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J H Martin

Publications and source records attributed to J H Martin.

At least 19 recordsLinked to original sources
PubMed1999

Activity-dependent development of cortical axon terminations in the spinal cord and brain stem.

Corticospinal (CS) axon terminations in several species are widespread early in development but are subsequently refined into a spatially more restricted distribution. We studied the role of neural activity in sensorimotor cortex in shaping postnatal development of CS terminations in cats. We continuously infused muscimol unilaterally into sensorimotor cortex to silence neurons during the postnatal CS refinement period (weeks 3-7). Using anterograde transport of WGA-HRP, we examined the laterality of terminations from the muscimol-infused (i.e., silenced) and active sides in the spinal cord, as well as in the cuneate nucleus and red nucleus. We found that CS terminations from the muscimol-infused cortex were very sparse and limited to the contralateral side, while those from the active cortex maintained an immature bilateral topography. Controls (saline infusion, noninfusion) had dense, predominantly contralateral, CS terminations. There was a substantial decrease in the spinal gray matter area occupied by terminations from the side receiving the blockade and a concomitant increase in the area occupied by ipsilateral terminations from the active cortex. Optical density measurements of HRP reaction product from the active cortex in muscimol-infused animals showed substantial increases over controls in the ratio of ipsilateral to contralateral CS terminations for all laminae examined (IV-V, VI, VII). Our findings suggest that ipsilateral dorsal horn terminations reflect new axon growth during the refinement period because they are not present there earlier in development. Those in the ventral horn are present earlier in development and thus could reflect maintenance of transient terminations. Increased ipsilateral terminations from active cortex were due to recrossing of CS axons in lamina X and not to an increase in labeled CS axons in the ipsilateral white matter. Examination of brain stem terminations suggested that, between postnatal weeks 3 and 7, development of corticocuneate terminations also is activity-dependent but that development of corticorubral terminations is not. Activity-dependent CS development is a plausible mechanism by which early motor experiences could shape the anatomical and functional organization of the motor systems during a critical postnatal period.

Aging↗
PubMed1999

Pharmacological inactivation in the analysis of the central control of movement.

In this review, we describe how pharmacological inactivation can be used to elucidate the central control of skilled limb movement. Local anesthetics and tetrodotoxin block neuronal cell bodies and passing fibers while gamma-aminobutyric acid (GABA) and muscimol only block cell bodies. Blockade induction time is short (several minutes) for all the agents. Blockade duration produced by local anesthetics and GABA is 15-60 min, while that of tetrodotoxin and muscimol is up to several days. We describe our drug injection system, with an integrated microelectrode and a viewing port for visually monitoring drug flow into the injection cannula. We used glucose metabolism to assess the extent of inactivation. Intracortical lidocaine or muscimol injection produces a central core of maximal hypometabolism (1 mm radius), which could be due to drug spread, surrounded by an extensive region (several millimeters) of reduced hypometabolism, possibly due to reduced synaptic activity of neurons receiving projections from the core region. Drug injection only depresses neuronal activity, which contrasts with cooling, where there can be neuronal hyperexcitability at the periphery of the inactivation site. Our experiments in behaving animals show how pharmacological inactivation is an effective analytical tool for dissecting the differential functional contributions of subcortical and cortical forelimb representations to limb movement control.

Animals↗
PubMed1998

ZR-75-1 human breast cancer cells: expression of inducible nitric oxide synthase and effect of tamoxifen and phorbol ester on nitric oxide production.

The existence of the L-arginine-nitric oxide pathway was investigated in ZR-75-1 human breast cancer cells. The presence of inducible nitric oxide synthase in these cells was confirmed by staining with an anti-iNOS antibody. ZR-75-1 cells spontaneously produced nitric oxide (NO) and this production could be significantly (P < 0.001) enhanced by L-arginine (0.01-10 mM) and was inhibited by L-NAME (2 mM). Stimulating the cells with phorbol 12-myristate 13-acetate (PMA) (200-1000 nM) resulted in a significant (P < 0.001) increase in NO2- secreted into the medium. Although treatment of the same cells with tamoxifen (10(-10)-10(-6) M) had no effect on NO production, tamoxifen was able to significantly (P < 0.001) downregulate PMA-enhanced nitrite production. Our results suggest that tamoxifen could play a role in the biology of nitric oxide in breast tumours.

Arginine↗
PubMed1998

Divergent effect of taxol on proliferation, apoptosis and nitric oxide production in MHH225 CD34 positive and U937 CD34 negative human leukaemia cells.

Paclitaxel (Taxol) has been shown to be clinically effective in treatment of patients with breast and ovarian cancer. It has also shown promising results in various other solid tumours. Paclitaxel has induced apoptosis in the G2/M phase of the cell cycle in both HL-60 and U937 human leukaemia cells. A recent study has shown a dose-dependent cytotoxicity for both taxanes: paclitaxel (taxol) and docetaxel (Taxotere) on fresh leukaemia cells in primary culture from 16 ALL and four AML patients and proposed their use in treatment of acute leukaemia patients. AML is a heterogeneous disease in which malignant transformation and disease progression occur at the level of CD34 positive cells. Also, the multi-drug resistance gene product, P-glycoprotein is expressed only in CD34 positive AML cells. Therefore, an in vitro evaluation of the efficacy of paclitaxel, a P-glycoprotein substrate, in CD34 positive AML cells is warranted before considering its clinical use in acute leukaemia patients. Since all in vitro studies of paclitaxel reported so far have involved only CD34 negative (HL-60, U937, K562) human AML cells, the aim of the present study was to evaluate paclitaxel efficacy against CD34 positive AML cells. The IC50 of paclitaxel for apoptosis was significantly higher in MHH225 CD34 positive cells (12 +/- 2 microM) than in U937 CD34 negative cells (1.7 +/- 0.2 microM), P < 0.001. Paclitaxel has a significantly weaker cytotoxic effect on CD34 positive AML cells. One log higher concentration of paclitaxel was required in MHH225 CD34 positive AML cells to achieve the same apoptosis level achieved in U937 CD34 negative leukaemia cells. Also, at the high concentration achievable in vivo: 10 microM paclitaxel, only half the MHH225 CD34 positive AML cells were apoptotic versus 72% of U937 CD34 negative leukaemia cells. Clearly, paclitaxel has only weak or modest in vitro efficacy compared with several conventional anti-leukaemia drugs used in AML treatment. The present results support the poor level of in vivo induction of apoptosis achieved during a phase I clinical study with paclitaxel therapy in 26 leukaemia patients. Also, the present results have shown a significant increase in nitric oxide production during paclitaxel-induced apoptosis in U937 monocytic leukaemia cells, confirming the vital role of nitric oxide in mediating paclitaxel-induced apoptosis by monocytic cells. In conclusion, the present study has demonstrated a clear difference between the effect of paclitaxel on CD34 negative and CD34 positive AML cells. Given its poor performance in the phase I clinical study of 26 acute leukaemia patients and the present weak in vitro cytotoxic effect, it is unlikely that paclitaxel will have a role in the treatment of acute leukaemia. Also, the present study emphasises the need to use CD34 positive AML cells such as MHH225 rather than the unsuitable lineage-specific CD34 negative cells such as HL-60 or U937 for in vitro pre-clinical screening of potential novel effective anti-leukaemia agents.

Acute Disease↗
PubMed1997

Automated reticulocyte counting: evaluation of the Coulter STKS Haematology Analyser reticulocyte counting function.

This study evaluated reticulocyte counting with the automated reticulocyte function of the Coulter STKS Haematology Analyser. This is an upgrade option for Coulter STKS and MAXIM haematology analysers. Reticulocyte counts obtained with the automated reticulocyte counting function were compared with those obtained by visual counting. Reticulocyte counting with both methods gave excellent comparability with a correlation coefficient of 0.98. Results were consistent with the well documented imprecision of the manual method with a coefficient of variation (CV) of 16-22%. In contrast, the automated reticulocyte counting function was more precise with a CV of 12.3%. In both cases, counts were stable after storage for 24 h at room temperature and 4 degrees C. Our results suggest that the use of this upgrade will be beneficial for many laboratories.

Autoanalysis↗
PubMed1997

Silent laryngopharyngeal sensory deficits after stroke.

Dysphagia and aspiration are two devastating sequelae of stroke. Recent work has shown that laryngopharyngeal (LP) sensory deficits are associated with aspiration in stroke patients with dysphagia. The phenomenon of silent LP sensory deficits, where the patient exhibits no subjective or objective evidence of dysphagia, yet has an LP sensory deficit, has not been previously described. The aim of this study was to evaluate the sensory capacity of the laryngopharynx in stroke patients who had no subjective or objective complaints of dysphagia. We determined the sensory threshold in the laryngopharynx using air pulse stimulation of the mucosa of the pyriform sinus and aryepiglottic fold. Eighteen stroke patients (mean age 65.6 +/- 11.5 years) and 18 age-matched controls were prospectively evaluated. Normal thresholds were defined as < 4.0 mm Hg air pulse pressure (APP). Deficits were defined as either a moderate impairment in sensory discrimination thresholds (4.0 to 6.0 mm Hg APP) or a severe sensory impairment (> 6.0 mm Hg APP). Stroke patients were followed up for 1 year to determine the incidence of aspiration pneumonia (AP) as verified by chest radiography. In 11 of the stroke patients studied, either unilateral (n = 6) or bilateral (n = 5) severe sensory deficits were identified. The elevations in sensory discrimination thresholds were significantly greater than those in age-matched controls (7.1 +/- 0.6 mm Hg APP versus 2.5 mm Hg APP; p < .01, Wilcoxon score). Among patients with unilateral deficits, sensory thresholds were severely elevated in all cases on the affected side compared with the unaffected side (p < .01, Wilcoxon score). Moreover, the sensory thresholds of the unaffected side were not significantly different from those of age-matched controls. Aspiration pneumonia did not occur in the patients with normal LP sensation or in the patients with unilateral severe LP sensory deficits. However, in the 5 patients with bilateral, severe LP sensory deficits, 2 developed AP, both within 3 months of their LP sensory test. The results of this study showed, for the first time, that stroke patients without subjective or objective clinical evidence of dysphagia could have silent LP sensory deficits. These impairments could contribute to the development of AP following stroke. The findings in this study suggest that LP sensory discrimination threshold testing should not be restricted only to patients with clinical dysphagia.

Aged↗
PubMed1997

Effect of storage temperatures and ingredients on growth of Bacillus cereus in coffee creamers.

Growth of Bacillus cereus ATCC 33018 was evaluated in half and half (10.5% fat), whipping cream (30% fat), and nondairy creamer (7.5% fat). Samples were inoculated with approximately 10 vegetative cells/ml or 100 spores/ml and were subsequently stored at 4, 7, 23 and 32 degrees C. Within 9 h at 32 degrees C and 11 h at 23 degrees C, in both half and half and whipping cream, vegetative cells and spores reached population levels that can cause foodborne illness. No growth occurred in any product stored at 4 or 7 degrees C. Sodium stearoyl lactylate, a fatty acid derivative that is used as an emulsifier, inhibited growth of spores and vegetative cells in the nondairy creamers stored at either 32 or 23 degrees C.

Bacillaceae Infections↗
PubMed1997

Effects of Microfluidizer technology on Bacillus licheniformis spores in ice cream mix.

We studied the effect of Microfluidizer technology (sometimes referred to as "microfluidization"), a new ultra-high pressure homogenization process, on spores of Bacillus licheniformis in ice cream mix. Four batches of pasteurized ice cream mix were preheated to 33, 36, 44, or 50 degrees C, and spores of B. licheniformis were added to yield an inoculum of 2.0 x 10(4) spores/ ml of mix. Samples were treated at 50,000, 100,000, 150,000, and 200,000 kPa. Respective percentages of spore destruction ranged from 6 to 68%. As process pressure in the Microfluidizer system increased, the temperature of the product also increased. At the Microfluidizer system outlet, temperatures ranged from 46 to 88 degrees C. Therefore, a combination of forces, including high pressure and temperature, likely had a multiplier effect on spore destruction during Microfluidizer processing of ice cream mix. Data suggest that it might be possible to design a pasteurizer-Microfluidizer system that would inactivate most bacterial spores in dairy foods without the extreme heat treatment currently required in commercial processing operations.

Bacillus↗
PubMed1996

Characterization of three components of human adenovirus proteinase activity in vitro.

Human adenovirus contains a virion-associated proteinase activity essential for the development of infectious virus. Maximal proteinase activity in vitro had been shown to require three viral components: the L3 23-kDa protein, an 11-amino acid cofactor (pVIc), and the viral DNA. Here, we present a quantitative purification procedure for a recombinant L3 23-kDa protein (recombinant endoproteinase (rEP)) expressed in Escherichia coli and the procedure that led to the purification and identification of pVIc as a cofactor. The cofactors stimulate proteinase activity not by decreasing Km, which changes by no more than 2-fold, but by increasing kcat. rEP alone had a small amount of activity, the kcat of which increased 355-fold with pVIc and 6072-fold with adenovirus serotype 2 (Ad2) DNA as well. Curves of Vmax of rEP.pVIc complexes with the substrate (Leu-Arg-Gly-NH)2-rhodamine as a function of pH in the absence and presence of Ad2 DNA indicate that the pKa values of amino acids that affect catalysis are quite different from those that affect catalysis by the cysteine proteinase papain. The pKa values in the absence of Ad2 DNA are 5.2, 6.4, 6.9, 7.5, and 9.4, and those in its presence are 5.2, 6.5, 7.4, and 8.8.

Adenoviruses, Human↗
PubMed1996

Differential spinal projections from the forelimb areas of the rostral and caudal subregions of primary motor cortex in the cat.

We used anterograde transport of WGA-HRP to examine the topography of corticospinal projections from the forelimb areas within the rostral and caudal motor cortex subregions in the cat. We compared the pattern of these projections with those from the somatic sensory cortex. The principal finding of this study was that the laminar distribution of projections to the contralateral gray matter from the two motor cortex subregions was different. The rostral motor cortex projected preferentially to laminae VI-VIII, whereas caudal motor cortex projected primarily to laminae IV-VI. Confirming earlier findings, somatic sensory cortex projected predominantly to laminae I-VI inclusive. We found that only rostral motor cortex projected to territories in the rostral cervical cord containing propriospinal neurons of cervical spinal segments C3-4 and, in the cervical enlargement, to portions presumed to contain Ia inhibitory interneurons. We generated contour maps of labeling probability on averaged segmental distributions of anterograde labeling for all analyzed sections using the same algorithm. For rostral motor cortex, heaviest label in the dorsal part of lamina VII in the contralateral cord was consistently located in separate medial and lateral zones. In contrast, no consistent differences in the mediolateral location of label was noted for caudal motor cortex. To summarize, laminae I-III received input only from the somatic sensory cortex, while laminae IV-V received input from both somatic sensory and caudal motor cortex. Lamina VI received input from all cortical fields examined. Laminae VII-IX received input selectively from the rostral motor cortex. For motor cortex, our findings suggest that projections from the two subregions comprise separate descending pathways that could play distinct functional roles in movement control and sensorimotor integration.

Animals↗
PubMed1996

Developmental expression in the mouse nervous system of the p493F12 SAP kinase.

Mitogen-activated protein (MAP) kinases are proline-directed, serine/threonine kinases that respond to a variety of extracellular signals. A subgroup of these kinases, stress-activated protein (SAP) kinases, phosphorylate c-jun in response to cellular stress. Using monoclonal antibody (MAb) 3F12, we have cloned and partially characterized p493F12 kinase, a mouse homologue of the rat SAP beta kinase and described its expression in the adult and developing mouse. Unlike previously reported MAP and SAP kinases, it is primarily expressed as a 2.7 kb transcript in neurons in the nervous system of the adult mouse. A 2.4 kb transcript is also expressed in the testis. Immunocytochemically, MAb 3F12 decorates a loop-like structure encircling the nucleus in the cytoplasm of neurons in the adult brain, and distinct perinuclear dots in the embryos. In situ hybridization first reveals expression in post-mitotic neurons, on embryonic day 11. The mRNA is also expressed in the Neuro-2A neuroblastoma cell line and is not upregulated in response to differentiating agents. The neuronal specificity of this kinase suggests the presence of a signal transduction cascade unique to neurons. As the amino acid sequence is highly conserved in the human and mouse, the latter may serve as a model for regulation and expression of this kinase.

Aging↗
PubMed1996

Supraglottic and pharyngeal sensory abnormalities in stroke patients with dysphagia.

Dysphagia and aspiration are two devastating sequelae of stroke, accounting for nearly 40,000 deaths from aspiration pneumonia each year in the United States. While motor deficits in the larynx and pharynx are thought responsible for dysphagia and aspiration in stroke patients, no prior study has evaluated whether these patients also have sensory deficits. The aim of this study was to evaluate the sensory capacity of the laryngopharynx (LP) in supratentorial or brain stem stroke patients who presented with dysphagia. Fifteen stroke patients (mean age, 66.7 +/- 13.8 [SD] years) were prospectively evaluated by means of our previously described method whereby air pulse stimuli were delivered via a flexible fiberoptic telescope to the mucosa innervated by the superior laryngeal nerve. There were 15 age-matched controls. No LP sensory deficits were found in any of the age-matched controls. In all stroke patients studied, either unilateral (n = 9) or bilateral (n = 6) sensory deficits were identified. Deficits were defined as either a moderate impairment in sensory discrimination thresholds (3.5 to 6.0 mm Hg) or a severe sensory impairment (> 6.0 mm Hg). These sensory discrimination thresholds were significantly greater than in age-matched controls (7.05 +/- 0.17 mm Hg for the supratentorial group and 6.05 +/- 1.22 mm Hg for the infratentorial group versus 2.61 +/- 0.69 mm Hg for the controls). Among patients with unilateral deficits, sensory thresholds were moderately to severely elevated in all 9 cases on the affected side compared with the unaffected side (p < .01, Fisher's exact test). Moreover, the sensory thresholds of the unaffected side were not significantly different from those of age-matched controls (2.51 +/- 0.25 mm Hg versus 2.61 +/- 0.69 mm Hg, respectively). All 6 patients with bilateral deficits had severe impairments. The results of an outcome assessment in 13 of 15 patients revealed that 2 out of 5 patients with moderate LP sensory impairment and 5 out of 8 with severe impairment developed aspiration. Our results show for the first time that stroke patients with dysphagia have significant sensory deficits in the LP and that these impairments are likely to contribute to the development of aspiration.

Aged↗
PubMed1995

Kinematic analysis of reaching in the cat.

The present study examines the kinematic features of forelimb movements made by cats reaching for food in horizontal target wells located at different heights and distances. Wrist paths consisted of two relatively straight segments joined at a "via-point" in front of the aperture of the food well. In the initial lift phase, the paw was raised to the via-point in front of the target. In the second, or thrust phase, the paw was directed forward into the food well. During the lift, the paw was moved toward the target primarily by elbow flexion, accompanied by a sequence of biphasic shoulder and wrist movements. Thrust was accomplished primarily by shoulder flexion while the wrist and the paw were maintained at near-constant angles. The animals varied the height of the reach primarily by varying elbow flexion with proportional changes in elbow angular velocity and angular acceleration and with corresponding variations in wrist speed. Thus, cats reached for targets at different heights by scaling a common kinematic profile. Over a relatively large range of target heights, animals maintained movement duration constant, according to a simple "pulse-height" control strategy (isochronous scaling). For reaches to a given target height, animals compensated for variability in peak acceleration by variations in movement time. We examined the coordination between the shoulder and the wrist with the elbow. Early during the lift, peak shoulder extensor and peak elbow flexor accelerations were synchronized. Late during the lift phase, wrist extensor acceleration was found to occur during the period of elbow flexor deceleration. We hypothesize that these linkages could, in part, be due to passive mechanical interactions. To determine how the angular trajectories of the different joints were organized in relation to target location, we plotted joint kinematic changes directly on the wrist and MCP joint paths. These plots revealed that for all target heights and movement speeds, wrist extensor deceleration occurred at approximately the same spatial location with respect to the target. This analysis also demonstrated that the second phase of MCP flexion occurred when the paw was below the lower lip of the food well, while the subsequent extension occurred after the tip cleared this obstacle. During thrust, wrist and MCP angles were maintained, reflecting the need to align the paw within the food well. Our findings suggest that cats plan the reaching phase of prehension as a sequence of discrete movement segments, each serving a particular goal in the task, rather than as an single unit.

Animals↗
PubMed1995

p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system.

Monoclonal antibody 3F12 identifies a cytoplasmic antigen of 49 kDa in human hippocampus and neocortex. The distribution of 3F12 immunoreactive neurons closely matches that of Alzheimer's disease (AD) targeted neurons in these areas. In some hippocampal neurons of AD patients, this antigen colocalizes with ALZ-50, indicating the presence of AD pathology in these neurons. Molecular characterization of the 3F12 cDNA revealed it to be a member of the MAP kinase family, showing 43% amino acid sequence identity to human extracellular related kinase 2 (p42mapk). We have confirmed that p493F12 kinase autophosphorylates both threonine and tyrosine residues, as expected for a MAP kinase. The p49 mRNA is expressed exclusively in the nervous system. In the brain, the distribution of these neurons closely corresponds to 3F12 antigen-bearing neurons. The p493F12 gene maps to the human chromosome 21q21 region, a region that may be important in the pathogenesis of AD and Down's syndrome.

Adult↗
PubMed1994

Renal system changes in the elderly.

Fluid and electrolyte management in the elderly is a tenuous situation. Because elderly patients have a decreased capacity to regulate extracellular volume, health care personnel must administer i.v. fluids carefully. Age-related renal changes subject elderly patients to a variety of potential problems. Astute assessment skills by the perioperative nurse, however, may reduce the chance of complications and ensure optimal patient outcomes.

Acute Kidney Injury↗
PubMed1994

Age-related changes in pharyngeal and supraglottic sensation.

As one ages, sensory discrimination in the oral cavity progressively diminishes, and dysphagia and aspiration are more likely to occur. Whether similar age-related laryngeal and pharyngeal sensory abnormalities exist and contribute to dysphagia and aspiration is unknown. The purpose of this study was to determine if sensory discrimination in the area innervated by the superior laryngeal nerve diminishes with increasing age. By applying a previously described new device and technique that utilizes brief air pulse stimulation of the anterior wall of the pyriform sinus, sensory discrimination can be reliably determined. We carried out 672 trials in 56 healthy adults divided into three age groups: 20 to 40, 41 to 60, and 61 to 90 years of age. Overall, the average sensory discrimination was 2.30 +/- 0.50 mm Hg. In subjects 20 to 40 years of age, sensory discrimination was 2.07 +/- 0.20 mm Hg, while in subjects 61 to 90 years of age, sensory discrimination was 2.68 +/- 0.63 mm Hg (p < .05). There also was a statistically significant difference between the 41- to 60-year and 61- to 90-year age groups (p < .05). Progressive diminution in pharyngeal and supraglottic sensitivity with increasing age might be a contributing factor in the development of dysphagia and aspiration in the elderly.

Adult↗
PubMed1994

Interferon-gamma enhances monocyte cytotoxicity via enhanced reactive oxygen intermediate production. Absence of an effect on macrophage cytotoxicity is due to failure to enhance reactive nitrogen intermediate production.

Interferon-gamma (IFN-gamma) enhanced the cytotoxic capability of freshly isolated human blood monocytes but failed to enhance the tumoricidal competence of monocyte-derived macrophages. Treatment of monocytes with IFN-gamma (100 U/ml) caused a significant increase (P < 0.001) in lucigenin-dependent chemiluminescence and O2- production stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) during the first few days in culture but IFN-gamma was unable to prevent the decline to negligible levels of chemiluminescence and O2- production which occurred during the later days in vitro. Culture of monocytes in the presence of IFN-gamma had no effect on phorbol 12-myristate 13-acetate (PMA)-stimulated O2- production. However, IFN-gamma decreased PMA-stimulated lucigenin-dependent chemiluminescence during the first 24 hr in vitro but then significantly enhanced (P < 0.001) chemiluminescence after 2-4 days in culture. IFN-gamma was unable to prevent the eventual decline to undetectable levels in PMA-stimulated chemiluminescence during the later days in vitro. Nitrite production by macrophages was unaffected by IFN-gamma treatment. It is concluded therefore, that IFN-gamma enhanced the cytotoxicity of freshly isolated human blood monocytes by increasing reactive oxygen intermediate generation but was unable to enhance the tumoricidal competence of macrophages as reactive nitrogen intermediate production was unaffected.

Acridines↗