Can transplantation of neurons facilitate motor recovery in paraplegics? Study of an animal model

This review strives forward at least two goals. First, to take from the literature the arguments demonstrating that hindlimbs locomotion is controlled by a spinal network of neurons (the so-called Central Pattern Generator for locomotion--CPG) known to be able to generate locomotor activity independently of the control of supraspinal nervous structures, as it is after thoracic lesions of the spinal cord. The principles of work of the CPG and its intrinsic possibilities to adapt its working are reviewed. Special reference is made to the various ways used during experiments to activate the CPG in spinal animals or clinical practice in paraplegic men: training to walk, electrical stimulations, pharmacological stimulations. Second, to show, from our own results, obtained from the study of an animal model of paraplegia, the adult spinal rat, how it could be possible to take advantage of the autonomy of the CPG, with special reference to its sensibility to monoamines, to obtain locomotor recovery in hindlimbs after section of the thoracic spinal cord, by means of transplantation of noradrenergic and/or serotonergic embryonic neurons in the lumbo-sacral spinal cord. Section of the spinal cord at a thoracic level results in an important locomotor deficit in hindlimbs, likely linked to degeneration of monoaminergic terminals in the lumbar enlargement. In the adult spinal rat, sub-lesional injection of a suspension of embryonic nervous cells, taken from either locus coeruleus or raphe sites, leads to reinnervation of the lumbar enlargement with monoaminergic terminals. Despite the fact that connections with supraspinal structures are not reestablished, transplanted animals recover progressively a posture convenient for locomotion. The hindlimbs, which are in an extended position a few days after the lesion, become progressively flexed and able to support the body weight. This evolution does not appear in spinal but non transplanted animals. But, the main point is that transplanted animals develop, within the few weeks that follow transplantation, a good-quality locomotor activity in hindlimbs which had no equivalent in spinal but non transplanted animals. The reality of a lumbar CPG for locomotion and the efficacy of pharmacological treatments and training to walk, to elicit recovery of stepping, are discussed in man, in connection with the relevance to use transplantation of monoaminergic nervous cells in the spinal cord of paraplegics.     

SCID-Hu mouse as a model for human lung HIV-1 infection

HIV induces a multi-organ infection with a dual tropism for both lymphocytes and monocytes/macrophages. The lung is a target both for HIV infection and HIV-related opportunistic infections. The SCID mouse has provided the opportunity to develop a small animal model for HIV infection. However, HIV-1 infection of the human fetal thymus and liver (SCID Liv/Thy) implanted in these mice occurred only after direct intraimplant injection of HIV-1 and the resultant HIV-1 infection was restricted to the human thymus. Here we report that human foetal lung can develop in SCID Liv/Thy mice resulting in the development of normal human alveolar and bronchiolar lung compartments which can be productively infected with cell-free HIV-1 virus, leading to a systemic and bifocal infection. This SCID-Hu model should be useful for studying AIDS physiopathology, human viruses with lung tropism and for helping to define gene therapy protocols in lung human cells in vivo.     

Effect of dietary fats and sesamin on the lipid metabolism and immune function of Sprague-Dawley rats

We examined the effect of three dietary fats, safflower oil (SAF) rich in linoleic acid, borage oil (BOR) rich in gamma-linolenic acid, and perilla oil (PER) rich in alpha-linolenic acid, on the lipid metabolism, and chemical mediator and immunoglobulin levels in Sprague-Dawley rats, as well as the dietary effect of sesame-derived antioxidative sesamin. The serum cholesterol, phospholipid, triglyceride, prostaglandin E2 level and splenic leukotriene B4 level were lower in the rats fed on BOR or PER than in those fed on SAF. SES feeding suppressed the expression of the lipid-decreasing effect of BOR, but not in the rats fed on PER. In respect of the fatty acid composition of the liver and spleen, PER feeding gave a lower arachidonic acid level, and higher eicosapentaenoic and docosahexaenoic acid levels than SAF feeding did, while the effect of BOR feeding was marginal. The effect of SES feeding on fatty acid composition was much smaller than that of dietary fats. In respect of immunoglobulin production, PER + SES feeding gave the lowest IgE productivity in the mesenteric lymph node lymphocytes. These results suggest that PER feeding regulated lipid metabolism and exerted an anti-allergic effect by a different mechanism from that with BOR feeding.     

Cognitive screening examinations for silent cerebral infarcts in sickle cell disease

OBJECTIVE: In children with sickle cell disease (SCD), silent cerebral infarcts are the most frequent cause of neurologic injury. We determined the sensitivity and specificity of selective neurocognitive measures when separating children with silent cerebral infarcts and SCD from sibling controls. Additionally, we tested the validity of the same cognitive measures to identify patients with overt strokes. METHODS: We examined performance on a neuropsychologic battery containing measures of attention/executive, spatial, language, memory, and motor functioning for seven children with SCD and silent cerebral infarct, 21 children with SCD and overt stroke, and 17 normal siblings. Diagnosis of cerebral infarct was based on results of MRI. RESULTS: Measures from the attention and executive domains were the most useful for identifying children with silent cerebral infarct. The Test of Variables of Attention was the most robust measure and yielded a sensitivity rate of 86% and a specificity rate of 81%. This measure also showed a sensitivity rate of 95% in identifying overt stroke. CONCLUSIONS: Brief cognitive screening measures, if properly constructed, may be an effective means of identifying children with silent cerebral infarct. Future prospective studies should be pursued to assess the utility of cognitive screening for silent cerebral infarcts in SCD.     

An examination of spatial variation in mercury concentrations in otter (Lutra canadensis) in south-central Ontario

Hair samples were collected from otter (Lutra canadensis) trapped in several parts of south-central Ontario, Canada. The concentrations of total Hg in hair were compared with methyl mercury concentrations in liver tissues from the same individuals to determine if hair is a suitable monitoring tissue. Hg in the two tissues was significantly correlated. Hair was used to monitor Hg in 51 individuals from four townships. The concentrations of total Hg in hair ranged from 4 to 20 micrograms/g. No significant variation among the four sample regions existed. Generally the highest concentrations were found in the youngest members of the population. Some possible explanations for the observations are presented.     

The effect of portal hypertension on transforming growth factor-alpha and epidermal growth factor receptor in the gastric mucosa of rats

BACKGROUND: The physical activity levels of US children are declining. Opportunities for physical activity within city schools are constrained by time and space limits. This study determined whether a supplemental program of physical activity would significantly alter the fitness levels of low-income, minority, urban elementary schoolchildren. METHODS: Ninety-nine students from two Cleveland Public Schools served as subjects. One school received a 15-week intervention program where teams of two medical students met with urban elementary schoolchildren three times a week for physical activity sessions. The other school served as a control and received no supplemental activity other than a regularly scheduled physical education class held once a week. We obtained field measurements of skinfold thickness, heart rate response to submaximal exercise, and sit and reach flexibility. RESULTS: The supplemental activity group showed significant improvements in flexibility, body composition, and heart rate response to submaximal exercise. CONCLUSIONS: This investigation indicates that a program of fitness activities conducted within the classroom can significantly improve levels of fitness in urban elementary schoolchildren.     

Validation of [13C]urea breath test for Helicobacter pylori using a simple gas chromatograph-mass selective detector

OBJECTIVE: Isotope ratio mass spectrometry (IRMS) is the accepted method for accurately measuring the 13CO2:12CO2 ratio in the non-invasive and non-radioactive [13C]urea breath test (13C-UBT) for Helicobactor pylori. The IRMS instrument, an expensive and highly specialized analyser, is rarely available. The objective of this project was to modify and validate the use of a simple bench-top gas chromatograph-mass selective detector (GC-MSD) for 13C-UBT. METHODS: Breath samples from 71 patients were taken at baseline and 30 min after ingestion of 100 mg [13C]urea. The breath samples were analysed using GC-MSD in the selected ion monitoring mode. The reference 13CO2:12CO2 ratio was from NBS19 obtained from the US National Institute of Standards and Technology. 13CO2:12CO2 ratios of the breath samples were determined. Excess delta per thousand (per mil, delta/thousand) of the 30 min sample over the baseline (deltadelta/thousand) of > or = 6deltadelta/thousand was considered H. pylori positive. Results from 13C-UBT and histology determined blind to each other were compared. RESULTS: The coefficient of variation of the reference 13CO2:12CO2 ratio was 0.06%. Using histology as the 'gold standard', the sensitivity (97.9%) and specificity (95.8%) of the GC-MSD 13C-UBT were comparable to those of other methods of H. pylori diagnosis. CONCLUSION: A gas chromatograph coupled to a mass selective detector that is available in many analytical and biomedical laboratories can be used for the 13C-UBT. This method will increase the availability and reduce the cost of this non-invasive, non-radioactive diagnostic test.     

Charged amino acids at the carboxyl-terminal portions determine the intracellular locations of two isoforms of cytochrome b5

Outer mitochondrial membrane cytochrome b5 (OMb), which is an isoform of cytochrome b5 (cyt b5) in the endoplasmic reticulum, is a typical tail-anchored protein of the outer mitochondrial membrane. We cloned cDNA containing the complete amino acid sequence of OMb and found that the protein has no typical structural feature common to the mitochondrial targeting signal at the amino terminus. To identify the region responsible for the mitochondrial targeting of OMb, various mutated proteins were expressed in cultured mammalian cells, and the subcellular localization of the expressed proteins was analyzed. The deletion of more than 11 amino acid residues from the carboxyl-terminal end of OMb abolished the targeting of the protein to the mitochondria. When the carboxyl-terminal 10 amino acids of OMb were fused to the cyt b5 that was previously deleted in the corresponding 10 residues, the fused protein localized in the mitochondria, thereby indicating that the carboxyl-terminal 10 amino acid residues of OMb have sufficient information to transport OMb to the mitochondria. The replacement of either of the two positively charged residues within the carboxyl-terminal 10 amino acids by alanine resulted in the transport of the mutant proteins to the endoplasmic reticulum. The mutant cyt b5, in which the acidic amino acid in its carboxyl-terminal end was replaced by basic amino acid, could be transported to the mitochondria. It would thus seem that charged amino acids in the carboxyl-terminal portion of these proteins determine their locations in the cell.