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Biomedical subjects

J H Martin

Publications and source records attributed to J H Martin.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1993

Differential spinal projections of subregions in the forelimb area of the motor cortex in the cat.

Anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was used to examine the topography of projections from the forelimb area of motor cortex to the cervical spinal cord in the cat. Tracer was injected in sites in the rostrolateral (RL-MCx) and caudolateral (CL-MCx) subregions concerned with the distal forelimb. Whereas both subregions projected throughout the cervical cord, with the greatest density of label present in the cervical enlargement, the dorso-ventral distributions were different for the two injection sites. Injections in RL-MCx produced labeling in the lateral portions of laminae VI, VII, and VIII in the upper cervical segments. This corresponds to the locations of propriospinal neurons that project to forelimb motor nuclei used in reaching [Exp. Brain Res., 42 (1981) 299-318]. In the cervical enlargement, labeling was present in laminae V, VI, VII, and part of VIII. At all levels examined, the density of labeling was greatest in the intermediate zone. After CL-MCx injection, labeling was concentrated in the dorsal horn both in the upper cervical segments and in the cervical enlargement. These findings suggest that the two motor cortical subregions project to different propriospinal and interneuronal systems in the cervical cord and support the idea that the two subregions play different roles in controlling forelimb movements.

Animals↗
PubMed1993

Changes in mechanisms of monocyte/macrophage-mediated cytotoxicity during culture. Reactive oxygen intermediates are involved in monocyte-mediated cytotoxicity, whereas reactive nitrogen intermediates are employed by macrophages in tumor cell killing.

Freshly isolated human blood monocytes were spontaneously cytotoxic toward K562 tumor cells. During culture of the monocytes in vitro cytotoxicity decreased during the first 48 h but tumoricidal competence was restored after 3 to 4 days in vitro. These changes were accompanied by changes in both reactive oxygen intermediate generating capacity and reactive nitrogen intermediate production. Lucigenin-dependent chemiluminescence stimulated with either FMLP or PMA declined during the first 2 days in culture and was negligible during the later days in culture. Superoxide radical production in response to either FMLP or PMA remained fairly constant for the first few days in vitro and then declined. NO2- concentration in monocyte-conditioned medium was fairly constant during the first few days in vitro but increased after 6 days. The return to tumoricidal competence after 3 to 4 days in culture was decreased by the addition of NG-monomethyl-L-arginine. These results indicate that reactive oxygen intermediates are employed by monocytes in the killing of tumor cells. However, after maturation of monocytes to macrophages, this mechanism becomes less important and reactive nitrogen intermediates are employed in mediating macrophage cytotoxicity.

Arginine↗
PubMed1993

Calphotin: a Drosophila photoreceptor cell calcium-binding protein.

Monoclonal antibody 23E9 identifies a calcium-binding protein, calphotin, in photoreceptor cells of the Drosophila melanogaster compound eyes and ocelli. The antigen is restricted to a defined cytoplasmic region; it is not present in the rhabdomeres, nuclei, mitochondria, or rough endoplasmic reticulum. A corresponding cDNA recognizes a 3-kb mRNA with retinal specificity similar to the antigen and maps to band 86E/F-87A/B on chromosome 3. An open reading frame of 2595 bp encodes an estimated 85-kDa protein of unusual amino acid composition, with > 50% proline, alanine, and valine and very few basic residues. The C-terminal segment contains a leucine zipper motif uninterrupted by prolines. We found no significant similarities with the GenBank or National Biomedical Resource Foundation data bases. The location of the protein within a distinct cytoplasmic region suggests that it might function as a calcium-sequestering "sponge" to regulate the amount of free cytoplasmic calcium.

Amino Acid Sequence↗
PubMed1993

Differential effects of local inactivation within motor cortex and red nucleus on performance of an elbow task in the cat.

This study examined changes in the performance of a single-joint, elbow task produced by reversible inactivation of local regions within the proximal forelimb representation in area 4 gamma of motor cortex (MCx) and the red nucleus (RN) of the cat. Inactivation was carried out by microinjecting lidocaine, gamma-aminobutyric acid, or muscimol into sites where microstimulation evoked contraction of elbow muscles. Reaction time, amplitude, and speed (velocity or dF/dt) of position and force responses elicited during inactivation were compared to control values obtained immediately prior to inactivation. In addition, we assessed qualitatively the effects of inactivation on reaching, placing reactions, and proprioceptive responses to imposed limb displacement. In the single-joint task, injections in MCx did not increase reaction time (simple or choice) and produced modest and inconsistent reductions in response amplitude (mean -8%) and speed (mean -19%). In contrast, injections of the same amounts of inactivating agents in the forelimb representation of RN consistently increased reaction time (34.4%), and increased the reaction time coefficient of variability (32%). There were small reductions in response amplitude (-4%) and speed (-10%) which were less than those produced by MCx inactivation. During reaching, however, these same injections in MCx and RN produced a substantial loss of accuracy. For MCx, this was due, in part, to systematic hypometria: for RN, inaccuracy resulted from increased variability in paw paths. Placing reactions and corrective responses to imposed limb displacements were also depressed by the cortical and rubral injections. Our results suggest that the forelimb representation in RN plays a role in the initiation of the single-joint, elbow tracking response examined here. The RN may mediate cerebellar regulation of response timing, a function that is likely to be important for interjoint coordination. Although neurons in the forelimb representations of MCx may contribute to force generation in single-joint movements, their contribution to multijoint control appears to be more important and is examined in the subsequent report (Martin and Ghez 1993).

Animals↗
PubMed1993

Differential impairments in reaching and grasping produced by local inactivation within the forelimb representation of the motor cortex in the cat.

This study analyzed changes in the performance of a reaching task and its adaptive modification produced by reversible inactivation of three sites within the forelimb representation of the motor cortex (MCx, area 4 gamma) in five cats by microinjections of muscimol. Two sites were located in the lateral MCx, rostral (RL-MCx) and caudal (CL-MCx) to the end of the cruciate sulcus, where intracortical microstimulation (ICMS) produced contraction of the most distal muscles. The third site was located more medially, in the anterior sigmoid gyrus (RM-MCx) where ICMS primarily produced contraction of more proximal muscles. The task required the animals to reach into a horizontal target well, located in front of them at one of three possible heights, to grasp and retrieve a small piece of food. The height of the reach was primarily achieved by elbow flexion. Grasping consisted primarily of digit flexion, and food retrieval consisted of forearm supination and shoulder extension. In some blocks of trials, an obstacle was placed in the path of the limb to assess the animal's ability to adaptively adjust the kinematic characteristics of their response trajectory. In normal animals, contact with the bar on the first trial triggered a corrective response at short latency that allowed the paw to circumvent the bar. On all subsequent trials, the trajectory was adapted to prevent contact with the obstacle, with a safety margin of about 1 cm. Inactivation at all sites produced a slowing of movement, a protracted and extended forelimb posture, and increased variability of initial limb position. In addition, inactivation of RL-MCx immediately produced systematic reaching errors, consisting of hypermetric movements, as well as impaired grasping and food retrieval. The degree of hypermetria was similar for all target heights and was not associated with alterations in trajectory control. During inactivation, animals did not compensate for the hypermetria by reducing paw path elevation, suggesting a defect in kinematic planning or in adaptive control. This was confirmed by finding that trajectory adaptation to avoid bar contact was impaired during RL-MCx inactivation. The short latency corrective response, triggered by contact of the limb with the obstacle was, however, preserved. Inactivation of CL-MCx did not impair aiming, grasping, or adaptation immediately after injection. However, impairments occurred after about 1 h postinjection, and at that time mimicked the effects of RL-MCx inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

The relationship between affinity of progestins and antiprogestins for the progesterone receptor in breast cancer cells (ZR-PR-LT) and ability to down-regulate the receptor: evidence for heterospecific receptor modulation via the glucocorticoid receptor.

In a human breast cancer cell line (ZR-PR-LT) we have found a poor overall correlation between affinity of progestins and anti-progestins for the progesterone receptor (PGR), concentration required for receptor down-regulation and anti-proliferative potency. Medroxyprogesterone acetate (MPA) and the anti-progestin RU 38.486, which possess glucocorticoid and antiglucocorticoid activity, respectively, cause receptor down-regulation at lower concentrations than their Kdi for [3H] ORG 2058 binding sites. In addition dexamethasone markedly down-regulates PGR at concentrations which fail to interact with PGR suggesting that heterospecific modulation of PGR occurs via the glucocorticoid receptor. In contrast the progestin ORG2058 and the anti-progestin ZK 98.299 caused 50% PGR down-regulation at a concentration (EC50) 50-fold higher than their Kdi values. ZK 112.993 was 500-fold more potent at PGR down-regulation than ZK 98.299 but had only a 5-fold higher affinity for PGR. Anti-proliferative concentrations of progestins/anti-progestins showing were generally higher than either Kdi values or EC50 values.

Binding, Competitive↗
PubMed1993

Air pulse quantification of supraglottic and pharyngeal sensation: a new technique.

There are no published studies evaluating the sensory capacity of the region innervated by the superior laryngeal nerve. A normal sensory capacity is important in this area, since hypesthesia or anesthesia of the pharynx and supraglottic larynx may result in dysphagia and aspiration. This often occurs after stroke or after ablative surgery of the pharynx and larynx. Evaluating the efficacy of restorative procedures for supraglottic and pharyngeal sensation is dependent on defining and quantifying the sensory deficit. We have developed a new, noninvasive method to measure sensation in the pharynx and supraglottic larynx. A puff of air--of precisely controlled duration and pressure--was delivered via a flexible telescope to the anterior wall of the pyriform sinus. Surface sensibility was determined according to the psychophysical method of limits by varying air pressure while holding puff duration constant. We conducted 204 trials in 20 healthy adults. The average sensory discrimination threshold was 2.09 +/- 0.15 mm Hg. An intraclass correlation revealed excellent consistency (R = .80). There was no statistically significant difference between the right and left sides. Brief air pulse stimulation is an easy, relatively safe, and reliable method of determining supraglottic and pharyngeal sensory discrimination thresholds.

Adult↗
PubMed1993

Modification of the ultrastructure of the muscle larva of Trichinella pseudospiralis following exposure to acidified pepsin solution.

Examination of the cuticle of Trichinella pseudospiralis by transmission electron microscopy revealed an epicuticle, exocuticle, and mesocuticle, each divided into several layers. The epicuticle consisted of an outermost thin plasmalemmalike infracuticular material covering an inner trilaminar membrane. The exocuticle was granular and could be divided into 2 regions on the basis of density. The mesocuticle was fibrillar and 3 regions could be distinguished based on the orientation of fibrils. The cuticle appears attached to the hypodermis by hemidesmosomes. The infracticular structure was altered following isolation of larvae by pepsin-HCl digestion of host muscle.

Animals↗
PubMed1992

The relationship between delta 13C of organic matter and [CO2(aq)] in ocean surface water: data from a JGOFS site in the northeast Atlantic Ocean and a model.

The delta 13C of suspended particulate organic matter (SPOM) in surface waters increased from -22.9 to -18.1% during April 25-May 31, 1989 at the JGOFS North Atlantic Bloom Experiment Site (NABE Site; 47 degrees N, 20 degrees W). During the same period, nearly parallel increases in sinking POM delta 13C were also found, although these values were usually lower than those of the corresponding SPOM. Consistent with the hypothesis that plankton delta 13C and [CO2 (aq)] are inversely related, the increases in both sinking and suspended POM delta 13C were highly negatively correlated with mixed-layer [CO2(aq)] that generally decreased from 13.2-10.1 micromoles/kg during the five weeks. The change in SPOM delta 13C per change in [CO2(aq)], however, appears to be somewhat greater than that expected from previous, though less direct, ocean and laboratory evidence. By adapting a model of plant delta 13C by FARQUHAR et al. (1982), it is shown that under a constant phytoplankton demand for CO2 an inverse, nonlinear SPOM delta 13C response to ambient [CO2(aq)] is expected. Such trends are unlike the negative linear relationships indicated by data from the NABE Site and or from Southern Hemisphere waters. Such differences between predicted and observed SPOM delta 13C vs. [CO2(aq)] trends and among observed relationships can be reconciled, however, if biological CO2 demand is allowed to vary. This has significant implications for the use of the delta 13C of plankton (or their organic subfractions or sedimentary remains) as a proxy for past or present ocean CO2 concentrations and biological productivity.

Atlantic Ocean↗
PubMed1992

Susceptibility of corneas from various animal species to in vitro binding and invasion by Acanthamoeba castellanii [corrected].

A crucial requirement for establishing corneal infection by the extracellular protozoal parasite, Acanthamoeba, is the ability of the parasite to bind to the corneal surface. In a series of in vitro studies, we examined the ability of Acanthamoeba castellanii [corrected] to adhere, invade, and damage normal, intact corneas of 11 mammalian and one avian species. A. castellanii [corrected] (80-90% trophozoites and 10-20% cysts) were incubated with corneas for 24 hours in vitro and examined by scanning electron microscopy (SEM). Results of several independent SEM experiments revealed that parasites not only failed to produce cytopathic effects but did not even bind to the corneal epithelium of mice, rats, cotton rats, horses, guinea pigs, cows, chickens, dogs, and rabbits. However, parasites adhered, invaded, and produced severe damage to human, pig, and Chinese hamster corneas during the 24-hour in vitro incubation period. Additional in vitro experiments quantified the binding of A. castellanii [corrected] to the corneas of selected susceptible and nonsusceptible species. In vitro binding assays revealed scant binding of parasites to mouse, rat, and rabbit (range = 5-20 parasites/7.07 mm2 corneal button). In contrast, extensive binding was observed on Chinese hamster, pig, and human corneas (range = 100-200 parasites/7.07 mm2 button). The results indicate that A. castellanii [corrected] exercises rigid host specificity at the host cell surface.

Acanthamoeba↗
PubMed1991

Impairments in reaching during reversible inactivation of the distal forelimb representation of the motor cortex in the cat.

We report changes in the performance of a prehension task in the cat following focal inactivation of the rostrolateral subregion of the distal forelimb area of motor cortex (MCx) produced by muscimol microinjection. Animals reached into a cylindrical target to retrieve a morsel of food. Movements consisted of distinct lift and forward thrust phases following which the food was grasped and retrieved. In separate blocks of trials an obstacle was inserted in the path of the limb. Impact evoked an immediate compensatory trajectory change to bypass the obstruction and, on subsequent trials, an adaptive trajectory change to avoid impact. Inactivation produced three major defects: (1) uncompensated aiming biases to a location above the target; (2) loss of coordination of the grasp and food retrieval; and (3) impairment in trajectory adaptation to avoid impact of the limb with an obstacle. Thus, focal inactivation of the distal forelimb area of MCx produced disordered control of all forelimb joints. The impairment in trajectory adaptation and failure to compensate for aiming biases suggests that the MCx is important in motor learning.

Animals↗
PubMed1991

Autoradiographic estimation of the extent of reversible inactivation produced by microinjection of lidocaine and muscimol in the rat.

We used autoradiography to examine the extent of reversible inactivation produced by microinjection of lidocaine (40 micrograms/microliters saline) and muscimol (1 microgram/microliter saline). We measured intracortical spread of tracer amounts of labelled drug and local changes in uptake of [1-14C]glucose produced by the microinjection. The maximal average radii of regions of drug spread were 1.7 mm for both [14C]lidocaine and [3H]muscimol and were achieved within the first 20 min postinjection. The width of lidocaine injections decreased at longer postinjection times (30-60 min) but the width of muscimol injections remained relatively constant (30-120 min). Lidocaine radioactivity decreased faster from the injection site than muscimol radioactivity. Glucose autoradiograms showed a discrete region of maximally reduced glucose uptake (1.4 mm for lidocaine and 1.0 mm for muscimol) surrounded by a region of less reduced glucose uptake (up to approximately 3 mm). These findings suggest that, in the cortex, the effects of focal inactivation extend beyond the region of drug spread. Diffuse effects may be mediated of disfacilitation of cortico-cortical circuits.

Animals↗
PubMed1991

Cryofixation, ultracryomicrotomy, and X-ray microanalysis of enterocytes from chick duodenum: vitamin-D-induced formation of an apical tubulovesicular system.

New methods of tissue preparation were developed to study the morphology and distribution of calcium ions in duodenal enterocytes from normal, rachitic, and vitamin D-replete (either cholecalciferol [CC] or 1,25-dihydroxycholecalciferol [1,25-DHCC] treated) chicks. Frozen hydrated sections were prepared from cryofixed tissues by ultracryomicrotomy at -125 degrees C. Sections were subsequently freeze-dried by increasing the temperature to -100 degrees C. The latter temperature was maintained throughout both the structural and elemental analyses. In cells from normal, rachitic, and vitamin D-treated [CC] animals the brush border from lanthanum-infused tissues was electron dense and calcium-lanthanum positive by x-ray analysis. In the absence of lanthanum, i.e., sucrose-infused duodena, the microvilli were still calcium positive. In the terminal web region of normal and CC-treated enterocytes, numerous, apparently interconnected, tubules and vesicles were seen. Vacuole-like structures were also seen. Such structures were especially prominent in the enterocytes from the vitamin-treated [CC] animals. Except for the vacuoles, the tubules and vesicles were electron dense in the lanthanum-infused duodena, and clear in sucrose-infused tissues. In both instances, the structures were calcium positive. Similar, but even larger structures were seen below the terminal web. Here however, the tubules and vesicles seemed to be organized into multiple complex interconnecting networks, i.e., tubulo-vesicular complexes. Both the tubules and the vesicles seemed to be interconnected via smaller channel-like entities. The extensiveness of this structure was better appreciated in the enterocytes from lanthanum-infused tissues, where it appeared similar in structure and complexity to an en face view of the sarcoplasmic reticulum of skeletal muscle. These intestinal complexes were less well developed, decreased in number, and quite often absent, in the apical cytoplasm of absorptive cells from rachitic chicks. In the enterocytes from animals treated for 24 hours with 1,25-DHCC, the same highly developed tubulo-vesicular networks were again seen in the enterocyte apical cytoplasm. They were even more developed in the 1,25-DHCC-treated animals. All structures were intensely calcium positive in enterocytes from both the lanthanum- and the sucrose-infused preparations. Numerous endocytotic (pinocytotic) vesicles were seen at the lumenal plasmalemma. Similar structures were also apparent in the terminal web region of the 1,25-DHCC-treated enterocytes. Exocytotic vesicles were seen at the apical aspect of the lateral cell membrane, below the level of the junctional complex. All components of this unique system contained high concentrations of calcium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗