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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 721 records · Page 40Linked to original sources
PubMed1994

Colorectal tumourigenesis.

Colorectal cancer is significant because of its lethality and high incidence in the Western world. Furthermore, it is a particularly suitable model for studying the events involved in the progression from normal tissue to invasive cancer. There is a great deal of epidemiological and histopathologic evidence to implicate the adenomatous polyp as the precursor to colorectal cancer. Moreover in recent years investigators have uncovered some of the molecular genetic events that underlie the progression from normal epithelium to polyp to cancer. It is hoped that an increased understanding of the molecular changes will afford opportunities for new diagnostic, prognostic and therapeutic strategies in the management of this disease.

Adenoma↗
PubMed1994

Motor unit territories in the human perioral musculature.

The perioral region was divided into four quadrants, and electromyograms (EMGs) were recorded from each area. The coherence function (i.e., the squared cross correlation between two signals computed at each frequency in the spectrum) was used to determine aspects of the organization of motor unit territories and to examine potential higher level sources of input in speech and nonspeech tasks. Coherence functions were computed between pairs of EMGs and were examined for significant values in the range of 20-240 Hz. When two pairs of electrodes were intentionally placed to record the activity from a common subset of motor units in a single quadrant of the lower lip, all subjects exhibited significant broad-band coherence in every frequency in all experimental tasks. Thus, the presence of such a pattern of broad-band significant coherence for EMG pairs recorded from different quadrants would indicate that single motor unit territories extended across perioral quadrants. When separate EMG recordings were obtained from the four quadrants of the lips, coherence functions computed between EMG pairs were typically zero across the entire frequency range. These findings suggest that perioral motor unit territories are organized into nonoverlapping quadrants. Further, the present analyses suggest that, unlike bilateral pairs of jaw-closing muscles during chewing, these motor units are not driven by any correlated oscillatory activity in chewing or other oral motor tasks.

Adult↗
PubMed1994

Identification and characterization of an iron-regulated hemopexin receptor in Haemophilus influenzae type b.

Heme can serve Haemophilus influenzae as a source of both essential porphyrin and iron. In extracellular mammalian body fluids neither free heme nor free iron is available, since they are tightly bound to hemopexin and transferrin, respectively. Since H. influenzae grows in the presence of iron-transferrin and heme-hemopexin and is known to express a saturable receptor for transferrin, we investigated the process by which this pathogen acquired heme from hemopexin for use as an iron source. The ability of human and rabbit hemopexin to donate heme as a source of iron to H. influenzae type b strains was demonstrated by plate bioassays. With a dot enzyme assay with biotinylated hemopexin as ligand, H. influenzae bound heme-hemopexin and apo-hemopexin following growth in iron-restricted, but not in iron-sufficient, medium. Competitive binding studies with heme-hemopexin and apo-hemopexin demonstrated saturability of binding. Neither heme, protoporphyrin IX, hemoglobin, nor transferrin blocked the binding of hemopexin to whole cells, demonstrating the specificity of binding. Treatment of whole H. influenzae cells with trypsin abolished binding. Taken together, these observations suggest that H. influenzae type b expresses an outer membrane protein(s) which acts as a receptor for hemopexin and which is regulated by the availability of iron in the growth medium. In iron-restricted media, H. influenzae 706705 and DL42 did not express the 100-kDa hemopexin-binding protein previously reported (M.S. Hanson, S.E. Pelzel, J. Latimer, U. Muller-Eberhard, and E.J. Hansen, Proc. Natl. Acad. Sci. USA 89:1973-1977, 1992). The putative iron-regulated hemopexin receptor was solubilized from cell envelopes of H. influenzae 706705, DL42, and Eagan with the detergent CHAPS (3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate) and isolated by affinity chromatography on heme-hemopexin-Sepharose 4B. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins bound to the affinity resin revealed three proteins of 29, 38, and 57 kDa, of which the 57- and 29-kDa proteins bound hemopexin after Western blotting (immunoblotting). A monoclonal antibody to the 57-kDa hemopexin-binding protein of 706705 recognized a 57-kDa protein on Western blots of the cell envelope proteins of 706705, DL42, and Eagan; no reaction was observed with the 100-kDa hemopexin-binding protein of DL42. These data suggest that some H. influenzae strains possess at least two hemopexin receptors, the expression of which is determined by the prevailing growth environment.

Aerobiosis↗
PubMed1994

Hepatitis C virus in autoimmune liver disease in the UK: aetiological agent or artefact?

Hepatitis C virus antibody titres (anti-HCV) were measured in serum from 122 patients with autoimmune liver disease (96 with primary biliary cirrhosis and 26 with autoimmune chronic active hepatitis using three generations of enzyme immunoassay (EIA): first generation--Ortho, EIA1; second generation--Abbott, EIA2; and third generation--Murex, EIA3. Anti-HCV was below the positive cut-off level in all 26 autoimmune chronic active hepatitis patients for all tests, while seropositivity values in primary biliary cirrhosis were 31% (EIA1), 14% (EIA2), and 0% (EIA3). In primary biliary cirrhosis, anti-HCV values as measured by all three tests correlated positively with serum IgG concentrations, serum storage time, and a number of other indices of hepatic dysfunction. Multiple regression analysis showed that anti-HCV values were independently affected by both serum IgG and the length of storage time, although the magnitude of the effects varied between tests. When all three multiple regression models were applied to an extreme clinical example, however, EIA3 was least likely to give a false-positive result. The difference in test performance was emphasised further by examination of anti-HCV values in nine primary biliary cirrhosis patients (confirmed negative by recombinant immunoblot assay 2) in whom serial samples were tested (seven to 14 per patient, stored for one to 138 months). Apparent anti-HCV values (EIA1 and EIA2) increased with increasing serum storage time, but were unchanged when measured by EIA3. A similar pattern was evident in a limited study of five autoimmune chronic active hepatitis patients. As the second generation EIA is in widespread use and confirmatory testing is not always available, the effect of serum storage in addition to hyperglobulinaemia should be considered in the interpretation of positive results in auto immune and in other types of chronic liver disease.

Autoimmune Diseases↗
PubMed1994

Morphology of left ventricular outflow tract structures in patients with subaortic stenosis and a ventricular septal defect.

OBJECTIVE: To compare the incidence and prognosis of subaortic stenosis associated with a ventricular septal defect and to define the morphological basis of subaortic stenosis. DESIGN: Presentation and follow up data on 202 patients with subaortic stenosis seen at the Royal Liverpool Children's Hospital between 1 January 1960 and 31 December 1991 were reviewed. Survivors were traced to assess their current clinical state. Necropsy specimens of 291 patients with lesions associated with subaortic stenosis were also examined. RESULTS: In the clinical study; 65 (32.1%) of the 202 patients with subaortic stenosis had a ventricular septal defect (excluding an atrioventricular septal defect). 32 of these patients had a short segment (fibromuscular) subaortic stenosis. 33 had subaortic stenosis produced by deviation of muscular components of the outflow tracts. In 17 patients (51.5%) this was caused by posterior deviation or extension of structures into the left ventricular outflow tract, resulting in obstruction above the ventricular septal defect. In the other 16 patients (48.5%) there was over-riding of the aorta with concordant ventriculoarterial connections, (without compromise to right ventricular outflow) producing subaortic stenosis below the ventricular septal defect. Additional fibrous obstruction occurred in 39% of the patients with deviated structures. The age at presentation was lower (P < 0.01) in patients with deviated structures (median (range) 0.4 (0 to 9.2) months) than in those with short segment obstruction (median (range) 4.2 (0 to 84.9) months). The incidence of aortic arch obstruction was higher (P < 0.002) in patients with deviated structures than in those with short segment obstruction (38%). In the morphological study 35 pathological specimens showed obstructive muscular structures in the left ventricular outflow tract either above or below the ventricular septal defect. 16 had either posterior deviation of the outlet septum or extension of the right ventriculoinfundibular fold, or both of these together into the left ventricle. 19 had anterior deviation of the outlet septum into the right ventricle with overriding of the aorta (without compromise to right ventricular outflow). The earliest age at which additional fibrous obstruction was seen was 9 months. The aortic valve circumference was small in 18% of specimens. FOLLOW UP: The median (range) duration of follow up in survivors from the clinical study was 6.6 (1 to 25.7) years. 16 patients with deviated musculature (49%) and 16 with short segment fibromuscular stenosis (50%) underwent operation for subaortic stenosis. Patients with deviated structures were younger at operation than those with short segment stenosis (P < 0.005). Patients with posterior deviation or extension of structures into the left ventricular outflow tract underwent operation for subaortic stenosis more frequently (P < 0.05) than those with anterior deviation of the outlet septum and aortic override. The ventricular septal defect required surgical closure more frequently (P < 0.005) in patients with deviation (93.9%) than in those with short segment obstruction (21.9%). There was no significant difference in the mortality between patients with deviation (27%) and those with short segment obstruction (12%). CONCLUSIONS: 32% of patients in the clinical study with subaortic stenosis had a ventricular septal defect. Only 51% of these had obstructive and deviated muscular structures in the left ventricular outflow tract. These patients had a significantly higher incidence of aortic arch obstruction and required surgery for subaortic stenosis at a younger age than those with short segment obstruction. The ventricular septal defect also required surgical closure more frequently in those patients with deviation. The morphological study defined the two sites of obstruction. The presence or absence and type of deviation should be clearly defined in all patients with a ventricular septal defect,

Aortic Stenosis, Subvalvular↗
PubMed1994

Strength training increases resting metabolic rate and norepinephrine levels in healthy 50- to 65-yr-old men.

Resting metabolic rate (RMR) decreases with age, largely because of an age-related decline in fat-free mass (FFM). We hypothesized that a strength-training program capable of eliciting increases in FFM would also increase RMR in older individuals. To test this hypothesis, RMR, body composition, and plasma concentrations of certain hormones known to affect RMR were measured before and after a 16-wk heavy-resistance strength-training program in 13 healthy men 50-65 yr of age. Average strength levels, assessed by the three-repetition maximum test, increased 40% with training (P < 0.001). Body weight did not change, but body fat decreased (25.6 +/- 1.5 vs. 23.7 +/- 1.7%; P < 0.001) and FFM increased (60.6 +/- 2.2 vs. 62.2 +/- 2.1 kg; P < 0.01). RMR, measured by indirect calorimetry, increased 7.7% with strength training (6,449 +/- 217 vs. 6,998 +/- 226 kJ/24 h; P < 0.01). This increase remained significant even when RMR was expressed per kilogram of FFM. Strength training increased arterialized plasma norepinephrine levels 36% (1.1 +/- 0.1 vs. 1.5 +/- 0.1 nmol/l; P < 0.01) but did not change fasting glucose, insulin, or thyroid hormone levels. These results indicate that a heavy-resistance strength-training program increases RMR in healthy older men, perhaps by increasing FFM and sympathetic nervous system activity.

Aged↗
PubMed1994

Labeled Schwann cell transplants versus sural nerve grafts in nerve repair.

This study evaluated the ability of Schwann cell transplants to enhance the recovery of function in injured nerves and compared the results to those produced by sural nerve grafts. Schwann cells were isolated from sciatic nerves, prelabeled with gold fluorescent dye admixed with collagen gel, and placed in resorbable collagen tubes. Twenty-four adult rats underwent severing of the bilateral sciatic nerves, with a 10-mm gap between the nerve stumps. The rats were then divided into two groups. A collagen tube with implanted Schwann cells was implanted in one leg of the Group I rats, and the contralateral leg served as a control and was repaired with a collagen tube filled with collagen gel only. The Group II animals received conduits packed with labeled Schwann cells in one leg to bridge the 10-mm gap; the contralateral leg was repaired with an autogenous sural nerve graft. Recovery of function was assessed physiologically and morphologically. Nerve conduction velocity and nerve action potential amplitude measurements showed that the Schwann cell implants induced return of function comparable to that of the sural nerve grafts. Morphological assessments of myelination suggested a tendency toward greater numbers of myelinated axons in Schwann cell implants than in sural nerve grafts. Anatomical analyses of gold fluorescent dye showed both high viability of prelabeled Schwann cells at 120 days after transplantation and migration as far as 30 mm away from the implant site.

Animals↗
PubMed1994

The wild side of EMS.

Explore the source record for details and available documents.

Emergency Medical Services↗
PubMed1994

Harvesting, characterization, and culture of CD34+ cells from human bone marrow, peripheral blood, and cord blood.

Stem and progenitor cells from a variety of sources including bone marrow, cord blood, and peripheral blood have been used for transplantation. This study compares CD34 cells from all three sources. Flow cytometry analysis of CD34 cells in multiple samples of normal peripheral blood and patient peripheral blood mobilized with chemotherapy (cyclophosphamide/VP16), chemotherapy plus granulocyte colony stimulating factor (G-CSF), and G-CSF alone were compared to bone marrow and cord blood. Although the relative distribution of CD34 percentages in each preparation of cells varied widely, on average the percentage of CD34 cells in these different preparations was 0.15%, 0.6%, 2%, 0.45%, 1.68%, and 0.83% respectively. CD34 subset analysis was performed on these cell preparations using multicolor flow cytometry and antibodies to CD33, CD13, CD45RA, CD19, CD71, and CD38. The major differences observed were that bone marrow CD34 cells contain high percentages of CD19+ cells not found in significant quantity in the other cell preparations and cord blood CD34 cells contained a higher percentage of CD38-cells than the other cell preparations. A magnetic bead system was used with anti-CD34 antibody to purify CD34 cells from mobilized peripheral blood apheresis products, cord blood, and bone marrow. Efficient selection with high purities of CD34 cells was achieved with each of the cell preparations. Comparison of colony-forming activity of each of the cell preparations showed cord blood and mobilized peripheral blood to have slightly higher cloning efficiencies than bone marrow with higher numbers of erythroid blast-forming units (BFU-E) also observed in cord blood CD34 cells. Culture of isolated CD34 cells in liquid culture with interleukin-3, stem cell factor, G-CSF, and granulocyte-macrophage GM-CSF showed over a 100-fold expansion in cell numbers after 25 days, with the peak expansion of colony-forming cells occurring between days 11 and 16. Analysis of day-10 cells from these cultures showed them to be predominantly promyelocytes, myelocytes, and metamyelocytes, with cord blood CD34 cultures showing more promyelocytes than peripheral blood or bone marrow and bone marrow showing more metamyelocytes. Comparison of the proliferation of CD34 cells from these different cell preparations showed that cord blood CD34 cells cultured for 10 days averaged an 85-fold increase in cell numbers followed by mobilized peripheral blood CD34 cells, with an average 56-fold increase, and bone marrow CD34 cells, with an average 49-fold increase.

Adult↗
PubMed1994

Influence of radiolabel on the in vivo processing of intact and fragmented anti-tumour monoclonal antibody.

The anti-colon carcinoma MoAb35 and its F(ab')2 fragment were labelled with 131I or 67Cu and their biodistributions compared in nude mice bearing human tumour xenografts. Two-fold higher levels of 67Cu were found in the xenografts than 131I, with no significant difference in whole-body distribution. For the F(ab')2 fragment tumour levels were not significantly different between 131I and 67Cu. A very high accumulation of 67Cu was found in the kidney (36.7% ID/g). Whether deiodination in the kidney could account for the difference in nuclide accumulation was checked by repeating the study with 131I, linked to the F(ab')2 by a method known to resist deiodination. The results showed a slight increase in tumour accumulation of 131I but kidney levels remained low at 3.1% ID/g 24 hours post-injection compared to 42.4% ID/g for 67Cu, suggesting that deiodination does not play a role in the observed low levels of 131I in the kidney. Ongoing studies on the distribution and processing of radioimmunoconjugates will hopefully assist in their application in clinical studies.

Animals↗
PubMed1994

Diagnostic reassessment and treatment response in schizophrenia.

BACKGROUND: The reasons for poor treatment response in some patients with schizophrenia remain unclear. It is possible that misdiagnosis of nonschizophrenic disorders as schizophrenia could result in suboptimal pharmacotherapy in some patients. METHOD: To assess this possibility, 110 severely ill, chronic patients with a referral diagnosis of schizophrenia were comprehensively assessed and rediagnosed according to DSM-III-R criteria. Global Assessment of Function (GAF) and Clinical Global Impressions (CGI) ratings were made at admission and at discharge from the ward, after the implementation of individualized treatment plans. RESULTS: The diagnosis of schizophrenia was confirmed in 80 patients (73%) and revised to another type of psychotic illness in 30 patients (27%). The GAF and CGI ratings were similar at admission in patients with confirmed and revised diagnoses. All patients improved by the time of discharge (p = .0001); however, patients with a revised diagnosis improved more than those with confirmed schizophrenia (p = .02). Patients with a revised diagnosis were less likely to require continued hospitalization on chronic care wards (p = .004). At admission, medication regimens were similar in the two groups of patients. At discharge, patients with a revised diagnosis were less likely to have received neuroleptics (p = .007) and more likely to have received antimanic drugs (p = .0002) or electroconvulsive therapy (p = .0004). CONCLUSION: These findings from a clinical sample suggest that diagnostic reassessment is an important first step in the management of apparently refractory schizophrenia.

Adolescent↗
PubMed1994

Erosion in children: an increasing clinical problem?

Tooth wear is becoming more common in both adults and children. The triad of attrition, abrasion and erosion has been known for many years, but the contribution of erosion (irreversible loss of dental hard tissue due to a chemical process not involving bacteria, or the loss of tooth surface not directly associated with mechanical or traumatic factors or caries) to excessive loss of tooth tissue is now being emphasized. The authors of this paper examine the problem and suggest ways of overcoming it.

Beverages↗
PubMed1994

Psychosocial needs of family members of liver transplant patients.

Recent literature is beginning to reflect the importance of psychosocial needs of liver transplant patients, examining functional outcome, quality of life, daily living, and psychiatric and neurocognitive outcome. Little attention has been paid to the psychosocial needs of the liver transplant patient's family or significant other. Family members, along with the patient, must cope with disease chronicity, an uncertain organ donor waiting period, role reversal, a protracted postoperative hospital course, and a complicated medical regimen after discharge. Consequently, demands on time, energy, finances, and relationships can strain an already stressed family structure. Psychosocial needs of the liver transplant patient's family are discussed in this article, including aspects of chronic disease, the transplant evaluation, the waiting period, the immediate postoperative period, and long-term adjustment and recovery. Nursing interventions to facilitate effective coping strategies are suggested. Gaps in the existing literature are identified and suggestions for future research are made.

Adult↗