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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 271 records · Page 15Linked to original sources
PubMed1994

Role of angioscopy in reoperation for the failing or failed infrainguinal vein bypass graft.

The purpose of this retrospective study is to review our ongoing experience with the use of angioscopy during reoperation for failed or failing infrainguinal vein bypass grafts and define the role of angioscopy in the management of this clinically demanding patient group. All hospital records, arteriograms, and intraoperative angioscopic video recordings of 79 consecutive failed or failing grafts (76 patients) examined with angioscopy during reoperation between 1987 and 1993 were reviewed. Clinical and intraoperative data, comparison of the preoperative arteriogram and intraoperative angioscopic findings, and surgical decisions or interventions resulting from the additional angioscopic findings were collated and analyzed according to a predetermined protocol. Sixty-six additional angioscopic findings were noted during the 79 reoperations and resulted in 61 additional interventions and surgical decisions with salvage of all or part of the graft in 90.9% in the early (< 30 day) failed (group 1), 84.6% in the late (> 30 day) failed (group 2), and 90.3% in the late (> 30 day) failing grafts (group 3). The amount of residual thrombus within the graft, as assessed by angioscopy after all interventions, was the critical determinant for overall early graft patency (p < 0.001) and long-term patency for all the subgroups after reoperation (group 1, p < 0.001; group 2, p = 0.0016; and group 3, p = 0.0194). Intraoperative angioscopy has an important role in these challenging procedures. It provides additional and useful information that not only influences the conduct and extent of the reoperative surgery but may provide insights into the pathogenesis of graft failure.

Adult↗
PubMed1994

Two dimensional gel electrophoresis identifies minor differences in immunologically cross-reactive 64 KDa autoantigens in the thyroid and eye muscle.

Among the candidate eye muscle autoantigens proposed as being relevant to the pathogenesis of thyroid-associated ophthalmopathy (TAO), a 64 kDa membrane autoantigen appears to be most closely associated with the eye disorder. We have examined the tissue localization and some of the physicochemical properties of this molecule in 3 human tissues, namely thyroid (THY), eye muscle (EM) and skeletal muscle (SKE), and in pig eye muscle (PEM), by two-dimensional (2-D) [isoelectric focusing (IEF)/sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE)] gel electrophoresis followed by Western blotting. Antibody probes used were whole sera from patients with TAO and antibodies affinity purified from TAO sera by binding to, and elution from, a sepharose-4B column conjugated with D1, a 98 amino acid peptide fragment of a recombinant 64 kDa thyroid autoantigen. Soluble membrane proteins eluted from a slice of SDS-PAGE gel containing 60-70 kDa material was prepared from the four tissues and used as antigen for 2-D gel separation. The presence of a 64 kDa antigen in THY and EM recognized by sera from patients with TAO, but only rarely by those from normal individuals, was confirmed. Pretreatment of the eluted 60-70 kDa material with N-Glycosidase F to eliminate charge heterogeneity resulting from glycosylation differences, changed the pI and MW of molecules recognized by TAO sera, in THY and EM. This suggests that the 64 kDa molecule(s) in EM and THY targeted by sera from patients with TAO are glycoproteins and that they are different in the two tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Heparin binding to monodisperse plasma fibronectin induces aggregation without large-scale changes in conformation in solution.

Plasma fibronectin was purified by gelatin affinity chromatography in the absence of urea and studied by photon correlation spectroscopy. Polydispersity in the observed translational diffusion coefficient (D20,w) was minimized by subsequent gel permeation fast protein liquid chromatography (FPLC) on Superose 6, which separated fibronectin monomers (D20,w = 2.15 +/- 0.03 x 10(-7) cm2 sec-1; polydispersity 5.2%) from aggregates. Addition of heparin to FPLC-purified fibronectin, at physiological pH, ionic strength and temperature, induced fibronectin aggregation, as shown by an increase of up to 60% in the static light-scattering intensity. Additional changes induced by heparin were an approximate 40% decrease in D20,w and an increase in polydispersity to 33%. After removal of aggregates by FPLC, the translational diffusion coefficient for fibronectin monomers was unaffected by the presence of heparin, in conditions where fluorescence polarization with fluoresceinamine-labelled heparin showed that 80% of the available heparin binding sites on fibronectin were occupied. Small differences in the circular dichroism spectrum of gelatin affinity-purified fibronectin were observed before and after removal of aggregates by gel permeation FPLC, and similar changes were seen when heparin was added to FLPC-purified fibronectin, without subsequent removal of aggregates. The results demonstrate the importance of minimizing polydispersity in the biophysical analysis of fibronectin in solution. We conclude that heparin binding to monomeric fibronectin occurs without large-scale changes in the conformation of the fibronectin molecule, although the possibility of more extended conformations in aggregated forms of fibronectin cannot be excluded.

Amino Acid Sequence↗
PubMed1994

The effects of cooperative and individualistic reward on intrinsic motivation.

The effects of cooperative versus individualistic reward on students' intrinsic motivation were investigated. The controlling aspects of extrinsic reward may be heightened or produce greater ego threat in the individualistic situation when compared with a group situation. We predicted that students in the cooperative social situation would show higher levels of intrinsic motivation. Fifth-grade students from existing cooperative groups were assigned randomly to receive a tangible reward based on either cooperative or individualistic achievement for completing pattern block designs. Cooperation affected intrinsic motivation positively. Students in the cooperative dyad solved the block designs more quickly, interacted positively, and viewed the task as easier than did those in the individualistic situation, and they reported that their peers were helpful. There was little evidence that the controlling functions of reward or ego-threat were factors in producing the outcome. Some evidence supporting the importance of the social nature of cooperation was provided.

Child↗
PubMed1994

Vaccination of the Leishmania major susceptible BALB/c mouse. I. The precise selection of peptide determinant influences CD4+ T cell subset expression.

BALB/c mice are susceptible to cutaneous leishmaniasis upon infection with Leishmania major while C57BL/6 are not. There is a major promastigote surface protease (PSP or gp63) which is available in both native and recombinant forms, and for which the primary amino acid sequence is known. Immunization with PSP has been shown to offer some protection against challenge with the live organism. Therefore, we attempted to develop a peptide vaccine with PSP peptides. In the first experiments, recall proliferative responses to PSP were measured using a set of 15mer peptides spanning the entire PSP molecule which allowed designation of major determinant regions in BALB/c, C57BL/6, and CBA mice. Several of these determinants were promiscuous and shared almost the identical core amino acid residues in the different strains. Immunization with major determinant peptides was recalled vigorously with L. major soluble antigen as well as with PSP. The response to peptide was almost entirely Th1 as measured by a localized ELISA assay for single-cell production of IFN-gamma. A similar assay for IL-5, which overcomes problems of sensitivity and inhibition by lymphokines produced by Th1 cells, indicates very little production of Th2 cells even by BALB/c. It was found that if a major responsive peak was examined by recall with overlapping peptides, the highest, central peptide gave a mainly Th1 response while the boundary, less efficient peptides gave more of a Th2 response. Possible reasons for this were discussed. These results point to the importance of selecting the exactly appropriate peptide in considering a vaccinogen that might protect susceptible individuals. Even the choice of a somewhat immunogenic peptide within the determinant envelope might actually exacerbate infection by steering the response in a Th2 direction.

Amino Acid Sequence↗
PubMed1994

Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens.

Oral tolerance is a long recognized method to induce peripheral immune tolerance. The primary mechanisms by which orally administered antigen induces tolerance are via the generation of active suppression or clonal anergy. Low doses of orally administered antigen favor active suppression whereas higher doses favor clonal anergy. The regulatory cells that mediate active suppression act via the secretion of suppressive cytokines such as TGF beta and IL-4 after being triggered by the oral tolerogen. Furthermore, antigen that stimulates the gut-associated lymphoid tissue preferentially generates a Th2 type response. Because the regulatory cells generated following oral tolerization are triggered in an antigen-specific fashion but suppress in an antigen nonspecific fashion, they mediate "bystander suppression" when they encounter the fed autoantigen at the target organ. Thus it may not be necessary to identify the target autoantigen to suppress an organ-specific autoimmune disease via oral tolerance; it is necessary only to administer orally a protein capable of inducing regulatory cells that secrete suppressive cytokines. Orally administered autoantigens suppress several experimental autoimmune models in a disease- and antigen-specific fashion; the diseases include experimental autoimmune encephalomyelitis (EAE), uveitis, and myasthenia, collagen- and adjuvant-induced arthritis, and diabetes in the NOD mouse. In addition, orally administered alloantigen suppresses alloreactivity and prolongs graft survival. Initial clinical trials of oral tolerance in multiple sclerosis, rheumatoid arthritis, and uveitis have demonstrated positive clinical effects with no apparent toxicity and decreases in T cell autoreactivity.

Administration, Oral↗
PubMed1994

Six-month stability of psychiatric diagnoses in first-admission patients with psychosis.

OBJECTIVE: The short-term diagnostic stability of schizophrenic and other psychotic disorders was examined in first-admission patients, with attention to the principal reasons for diagnostic change. METHOD: Hospitalized first-admission patients (N = 278) participating in an epidemiologic study were interviewed at baseline and after 6 months with the Structured Clinical Interview for DSM-III-R. A best estimate diagnosis was made at both time points with the use of all available sources of information. Reasons for changes in diagnosis were determined by two psychiatrists. RESULTS: Affective psychosis and schizophrenic disorders were relatively stable broad diagnostic categories over the 6-month period, with 86.5%-88.9% of the patients remaining in the same category, although findings for specific diagnoses within these categories ranged from 61.5% to 85.7%. The groups with unknown and nonspecific diagnoses showed less stability; the diagnoses of more than one-third of these patients remained unknown or nonspecific at the 6-month evaluation. If the 6-month diagnoses are used as the research standard, somewhat lower percentages of patients received the same diagnoses at baseline. Forty-three percent of the changes in diagnosis were attributed to the clinical course of illness; the rest were attributed to the diagnostic process itself. CONCLUSIONS: A longitudinal diagnostic assessment based on multiple sources of information is crucial for categorizing first-admission psychotic patients, particularly those who do not initially fit into a DSM-III-R category. The short-term stability of a diagnosis is a function of multiple factors, including the changing clinical picture, additional sources of information, and new interpretations of original data.

Adolescent↗
PubMed1994

Parent-professional agreement on diagnosis and recommendations for children with developmental disorders.

Twenty-eight children with developmental disorders underwent an interdisciplinary assessment for diagnosis and recommendations about management. Following this assessment, the degree of agreement on diagnosis and recommendations between parents and the team was determined. There was substantial agreement for diagnosis of clearly identifiable conditions such as genetic disorders, autism, and mental retardation but less agreement for milder disorders such as learning disabilities, attention deficit disorder, and emotional disorders. Agreement on management varied, being higher for speech therapy and psychosocial interventions but lower for use of stimulant medication and diet. The parents identified additional diagnostic labels in their child and mentioned more recommendations than the clinicians prescribed. The results suggest the need for careful attention to parent perceptions following interdisciplinary assessment.

British Columbia↗
PubMed1994

Spirometric impairments in long-term insulators. Relationships to duration of exposure, smoking, and radiographic abnormalities.

A study of 2,611 long-term asbestos insulators was well suited to provide information on (1) the prevalence of spirometric impairments in a large, well-defined population and (2) the effects of cigarette smoking, radiographic abnormalities, and duration from onset of exposure on pulmonary function. Prevalences are reported by a mutually exclusive classification of impairments (normal, restrictive, obstructive, small airways, and combined) as well as by abnormality of specific spirometric tests (FVC, FEV1/FVC, and midexpiratory time). Only 3 percent of nonsmokers (NS) had obstruction and 6 percent a decreased FEV1/FVC. Frequency of restriction did not vary by smoking history; it was 31 percent in NS and current smokers (CS) and 34 percent in ex-smokers (XS). Obstruction (present in 17 percent) and combined impairment (in 18 percent) were most common in CS. The FEV1/FVC was decreased in 35 percent of CS and 18 percent of XS. The FVC was decreased in 49 percent of CS, 44 percent of XS, and 33 percent of NS. Normal spirometry was most common when the radiograph was normal (almost half the workers with normal radiographs had normal spirometry). Nevertheless, FVC was reduced in 27 percent of those with normal radiographs and a normal radiograph was seen in 11 percent of workers with restriction. Restrictive and combined impairments were most frequent when both parenchyma and pleura were abnormal. Restriction was more frequent in isolated pleural disease (seen in 34 percent such subjects) than in isolated parenchymal disease (22 percent). The contribution of pleural fibrosis to reduced FVC and of asbestos exposure and smoking both to reduced FVC and to reduced FEV1/FVC was confirmed by regression analysis. That reduced FVC and reduced FEV1/FVC are both more frequent in insulators who have smoked (compared with NS insulators or smokers in the general population) suggests an interaction between asbestos and smoking in producing both these physiologic abnormalities.

Asbestosis↗
PubMed1994

Estimated vs actual values for dead space/tidal volume ratios during incremental exercise in patients evaluated for dyspnea.

The physiologic dead space/tidal volume ratio (VD/VT) at rest and during exercise is a sensitive measurement of gas exchange that reflects matching of ventilation to perfusion, but requires an invasive measurement for its calculation. Determining VD/VT noninvasively uses estimations of arterial PCO2 based on the end-tidal PCO2. To further standardize incremental cardiopulmonary exercise testing, we compared actual VD/VT with estimated VD/VT values in 35 patients referred for evaluation of dyspnea. Estimates of VD/VT used the Jones' equation (VD/VT[J]) derived from healthy subjects during steady-state exercise or PETCO2 alone (VD/VT[ET]) to approximate PaCO2. At rest, mean values for VD/VT(J) and actual VD/VT were not different: 0.372 +/- 0.08 vs 0.376 +/- 0.09, p = not significant (NS). Each method identified 61 percent of values > or = to 0.36. In 26 subjects who achieved higher work rates, the mean difference between actual VD/VT and VD/VT(J) increased from 0.009 +/- 0.04 (NS) at low work rate (VO2 = 28.3 percent pred max) to 0.040 +/- 0.06 at high work rate (VO2 = 54.7 percent pred max), p = 0.006. Actual VD/VT identified 18 (69 percent) patients as abnormal vs 13 (50 percent) so identified by VD/VT(J). With exercise, VD/VT(J) was no better than VD/VT(ET). We conclude that during incremental exercise in a patient population, methods for estimating VD/VT progressively underestimate this measurement; and therefore, "normal" estimated VD/VT values may fail to identify underlying pulmonary and/or pulmonary vascular impairment.

Adult↗
PubMed1994

Hippocampal involvement associated with human immunodeficiency virus encephalitis in Mexico.

The objective of the present study was to review the alterations of the central nervous system (CNS) in a group of deceased Mexican patients with acquired immunodeficiency syndrome; autopsies were reviewed with a special emphasis on the damage to the hippocampal formation. Of these 19 deceased patients with acquired immunodeficiency syndrome, nine (47%) had opportunistic infections in the CNS that were accompanied by human immunodeficiency virus encephalitis (HIVE), three (16%) had evidence of opportunistic infections in the brain without HIVE, and two (11%) had HIVE alone. All of the patients who had presented with neurological and neurobehavioral alterations had evidence of HIVE and/or opportunistic infections in the CNS. Of these 19 patients, 11 (58%) had presented with evidence of HIVE (with or without opportunistic CNS infections), as evidenced by the presence of gp41-positive microglial cells in the basal ganglia, neocortex, and hippocampus. The subiculum was the region that displayed the most abundant infiltration by gp41-positive microglial cells. The percentage of cases of acquired immunodeficiency syndrome with HIVE and/or CNS opportunistic infections in our series was similar when compared with that of other series in which similar methods of detection of human immunodeficiency virus in the CNS were used. We conclude that evidence of human immunodeficiency virus-associated lesions in the hippocampal formation might in part explain the selective neuronal alterations in this limbic structure, and we suggest that damage to this circuitry might be in part involved in the cognitive alterations in HIVE.

AIDS-Related Opportunistic Infections↗
PubMed1994

The in vitro binding of acetaldehyde to collagen studied by neutron diffraction.

The location of acetaldehyde binding sites in the axial unit cell of tendon collagen was investigated by neutron diffraction. Acetaldehyde forms spontaneous cross-links with specific residues in collagen. The use of deuterated acetaldehyde increased the neutron scattering length of these groups. The introduction of deuterated acetaldehyde at specific locations allowed the acetaldehyde-reacted collagen to be treated as multiple isomorphous derivatives for neutron fibre diffraction. The low resolution axially projected structure was determined using amplitudes of the first eight meridional reflections (d = 67 nm). Results indicate that the process of acetaldehyde labelling takes place at different rates at different sites within the collagen fibril. The position of acetaldehyde attachment correlates well with the position of lysine and hydroxylysine residues especially in the regions of the molecular termini. This information is relevant to the process of cirrhosis and fibrosis of the liver since adduction of collagen by acetaldehyde may interfere with normal Schiff base cross-link formation at the C- and N-termini. This may result in subsequent alterations in the intra- and inter-molecular cross-linking pattern of collagen molecules.

Acetaldehyde↗
PubMed1993

Crystallization and preliminary X-ray analysis of human tissue factor extracellular domain.

The extracellular domain (residues 1 to 220) of human tissue factor has been cloned and expressed in Escherichia coli and purified to isoelectric homogeneity. Single crystals suitable for X-ray analysis have been obtained by vapour diffusion. They belong to the tetragonal space group P4(1)2(1)2 or P4(3)2(1)2 with a = b = 45.2 A, c = 231.5 A, contain one molecule per asymmetric unit and diffract to 2.6 A resolution. Native and derivative data sets have been collected to 3.6 and 3.9 A, respectively.

Crystallography, X-Ray↗