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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 19 recordsLinked to original sources

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

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

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

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

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

Predictive equations for total lung capacity and residual volume calculated from radiographs in a random sample of the Michigan population.

BACKGROUND: Published predicted values for total lung capacity and residual volume are often based on a small number of subjects and derive from different populations from predicted spirometric values. Equations from the only two large studies gave smaller predicted values for total lung capacity than the smaller studies. A large number of subjects have been studied from a population which has already provided predicted values for spirometry and transfer factor for carbon monoxide. METHODS: Total lung capacity was measured from standard posteroanterior and lateral chest radiographs and forced vital capacity by spirometry in a population sample of 771 subjects. Prediction equations were developed for total lung capacity (TLC), residual volume (RV) and RV/TLC in two groups--normal and total. Subjects with signs or symptoms of cardiopulmonary disease were combined with the normal subjects and equations for all subjects were also modelled. RESULTS: Prediction equations for TLC and RV in non-smoking normal men and women were square root transformations which included height and weight but not age. They included a coefficient for duration of smoking in current smokers. The predictive equation for RV/TLC included weight, age, age and duration of smoking for current smokers and ex-smokers of both sexes. For the total population the equations took the same form but the height coefficients and constants were slightly different. CONCLUSION: These population based prediction equations for TLC, RV and RV/TLC provide reference standards in a population that has provided reference standards for spirometry and single breath transfer factor for carbon monoxide.

Adult

Effect of an anesthetic injected into the temporomandibular joint space in patients with TMD.

Twenty-three adult female patients were studied before and after injection of one temporomandibular joint to relieve pain. These patients had exhibited a persistent history of pain within their mandibular, neck, and somatic muscles, despite repeated treatment involving occlusal splints, physical therapy, and biofeedback. Patients were also screened for possible condylar degeneration using corrected tomograms. Initially, patients rated their pain on a linear scale from 0 to 10 and designated the site of the pain on a full-body-profile chart. The presence and location of the pain was determined by manual palpation using a rating scale of 0 to 10, and by the patients designating those regions perceived as painful by marking a full-body-profile chart. After this initial screening, subjects received an injection of 1% lidocaine (1:100,000) to the upper intracapsular space of one joint. The pain profile chart was completed by the patients 15 minutes after injection. Twenty of the 23 patients demonstrated a significant decrease in pain located in facial, head, and neck regions. These data suggest that injection of a local anesthetic to the temporomandibular joint will decrease pain for a short time in ipsilateral and contralateral regions of the head and neck.

Adolescent

Adenosarcoma of the uterus: a Gynecologic Oncology Group clinicopathologic study of 31 cases.

We report on the clinical and pathologic findings in 31 cases of adenosarcoma of the uterus subjected to hysterectomy and staging laparotomy. Nine of 30 patients (30%) have had recurrent tumor and six of 30 (20%) have already died of tumor in a relatively short follow-up period (mean, 38.3 months). Seventeen of 31 cases were diagnosed as adenosarcoma with sarcomatous overgrowth (SO). Ten of these 17 with SO contained focal or extensive rhabdomyosarcoma. In six cases, extrauterine spread was identified as follows (two patients had two sites each): vaginal involvement (two cases), pelvic lymph node metastases (two), positive peritoneal cytologic findings (two), parametrial invasion (one), and ovarian metastasis (one). Extrauterine spread (stage III) (p less than 0.001) and myometrial invasion (p = 0.04) were associated with higher rates of recurrence. The presence of lymphatic and/or vascular invasion, SO, and rhabdomyosarcomatous differentiation also indicated poor prognosis but did not attain statistical significance. Based on this experience, staging laparotomy including peritoneal cytology is suggested in cases of clinical stages I and II adenosarcoma. The differential diagnosis of these tumors is also discussed.

Adult

Lysozyme-induced T-suppressor cells and antibodies have a predominant idiotype.

The existence of shared idiotypic determinants on the surfaces of T and B cells is now firmly established, suggesting that on both these cell types immunoglobulin variable regions are expressed which presumably function as antigen receptors. In most systems this has been inferred through the use of anti-idiotypic antibody instead of antigen to induce either helper or suppressor T cells. Recent evidence demonstrates that antigen-specific suppressor or helper factors can also bear idiotypic determinants. It is possible that these factors represent released receptors or portions of receptors. We show here the direct elimination of an antigen-induced T-suppressor population by an anti-idiotypic serum and complement. These suppressor T cells as well as the idiotypic population used to generate the antiserum are each specific for the same limited portion of the multi-determinant antigen, lysozyme. Apparently, these suppressor cells are restricted in specificity as well as share idiotypy with antibodies of the same specificity.

Animals

An analysis of a continuing medical education questionnaire sent to psychiatrists in the Southern Transvaal.

The problem of continuing medical education (CME) for psychiatrists was studied by questionnaire. Of the 16 out of 40 people who responded, all felt CME was necessary and most favoured symposia, lectures and congresses. While nearly everyone read journals in psychiatric and non-psychiatric fields, group journal reviews as a form of CME were categorically rejected. Most respondents are prepared to contribute time and effort. The implications of CME are discussed, and the need for further research is emphasized.

Congresses as Topic

Fine specificity of regulatory T cells. II. Suppressor and helper T cells are induced by different regions of hen egg-white lysozyme in a genetically nonresponder mouse strain.

We have examined the ability of two purified peptide fragments derived from hen (chicken) egg-white lysozyme (HEL); N-terminal, Co-terminal peptide (a.a. 1--17:cys 6--cys 127:120--129) and mixed disulfide LII peptide (LII) (a.a. 13--105) to induce antigen-specific suppression or help in B10 (H-2b) nonresponder and B10.A (H-2a) responder mice. An anti-HEL primary in vitro antibody response can be obtained in either strain by stimulation with HEL coupled to erythrocytes (RBC). Preimmunization with HEL-complete Freund's adjuvant-(CFA) or N-C-CFA-induced suppression of the anti-HEL PFC response to HEL-RBC in spleen cell cultures from B10 mice, whereas helper activity was demonstrated in cultures from B10.A mice similarly immunized. LII-CFA priming elicited helper cells in both C57BL/10 Sn (B10) and B10.A/SgSn (B10.A) mice. The genetic nonresponsiveness of B10 mice to HEL can therefore be attributed to the activation of suppressor T cells by a limited portion of the molecule (e.g., N-C) which prevent the potential response directed against other epitopes on the same molecule (e.g., LII). One manifestation of major histocompatibility complex gene activity appears to be the intramolecular selection of different antigenic determinants leading to activation of functionally different T-cell subpopulations.

Amino Acid Sequence

Decrease in vital capacity in PCB-exposed workers in a capacitor manufacturing facility.

Pulmonary function was evaluated in 243 workers exposed to PCB in the manufacture of capacitors. Mean employment was greater than 15 years. Thirty-four of the workers (14%) were found to have a reduced Forced Vital Capacity (FVC less than 80% of Morris' predicted). Of the 34 with reduced FVC, 27 (80%) demonstrated a restrictive pattern of impairment (FEV1/FVC greater than 0.7). Only one of these 27 workers had an abnormal chest roentgenogram (greater than or equal to 1/0 by ILO UC Classification of Radiographs of Pneumoconioses). These findings are of interest in view of recent experimental data indicating the accumulation of PCBs and PCB metabolites in lung tissue (Brandt and Jansson). Restrictive spirometric impairment with no radiographic change is unusual in occupational exposure.

Adult