Search PubMed⌕ Search

Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 235 records · Page 13Linked to original sources
PubMed1991

Effects of inhibitors of oligosaccharide processing on P0 protein synthesis and incorporation into PNS myelin.

Four inhibitors of oligosaccharide processing were used to investigate their effects on the transport of PNS myelin glycoproteins through the secretory pathway, as well as to gain further insight into the structure of the oligosaccharide chains of the P0 and 19-kDa glycoproteins. Several different inhibitors of oligosaccharide processing were incubated with chopped peripheral nerves from young rats (21-24 days of age) and the uptake of 14C-amino acid and [3H]fucose or [3H]mannose was measured in P0 and the 19-kDa glycoprotein after separation of homogenate and myelin proteins on polyacrylamide gels. [3H]Mannose was not found as suitable as [3H]fucose as an oligosaccharide precursor because glucose used as an energy source profoundly inhibited the uptake of [3H]mannose. The substitution of pyruvate as an energy source, however, resulted in incomplete glycosylation, poor amino acid uptake, and truncated oligosaccharide chains. Endoglycosidase H cleaved approximately 50% of the P0 labeled with [3H]fucose and 14C-amino acid. The lower molecular weight protein resulting from endoglycosidase H cleavage contained approximately one-half the [3H]fucose label on the protein, whereas one-half remained on the oligosaccharide chain of the undegraded P0, indicating that at least one-half the P0 has a hybrid structure. Deoxynojirimycin, deoxymannojirimycin, and castanospermine inhibited incorporation of [3H]fucose into the oligosaccharide chains of P0 and the 19-kDa glycoprotein as predicted from their action in blocking various stages of trimming of high mannose structures before the addition of fucose. P0 synthesized in the presence of these inhibitors was cleaved to a greater extent by endoglycosidase H than the normal protein, indicating increased vulnerability to this enzyme with arrest of normal processing. Similar results were obtained for the 19-kDa glycoprotein. Both the incompletely processed P0 and the 19-kDa glycoprotein formed in the presence of these inhibitors appeared to be transported normally into myelin.

1-Deoxynojirimycin↗
PubMed1991

Tanning salon exposure suppression of DNA repair capacity and mitogen-induced DNA synthesis.

Mitogen responsiveness and the capacity to repair genetic damage were measured in lymphocytes collected from young, healthy, adult Caucasians immediately before exposure in commercial tanning salons and again 24 h after exposure. For every individual studied, tanning exposure produced significant inhibition of phytohemagglutinin-induced mitogenesis or of the ability to repair DNA lesions by unscheduled DNA synthesis. The results imply that such exposure could: (1) pose a significant hazard for individuals who are already immunosuppressed (e.g. cancer patients, AIDS patients or carriers of latent HIV) and (2) increase the carcinogenic effects of environmental mutagens.

Adult↗
PubMed1991

Experimental evidence in the in vivo canine for the collapsible tube model of phonation.

The in vivo canine model of the larynx was used to measure transglottic pressures and airflow during phonation. Conditions of supraglottal resistance were also simulated. Pressure drop-flow curves were compared with data on collapsible tubes. The in vivo in canine model of the larynx demonstrates a number of features similar to oscillation in collapsible tubes.

Air Movements↗
PubMed1991

Posttranscriptional regulation of surfactant protein-A messenger RNA in human fetal lung in vitro by glucocorticoids.

Surfactant protein-A (SP-A), the major pulmonary surfactant-associated protein, is a developmentally and hormonally regulated sialoglycoprotein of about 35,000 mol wt. In previous studies we observed that dexamethasone has dose-dependent biphasic effects on the levels of SP-A and its mRNA in human fetal lung in vitro. At concentrations of 10(-10)-10(-9) M, dexamethasone increased the levels of SP-A and its mRNA over those of control tissues, whereas at concentrations greater than or equal to 10(-8) M, the steroid was markedly inhibitory. Our findings suggest that the inhibitory action of dexamethasone (greater than 10(-8) M) on SP-A mRNA levels was mediated by an effect to reduce SP-A mRNA stability, since the steroid caused a dose-dependent increase in the rate of transcription; however, an effect to increase transcription with premature termination leading to instability of mRNA transcripts could not be ruled out. In the present investigation we have studied in detail the mechanisms underlying the biphasic effects of glucocorticoids on SP-A mRNA levels in human fetal lung tissues in vitro. Our findings indicate that dexamethasone (10(-7) M) has no adverse effect on the elongation of nascent mRNA transcripts throughout the SP-A gene; elongation of SP-A mRNA transcripts in dexamethasone-treated tissue explants was similar to that observed in tissues incubated in control medium or medium containing (Bu)2cAMP. Therefore, premature termination of SP-A mRNA transcription leading to the instability of SP-A mRNA can be ruled out. On the other hand, we found that dexamethasone (10(-7) M) had a pronounced effect to reduce the apparent half-life of SP-A mRNA; in control explants maintained in the presence of actinomycin-D to block gene transcription, the SP-A mRNA half-life was estimated to be 11.4 h, whereas in tissues also treated with dexamethasone, the SP-A mRNA half-life was reduced by more than 60% to 5.0 h. Dexamethasone also was found to have dose-dependent effects on the degradation of SP-A mRNA. After 12 h of incubation in the presence of actinomycin-D and dexamethasone at 10(-9) and 10(-7) M, the levels of SP-A mRNA were reduced by 50% and 80%, respectively, compared to those in tissue incubated with actinomycin-D alone. The inhibitory effects of glucocorticoids on SP-A mRNA levels were completely reversible and were blocked by the glucocorticoid antagonist RU486.(ABSTRACT TRUNCATED AT 400 WORDS)

Bucladesine↗
PubMed1991

MHC antigen expression in colorectal tumours.

This article reviews abnormalities in the expression of major histocompatibility antigens in colorectal neoplasia. These include the loss of HLA-A, B, C antigens and the loss of HLA-D antigen inducibility. Since these abnormalities are not seen in normal colorectal epithelium they are probably selected for during tumour progression. The crucial role of HLA-A, B, C and HLA-D molecules in the presentation of foreign antigens to the immune system suggests that their loss could directly confer a selective growth advantage to tumour cells expressing tumour specific antigens, through resistance to anti-tumour lymphocyte attack. The possible relationships between abnormalities in tumour HLA antigen expression and the presence of tumour specific antigens are discussed.

Adenocarcinoma↗
PubMed1991

Angiographic yield in penetrating extremity trauma.

Indications for angiography in the evaluation of penetrating extremity trauma remain controversial. Our experience was reviewed to determine the yield of angiography in penetrating extremity trauma and to correlate clinical findings with angiographic results. During an 81-month period from 1983 through 1989, 284 extremity arteriograms were carried out in 268 patients. The angiographic yield in patients with abnormal clinical findings was 51%. The angiographic yield in patients when proximity of the injury to major vessels was the only indication was 6% (7% with gunshot wounds and 0% with stab wounds). Neurologic deficit alone as an indication for angiography accounted for 55% of the angiograms interpreted as "negative" and none of those interpreted as "positive". We conclude that the use of angiography in patients with gunshot wounds to the extremity with "proximity injuries" to major vessels should continue, its use is not warranted in extremity stab wounds when proximity is the sole indication, and abnormal neurologic findings in the absence of other findings are a poor predictor of vascular injury.

Adolescent↗
PubMed1990

Histologic study of eyes with transsclerally sutured posterior chamber intraocular lenses.

We studied the postmortem histologic characteristics of two eyes that had undergone penetrating keratoplasty and transscleral suturing of a posterior chamber intraocular lens for bullous keratopathy. The eyes were studied three days postoperatively in a 79-year-old man with pseudophakia and six months postoperatively in an 83-year-old man with aphakia. We also removed a posterior chamber intraocular lens in a 73-year-old woman who had an epithelial downgrowth three months postoperatively. In the first two cases, only one of four haptics was successfully positioned in the sulcus. Histologic study disclosed a thin fibrous capsule surrounding the haptics at their attachment site, no inflammation around the transscleral portion of the suture, and exposure of a suture tip externally. In the third case, the intraocular lens fell back into the vitreous cavity after the fixation sutures were cut externally at the time of surgical removal. Stability of the lens in all three cases was primarily a result of intact transcleral sutures and not fibrous encapsulation or ciliary sulcus placement of haptics.

Aged↗
PubMed1990

Opioid receptors in skeletal muscle of normal and dystrophic mice.

Autoradiography was used to investigate the presence of opioid receptors in soleus, extensor digitorum longus (EDL) and diaphragm muscles in two strains (C57BL/6J and C57BL/10) of mice which can inherit muscular dystrophy. Binding sites for two radiolabelled opioid ligands [125I]beta-endorphin and [3H]naloxone, were seen in a few muscle fibres in the normal mice. However, a significantly greater number of fibres exhibited the binding sites in the dystrophic individuals of both strains. The binding sites were not restricted to the endplate regions but were present over the entire surface in these fibres.

Animals↗
PubMed1990

Localisation of acetylcholinesterase in rat myotubes in the presence of beta-endorphin and beta-endorphin-(1-27).

In rat embryo skeletal myotubes, acetylcholinesterase is present, as multiple forms, and can be detected in deposits at the cell surface. Myotubes cultured in the presence of beta-endorphin, exhibit an increased predominance of the globular (precursor) forms of the enzyme, which are largely restricted to intracellular sites associated with nuclei. In the presence of beta-endorphin-(1-27), the relative proportions of the different forms of acetylcholinesterase is similar to that seen in the controls, but the enzyme is intracellular and has a characteristic focal localisation in the myotube.

Acetylcholinesterase↗
PubMed1990

Polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction: POLIP syndrome.

We describe 5 individuals (from three separate families) with a progressive neurological disorder characterized by sensorimotor peripheral polyneuropathy, cranial neuropathies (external ophthalmoplegia, deafness), and the syndrome of chronic intestinal pseudo-obstruction. Magnetic resonance imaging showed widespread abnormality of the cerebral and cerebellar white matter in the 2 patients studied. Autopsy examination in 3 revealed widespread endoneurial fibrosis and demyelination in the peripheral nervous system, possibly secondary to axonal atrophy, and poorly defined changes in cerebral white matter (leukoencephalopathy). The cranial nerves and spinal roots were less severely involved and the neurons in the brainstem and spinal cord were intact. The fatal gastrointestinal dysmotility was due to a severe visceral neuropathy. We suggest that these patients manifested a hereditary disorder with distinctive clinical, radiological, and neuropathological features, and propose the acronym POLIP to emphasize the distinctive tetrad of polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction.

Adult↗
PubMed1990

Sequence of tissue responses in the early stages of experimental allergic encephalomyelitis (EAE): immunohistochemical, light microscopic, and ultrastructural observations in the spinal cord.

Experimental allergic encephalomyelitis (EAE) was induced in adult Lewis rats with purified guinea pig CNS myelin and Freund's adjuvant. As soon as the very earliest clinical signs appeared the animals were perfused with fixatives and the spinal cord analyzed by electron microscopy, silver methods, and immunocytochemistry. Our findings suggest that in the early stages of EAE a sequence of events can be traced, although these events frequently overlap. The earliest morphological change appears to be astrocytic edema in both the cell body and processes. Increased amounts of glycogen particles and dispersion of glial filaments are prominent. These changes seem to occur just prior to the time when inflammatory cells begin to penetrate the capillary walls. Invasion of the neuropil mainly by macrophages and lymphocytes closely follows. Both macrophages and microglia seem to participate in phagocytosis of oligodendrocytes and myelin. Demyelination, however, is not a prominent feature at this early stage.

Animals↗
PubMed1990

Phagocytosis of peripheral nerve myelin in vitro: effect of antibody.

We have previously shown that antisera to whole CNS myelin, whole PNS myelin, galactocerebroside (GC), and myelin basic protein (MBP) promote the uptake of CNS myelin by cultured macrophages, and stimulate the conversion of myelin lipids to cholesterol ester and triglycerides. Here we report the results of similar studies using PNS myelin purified from the rat sciatic nerve. Antisera to whole CNS myelin, whole PNS myelin, GC, and MBP preincubated with 14C-labeled PNS myelin increased the production of radioactive cholesterol ester by macrophages in culture to a level about twice that with preimmune serum, and five to six times that of untreated myelin. The amounts of [14C]triglyceride were similarly increased with these antisera, whole P0 and P2 antisera had little or no effect. IgG prepared from the antisera stimulated lipid metabolism to almost the same extent, while heating the antisera did not decrease the stimulatory effect, indicating that myelin was opsonized by IgG, but not likely by complement. With a few exceptions, the four active sera and their IgGs promoted the macrophage metabolism of CNS and PNS myelin almost equally. The cultured macrophages converted about 3% of untreated CNS myelin and about 6% PNS myelin cholesterol to cholesterol ester. Under phase contrast microscopy it was noted that vesicles of CNS myelin appeared to bind individually to macrophages, whereas PNS myelin vesicles tended to self-associate to form large clumps which were found to macrophages. Binding studies showed PNS myelin to be bound more firmly to macrophages than CNS myelin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The intracranial topography of the P3 event-related potential elicited during auditory oddball.

In order to isolate the anatomical locus of neural activity primarily responsible for generating the scalp-recorded P3 (or P300), the topography of event-related potentials (ERPs) elicited during an auditory oddball task was compared between medial-to-lateral aspects of the frontal, parietal, and temporal lobes in 10 epileptic patients undergoing stereoelectroencephalography for seizure localization. Evidence of local ERP generation was obtained from each of these areas. Small amplitude P3-type potentials were sometimes observed to invert polarity across recording contacts in the frontal lobe. Large amplitude positive polarity P3-type components were observed in the lateral neocortex of the inferior parietal lobule (IPL), that rapidly attenuated in amplitude at more anterior, posterior, superior, inferior, and medial recording contacts. Large amplitude polarity inverting P3-type components were also observed to be highly localized to hippocampal contacts of temporal lobe electrodes. These data are discussed in the context of other recent studies of lesion effects, scalp topography, and intracranial recordings, and it is concluded that activity generated in the IPL is likely to make the major contribution to the scalp-recorded P3, with smaller contributions from these other sources. Finally, salient topographical differences between the intracranial distribution of the P3 and those of the N2 (or N200) and slow wave (SW) suggest that the generators of these components are not identical.

Acoustic Stimulation↗
PubMed1990

Repetition priming of words and pseudowords in divided attention and in amnesia.

Repetition priming of novel stimuli (pseudowords) and stimuli with preexisting representations (words) was compared in two experiments. In one, 19 normal male subjects performed a lexical decision task with either focused or divided attention. In another, lexical decision performance was compared between 8 male Korsakoff patients and 8 alcoholic control subjects. In control conditions, repetition speeded responses to both stimulus types. Experimental conditions that minimized the contribution of episodic memory to task performance eliminated reaction time priming for pseudowords but not for words. However, in these same conditions, repetition increased the likelihood that pseudowords would be incorrectly classified. These results indicate that preserved repetition priming effects in amnesia do not solely reflect activation of representations in semantic memory.

Alcohol Amnestic Disorder↗