Effect of previous supramaximal work on lacticaemia during supra-anaerobic threshold exercise

Summary Twelve male and female subjects (eight trained, four untrained) exercised for 30 min on a treadmill at an intensity of maximal O₂ consumption (% O_2max) 90.0%, SD 4.7 greater than the anaerobic threshold of 4 mmol ·1^–1 (Th_an =83.6% O_2max, SD 8.9). Time-dependent changes in blood lactate concentration ([la_b]) during exercise occurred in two phases: the oxygen uptake ( O₂) transient phase (from 0 to 4 min) and the O₂ steady-state phase (4–30 min). During the transient phase, [la_b] increased markedly (l.30 mmol · l ^–1 · min ^–1, SD 0.13). During the steady-state phase, [la_b] increased slightly (0.02 mmol · 1^–1 · min^–1, SD 0.06) and when individual values were considered, it was seen that there were no time-dependent increases in [la_b] in half of the subjects. Following hyperlacticaemia (8.8 mmol -l^–1, SD 2.0) induced by a previous 2 min of supramaximal exercise (120% O_2max), [la_b] decreased during the O₂ transient (–0.118 mmol · 1^–1 · min^–1, SD 0.209) and steady-state (–0.088 mmol · 1^–1 · min ^–1, SD 0.103) phases of 30 min exercise (91.4% O_2max, SD 4.8). In conclusion, it was not possible from the Th_an to determine the maximal [la_b] steady state for each subject. In addition, lactate accumulated during previous supramaximal exercise was eliminated during the O₂ transient phase of exercise performed at an intensity above the Th_an. This effect is probably largely explained by the reduction in oxygen deficit during the transient phase. Under these conditions, the time-course of changes in [la_b] during the O₂ steady state was also affected.     

Early embryonic expression patterns of the mouse Flamingo and Prickle orthologues.

The Drosophila melanogaster proteins Flamingo and Prickle act in the planar cell polarity (PCP) pathway, which is required for acquisition of epithelial polarity in the wing, eye, and epidermis. In mammals, PCP signaling has been shown to regulate cell movements and polarity in a variety of tissues. Here, we show that the murine Flamingo orthologues Celsr1-3 and the Prickle orthologues Prickle1, Prickle2, and Testin have dynamic patterns of expression during pregastrulation and gastrulation stages. Celsr1 is expressed in the anterior visceral endoderm and nascent mesoderm, Celsr2 and Celsr3 mark the prospective neuroectoderm, Prickle1 is expressed in the primitive streak and mesoderm, Prickle2 in the node, and Testin in the anterior visceral endoderm, the extraembryonic ectoderm, primitive streak, and mesoderm. Analysis of a gene-trap mutation in Testin indicates that this gene is not required for embryogenesis; therefore, other Prickle homologues may compensate for its function during development.     

Multicontrast MRI of remyelination in the central nervous system

Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de- and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts. While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, demyelinated or remyelinated white matter by one contrast alone was less specific than by histology or electron microscopy. However, an accurate MRI prediction of the in vivo myelin status was achieved by a discriminant function analysis using a combination of T1, T2 and magnetization transfer contrast. With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved remyelination.     

Frequent carriage of Panton-Valentine leucocidin genes by Staphylococcus aureus isolates from surgically drained abscesses

Between 1 February and 15 April 2002, 95 patients were admitted to Gaston Bourret Territorial Hospital (New Caledonia, France) for drainage of community-acquired soft tissue abscesses. Staphylococcus aureus was detected in 68 cases (72%). Two-thirds of the patients with S. aureus infection had furuncles, which were located on the limbs in 82% of cases. The median interval between symptom onset and hospital admission was 5.7 days. Three-quarters of the patients were Melanesians living in tribes. Fifty-four S. aureus isolates were screened for toxin genes. Panton-Valentine leucocidin (PVL) genes were detected in 48 isolates (89%), the exfoliative toxin A gene was detected in 1 isolate, and no toxin genes were detected in 4 isolates. S. aureus nasal carriage was detected in 39.7% of patients with S. aureus infections. Two infecting S. aureus strains and two nasal carriage strains were resistant to methicillin. Comparative pulsed-field gel electrophoresis, performed in 16 cases, showed that five of six patients with PVL-positive nasal carriage strains were infected by the same strains. In contrast, 8 of 10 patients with PVL-negative nasal carriage strains were infected by PVL-positive strains. PVL genes thus appear to be a major virulence factor in both primary and secondary S. aureus skin infections.     

Fungi in megakaryocytes. An unusual manifestation of fungal infection of the bone marrow.

When fungi infect the bone marrow, typically they are associated with granuloma formation and/or necrosis, and the fungi are found within histiocytes or admixed with necrotic debris. Recently two bone marrow biopsy specimens were encountered in which fungi were confined to the cytoplasm of megakaryocytes, a finding not previously reported in the literature. The first case was that of a 46-year-old man with pulmonary histoplasmosis and no known immunodeficiency. The second was that of a 38-year-old man with the acquired immune deficiency syndrome and cryptococcal meningitis. In the first case, many megakaryocytes contained fungal forms consistent with Histoplasma. In the second, one small cluster of megakaryocytes contained several budding yeast consistent with Cryptococcus. Neither marrow biopsy specimen had necrosis, granulomas, or histiocytic infiltration. In both cases, because of the unusual localization of the fungi, they were initially overlooked. The bone marrow may contain fungi even in the absence of abnormalities suggesting fungal infection on routinely stained sections. A silver stain or a periodic acid--Schiff stain should be performed on all marrow biopsy specimens in cases of known or suspected fungal infection outside the marrow. The phenomenon of megakaryocyte emperipolesis is well known, and this process may be responsible for the apparent ability of megakaryocytes to internalize fungi.     

Extensive transmission of Mycobacterium tuberculosis from a child

BACKGROUND AND METHODS: Young children rarely transmit tuberculosis. In July 1998, infectious tuberculosis was identified in a nine-year-old boy in North Dakota who was screened because extrapulmonary tuberculosis had been diagnosed in his female guardian. The child, who had come from the Republic of the Marshall Islands in 1996, had bilateral cavitary tuberculosis. Because he was the only known possible source for his female guardian's tuberculosis, an investigation of the child's contacts was undertaken. We identified family, school, day-care, and other social contacts and notified these people of their exposure. We asked the contacts to complete a questionnaire and performed tuberculin skin tests. RESULTS: Of the 276 contacts of the child whom we tested, 56 (20 percent) had a positive tuberculin skin test (induration of at least 10 mm), including 3 of the child's 4 household members, 16 of his 24 classroom contacts, 10 of 32 school-bus riders, and 9 of 61 day-care contacts. A total of 118 persons received preventive therapy, including 56 young children who were prescribed preventive therapy until skin tests performed at least 12 weeks after exposure were negative. The one additional case identified was in the twin brother of the nine-year-old patient. The twin was not considered infectious on the basis of a sputum smear that was negative on microscopical examination. CONCLUSIONS: This investigation showed that a young child can transmit Mycobacterium tuberculosis to a large number of contacts. Children with tuberculosis, especially cavitary or laryngeal tuberculosis, should be considered potentially infectious, and screening of their contacts for infection with M. tuberculosis or active tuberculosis may be required.     

Effect of physical exercise on adoptive experimental auto-immune encephalomyelitis in rats

The aim of the study was to determine whether different programmes of exercise influence adoptive monophasic experimental auto-immune encephalomyelitis (adoptive EAE), a paralytic disease mediated by T-cells. Adoptive EAE was induced by the transfer of activated encephalitogenic T-lymphocytes into syngeneic recipients (Lewis rats, n = 85) and its development was followed by two independent observers. The results showed that 2 days of severe exercise (250 and 300 min) performed after the adoptive transfer of EAE slightly delayed the onset of the disease (P < 0.008) and the day of its maximal severity (P < 0.016) without affecting the overall severity of the disease. When this programme of exercise was performed before the cell transfer, it had no effect (P > 0.05). Two more moderate exercise programmes (5 × 120 min of running at constant speed or 5 × 60 min of running at variable speed, 5 consecutive days) performed between the adoptive transfer and the onset of the disease did not modify the development of the clinical signs of adoptive EAE (P >0.05). These results showed that severe exercise slightly influenced the effector phase of monophasic EAE and confirmed that physical exercise performed before the onset of experimental auto-immune diseases did not exacerbate the clinical signs.     

Splenic immunomodulation with swimming-induced stress in rats.

In order to determine the effects of swimming-induced stress, young male Wistar rats swam for a single session of 2 h duration, or for one 2-h session a day for five consecutive days. The absolute number of splenic mononuclear cells and the in vitro proliferation of mitogen-stimulated (PHA) T lymphocytes were studied. A single swimming session did not significantly diminish the number of splenic mononuclear cells, but it did significantly reduce splenic T-lymphocyte proliferation. This effect on T-lymphocyte proliferation was significantly blocked, in part, by subcutaneous injection of naltrexone before a swimming session. It was not significantly blocked by pre-exercise oral administration of aminoglutethimide. Repeated swimming sessions induced no significant changes in immune parameters. In conclusion, these data suggest that immunosuppression seen with a single swimming-induced stress period may partly be due to endogenous opioids, and that repetition of the swimming session reduced swimming-induced immunomodulation.     

Regional mapping of the gene encoding dihydroorotate dehydrogenase,an enzyme involved in UMP synthesis,electron transport,and superoxide generation,to human chromosome region 16q22

De novo UMP synthesis is a critical metabolic pathway for nucleic acid synthesis and for a variety of metabolic pathways. The pathway is a target for many widely used cancer chemotherapy agents, several of which are pyrimidine analogs. Humans and cattle have been described with mutations in UMP synthesis that lead to serious inborn errors of metabolism. Dihydroorotate dehydrogenase (EC 1.3.3.1) (DHODH) carries out the fourth committed step in the pathway and may also be important for mitochondrial electron transport and oxygen radical metabolism. We report here that the gene encoding this enzyme in humans is located in the chromosomal region 16q22. With the mapping of DHODH, the mapping of all the steps of UMP synthesis is complete. All three genes involved map to different human chromosomes. This information is important in consideration of regulation of UMP synthesis in mammals, including humans.     

Increasing access to medical education for students from medically underserved communities: one program's success.

The Premedical Honors College (PHC) is an eight-year, BS-MD program created in 1994 by Baylor College of Medicine (BCM) and The University of Texas-Pan American (UT-PA) to increase the number of physicians addressing the health care needs of underserved populations in Texas. The PHC targets South Texas, a 13-county, medically underserved area with a population that is 82% Hispanic. To date, the PHC has had 159 matriculants and 71 graduates, of whom 60 (84.5%) have matriculated into medical school. These results are significant considering that in 1996, only four students from all five South Texas colleges (combined enrollment of 30000 students) were accepted to medical school. An outcomes study comparing PHC matriculants with students of similar academic ability, ethnicity, and interest in medicine revealed that the odds of medical school matriculation were seven times higher for PHC students than for non-PHC students. The PHC's initial success has been acknowledged by the Texas legislature, which recently passed a bill to promote the PHC's replication. In addition, the number of PHC students-of whom 95% are Mexican American-who matriculate into medical school annually is significant nationally. In 2001, only 386 U.S. medical school matriculants (2.3% of all matriculants) were Mexican American; 17 of these students (4.4%) were PHC graduates. If current trends continue, the PHC could significantly expand the number of physicians serving minority and medically underserved populations in Texas and the nation. Also, the PHC provides an opportunity for research on programs designed to create pathways from high school to medical school.