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Biomedical subjects

R E Martin

Publications and source records attributed to R E Martin.

At least 19 recordsLinked to original sources

Growth-associated protein GAP-43 and nerve cell adhesion molecule in sensory nerves of cornea.

We used dual-wavelength fluorescence microscopy and monoclonal antibodies to growth-associated protein (GAP-43) and nerve cell adhesion molecule (N-CAM) to identify these proteins in nerve fibers of normal rat and rabbit corneas. Overlapping immunoreactivity of GAP-43 and N-CAM was evident along nerve fibers of rabbit corneal sections, suggesting that GAP-43 is constitutively expressed in these sensory nerves. The immune reaction of monoclonal antibody to GAP-43 and [125I]protein A was used to quantitate relative amounts of GAP-43 in the normal cornea and in a cornea subjected to a de-epithelializing wound. Collectively these findings imply that GAP-43 is axoplasmically transported from cells in the trigeminal (or superior cervical) ganglion to the cornea. Moreover, these data indicate that GAP-43 appears to be involved in the remodeling of corneal nerves that is necessary for normal innervation.

Animals

Changing fatty acid content of growth cone lipids prior to synaptogenesis.

The developing mouse was used to assess biochemical changes in membrane lipids during the period when nerve growth cones become synapses. Growth cone particles and synaptosomes were simultaneously obtained from common brain homogenates. Incorporation of the essential fatty acid, docosahexaenoic acid (22:6 omega-3), was correlated with the developmental changes in endogenous fatty acid content of growth cones and synaptosomes. Analysis of endogenous lipid content indicated that, at all ages studied, the growth cones contained more arachidonoyl acyl chains (20:4 omega-6) than did synaptosomes. Before the onset of synaptogenesis, levels of arachidonoyl chains increased and levels of 22:6, oleoyl and linoleoyl chains decreased in synaptosomes. Although stearoyl and palmitoyl (16:0) remained stable in synaptosomes, 16:0 decreased in growth cones. With the exception of 16:0 and 20:4, endogenous fatty acyl content of growth cones and synaptosomes became similar by postnatal day 10, which coincides with the onset of synaptogenesis. When 5-day-old mouse pups were injected intraperitoneally with [3H]22:6, the incorporation into growth cone and synaptosome phospholipids was greatest in phosphatidylethanolamine, followed by phosphatidylserine and phosphatidylcholine. Nominal labeling was present in phosphatidic acid and phosphatidylinositol. Labeling in neutral lipids was less than that of phospholipids, with triacylglycerol incorporating most of the neutral lipid label, followed by diacylglycerol and free 22:6. Only the growth cone fraction contained detectable amounts of 22:6-labeled cholesterol esters. The distribution of 22:6 label in plasma 72 h after injection indicated that approximately 60% of the label was in phospholipids with approximately 40% in neutral lipids and less than 5% in free fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Structure-activity relationships in calcitonin gene-related peptide: cyclic AMP response in a preosteoblast cell line (KS-4).

Synthetic analogs of chicken and human CGRP were used to define structure-function relationships in a murine osteoblast precursor cell line, KS-4, that exhibits a substantial cyclic AMP response to CGRP but no response to calcitonin. Human CGRP had 40% of the activity of chicken CGRP, but [Asp-14]-human CGRP was equipotent with chicken CGRP. Similar observations were made previously for calcium- and phosphate-lowering effects. Des-1-Ala,deamino CGRP compounds of both human and chicken origin were three-fold more potent than the respective native CGRPs. The [4-F-Phe)-37]-chicken CGRP analog had a four-fold enhanced activity. In all of the 13 analogs either truncated amino-terminally or missing the (2-7)-disulfide bridge, biologic activity was greatly reduced (0.1% of chicken CGRP), as it was in chicken CGRP-(1-36)-OH, which lacks the C-terminal amino acid. The same analog has been shown to retain a hypocalcemic effect, which is most likely mediated through calcitonin receptors. In confirmation of their antagonistic effect reported in liver, analogs that lack the N-terminal ring structure exhibited significant antagonistic activity. The data illustrate the specificity of CGRP receptors in promoting cyclic AMP formation in osteoblast-like cells. Such CGRP analogs will be useful in investigating structure-function relationships of CGRP.

Animals

Speech deterioration in amyotrophic lateral sclerosis: a case study.

Few detailed reports have been published on the nature of speech and voice changes during the course of amyotrophic lateral sclerosis (ALS). The subject of this case study is a woman who was diagnosed as having ALS with bulbar signs at the age of 53. Speech intelligibility, pulmonary function, and selected speech and voice functions were tested during an approximately 2-year course of her disease. Over this period, her speech intelligibility, as measured by a multiple-choice word identification test, declined from 98% to 48%. Phonetic features that were most affected during the intelligibility decline included voicing contrast for syllable-initial and syllable-final consonants, place of articulation contrasts for lingual consonants, manner of articulation for lingual consonants, stop versus nasal manner of production, features related to the liquid consonants, and various features related to syllable shape. An acoustic measure, average slope of the second-formant frequency, declined in association with the intelligibility reduction and is thought to reflect the loss of lingual motoneurons. Her pulmonary function also declined over the observation interval, with particularly severe reduction in measures of air flow. Oral diadochokinesis and measures of vocal function (including jitter, shimmer, and signal-to-noise ratio) were highly variable across test sessions. These results are discussed in terms of the challenges they present to sensitive assessment of change and to management of the communication disability in ALS.

Amyotrophic Lateral Sclerosis

Atypical pneumonia.

The atypical pneumonia syndrome usually implies a benign illness where systemic complaints predominate over respiratory symptoms. Cough is prominent; chest radiographic findings are varied. Many organisms are associated with this syndrome. Mycoplasma pneumoniae, Chlamydia psittaci, Chlamydia pneumoniae, Coxiella burnetii, and Francisella tularensis are reviewed in this article.

Chlamydia Infections

Impairment of speech intelligibility in men with amyotrophic lateral sclerosis.

Speech intelligibility was studied in a group of 25 male patients with amyotrophic lateral sclerosis (ALS). The object of the study was to determine the phonetic impairments underlying the speech intelligibility deficits that frequently accompany ALS. Analyses with a word intelligibility test indicated that the most disrupted phonetic features involved phonatory (voicing contrast) function, velopharyngeal valving, place and manner of articulation for lingual consonants, and regulation of tongue height for vowels. The mean error proportion for the five most severely affected features correlated highly (0.97) with the intelligibility score (percent correct). The phonetic feature analyses are one index of bulbar muscle impairment in amyotrophic lateral sclerosis and also may help to direct the speech management in these individuals.

Adult

Multiple trauma and the elderly patient.

The elderly patient is likely to suffer severer immediate effects and more long-term complications from equivalent forces of injury. However, with an aggressive approach to evaluation, monitoring, and treatment, there is hope for successful recovery in the majority of cases.

Aged

Tissue and ultrastructural localization of 5-hydroxytryptamine (serotonin) in the tissues of Ascaris suum with energy dispersive X-ray spectrometry of immunoreactive structures.

Muscle, hypodermis and gastrointestinal epithelial cells from adult female Ascaris lumbricoides var. suum were found to contain serotonin based upon glyoxylic acid induced histofluorescence and indirect immunolabeling with an antiserotonin monoclonal antibody conjugated to protein A-colloidal gold. Histofluorescence indicated that muscle-hypodermis and intestinal epithelial cells contained significant concentrations of 5-hydroxytryptamine while fluorescence was absent in the nerve cord and cuticle. Immunolabeling at the ultrastructural level indicated that serotonin was sequestered in electron-opaque patches, dense vesicles and mitochondria of the muscle-hypodermis and intestinal tissue. Perfusion of whole worms and isolated tissues with 10(4) M-serotonin further indicated: (1) immunolabeled patches and dense vesicles were often associated with cytoskeletal elements, (2) serotonin did not appear to enter the intestinal or muscle cells by endocytosis, (3) immunolabeled patches examined with energy dispersive X-ray spectrometry (X-ray microanalysis) were found to contain iron at concentrations approximately double that of the surrounding cytoplasm.

Animals

A multivariate approach to analyzing the relation between occlusion and craniofacial morphology.

This study examined the association between occlusion and craniofacial morphology using univariate and multivariate statistical methods. Data were obtained from study casts and lateral cephalometric radiographs of 164 children in the early permanent dentition. The following multiple features of occlusion were assessed: molar relation, overjet, overbite, and anterior crowding. Angular skeletal measures assessed cranial base flexure, maxillary horizontal and vertical positions, mandibular horizontal and vertical positions, horizontal and vertical maxillary-mandibular relations, and positions of the incisors. The relation between the Occlusal Index, which is a malocclusion severity index, and skeletal morphology was also investigated. Associations were examined by use of linear correlation, stepwise multiple regression, and canonical correlation analyses. Individually and in combination, occlusal features were poorly associated with individual skeletal measures (r2 less than or equal to 0.35). The strongest association occurred between a linear combination of occlusal features and a linear combination of skeletal measures (R2 = 0.66, p = 0.0001). A malocclusion severity index did not aid in the identification of craniofacial morphology. The results suggested that combinations of certain occlusal characteristics may be associated with specific skeletal types; however, a generalized statement of this concept could not be supported.

Adolescent

Effect of postnatal nutritional status on subsequent growth and reproductive performance of gilts.

Two trials involving 128 gilts were conducted to determine the effect of nutritional status during the first 28 d postnatally on subsequent growth and reproductive performance. Nutritional status was altered by adjusting litter size at birth to either 6 or 12 pigs and maintaining a lactation length of either 13 or 28 d. Pigs weaned at d 13 were fed on an ad libitum basis or at 50% of ad libitum through d 28. After d 28, all pigs were fed the same diets through the first parity. By market weight (d 154) pigs recovered differences in body weight imposed during the early postnatal period. Postnatal nutritional status did not alter age at puberty. Gilts weaned at d 28 from litter size 6 produced 2.4 more (P less than .05) ova than gilts from litter size 12; however, when weaned at d 13, gilts from litter size 6 produced 2.3 fewer ova than gilts from litter size 12. Feed restriction for 15 d postweaning did not depress ovulation rate in gilts. Subsequent litter size was not affected by postnatal litter size, lactation length or feed restriction, even though growth rate and ovulation rate had been altered by treatments imposed during the first 28 d postnatally. Assuming no difference in fertilization, these data suggest that prenatal mortality was altered by the early postnatal treatments and was the limiting factor for litter size. Until factors that influence prenatal losses are characterized and controlled, the alteration of nutritional status by changes in postnatal litter size, lactation length or feeding level will not detrimentally affect subsequent litter size in gilts.

Age Factors

Auditory evoked heart rate responses in pigtailed macaques (Macaca nemestrina) raised in isolation.

Heart rate (HR) responses evoked by 1 sec of 85-dB white noise were studied in 12 1-year-old pigtailed macaques, 6 of which were raised in social isolation and 6 with mothers and peers. Tests were given for 5 days, with 25 trials each day. Although baseline HR did not differ between groups, the pattern of change from baseline was not the same. Isolates showed only HR acceleration, returning to baseline within 10-11 sec of stimulus onset. Socially reared monkeys had a 10- to 11-sec biphasic response of acceleration followed by deceleration, with subsequent return to baseline. The same group difference in HR pattern occurred when subjects were tested with a less intense 65-dB stimulus. These findings were discussed in terms of activity, emotionality, and autonomic regulatory functions. It was concluded that early rearing experiences may affect later physiological processes involving autonomic nervous system balance. This conclusion was related to observations of persistent individual differences in HR by human children classified as inhibited.

Acoustic Stimulation

Serotonin (5-hydroxytryptamine) turnover in adult female Ascaris suum tissue.

1. The 5-hydroxytryptamine (5-HT, serotonin) turnover was examined in the tissues of adult female Ascaris suum. The 5-HT turnover was highest in the intestine at 34.7 ng 5-HT produced/mg protein/hr and 13.8 ng 5-HT produced/mg protein/hr in muscle tissue. 2. The levels of 5-HT metabolites namely tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine, 5-hydroxyindole acetic acid and 5-hydroxytryptophol were measured in muscle and intestinal tissue of adult A. suum. 3. Parachlorophenylalanine inhibited 5-HT production in muscle and intestinal tissue providing in situ evidence for the presence of tryptophan hydroxylase in this tissue. 4. Pargyline increased 5-HT production in muscle and intestinal tissue providing in situ evidence for the presence of monoamine oxidase in this tissue.

Animals

Evidence for the absorption and synthesis of 5-hydroxytryptamine in perfused muscle and intestinal tissue and whole worms of adult Ascaris suum.

The metabolites of 5-hydroxytryptamine (5-HT, serotonin) namely, L-tryptophan, 5-hydroxytryptophan, 5-hydroxyindole acetic acid and 5-hydroxytryptophol were measured in perfused tissue and whole worms from adult female Ascaris suum using reversed-phase liquid chromatography with electrochemical detection. The intracellular levels of each metabolite were quantitated in response to several physiological effectors but only L-tryptophan (TRP) caused dose-dependent changes in these metabolites. Serotonin itself could also be absorbed by perfused A. suum muscle and intestinal tissue. When live A. suum were tied at the anterior and posterior regions to restrict TRP absorption by the intestine, TRP was absorbed through the cuticle and converted into 5-HT by the muscle tissue. In united live parasites TRP absorption was observed in both muscle and intestinal tissue. Collectively, the data indicated that 5-HT may be either absorbed directly or synthesized de novo from absorbed TRP in the isolated tissue of A. suum. The 5-HT, in the adult female A. suum, can be synthesized de novo from TRP, or 5-HT can be absorbed from the environment both through the cuticle and by the intestine of living parasites. Data also indicated that there was preferential sequestering of 5-HT and the metabolites of 5-HT in the anterior tissues of the worms.

5-Hydroxytryptophan

Ascaris lumbricoides suum: morphological characterization of apparent cuticular pores by ionic permeability and electron microscopy.

The cuticle of the parasitic roundworm Ascaris lumbricoides suum has been found to contain apparent pores, using scanning and transmission electron microscopy. However, X-ray spectral analysis and dot mapping analysis of diffusing divalent cations in the cuticle found these ions to be randomly distributed on the pseudocoelomic surface of the cuticle. This indicates that the pores seen with the electron microscope were not true structural pores and that the cuticle is homogeneously permeable to ions.

Animals

Correlation of myosin light chain phosphorylation and gamma aminobutyric acid receptors in Ascaris suum muscle.

Four different muscle relaxants were compared as to their effects on tonic Ascaris suum muscle to: physiological activity, intracellular response to regulatory light chain phosphorylation, and receptor pharmacology. Perfusion of Ascaris suum muscle with each relaxant, gamma-aminobutyric acid, avermectin, piperazine and chlorpromazine resulted in a dose-dependent loss of muscle tone. Comparison of intracellular effects indicated that gamma-aminobutyric acid and avermectin perfusion initiated an increase in the levels of dephosphorylated regulatory light chain while piperazine increased first site phosphorylation and chlorpromazine increased second site phosphorylation. Receptor pharmacology studies were used to compare the actions of gamma-aminobutyric acid and piperazine. It was found that bicuculline-methiodide and picrotoxin inhibited the effects of gamma-aminobutyric acid in a dose-dependent manner, but these drugs had no effect on muscle relaxation stimulated with piperazine.

Acetylcholine

Ascaris suum: regulation of myosin light chain phosphorylation from adult skeletal muscle.

The regulatory myosin light chain in Ascaris suum muscle was isolated in a phospho and dephosphoform. In freshly dissected tissue or in control muscle segments perfused with saline, approximately 48% of the total myosin light chain pool was phosphorylated. Perfusion with acetylcholine caused a dose dependent increase in muscle contraction but no change in myosin light chain phosphorylation. In contrast, perfusion with gamma-aminobutyric acid resulted in a dose dependent relaxation of A. suum muscle and a decrease in myosin light chain phosphorylation so that only 18% of the total myosin light chain remained phosphorylated. Trifluoroperizine, an inhibitor of myosin light chain phosphorylation, did not inhibit acetylcholine induced muscle contraction. Collectively, the data support the hypothesis that A. suum muscle contraction is mediated by actin.

Acetylcholine