muscle fibres from mdx mice to act as in situ factories of retroviral vector production. Tibialis anterior (TA) muscles from 4-week-old mdx mice were injected with an adenoviral vector expressing LacZ within a retroviral expression cassette (AdLZIN). Retroviral vector production was induced by the inclusion of two additional adenoviral vectors expressing retroviral gag-pol (AdGagPol) and 10A1 env genes (Ad10A1). Upon introduction of infected muscles into cell culture, colonies of beta-galactosidase-expressing myotubes formed only in cultures where the muscle was injected with AdLZIN, AdGagPol and Ad10A1, but not from muscle injected with AdLZIN only. Muscles from mdx/nude mice producing retroviral vector displayed a 4.6-fold increase in beta-galactosidase-positive myofibres after 1 month, compared with contralateral muscle in the same animal injected with AdLZIN and AdGagPol only. By constructing a hybrid adeno-retroviral vector expressing a truncated micro-dystrophin construct (AdmicroDyIN), we were able to partially correct the mdx dystrophic phenotype. AdmicroDyIN-mediated expression of micro-dystrophin in mdx TA muscle restored the formation of the dystrophin-associated glycoprotein complex and significantly reduced the level of muscle degeneration over uninjected controls. By stimulating in situ production of retroviral vector expressing micro-dystrophin, we achieved 92%+/-6% transduction of myofibres in the TA muscle by 4 weeks. Strikingly, by 3 months post injection, micro-dystrophin was still expressed to high levels in nearly all the myofibres of the TA muscle. By comparison, there was a pronounced drop in the levels of micro-dystrophin expressed by muscles injected with AdmicroDyIN only. Finally, using a novel PCR approach, we detected reverse-transcribed, integrated proviral sequences in TA muscle genomic DNA by 4 weeks post injection, the levels of which were found to increase after 3 months.     

Occurrence of schizotypal and borderline symptoms in parasuicide patients: comparison between subjective and objective indices

Seventy-six patients were interviewed within a week of admission following a parasuicide episode. Axis II diagnosis on DSM-III was made for schizotypal, borderline, histrionic, and antisocial personality disorder. In addition patients completed a self-rating questionnaire, the Schizotypy Questionnaire of Claridge & Broks (1984), which assesses schizotypal and borderline personality traits. The objective and subjective indices of schizotypal and borderline symptoms correlated significantly but allocation of patients to a diagnosis missed several patients who nevertheless rated themselves as having a high frequency of these symptoms. There was an asymmetry of symptom pattern reminiscent of Foulds & Bedford's (1975) hierarchy model. The presence of schizotypal symptoms appeared to be higher in the hierarchy: they predicted borderline symptoms, but a high frequency of borderline symptoms did not necessarily predict schizotypy. We suggest that the occurrence of schizotypal symptoms should become a more explicit focus of clinical assessment and treatment of these patients, especially those who repeatedly harm themselves and we suggest ways in which cognitive therapies may be adapted to do this.     

Identification of a 33-kilodalton immunodominant antigen of Trypanosoma congolense as a cysteine protease.

A 33-kDa protein of Trypanosoma congolense is a major antigen in infected cattle and the production of antibody to this antigen appeared to correlate with enhanced resistance to trypanosomiasis [4]. Immunoelectron microscopy using a monoclonal antibody (mAb 4C5) raised against the 33-kDa antigen showed a lysosomal localisation, similar to that of a previously described 32-kDa cysteine protease of T. congolense. Both mAb 4C5 and anti-33 kDa antibody from infected cattle bound on Western blots to the cysteine protease that had been purified by affinity chromatography on cystatin-Sepharose. Sepharose-coupled mAb 4C5 was used to affinity purify the antigen from bloodstream forms of T. congolense. On sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), the affinity-purified antigen had a molecular mass of 33 kDa under non-reducing conditions, and 40 kDa under reducing conditions. Anti-33-kDa antibody from infected cattle bound to both non-reduced and reduced affinity-purified antigen on Western blots. Serum from a rabbit immunised with the biochemically purified enzyme also bound the affinity-purified antigen. The affinity-purified antigen displayed proteolytic activity in fibrinogen-containing SDS-PAGE and against Azocoll. It hydrolysed benzyloxycarbonyl-Phe-Arg-7-amino-methyl coumarin (Z-Phe-Arg-NHMec) with a Km similar to that of the biochemically purified enzyme. Proteolytic and peptidolytic activities of the antigen were inhibited by the inhibitors of cysteine proteases, cystatin and trans-epoxysuccinyl-L-leucyl-amido (4-guanidino)butane (E-64). On two-dimensional gel electrophoresis, the antigen displayed similar characteristics to those of the biochemically purified enzyme. We conclude that the 33-kDa antigen of T. congolense and the cysteine protease are the same molecule.     

Effect of iron status on reticulocyte mean channel fluorescence.

Flow cytometric reticulocyte enumeration measures the fluorescence intensity of the reticulocyte population, the reticulocyte mean channel fluorescence. Reticulocyte mean channel fluorescence, used as an indicator of reticulocyte maturation, is directly proportional to the amount of intracellular RNA. Other factors, such as iron stores, may affect reticulocyte mean channel fluorescence. Iron status in normal controls, patients with anemia of chronic disease, and pregnant women was evaluated by hemoglobin, hematocrit, red blood cell indices, iron, total iron-binding capacity, and ferritin. Reticulocyte mean channel fluorescence was significantly elevated (P less than 0.0001) to 85.6 +/- 4.6 (mean +/- 1 standard deviation) in iron-deficient anemic patients and to 81.1 +/- 8.4 in iron-depleted patients compared to healthy individuals (69.7 +/- 2.6). The reticulocyte mean channel fluorescence in anemia of chronic disease was 71.3 +/- 5.8 and was not significantly different from that of normal controls. Reticulocyte mean channel fluorescence showed significant correlations with total iron-binding capacity (P less than 0.0001, r = 0.62) and ferritin (P less than 0.0001, r = 0.40). A possible explanation for these findings, describing differences in cytoplasmic levels of transferrin receptor mRNA, is discussed.     

Lack of lysosomal fusion with phagosomes containing Ehrlichia risticii in P388D1 cells: abrogation of inhibition with oxytetracycline.

Fusion of lysosomes with phagosomes containing Ehrlichia risticii, an obligate intracellular parasite, was evaluated in P388D1 murine macrophagelike cells. Lysosomes in cells ranging in infectivity from 30 to 70% were labeled cytochemically with acid phosphatase or via endocytosis of thorium dioxide or cationized ferritin to document phagosome-lysosome (P-L) fusion in untreated cells and cells treated with oxytetracycline. Regardless of the marker used, P-L fusion was generally not observed in E. risticii-containing vacuoles in untreated cells, while significantly greater P-L fusion with ehrlichia-containing vacuoles was observed after oxytetracycline treatment. When latex beads were introduced into uninfected cell cultures, P-L fusion was observed with vacuoles containing latex. Fusion of lysosomes with latex-containing vacuoles in cells was significantly greater than fusion of lysosomes with ehrlichia-containing vacuoles in the same infected cells. These findings indicate that E. risticii is able to inhibit P-L fusion, whereas oxytetracycline deprives organisms of this ability.     

Lumbrical muscle function as revealed by a new and physiological approach

The lumbrical muscle is clearly one of several possible extensors of the interphalangeal joints. With an origin on the flexor digitorum profundus tendon it is credited with unloading the elastic tension across the interphalangeal joints and thereby facilitating their extension. Its role at the metacarpophalangeal joint is not a matter of universal agreement. Attempts to simulate its action with weights over pulleys have not clarified this role, since true simulation would require the development of a means of applying force along the course of the lumbrical without pre-determining which end would move. Such a system is herein described; it uses a Bowden cable, which is commonly used to activate the brakes of a bicycle. After constructing length-tension curves of the profundus muscle in four fresh cadavers prior to the onset of rigor mortis, the interaction of realistic lumbrical loads with profundus elastic tension was studied. By contraction a lumbrical muscle adds a small but significant flexor force at the metacarpophalangeal joint, and thereby it is also capable of contributing to radial deviation and possibly rotation. As it runs from a flexor tendon to an extensor tendon and is endowed with a great many muscle spindles, the lumbrical could play a part in the control of finger movement by monitoring the rate of hand closing during grasp.     

Development of acute lymphoblastic leukemia following treatment for acute myeloid leukemia in children with Down syndrome: A case report and retrospective review of Children's Oncology Group acute myeloid leukemia trials

Children with Down syndrome have a 150‐fold increased risk of developing acute myeloid leukemia (AML) and 20‐fold increased risk of developing acute lymphoblastic leukemia (ALL). Although the risk of developing AML and ALL is significantly increased in children with Down syndrome, the development of both malignancies in the same patient is very rare. We describe a patient with Down syndrome who developed ALL 6 years after being diagnosed with AML. We performed a literature review and Children's Oncology Group query and discovered eight published cases and five cases of ALL following AML in pediatric patients with Down syndrome, as well as six cases of ALL following AML in non‐Down syndrome patients. There was a similar cumulative incidence of ALL after treatment for AML in the Down syndrome and non‐Down syndrome populations. Overall survival in patients with Down syndrome who developed ALL after treatment for AML was comparable to overall survival for patients with Down syndrome with de novo ALL with an average follow‐up of 7 years after ALL diagnosis. Clinical data collected were used to discuss whether this phenomenon represents a secondary leukemia, second primary cancer, or mixed‐lineage leukemia.