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D Martin

Publications and source records attributed to D Martin.

At least 451 records · Page 25Linked to original sources
PubMed1994

Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo.

Fischer 344 rats were unilaterally injected into the medial forebrain bundle with 6-hydroxydopamine (6-OHDA). Apomorphine-induced rotational behavior was used to select animals whose rotation exceeded 300 turns/h, corresponding to greater than 95% dopamine (DA) depletion in the ipsilateral striatum. Four weeks later, glial cell line-derived neurotrophic factor (GDNF) or vehicle was injected intranigrally ipsilateral to the lesion (0.1-100 micrograms). The highest dose of GDNF tested produced a marked decrease in rotational behavior. This dose also produced levels of DA in the ipsilateral substantia nigra (SN) which were not statistically different from the contralateral side. Vehicle-treated animals showed a marked DA depletion in the ipsilateral SN. These results demonstrate neurochemical and behavioral improvements in unilaterally DA-lesioned rats following intranigral administration of GDNF, suggesting that GDNF may develop into a useful therapy for Parkinson's disease.

Animals↗
PubMed1994

[Replantation of the hand and fingers].

Using microsurgical techniques to replant an amputated hand or digit is one of the most important progress in the field of hand surgery during the last three decades. The result of a replantation depends on: the mechanism and the level of amputation, the length and the type of ischaemia of the amputated segment, the surgical techniques, the postoperative care, the rehabilitation and so on. Although the success of a replantation is first judged on the survival of the replanted segment, it nevertheless should be assessed on the function achieved. Thanks to the 30-year clinical experience, the final functional result of a replantation can now be anticipated at initial examination; thus indications can be better established by patient selection criteria. The replantation of the hand and the digits is henceforth reasonable only if there is a possibility of a useful functional result.

Amputation, Traumatic↗
PubMed1994

Towards a vaccine for rheumatic fever: identification of a conserved target epitope on M protein of group A streptococci.

Rheumatic fever and rheumatic heart disease remain very common in developing countries, and a vaccine to protect against these disorders would have a great impact on public health. A vaccine must target the M protein of group A streptococci (Streptococcus pyogenes), but until lately immunity was thought to be strain-specific and dependent on antibodies to the variable serotype-specific regions of the protein. Experiments in animals have suggested the conserved region of the M protein as a possible alternative target for protective antibodies. We constructed a 20-aminoacid peptide (peptide 145) within the conserved region of the carboxyl terminus of the protein. In mice the peptide induced serum antibodies that could opsonise reference type 5 streptococci. By enzyme-linked immunosorbent assay, positive responses to peptide 145 were obtained with serum from 77 (90%) of 86 Aboriginal subjects and 135 (81%) of 167 Thai subjects living in areas with high exposure to streptococci. Only 10 (14%) of 71 Caucasian subjects with low exposure to streptococci showed positive responses. There was no difference in the proportion positive between subjects with rheumatic heart disease and control groups (other or no heart disease). Antibodies to peptide 145 were able to opsonise isolates of streptococci from Aboriginal and Thai subjects with acute rheumatic fever as well as reference strains. This highly conserved part of the M protein may be a suitable target for vaccines to prevent streptococcal infections and their sequelae.

Amino Acid Sequence↗
PubMed1994

Tenm, a Drosophila gene related to tenascin, is a new pair-rule gene.

We describe the molecular characterization of the Drosophila gene tenm, a large transcription unit spanning > 110 kb of DNA. tenm encodes a large extracellular protein of 2515 amino acids related to the extracellular matrix molecule tenascin. The Tenm protein is found in seven stripes during the blastoderm stage, and each stripe overlaps with the even-skipped stripes. tenm mutants show a phenotype resembling that of odd-paired (opa), a member of the pair-rule class of segmentation genes. Thus, Tenm is the first example of a pair-rule gene product acting from outside the cell. While the Tenm protein is under the control of fushi tarazu and even-skipped, but not of opa, at least two pair-rule genes, paired (prd) and sloppy paired (slp), and all segment-polarity genes analysed to date are under the control of tenm. Our data suggest that Tenm initiates a signal transduction cascade which acts, via or in concert with opa, on downstream targets such as prd, slp, gooseberry, engrailed and wingless, leading to an opa-like phenotype.

Amino Acid Sequence↗
PubMed1994

Characterization of cytokine-induced hyperalgesia.

Agents which induce symptoms of illness, such as lipopolysaccharide (LPS), cause diverse effects including hyperalgesia. While previous studies have examined central pathways mediating LPS hyperalgesia, the initial steps in activating this system remain unknown. Since LPS induces the release of various cytokines and eicosinoids from immune cells, the present series of experiments examined the potential involvement of these substances in LPS hyperalgesia. This work demonstrates that: (a) Interleukin-1 beta (IL-1 beta) can produce hyperalgesia following either intraperitoneal or intracerebroventricular injection. In contrast, IL-1 beta delivered intrathecally did not affect pain responsivity. (b) Liver macrophages (Kupffer cells) appear to be critically involved, and relay signals to the brain via hepatic vagal afferents. (c) Both IL-1 beta and tumor necrosis factor appear to be critical mediators of LPS hyperalgesia. In contrast, prostaglandins do not appear to be involved. Taken together, these studies suggest that substances classically thought of as products of the immune system may dynamically enhance pain responsivity via actions either on the hepatic vagus or at central sites.

Animals↗
PubMed1994

Autoradiographic localization of receptors for neuropeptide FF, FLFQPQRFamide, in human spinal sensory system.

The regional distribution of FLFQPQRFamide binding sites on fresh unfixed cryostate sections from post mortem specimens of human spinal cord and lower medulla oblongata was studied by quantitative autoradiographic methods using [125I]YLFQPQRFamide as ligand. Samples were taken from five cases who had died with no history of neurological disease at ages ranging from 5 months to 66 years. The biochemical and pharmacological characteristics of [125I]YLFQPQRFamide binding to mounted tissue sections were comparable to those reported for the rat in a previous study. [125I]YLFQPQRFamide appeared to interact reversibly with high affinity binding sites (Kd = 0.06 nM), distinct from opiate receptors. Sites labelled with [125I]YLFQPQRFamide were distributed unevenly within the human spinal cord and lower medulla oblongata, with the highest density in the superficial layers of the dorsal horn and the spinal trigeminal nucleus. Although moderate labelling was observed in the ventral part of spinal grey matter, dense labelling appeared in the gracile and cuneate nuclei. No binding sites were detected in white matter. These results show that, as in the rat, FLFQPQRFamide receptors in the human spinal cord and lower medulla oblongata, are mainly concentrated within spinal areas implicated in the analgesic action of opiates. The possible role of these receptors in modulating spinal nociceptive information is discussed with respect to the pharmacological effects of substances acting on FLFQPQRFamide receptors in animals.

Aged↗
PubMed1994

Effects of breathing a normoxic helium mixture on exercise tolerance of patients with cystic fibrosis.

Breathing helium-oxygen (He-O2) mixtures of 20.9% O2/79.1% He has been shown to increase exercise ventilation and peak oxygen uptake in healthy subjects. The improved exercise performance is thought to be due to the reduced density of He-O2 compared to air and the resulting increases in ventilation. Patients with cystic fibrosis (CF) frequently have abnormal pulmonary function test results, low exercise ventilations and diminished exercise tolerance. This led to the hypothesis that in CF the exercise tolerance of patients might improve when breathing He-O2. To test this hypothesis, 11 patients with CF or mild to severe airway obstruction performed spirometry and progressive maximal exercise tests while breathing air or He-O2. The He-O2 mixture significantly increased (P < 0.05) forced expiratory volume in 1 sec (FEV1) by 8.2%, peak expired flow by 39%, and maximal voluntary ventilation (MVV) by 17.9% compared to air, while forced vital capacity (FVC) and forced mid-expiratory flow rate (FEF25-75%) were unchanged by breathing He-O2. Ventilation and oxygen uptake at matched submaximal power outputs were not increased while breathing He-O2, nor were peak exercise ventilation (VEpeak) or peak exercise oxygen uptake (VO2peak). Estimated hemoglobin saturation and total exercise time were also unchanged during He-O2 breathing. However, there was a trend for the subjects with the better FEV1 to increase VO2peak. Increases in VO2peak when breathing He-O2 and air were correlated (r = 0.67, P < 0.05) with the percent of predicted FEV1 values. Still, in the 11 patients as a group, breathing He-O2 did not significantly improve VO2peak, VEpeak, or exercise tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

The interleukin-1 receptor antagonist (rhIL-1ra) protects against cerebral infarction in a rat model of hypoxia-ischemia.

We assessed the cerebral protective effects of the competitive interleukin-1 antagonist rhIL-1ra in 7-day-old rats that were subjected to brain hypoxia-ischemia by unilateral carotid artery ligation and subsequent exposure to 2 h of 7.5% O2-balanced N2. This procedure leads to atrophy in the cerebral hemisphere ipsilateral to carotid occlusion, with prominent foci of neuronal infarction in the striatum. Systemic administration of 100 mg/kg of rhIL-1ra before and/or after the hypoxic exposure limited the insult. The results indicate that rhIL-1ra has potent neuroprotective properties against morphologic brain injury from hypoxia-ischemia. rhIL-1ra may prove to be clinically useful in protecting against hypoxia-ischemia-related disorders.

Animals↗
PubMed1994

Radiation-induced myelopathy and vertebral necrosis.

Radiation-induced myelopathy is often a diagnosis of exclusion. In addition to the classic criteria needed to support the diagnosis, the presence of another radiation-induced lesion, such as aseptic vertebral necrosis, is useful to confirm the cause of the spinal cord lesion.

Aged↗
PubMed1994

Regional training-induced alterations in diaphragmatic oxidative and antioxidant enzymes.

We examined the relationship between the intensity and duration of exercise training and the up-regulation of diaphragmatic oxidative and antioxidant enzyme activities. Nine groups of rats exercised for 10 weeks (4 days/week). Groups of animals exercised at three intensities (low, moderate, and high); at each exercise intensity, a group of animals ran at one of three exercise durations (30, 60, and 90 min/day). Sedentary animals served as controls. Muscle oxidative capacity was assessed by citrate synthase (CS) activity while antioxidant capacity was evaluated by total superoxide dismutase (SOD) and total glutathione peroxidase (GPX) activities. All intensities and durations of exercise training promoted significant (P < 0.05) increases in costal diaphragmatic CS, SOD, and GPX activities. Increases in costal CS, SOD, and GPX activity were independent of the exercise intensity and duration. High and moderate intensity exercise of 90 min duration significantly elevated (P < 0.05) crural diaphragm CS activity. Further, high and moderate intensity exercise of durations > or = 60 min promoted significant (P < 0.05) increases in crural diaphragm SOD activities. Exercise did not influence (P > 0.05) crural diaphragm GPX activity. We conclude that the training threshold for up-regulation of oxidative and antioxidant enzyme activities differs between the costal and crural diaphragm.

Animals↗
PubMed1994

Post-embedding tem signal-to-noise ratio of S-100.

We assessed the reactivity of purified S-100 antiserum in immuno-electron microscopy by counting the number of gold particles per microns 2 over inner ear tissues embedded in different media. Sections containing predominantly Schwann's cell cytoplasm and nucleus, afferent fiber axoplasm and myelin sheath of chick cochleae were reacted with anti-S-100 IgG, an antibody to a calcium binding protein of neuronal tissues, then labeled with anti-IgG-gold conjugate. This investigation was conducted because previously published procedures, unmodified, did not yield acceptable results. Preparation of all specimens was identical. Only the medium (PolyBed 812, Araldite or Spurr epoxies; and LR White, LR Gold or Lowicryl plastics) was changed. The medium was made the changing variable because antigens available in post-embedding immuno-electron microscopy are decreased by heat, either used and/or released during polymerization of the embedding medium. The results indicate that: (a) none of the embedding media above provided optimal signal-to-noise ratio for all parts of the nerve stained in the same section; (b) aggregation of gold particles over cells was highest in embedding media with high background labeling over areas devoid of tissue (noise); (c) aggregation occurred randomly throughout both cellular and acellular regions; and (d) particles aggregated less and were distributed more evenly in tissues from media yielding good ultrastructural integrity.

Animals↗
PubMed1994

Bidirectional modulation of GABA-gated chloride channels by divalent cations: inhibition by Ca2+ and enhancement by Mg2+.

The effects of the divalent cations Ca2+, Sr2+, Ba2+, Mg2+, Mn2+, and Cd2+ were studied on gamma-aminobutyric acidA (GABAA) responses in rat cerebral cortical synaptoneurosomes. The divalent cations produced bidirectional modulation of muscimol-induced 36Cl- uptake consistent with their ability to permeate and block Ca2+ channels. The order of potency for inhibition of muscimol responses was Ca2+ > Sr2+ > Ba2+, similar to the order for permeation of Ca2+ channels in neurons. The order of potency for enhancement of muscimol responses was Cd2+ > Mn2+ > Mg2+, similar to the order for blockade of Ca2+ channels in neurons. Neither Ca2+ nor Mg2+ caused accumulation of GABA in the extravesicular space due to increased GABA release or decreased reuptake of GABA by the synaptoneurosomes. The inhibition of muscimol responses by Ca2+ was most likely via an intracellular site of action because additional inhibition could be obtained in the presence of the Ca2+ ionophore, A23187. This confirms electrophysiologic findings in cultured neurons from several species. In contrast, the effects of Cd2+, Mn2+, and Mg2+ may be mediated via blockade of Ca2+ channels or by intracellular sites, although the results of these studies do not distinguish between the two loci. The effects of Zn2+ were also studied, because this divalent cation is reported to have widely divergent effects on GABAA responses. In contrast to other studies, we demonstrate that Zn2+ inhibits GABAA responses in an adult neuronal preparation. Zn2+ produced a concentration-dependent inhibition (limited to 40%) of muscimol responses with an EC50 of 60 microM. The inhibition of muscimol-induced 36Cl- uptake by Zn2+ was noncompetitive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Tenascin-C expression by fibroblasts is elevated in stressed collagen gels.

Chick embryo fibroblasts cultured on a collagen matrix exert tractional forces leading to the contraction of unrestrained, floating collagen gels and to the development of tension in attached, restrained gels. On a restrained, attached collagen gel the fibroblasts synthesize large quantities of tenascin-C, whereas in a floating, contracting gel tenascin-C synthesis is decreased. This regulation of tenascin-C synthesis can be observed by the secretion of metabolically labeled tenascin-C into the conditioned medium, as well as by the deposition of tenascin-C into the collagen matrix as judged by immunofluorescence. Regulation appears to occur at the transcriptional level, because when cells on attached or floating collagen gels are transfected with promoter constructs of the tenascin-C gene, luciferase expression driven by the tenascin-C promoter parallels the effects measured for endogenous tenascin-C synthesis, whereas luciferase expression under the control of the SV40 promoter does not depend on the state of the collagen gel. The promoter region responsible for tenascin-C induction on attached collagen gels is distinct from the region important for the induction of tenascin-C by serum, and may define a novel kind of response element. By joining this tenascin-C sequence to the SV40 promoter of a reporter plasmid, its activity can be transferred to the heterologous promoter. We propose that the tenascin-C promoter is directly or indirectly activated in fibroblasts generating and experiencing mechanical stress within a restrained collagen matrix. This may be an important aspect of the regulation of tenascin-C expression during embryogenesis as well as during wound healing and other regenerative and morphogenetic processes.

Animals↗
PubMed1994

A review of the principles of pulse oximetry and accuracy of pulse oximeter estimates during exercise.

This article reviews the principles of pulse oximetry and assesses the accuracy of pulse oximeter measurements obtained during exercise, based on reports of 10 studies that evaluated 24 pulse oximeters. Nine of the studies used cycle exercise, and 1 study utilized treadmill running for mode of activity. Subject populations included patients with cardiovascular or pulmonary disorders, nondisabled individuals, and athletes. Studies were performed under normoxic and hypoxic conditions, and 5 of the 10 studies validated 18 pulse oximeters at arterial oxyhemoglobin saturation (%HbO2) levels of < or = 78%. Sixteen of the 24 pulse oximeters (67%), from 7 of the 10 studies, observed pulse oximeter estimates (%SpO2) during exercise to be accurate, at least when %HbO2 was > or = 85% in nonsmokers. However, the degree of accuracy of the pulse oximeters was variable, even among the same models. Recent studies suggest the current generation of finger-probe-equipped pulse oximeters may be more accurate than ear-probe-equipped models. We recommend that clinicians carefully secure the probe; monitor signal strength; be wary of %SpO2 values of < or = 68% to 78% to avoid undetected severe hypoxemia; and be alert to whether a patient is a smoker, in which case %SpO2 will likely be overestimated. Researchers interested in using pulse oximeter estimates should validate their particular pulse oximeter(s) via arterial blood sampling.

Diagnostic Errors↗