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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 127 records · Page 7Linked to original sources

Effects of pyridostigmine on acetylcholinesterase in different muscles of the mouse.

1. Pyridostigmine bromide was administered subcutaneously in mice, in a dose of 4.0 or 2.0 mu moles/kg, and the activity of the predominant (G1, G4 and A12) molecular forms of acetylcholinesterase were examined in diaphragm, extensor digitorum longus (EDL), and soleus muscles at 3 h, 6 h, 24 h and 5 days. 2. In diaphragm, no effect was apparent after the low dose, but after the high dose there was a reduction in activity of the functional A12 form at 24 h, followed by an increase which had overshot the control level at 5 days. 3. In the fast EDL, after the low dose, all three molecular forms were decreased at 3 h but had returned to normal by 6 h. This effect was not apparent after the high dose. 4. In the slow soleus the low dose caused a significant increase in total enzyme activity at 5 days, but the high dose caused significant increases in all molecular forms at 3 hours. 5. Thus pyridostigmine had delayed effects on the levels of acetylcholinesterase. The three muscles displayed different sensitivities to the drug, but the changes were consistent with initial inhibition of the activity leading to down-regulation of the enzyme followed by up-regulation, which could overshoot the normal levels.

Acetylcholinesterase↗

Effect of repeated treatment with pyridostigmine on acetylcholinesterase in mouse muscles.

1. Pyridostigmine bromide was administered subcutaneously (0.4 mumoles/kg) in mice twice a day for 3 weeks. The activities of the predominant (G1, G4 and A12) molecular forms of acetylcholinesterase were determined in diaphragm, extensor digitorum longus (EDL) and soleus muscles. 2. After the treatment the G4 and A12 forms were reduced in diaphragm, but increased in EDL and soleus. One week later all forms were elevated in all three muscles. At 2 weeks the activity had returned to normal in diaphragm but not in EDL and soleus. 3. A single dose of pyridostigmine was administered in mice which had been pretreated for 3 weeks and left untreated for 2 weeks, and in control mice. 4. In the controls there was no significant effect on the enzyme activities in diaphragm up to 5 days, but there were decreases in EDL, and increases in soleus. In the pretreated group all three forms were increased in diaphragm, especially the A12 form. In soleus and EDL there was a prolonged decrease in all forms, although in the soleus the A12 activity remained above normal. 5. Repeated treatment with pyridostigmine caused delayed changes in functional acetylcholinesterase. Furthermore the treatment had altered the sensitivity of the muscles to the drug.

Acetylcholinesterase↗

Evidence for a hormonal action of beta-endorphin to increase glucose uptake in resting and contracting skeletal muscle.

The uptake of 2-[3H]deoxyglucose, a non-metabolisable derivative of glucose, was studied in resting and contracting muscle. An isolated phrenic nerve/hemidiaphragm preparation of the mouse was used, and contractions of the muscle were elicited by electrical stimulation of the nerve. beta-Endorphin stimulated the uptake of 2-deoxyglucose in resting diaphragm muscle. The rate of uptake in the presence of the optimum concentration of beta-endorphin was similar to that in the presence of the optimum concentration of insulin over the short incubation period. beta-Endorphin also stimulated the uptake of 2-deoxyglucose in contracting muscle, but the optimum concentration of the peptide for this effect was three orders of magnitude lower than in resting muscle. The optimum concentration for insulin, however, was similar in resting and contracting muscle. An analogue of the C-terminal tetrapeptide of beta-endorphin also stimulated 2-deoxyglucose uptake, but this peptide was equally efficacious in resting and contracting muscle. It is suggested that beta-endorphin, which is released into the circulation during exercise, may have a hormonal action to increase the uptake of glucose during muscular activity. This peptide or its metabolites may be partly responsible for the insulin-independent uptake of glucose during exercise.

Animals↗

Cadherin expression in melanocytic naevi and malignant melanomas.

An immunocytochemical study has been undertaken of cadherin expression in 11 benign melanocytic naevi and 14 malignant melanomas. Anti-pan-cadherin rabbit antibodies, which recognize multiple cadherin subtypes, demonstrated cadherin expression of moderate or strong intensity in 8 of 11 naevi. Expression was restricted to the more superficial melanocytes which possessed abundant cytoplasm (type A melanocytes). More deeply located melanocytes possessing little cytoplasm (type B melanocytes) or having a spindle cell morphology (type C melanocytes) lacked detectable pan-cadherin expression. The monoclonal antibody HECD-1 detected weak E-cadherin immunostaining in all 11 naevi, expression again being limited, with a single exception, to type A melanocytes. Cadherin immunostaining of moderate or strong intensity was detected by the pan-cadherin antibody in all 14 malignant melanomas. In contrast to naevi, cadherin expression in melanomas frequently extended into the deepest portions of the tumours. E-cadherin immunostaining in malignant melanomas was generally much stronger than that seen in naevi, often being of comparable intensity to the pan-cadherin staining. In summary, cadherins are frequently expressed in melanocytic tumours. In naevi, cadherin expression is related to the degree of melanocytic maturation. Cadherin expression, and particularly E-cadherin expression, tends to be greater in malignant melanomas than in naevi.

Cadherins↗

High resolution evoked potential imaging of the cortical dynamics of human working memory.

High resolution evoked potentials (EPs), sampled from 115 channels and spatially sharpened with the finite element deblurring method, were recorded from 8 subjects during working memory (WM) and control tasks. The tasks required matching each stimulus with a preceding stimulus on either verbal or spatial attributes. All stimuli elicited a central P200 potential that was larger in the spatial tasks than in the verbal tasks, and larger in the WM tasks than in the control tasks. Frequent, non-matching stimuli elicited a frontal, positive peak at 305 msec that was larger in the spatial WM task relative to the other tasks. Irrespective of whether subjects attended to verbal or spatial stimulus attributes, non-matching stimuli in the WM tasks also elicited an enhanced P450 potential over the left frontal cortex, followed by a sustained potential over the superior parietal cortex. A posterior P390 potential elicited by infrequent, matching stimuli was smaller in amplitude for both spatial and verbal WM tasks compared to control tasks, as was a central prestimulus CNV. These results indicate that WM is a function of a distributed system with both task-specific and task-independent components. Lesion studies and course temporal resolution functional imaging methods, such as PET and fMRI, tend to paint a fairly static picture of the cortical regions which participate in the performance of WM tasks. In contrast, the fine-grain time resolution provided by imaging brain function with EP methods provides a dynamic picture of subsecond changes in the spatial distribution of WM effects over the course of individual trials, as well as evidence for differences in the activity elicited by matching and non-matching stimuli within sequences of trials. This information about the temporal dynamics of WM provides a critical complement to the fine-grain spatial resolution provided by other imaging modalities.

Acoustic Stimulation↗

Distribution of opioid peptide receptors in muscles of lean and obese-diabetic mice.

Autoradiography was used to demonstrate beta-endorphin and delta-opioid receptors in muscles of normal and obese-diabetic mice. The density of the receptors was significantly higher in the obese-diabetic mice. In both normal and diabetic mice, glycolytic and oxidative fibers exhibited the beta-endorphin receptors. However, a significantly greater density of beta-endorphin receptors was observed in the extensor digitorum longus muscles than in the soleus muscles in the diabetic mice. In normal muscles the beta-endorphin receptors were largely restricted to regions where endplates were present, but in the obese-diabetic mice they were densely distributed along the length of the muscle fibers.

Acetylcholinesterase↗

Solid state NMR characterisation of crystalline Na2O-ZrO2-SiO2 phases.

The NMR interactions of crystalline phases in the system Na2O-ZrO2-SiO2 have been studied by a combination of static and magic angle spinning NMR methods for the first time. A full multinuclear (17O, 23Na, 29Si and 91Zr) approach has been employed that allows the phases to be clearly identified. NMR interactions such as 29Si isotropic chemical shift correlate with the known structural units present. For 23Na the the different sites can often be distinguished on the basis of differing quadrupolar interactions.

Crystallization↗

Merkel cell carcinoma of the eyelid.

PURPOSE: To demonstrate the clinical variability and histologic characteristics of Merkel cell carcinoma of the eyelid. METHODS: We investigated two cases of Merkel cell carcinoma of the eyelid in a 67-year-old man and an 83-year-old woman, respectively. Both lesions were initially misdiagnosed as benign tumors on clinical examination. RESULTS: After the correct diagnosis was made, both lesions were treated with wide resection aided by frozen sections, and reconstructive surgery. CONCLUSIONS: Merkel cell carcinoma is an aggressive tumor with variable clinical manifestation. Radical surgical therapy and close follow-up are indicated.

Aged↗

Cystic hydrops and spontaneous perforation in Fuchs' superficial marginal keratitis.

PURPOSE: We studied a case of Fuchs' superficial marginal keratitis in which cystic corneal hydrops developed in one eye, and spontaneous corneal perforation occurred in the fellow eye. METHODS: The patient underwent bilateral annular corneoscleral lamellar patch grafts for tectonic support. RESULTS: The patient had an uncomplicated postoperative course and visual acuity of 20/25 bilaterally. CONCLUSION: Stromal loss in Fuchs' superficial marginal keratitis may be severe enough to result in cystic corneal hydrops. Patients with this disorder should be counseled regarding the possibility of corneal perforation.

Adult↗

Voice disorders in children.

Pediatric patients with voice or speech problems usually should receive a team assessment in which communication between the pediatrician or primary care physician, the otolaryngologist, and speech pathologist occurs. Although speech or voice problems may prompt an otolaryngologic evaluation, the voice or speech problem simply may be the manifestation or symptom of a larger or more complex disease process. Whether that is the case of hypernasal speech, eventually leading to the diagnosis of velocardiofacial syndrome, or bilateral vocal fold paralysis, eventually leading to the diagnosis of hydrocephalus, it is apparent that patients with speech or voice disorders may eventually require multidisciplinary evaluation. The outlook for children with speech and voice difficulties is better than ever. Recent equipment advances, such as flexible laryngoscopy, video stroboscopy, and nasometry, for detection, evaluation, and management of speech problems have created a better environment than ever existed for care of these problems. Much research is being performed in the area of pediatric voice and speech problems. The National Institute of Deafness and Communicative Disorders and the National Institute of Dental Research have funded and currently fund many projects in these areas. Many pediatric hospitals now have voice or speech disorder clinics in which multiple disciplines are brought together to evaluate children with these problems. Children benefit best when speech and voice problems are managed in an interdisciplinary setting when necessary and by professionals who have experience and training in these specialized pediatric problems. Given the local, professional, and national resources that are expended toward recognition and treatment of speech disorders in children, it is truly a tragedy when those resources cannot be brought to assist children with voice and speech problems. Although voice and speech problems usually are recognized by parents or concerned family members, this task may rest on the pediatrician or other primary caregiver.

Child↗

The Parkinson larynx: tremor and videostroboscopic findings.

Patients with Parkinson's disease have a high incidence of speech, voice, and laryngeal abnormalities. To characterize laryngeal abnormalities, visual-perceptual ratings of endoscopic and stroboscopic examinations of 22 patients diagnosed with idiopathic Parkinson's disease and 7 patients with Parkinson's-plus syndromes were carried out by for trained viewers. Incidence of tremor, tremor location, phase closure, phase symmetry, amplitude, and mucosal waveform were scored. Tremor was observed in one or more of these conditions-rest, normal pitch and loudness, or loud phonation-for most of the 29 patients. Fifty-five percent of the idiopathic Parkinson's disease patients had tremor, with the primary location being vertical laryngeal tremor. Sixty-four percent of the Parkinson's-plus patients had tremor, with the arytenoid cartilages being the primary location. Laryngeal tremor was observed early in the disease in these Parkinson's disease patients. The most striking stroboscopic findings for the idiopathic Parkinson's disease patients were abnormal phase closure and phase asymmetry. Amplitude and mucosal wave-form were essentially within normal limits in the majority of the idiopathic Parkinson patients.

Aged↗

Cadherins in reactive lymph nodes and lymphomas: high expression in anaplastic large cell lymphomas.

Using a polyclonal pan-cadherin antibody and a monoclonal E-cadherin antibody (HECD-1) we have investigated cadherin expression in lymphomas and reactive lymph nodes. Routinely processed tissue from nine reactive lymph nodes and 48 lymphomas (six T-cell, six high-grade B-cell, 15 low-grade B-cell, 13 anaplastic large cell and eight Hodgkin's disease) were immunostained. The reactive cases showed pan-cadherin membrane associated staining of endothelium and epithelioid granulomas. No staining of lymphoid cells was seen. Pan-cadherin immunostaining was present in three of six T-cell lymphomas, two of six high-grade B-cell lymphomas, 12 of 13 anaplastic large cell lymphomas and three of eight cases of Hodgkin's disease. No staining of low-grade B-cell lymphomas was identified with the pan-cadherin antibody. E-cadherin was not detected in any of the lymphomas that showed pan-cadherin expression. The frequent and strongest cadherin expression in anaplastic large cell is noteworthy. The tumour cells of this lymphoma subtype are characterized by copious cytoplasma and a cohesive appearance, features which impart a superficial resemblance to carcinoma cells. Since cadherin molecules are known to have major morpho-regulatory functions our data suggests that the expression of cadherin molecules by anaplastic large cell lymphomas may play an important role in determining their characteristic epithelioid phenotype.

Adolescent↗

Pleomorphic hyalinizing angiectatic tumor of soft parts. A low-grade neoplasm resembling neurilemoma.

Fourteen examples of an unusual mesenchymal tumor characterized by sheets and fascicles of mitotically inactive, hemosiderin-stippled, spindled, and pleomorphic cells, situated around an angiectatic vasculature, are described. The 14 tumours developed in eight women and six men (aged 32-83 years) and ranged in size from 2.3 to 8 cm. Eleven cases presented in the subcutaneous tissues, of which eight were located in the lower extremity. All featured prominent clusters of thin-walled ectatic vessels surrounded by perivascular hyaline material representing a combination of fibrin and collagen. In three cases the perivascular hyalinization was so extensive that it constituted more than half of the total tumor area. The tumor cells were similar to those of malignant fibrous hystiocytoma but differed from them by the presence of prominent intranuclear cytoplasmic inclusions, the extreme scarcity of mitotic figures, and the occasional presence of CD-34 expression. These tumors also shared several features with neurilemomas, such as their unusual vasculature, intranuclear cytoplasmic inclusions, lack of mitotic figures, and abundance of mast cells. They could be distinguished from neurilemomas, however, by the usual presence of infiltrative margins and the absence of S-100 protein. Follow-up information on eight patients (6 months to 25 years) indicated recurrences in four cases, with one of the three patients experiencing numerous recurrences over a 25-year period. No patient has developed metastases, however. We suggest that this tumor is a low-grade sarcoma of uncertain lineage in which the vascular changes are, in part, reflective of its slow growth.

Adult↗

Data and information requirements for determining veterans' access to health care.

The Department of Veterans Affairs (VA) is responding to changing requirements for decision-support data by maximizing the value of data contained in VA and non-VA sources. The data are used to answer questions relating to the accessibility and utilization of VA and non-VA health services. Access studies require accurate estimates of the number of persons served and the number of persons who could be served. To derive these population estimates, VA employs census data to develop projections of the veteran population at the national, state, and county levels. Data from many surveys are used to supplement the census data. Access studies also require quantitative and qualitative data on the characteristics of VA and non-VA health care delivery systems at the national, state, and local levels. The Department of Veterans Affairs obtains health care system data from external sources, including the US Department of Health and Human Services, the American Medical Association, and the American Hospital Association, and from internal sources, including VA surveys and the VA administration inpatient and outpatient files. Utilization studies need more detailed patient-level information than access studies. Data elements pertaining to the reason for health care encounters and the services rendered are obtained from survey data, the VA inpatient and outpatient administration files, the national Medicare database, and state Medicaid databases. The Department of Veterans Affairs'decision-support analyses for eligibility reform and health care system reform demonstrate the effectiveness of VA in analyzing data from many sources.

American Hospital Association↗

Prevention of ischemia-reperfusion injury with a synthetic metalloprotein superoxide dismutase mimic, SC52608.

Superoxide dismutase (SOD) scavenges free superoxide radicals generated during reperfusion of ischemic tissue and decreases cellular injury. A synthetic manganese-based metalloprotein superoxide dismutase mimic, SC52608 (Monsanto Co.), was tested in the isolated rabbit rectus femoris muscle flap to determine its effects on ischemia-reperfusion injury. The results of our experiments analyzing 38 isolated rectus femoris muscles in 19 New Zealand White rabbits show that administration of SC52608 at the onset of 4 hours of warm ischemia and before reperfusion significantly increases the survival of the muscle from 20.0 +/- 4.9 percent (control, HEPES) to 81.5 +/- 4.6 percent (SC52608) (p < 0.001). It preserved functional contraction in 8 of 10 muscles; only 1 of 12 control muscles (control, HEPES) had contractions (p = 0.0015). SC52608 decreased the neutrophil density from 4.63 +/- 0.6 x 10(4) cells/mm2 in the control (HEPES) muscle to 2.71 +/- 0.6 x 10(4) cell/mm2 in muscles perfused with SC52608 (p = 0.03). The level of malonyldialdehyde decreased from 6.12 +/- 0.26 nmol/gm (control, HEPES) to 4.64 +/- 0.41 nmol/gm (SC52608) (p = 0.0028). Postoperative weights of the muscles showed no statistical difference (p = 0.14) between the controls (16.0 +/- 0.9 gm) and the SC52608 (18.1 +/- 0.7 gm). Our investigation shows that direct intraarterial infusion of a synthetic superoxide dismutase mimic at the onset of ischemia and prior to reperfusion can reduce reperfusion injury in skeletal muscle.

Animals↗