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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 325 records · Page 18Linked to original sources
PubMed1993

Effects of irradiation on development of Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in genetically resistant mice.

Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a model for multiple sclerosis, is a chronic T cell-mediated disease. Development of clinical symptoms in susceptible mouse strains generally correlates with TMEV-specific delayed-type hypersensitivity (DTH) responses. These responses, minimal or absent in resistant mouse strains, have been proposed as the pathogenic basis for the central nervous system inflammation and demyelination characterizing the disease. We demonstrate here that normally resistant (C57BL/6 x DBA/2)F1 hybrid mice develop clinical symptoms and DTH responses against TMEV after low doses of gamma-irradiation. Parental C57BL/6 animals remain resistant after similar pretreatment. Thus low-dose irradiation elicits a "latent" susceptibility to TMEV-IDD in some, but not all, resistant mice. Adoptively transferred spleen cells from syngeneic, unirradiated donors reconfer resistance on irradiated, infected B6D2F1 hybrids and reduce DTH responsiveness against TMEV, suggesting a protective role for a radiation-sensitive splenic population(s). The closely related C57BL/6 and C57BL/10 strains differ with respect to intrinsic and latent susceptibility.

Animals↗
PubMed1993

The effects of sodium loading on blood pressure and pain responses to the cold pressor test.

Two cold pressor tests were administered to 18 healthy normotensive males on two occasions, after 2 weeks of dietary sodium loading and after 2 weeks of maintaining their normal diet. While the addition of an extra 10 g/day of sodium to the diet had no overall effect on resting cardiovascular activity, it produced significantly greater diastolic blood pressure and smaller heart rate responses to the pain stimuli. As well, consistent with the large animal literature indicating a relationship between high blood pressure and diminished pain sensitivity, pain ratings were found to be significantly lower during the sodium loaded testing session. The ratings were corroborated by evidence of lower skin conductance reactivity to the second cold pressor test in the sodium loaded condition. Information concerning an elevation of risk for hypertension, perhaps provided by baroreceptors, may lead to compensatory reactions with hypoalgesia as one effect.

Adolescent↗
PubMed1993

Voluntary intake and gastric emptying in pigs: effects of fat and a CCK inhibitor.

The influence of the cholecystokinin (CCK) antagonist MK-329 (0.1 mg/kg) on short-term control of voluntary food intake and gastric emptying was studied in five pigs. Arterial injection of MK-329 abolished the inhibition of intake resulting from duodenal infusion of emulsified fat (Intralipid, 24 g/h). However, MK-329 only reduced the inhibition of dry matter (DM) and liquid emptying, and hence increased stomach volume at satiety. Intralipid infusion decreased the rise in gastric pressure during feeding. All these changes are consistent with endogenous CCK, released by Intralipid, inhibiting intake independent of the concomitant slowing of gastric emptying. MK-329 alone significantly increased intake using two different diets, but had no effect on gastric emptying so that gastric volume at satiety was significantly increased. These results suggest that endogenous CCK may be part of short-term satiety control in the pig.

Animals↗
PubMed1993

Can ECT-induced cognitive effects be altered pharmacologically?

1. A systematic review of the literature revealed twelve clinical trials that evaluated nine different drugs, and used three different conceptual models to prevent, restore or treat ECT-induced cognitive deficits. 2. This review indicated inconclusive results regarding clinical utility of any of the drugs. 3. Major factors discussed include the complexities involved in the evaluation of ECT-induced cognitive deficits, and the techniques of evaluating changes in cognitive functions. 4. Our conclusion is that future research should emphasize understanding the neural mechanisms related to ECT-induced cognitive deficits. We suggest several areas for future exploration.

Cognition Disorders↗
PubMed1993

Age-related changes in expression and activity of DNA polymerase alpha: some effects of dietary restriction.

DNA polymerase alpha (pol alpha) purified from human diploid fibroblasts (HDF) and from livers of C57BL/6N mice showed age-related decreases in: (1) mRNA levels; (2) the amount of enzyme isolated per cell; and (3) enzyme activity (HDF); as well as: a) the amount of enzyme isolated; b) the specific activity; and c) the enzyme fidelity (liver). Hepatic pol alpha from dietary restricted (DR) mice exhibited less of a decline in specific activity and copied synthetic DNA templates with relatively higher fidelity than did enzymes from animals fed ad libitum (AL). Pol alpha from fetal-derived HDF exhibited increased expression compared with aged donor-derived HDF, with both fetal and old cell pol alpha in normal cells being expressed at lower levels than in their transformed cell corollaries. Treatment of human pol alpha from aged donor-derived HDF with a pol alpha accessory protein isolated from log phase murine cells resulted in increased pol alpha binding of DNA and increased pol alpha activity. However, highly active pol alpha isolated from fetal-derived or transformed HDF, or from transformed murine cells, showed little or no activity enhancement in the presence of accessory protein. These data indicate that, as a function of increased age, there is a decrease in pol alpha expression and specific activity in HDF, as well as decreases in specific activity and fidelity of pol alpha in essentially amitotic murine hepatic tissues. Dietary restriction impedes the age-related declines in both activity and fidelity of hepatic pol alpha in mice. The data further indicate that transformation of slowly dividing HDF is associated with increased expression of pol alpha, but suggest that increased expression alone is not sufficient to explain the difference in polymerase activity levels between parental and transformed HDF. Lastly, the data suggest that interaction of pol alpha with an essential accessory protein may be altered as a function of age, an alteration that appears to be correlated with the decline in pol alpha DNA binding and specific activity.

Aging↗
PubMed1993

Hyperopia and neovascularization in age-related macular degeneration.

PURPOSE: Refractive errors for phakic eyes of patients referred with age-related macular degeneration were reviewed to determine whether some range of refractive error might be a risk factor for the neovascular form. METHODS: The authors compared refractive errors of 198 patients with unilateral neovascular disease with refractive errors of 129 patients with bilateral dry disease. These groups had comparable distributions with respect to age, sex, and visual acuity of their better eyes. Student's t tests and multiple linear regression analyses were performed to assess group differences in mean refractive error. Contingency table and multiple logistic regression analyses were performed to determine odds ratios for having the neovascular form based on a stratification of refractive error. RESULTS: By comparing better eyes of the two groups, patients with the unilateral neovascular form had an average spherical equivalent that was 1.0 diopter (D) more hyperopic than that of patients with the bilateral dry form (P < 0.001). Patients with a refractive error of +0.75 D or greater were more likely to have the neovascular form compared with patients with other refractive errors (odds ratio, 2.40; 95% confidence interval, 1.53-3.78; P < 0.001). Similar relationships between the two groups of patients were found by comparing worse eyes. CONCLUSION: These findings suggest that hyperopia is a risk factor for choroidal neovascularization among patients referred with age-related macular degeneration.

Aged↗
PubMed1993

The effects of increased shooting distance in the basketball jump shot.

Three-dimensional video techniques (50 Hz) were used to obtain images of basketball jump shots from one of three distances--short range (group 1, n = 5); medium range (group 2, n = 5); long range (group 3, n = 5)--from the basket, as performed by members of the men's quarter-finalist teams at the games of the XVI Universiade in Sheffield in 1991. Fifteen sequences were digitized, beginning 20 frames prior to take-off to 10 frames after release. To facilitate analysis, the sequences were rotated about the ball position in the final frame so that the shot direction was parallel to one of the pre-defined orthogonal axes. Mean (+/- 1 S.D.) ball release speed was found to increase with distance from the basket (group 1 = 3.04 +/- 0.65 m s-1, group 2 = 4.71 +/- 0.74 m s-1, group 3 = 6.24 +/- 0.80 m s-1), while mean release angles were similar for all groups (group 1 = 48.8 +/- 10.1 degrees, group 2 = 47.8 +/- 5.8 degrees, group 3 = 51.9 +/- 5.5 degrees). The increased impulse necessary for the ball to reach the basket at increased shooting distances was derived from both an increase in angular velocity of the elbow joint of the shooting arm and an increased velocity of the centre of mass in the direction of the basket at release. Centre of mass speed at take-off was found to be influenced to a greater extent by the angular velocity of the ankle joint than that of the knee or hip joints.(ABSTRACT TRUNCATED AT 250 WORDS)

Ankle Joint↗
PubMed1993

Longitudinal study of central motor conduction time following stroke. 1. Natural history of central motor conduction.

A 12 month longitudinal study has been performed on 118 subjects following first-ever stroke to determine changes in central motor conduction time (CMCT) to upper limb muscles. The responses to electromagnetic stimulation of the motor cortex and cervical motor roots were recorded bilaterally in the surface electromyograms of pectoralis major, biceps and triceps brachii and thenar muscles. The CMCTs obtained from these recordings in stroke patients have been compared with those obtained in 53 normal healthy subjects of a similar age. The first measurements were made within the immediate post-stroke period (12-72 h of the onset of symptoms) and repeated at set time intervals over 12 months. The first assessment of CMCT identified three groups: those with normal responses, delayed responses and absent responses. During the first 12 months following stroke various changes in CMCT occurred. Central motor conduction time may remain unchanged, delayed CMCT may return to normal and previously absent responses may reappear and be delayed or normal. Using electromagnetic stimulation of the motor cortex the thresholds for motor evoked responses in the different muscles were initially high and fell over 12 months.

Adult↗
PubMed1993

Longitudinal study of central motor conduction time following stroke. 2. Central motor conduction measured within 72 h after stroke as a predictor of functional outcome at 12 months.

A longitudinal study was performed on 118 first-ever stroke patients to evaluate neurophysiological measurements of central motor conduction time (CMCT) in the period immediately following stroke as predictors of functional outcome and mortality at 12 months. Measurements of CMCT were made as described in the accompanying article (Heald et al., 1993, Brain, 116, 1355-1370), in which the following three groups of patients were recognized within 12-72 h after the onset of symptoms: normal response group, delayed response group and no response group. Neurophysiological and clinical investigations were commenced 12-72 h (designated as day 1) after the onset of symptoms and repeated at set time intervals up to 12 months. The subjects were examined neurologically and assessed using the Motricity Index for muscle strength, the Nine-hole Peg Test to measure manual dexterity, the Barthel Score for activities of daily living and the modified Rankin Scale for functional outcome. The duration of stay in hospital and the occurrence of stroke-related death were noted. During the first week following stroke, absence of responses correlated closely with the patient's symptoms and neurological observations of abnormal muscle tone and tendon reflexes. Correlations were made in the three groups of patients of functional scores at day 1 and at 12 months. Patients with normal CMCT had consistently higher scores throughout the 12 month period and achieved significantly better functional recovery. Patients with no responses showed poor performance in neurological and functional tests throughout the 12 month period. Patients with delayed CMCT had neurological and functional scores intermediate between those of the other two groups, but outcome at 12 months was similar to those in the normal response group. Where the threshold to cortical stimulation was abnormally high, functional outcome was generally poor. Mortality was highest in the group with absent responses and the survivors spent the longest period in hospital. In conclusion, the observation of normal or delayed CMCT at day 1 identifies a group of patients with a high probability of survival and functional recovery. The absence of responses to cortical stimulation at day 1 identifies a group of patients who are at high risk of poor functional recovery at 12 months and greater probability of stroke-related death during this period.

Cerebrovascular Disorders↗
PubMed1993

Recipient selection and evaluation for vascularized pancreas transplantation.

Vascularized pancreas transplantation (PT) is becoming an accepted therapy for selected type I diabetic patients. However, selection and evaluation criteria remain uncertain. In the last 3.5 years, we have interviewed 205 and evaluated 151 diabetic patients for PT. The degree of renal dysfunction (creatinine clearance below 45 ml/min) was used to select patients for combined pancreas-kidney transplantation (PKT) or solitary pancreas transplantation (PTA) (clearance above 70 ml/min). The cardiovascular evaluation (stress thallium study with liberal use of coronary angiography) was used to determine operative risk and provided the other major selection criterion. A total of 104 patients were selected as candidates for PT; 70 have undergone PKT with 98.6% patient survival (1 cardiovascular death), 97.1% kidney graft survival, and 94.2% pancreas graft survival. Thirty-three evaluated patients (24.1%) were not accepted as candidates for PT; 13 have undergone cadaveric kidney transplantation, 5 were placed on the kidney waiting list, and 9 have died. Criteria for PTA include 2 or more diabetic complications or hyperlabile diabetes. Patient (n = 12) and pancreas graft survival after PTA is 83.3 and 50%, respectively. Our conclusion is that a multidisciplinary approach was used for recipient selection for PT based on degree of nephropathy, cardiovascular risk, and presence of diabetic complications. Nearly 75% of diabetic patients evaluated were acceptable candidates for PT. Only 4 (3.8%) of these selected patients died while awaiting or undergoing PT, thus optimizing the use of scarce allograft resources and providing evidence for appropriate patient selection.

Adult↗
PubMed1993

A Campylobacter jejuni homolog of the LcrD/FlbF family of proteins is necessary for flagellar biogenesis.

A Campylobacter jejuni homolog of the lcrD/flbF family of genes was cloned and sequenced. The nucleotide sequence of the gene, called flbA, predicted a protein of 78,864 Da, with significant homology to a group of related proteins including the Yersinia pestis LcrD, Salmonella typhimurium InvA, and Caulobacter crescentus FlbF proteins. The greatest homology was seen with the C. crescentus FlbF protein, with an overall amino acid sequence homology of 57%. An insertion mutation in the C. jejuni 81-176 flbA gene was constructed. The resultant strain did not synthesize flagellin and was nonmotile.

Amino Acid Sequence↗
PubMed1993

Experimental otitis media with effusion induced by platelet activating factor.

This study tested the hypothesis that platelet activating factor (PAF) in the middle ear can induce otitis media with effusion (OME) and that PAF antagonists can prevent PAF-induced OME. An initial trial of 16 micrograms of PAF was injected into chinchilla bullae, and all ears developed middle ear effusion (MEE) within 48 hours. Subsequent trials were performed to test dose dependency. Interestingly, 1 or 16 micrograms of PAF caused more MEE and inflammation than did 4 or 8 micrograms. A dose of 0.5 micrograms PAF did not cause MEE. Middle ear effusion from injected bullae contained the full spectrum of lipoxygenase and cyclooxygenase products; additionally, more PAF was detected than was injected. Finally, a PAF antagonist (WEB 2170) injected intraperitoneally prevented PAF-induced OME. This study demonstrates that PAF injected into the middle ear can induce OME and that PAF antagonists effectively prevent PAF-induced OME. These findings suggest that PAF plays an important role in the pathogenesis of OME.

Animals↗