Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 19 recordsLinked to original sources

PubMed1992

Identification of a repetitive element in the snail Biomphalaria glabrata: relationship to the reverse transcriptase-encoding sequence in LINE-1 transposons.

BamHI-digested Biomphalaria glabrata DNA contains a repetitive 2.0-kb fragment which is readily discernible by ethidium bromide staining. We present evidence that this repetitive element is related at both the nucleotide and amino acid levels to long interspersed nuclear element (LINE)-like transposons. Although comparable elements have been described in several invertebrates, this is the first report of a molluscan homologue. In common with LINE transposons, an open reading frame in the B. glabrata element shows significant homology to reverse transcriptase--a feature believed to allow the dissemination of these elements in the eukaryotic genome.

Amino Acid Sequence↗

PubMed1992

Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen.

Immunization with myelin basic protein (MBP) induces experimental allergic encephalomyelitis (EAE), a prototype of CD4+ T-cell mediated autoimmune disease. In rodents, MBP-reactive T-cell clones are specific for a single, dominant determinant on MBP and use a highly restricted number of T-cell receptor genes. Accordingly, EAE has been prevented by various receptor-specific treatments, suggesting similar strategies may be useful for therapy of human autoimmune disease. Here we report that in (SJL x B10.PL)F1 mice, immune dominance of a single determinant, MBP:Ac1-11, is confined to the inductive phase of EAE. In mice with chronic EAE, several additional determinants of MBP in peptides 35-47, 81-100 and 121-140 recall proliferative responses. Most importantly, reactivity to the latter determinants was also detected after induction of EAE with MBP peptide Ac1-11 alone; this demonstrates priming by endogenous MBP determinants. Thus, determinants of MBP that are cryptic after primary immunization can become immunogenic in the course of EAE. Diversification of the autoreactive T-cell repertoire due to 'determinant spreading' has major implications for the pathogenesis of, and the therapeutic approach to, T-cell driven autoimmune disease.

Amino Acid Sequence↗

PubMed1992

Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering.

Oral administration of myelin basic protein (MBP) is an effective way of suppressing experimental autoimmune encephalomyelitis (EAE). We have previously shown that such suppression is mediated by CD8+ T cells, which adoptively transfer protection and suppress immune responses in vitro. In the present study we have found that modulator cells from animals orally tolerized to MBP produce a suppressor factor upon stimulation with MBP in vitro that is specifically inhibited by anti-transforming growth factor beta (TGF-beta) neutralizing antibodies. No effect was observed with antibodies to gamma interferon, tumor necrosis factor alpha/beta, or indomethacin. In addition, the active form of the type 1 isoform of TGF-beta 1 (TGF-beta 1) can be directly demonstrated in the supernatants of cells from animals orally tolerized to MBP or ovalbumin after antigen stimulation in vitro. Antiserum specific for TGF-beta 1 administered in vivo abrogated the protective effect of oral tolerization to MBP in EAE. Furthermore, injection of anti-TGF-beta 1 serum to nontolerized EAE animals resulted in an increase in severity and duration of disease. These results suggest that immunomodulation of EAE induced by oral tolerization to MBP and natural recovery mechanisms use a common immunoregulatory pathway that is dependent on TGF-beta 1. Implications of such an association are of therapeutic relevance to human autoimmune diseases and may help to explain one of the mechanisms involved in the mediation of active suppression by T cells.

Administration, Oral↗

PubMed1992

Trends in the care of the diabetic foot. Expanded role of arterial reconstruction.

In recent years, our operative approach to ulceration and gangrene in the diabetic foot has changed markedly. We now investigate all such patients for ischemia, even in the presence of neuropathy and localized infection. This strategy is based on a rejection of the concept of a microvascular occlusive lesion, an improved understanding of the pattern of atherosclerotic occlusion, an emphasis on arteriographic delineation of the foot arteries, and increasing success with extreme distal arterial reconstruction, especially vein bypass grafts to the dorsalis pedis artery. From 1984 through 1990, 2883 procedures were performed at our institution on patients with diabetes mellitus. There was a statistically significant decrease in every category of amputation, which correlated precisely with the increasing rate of dorsalis pedis artery bypass. Our indications for surgery, in-hospital mortality, and the bypass-associated amputation rate did not change.

Amputation, Surgical↗

PubMed1992

Bound vitamin B12 absorption in patients with low serum B12 levels.

In many patients with low serum levels of vitamin B12, the absorption of the free vitamin has been normal. The present study, using a total body counter 57CoB12 absorption method that clearly separated those with intrinsic factor deficiency from controls, found that of 94 patients with low B12 levels and intact stomachs in whom the absorption of free and bound B12 was determined, 44 (47%) had normal absorption of both. However, 20 of the 94 (21%) with normal absorption of free B12 had low absorption of bound B12. The remainder (32%) had low absorption of both free and bound B12. All patients with high serum gastrin levels had low bound B12 absorption, but so did 21% of those patients with normal serum gastrin levels.

Cobalt Radioisotopes↗

PubMed1992

On creativity.

Explore the source record for details and available documents.

Art↗

PubMed1992

T lymphocyte adhesion to the fibronectin and laminin components of the extracellular matrix is regulated by the CD4 molecule.

The adhesion of T cells to components of the extracellular matrix (ECM) is mediated by the beta 1 subfamily of integrin receptors, designated VLA. It has been recently demonstrated that the binding of VLA receptors to protein components of the ECM is rapidly augmented by the activation of the T cells without, however, any actual change in the level of expression of the VLA receptors for fibronectin (FN) or laminin (LN). Thus, it is likely that activation of existing VLA receptors is required for binding. The activation must be regulated by T cell surface molecules capable of transducing signals into the cell. We studied the role of the CD4 molecule in the binding of rat CD4+ T cells to the FN and LN components of the ECM. We now report that the CD4 molecule appears to play a major role in regulating T cell interactions with ECM. This conclusion is based on the following observations: (a) monoclonal antibodies directed against the CD4 molecule inhibited T cell adhesion to both FN and LN; (b) down-regulation of the CD4 molecule resulted in partial loss of the ability of CD4+ T cells to adhere to FN and LN; (c) a CD4+ T cell clone adhered to both FN and LN while a CD4-CD8- clone expressing an identical T cell receptor bound weakly to both proteins and (d) treatment of the CD4+ T cells with an inhibitor of the CD4-associated tyrosine protein kinase activity inhibited T cell adhesion to both ECM proteins.

Animals↗

PubMed1992

Safety of saline irrigation for angioscopy: results of a prospective randomized trial.

This study evaluates the hemodynamic effects and safety of saline irrigation necessary to obtain high-quality completion angioscopic studies, as compared with standard completion arteriography during infrainguinal bypass grafting. One-hundred ten patients undergoing primary infrainguinal bypass grafting, were prospectively randomized to either arteriography (N = 50) or angioscopy (N = 60) for a completion study to monitor the bypass procedure. All patients were hemodynamically monitored with pulmonary artery catheters and arterial lines. The arteriography group received an average of 27 ml (range 8-60 ml) of contrast per completion study, with a total administered intraoperative fluid volume of 2095 ml (range 650-4000 ml). The angioscopy group received an average bolus of 321 ml (range 90-650 ml) of irrigation fluid per completion angioscopy study, with a total administered intraoperative fluid volume of 2140 ml (range 850-5000 ml). Transient increases in pulmonary artery systolic and diastolic pressures and central venous pressures were measured during angioscopy. Although these changes reached statistical significance, the changes were of minimal clinical relevance, 1.9 (= 4.5), 1.6 (= 3.0) and 1.4 (= 2.3) mmHg respectively, and returned to baseline levels within 30 minutes. Intraoperative intervention with vasodilators and diuretics, the perioperative cardiac morbidity, and less than 30 day mortality, was not different between the two groups. Pressures generated within 24 bypass grafts were within physiologic arterial range for most of the study. With careful angioscopic technique applied and high quality care extended to the patient, irrigation with saline solution is simple, effective and safe.

Angiography↗

PubMed1992

Vertical dimension increases in the adult rhesus monkey: a pilot study.

Tooth impaction, increased muscle activity, and histologic changes in the bone of the temporomandibular joint have been reported following attempts to increase the vertical dimension of occlusion. The purpose of this research was to study the effects of increases in the vertical dimension of occlusion on bone density at five levels of the mandible in the adult rhesus monkey, and to assess dentoalveolar changes by lateral cephalometric radiographs and mounted diagnostic casts. Mandibular cobalt chromium splints measuring 3 mm in height at the first molar, providing even occlusal contact to the maxillary anterior and posterior teeth, were cemented in place on two monkeys. Five similar monkeys without splints were used as controls. Computed tomograms were completed to evaluate bone density bilaterally at five levels of the mandible after 3 months of splint wear. Pretreatment and posttreatment lateral cephalometric radiographs and mounted diagnostic casts were completed to assess tooth impaction. Periodontal ligament (PDL) thickening and mobility of molars and premolars were evaluated before splint placement and after splint removal. There was no statistically significant difference in the bone density levels of the animals with splints compared with the controls. Minimal dentoalveolar changes were observed.

Animals↗

PubMed1992

Comparison of the fracture strengths of ceramometal crowns versus several all-ceramic crowns.

Fracture resistance to forces applied to the incisal edges of four types of anterior crowns was tested. Ceramometal crowns fractured at significantly higher values (720 psi) than the all-ceramic crowns (approximately 360 psi). No significant difference was found among the fracture values of the Dicor crowns, the aluminous porcelain jackets, and the crowns fabricated from Dicor veneered with aluminous body and incisal porcelain.

Aluminum Oxide↗

PubMed1992

Restricted tissue reactivity of autoantibodies to a 64-kDa eye muscle membrane antigen in thyroid-associated ophthalmopathy.

We studied the tissue specificity of eye muscle (EM) membrane-reactive autoantibodies detected in the serum of patients with thyroid-associated ophthalmopathy (TAO). In preliminary studies, such antibodies were shown to react, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, with human thyroid (THY) and other human skeletal muscle (HSM) membrane antigens. We carried out absorption with human EM (HEM), THY, and HSM membranes of sera from patients with TAO and autoimmune thyroid disease without ophthalmopathy which reacted with one or more of 55-, 64-, and 95-kDa antigens in pig eye muscle (PEM) membrane in immunoblotting, the majority of which were also cytotoxic to HEM cells in an antibody-dependent cell-mediated cytotoxicity assay. In Western blotting, serum antibodies reactive with PEM membrane antigens of 55, 64, and 95 kDa were cross-absorbed by HEM, THY, and HSM but not by spleen or brain membranes and showed some species specificity, being absorbed by pig and human, but not bovine, EM membranes. When incubated with cultured HEM, THY, and HSM cells in vitro, autoantibodies in TAO sera immunoprecipitated a 64-kDa antigen from the first two tissues, but not from HSM, suggesting a specific binding to autoantigenic epitopes in HEM and THY. Sera from patients with TAO as well as those from patients with thyroid autoimmunity without ophthalmopathy immunoprecipitated a approximately 66-kDa protein, shown to be distinct from the 64-kDa antigen. The restricted immunological cross-reactivity of antibodies to a THY and HEM 64-kDa membrane antigen is discussed in the context of the association of ophthalmopathy with thyroid autoimmunity. Further experiments are needed to show whether autoantibodies to the 64-kDa eye muscle and thyroid shared antigen are cytotoxic, and thus likely to play a major role in the pathogenesis of the eye disease, or just markers of the orbital autoimmune process.

Adult↗

PubMed1992

Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. V. Hierarchy of suppression by myelin basic protein from different species.

We have been investigating the suppression of experimental autoimmune encephalomyelitis (EAE) by oral tolerization to autoantigens. In the present study the tolerizing effect of orally administered myelin basic protein (MBP) from different species was examined in the Lewis rat, Hartley guinea pig, and SJL/J mouse model of EAE. Animals were fed guinea pig, rat, bovine, human or mouse-MBP and then immunized with the homologous species of MBP or myelin: Lewis rats were immunized with rat MBP, Hartley guinea pigs with guinea pig-MBP, and SJL/J mice with mouse myelin. Clinical expression of EAE and delayed-type hypersensitivity (DTH) responses to MBP were assessed. In each species, suppression of disease and DTH responses were most pronounced by tolerization with the homologous species of MBP. In addition, cross-species tolerization was observed in each species and in general was less suppressive than homologous MBP although in some instances MBP from a heterologous species was as effective as tolerization with the homologous species. We also studied guinea pig-MBP induced EAE in the Lewis rat because it is a widely studied model of EAE and found that oral tolerization with guinea pig MBP was as suppressive as rat MBP. Of note is that oral tolerization with mouse MBP suppressed myelin-induced EAE in the SJL mouse in which autoimmunity to proteolipid protein appears to play a primary role, suggesting that antigen-driven bystander suppression following oral tolerization with autoantigens (Miller et al., 1991b) may be an important contributing mechanism for suppression of EAE following oral tolerization with MBP in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Radiation oncology residents' computer workstation.

We are investigating the feasibility of using the Macintosh computer as a workstation platform for radiation oncology residents because of its ease of use, graphics capability, and low cost. Hypercard was chosen as the programming environment because it easily mixes graphics, text, and control functions in an integrated screen display. Furthermore, it results in a system that can be relatively easily extended and customized by individual users with varying degrees of computer skills. We have developed several software modules in order to test the ability of this environment to support the demands of such a workstation. Modules created thus far include various clinical physics aids and tutorials, treatment planning guides, oncology databases, and others. The software runs on all Macintosh configurations, but calculation speeds are improved when a 68020 or greater processor is used. In general, we have been pleased with the implementation thus far. Graphics display capability is good, but design and entry of graphics have proved labor-intensive. Searching is fast and text is easily entered and manipulated. Finished modules can be customized with minimal computer training, but implementing complex new functions requires familiarity with Hypercard's programming language. New modules, once developed, are easily integrated into the workstation universe, suggesting that cooperative development of the workstation by multiple contributors is realistically achievable.

Computer Graphics↗

PubMed1992

Comparative quantitative evaluation of pleural fibrosis and its effects on pulmonary function in two large asbestos-exposed occupational groups--insulators and sheet metal workers.

Two large (N = 1584 and N = 1330) population groups of workers exposed to asbestos as insulators (I) or sheet metal workers (SM) were compared. Prevalence rates of radiographic changes including pleural fibrosis (circumscribed and diffuse) were found to be much higher in I than SM. An integrative index of pleural fibrosis (INDEX) showed similar distribution patterns in the two groups; the effect of INDEX on FVC% predicted was more marked in insulators. Factors that could contribute to this difference are thought to be the higher prevalence of interstitial pulmonary fibrosis (probably including that which is not yet radiologically detectable) in I than in SM, the possibility of more extensive pleural fibrosis in areas not accessible to the standard chest X ray (and thus not affecting INDEX) and a higher proportion of diffuse pleural fibrosis in the I group.

Asbestos↗

PubMed1992

Alternating unilateral lachrymation.

A 56-year-old woman displayed a condition of alternating unilateral lachrymation while she was undergoing psychotherapy. Although she was aware of this condition only since her marriage, hypnotic age regression revealed its existence in childhood, together with mutism and a catatonic trance-like state. Further investigation revealed the connection of this symptom with her family constellation and the reappearance of the unilateral crying as an adult. In this paper we review the neurophysiology of lachrymation, discuss the hypnosis sessions, discuss the symptom as a psychosomatic condition and as a dissociative phenomenon, and present a case report of her background.

Crying↗

PubMed1992

Defense behavior and coping in an autistic savant: the story of Temple Grandin, PhD.

The causal factors in the behaviorally defined syndrome of autism remain unclear, although the past decade has brought to bear two significant developments that shape our view of the disorder. The first of these developments is a growing body of biomedical research that indicates there are multiple etiologies associated with the disorder. This research has allowed for the formation of subgroups based upon neuroanatomical, neurobiological, and neurophysiological abnormalities (Damasio 1984; Piggot 1979; Ritvo et al. 1990). The second is neuropsychological research indicating that the socioemotional deficits are primary to the disorder and may underlie much of the behavioral symptomatology (Fein et al. 1986). These areas of concern undoubtedly have enhanced our understanding of the disorder, yet in their achievements they may too easily absorb what we know about autistics who experience a chronic state of physiological hyperarousal, evidence of which has been found in neurophysiological studies (Delius 1967; Hutt et al. 1965), neurochemical studies (Lake et al. 1977), psychopharmacologic studies (Ratey et al. 1987a), and behavioral studies (Kinsbourne 1980; Kootz et al. 1982; Tinbergen and Tinbergen 1972; Zentall and Zentall 1983). These individuals, perhaps constituting a subgroup of their own, experience an inner state of disorganization that markedly impairs their functioning (Sands and Ratey 1986).

Adaptation, Psychological↗

PubMed1992

Significance of antibodies reactive with a 64 kDa eye muscle membrane antigen in patients with thyroid autoimmunity.

SDS-polyacrylamide gel electrophoresis and Western blotting for antibodies reactive with a 64 kDa protein in pig eye muscle membrane was carried out in patients with lid lag and retraction, but no other signs of ophthalmopathy, associated with thyroid disease or nonimmunologic goiter and in patients with Graves' hyperthyroidism without ophthalmopathy who were studied prospectively to determine the relationship of eye muscle antibodies to clinical features of the ophthalmopathy as they appeared in this group of predisposed patients. Seventy-one percent of euthyroid patients with lid lag and retraction but no established ophthalmopathy had detectable serum antibodies to a 64 kDa eye muscle membrane protein. Much smaller proportions had antibodies to proteins of other MW. In normal subjects with previously detectable antibodies to a 64 kDa protein, serum titers, determined by carrying out immunoblotting at serum dilutions of 1:25-1:6400, were low (< or = 1:100) in all cases tested. On the other hand, titers were higher (1:200-1:6400) in 16 of 22 patients with established ophthalmopathy and in 5 of 7 patients with lid lag and retraction tested. Titers tended to be lower in patients with ophthalmopathy of > or = 3 years duration than in those of < or = 1 year duration. Antibody titers were low (1:25) in 6 of 7 patients with Graves' hyperthyroidism without evident eye disease tested. Antibodies to a 64 kDa eye muscle membrane protein were predictive of the development of ophthalmopathy in patients with Graves' hyperthyroidism studied prospectively for periods of 8-42 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The epidemiology of psychosis: the Suffolk County Mental Health Project.

This article describes the rationale, aims, and methodology of an epidemiological study of psychosis being conducted in Suffolk County, New York. A sample of first-admission patients is drawn from 10 inpatient and 25 outpatient facilities. Diagnostic psychosocial interviews are conducted shortly after admission to treatment, and at 6- and 24-month followup. Consensus diagnoses are made after each interview. Demographic and clinical background characteristics of the first 250 subjects enrolled over a 2-year period are presented here. The response rate was 76 percent. Based on the initial interview, 75 percent of subjects received a diagnosis involving psychosis. The three most common diagnoses were schizophrenia, bipolar disorder with psychotic features, and major depression with psychotic features. Among subjects with psychosis, 58 percent of males and 29 percent of females had a history of substance abuse/dependence. Gender differences were found on several background and clinical characteristics. Males were somewhat younger, less likely to have ever married, and had less education. Although the median length of hospitalization was the same for females and males (27 days), females were more likely to be hospitalized within 1 month of the occurrence of their first psychotic symptom (60% of females compared to 37% of males). Subjects with schizophrenia-related disorders were significantly more impaired on an assessment of negative symptoms than were affectively ill subjects, but clinical ratings of depression were not significantly different across diagnostic groups.

Adolescent↗