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Biomedical subjects

M D Miller

Publications and source records attributed to M D Miller.

At least 181 records · Page 10Linked to original sources
PubMed1990

Studies of cloned simian immunodeficiency virus-specific T lymphocytes. gag-specific cytotoxic T lymphocytes exhibit a restricted epitope specificity.

CD8+ CTL inhibit the replication of HIV and simian immunodeficiency virus of macaques (SIVmac) in PBL and, therefore, are likely to play an important role in containing the spread of the AIDS virus in infected individuals. We have generated a series of gag-specific lytic T lymphocyte clones from PBL: of an SIVmac-infected rhesus monkey. These T cell clones are CD3+CD8+ and are MHC class I-restricted in their target specificity. They are, therefore, CTL. Interestingly, all gag-specific CTL clones, as well as the gag-specific lytic activity of PBL of this monkey, demonstrated specificity for a single 25 amino acid fragment of the SIVmac gag protein. Moreover, they were restricted in their lytic function by a single MHC class I allele. These findings illustrate a powerful method for cloning AIDS virus-specific T lymphocytes and demonstrate a remarkably restricted epitope specificity of this AIDS virus-specific CTL response.

Animals↗
PubMed1990

The murine complement receptor gene family. III. The genomic and transcriptional complexity of the Crry and Crry-ps genes.

The murine CR genes Crry (previously termed mCRY) and Crry-ps (previously termed mCRX) are two distinct, but related, sequences which are the evolutionary homologs to sequences contained within the human CR1 gene. Screening a BALB/c genomic DNA library with the Crry/Crry-ps specific cDNA resulted in the isolation of two clusters of genomic sequences: those specific for Crry and those specific for Crry-ps. The coding sequences of the Crry gene encompass over 25 kb of DNA, whereas the Crry-ps sequences are included within a single 5.6-kb Eco-R1 fragment. The Crry gene consists of 10 separate exons. The first of these contains both the signal sequence and an alternatively spliced 129 bp present in approximately 10% of the Crry transcripts. Of the remaining exons, two encode a single sixty amino acid repeat domain each (A and E), two encode a split sixty amino acid repeat (B), and another encodes two 60 amino acid domains (C and D) fused as one exon. The transmembrane and cytoplasmic regions are both split into two exons each. RNA protection analysis indicates that although there is alternative splicing in the 5' region of the gene, the 3' exons encoding the terminal 60 amino acid repeat, the transmembrane region and cytoplasmic exons are used in the same order in all Crry transcripts. This suggests that the Crry gene product is not found as a secreted protein, but only as a cell surface bound protein. DNA sequence analysis of the Crry-ps gene indicates that this sequence most likely represents a pseudogene resulting from a processed mRNA transcript from the Crry gene. This conclusion is based on the lack of intervening sequences in the Crry-ps gene and the observation that the Crry-ps gene sequence contains both an 11-bp deletion within the "coding" region and a degenerate poly A tail at the 3' end of the homologous sequence. Additionally, RNA protection analysis indicates that mRNA cannot be detected which matches the Crry-ps sequence.

Amino Acid Sequence↗
PubMed1990

The gag-specific cytotoxic T lymphocytes in rhesus monkeys infected with the simian immunodeficiency virus of macaques.

The simian immunodeficiency virus of macaques (SIVmac) is a lentivirus which induces an AIDS-like disease in rhesus monkeys. We have explored the virus-specific cellular immune response in SIVmac-infected rhesus monkeys. Con A-activated, IL-2 expanded PBL of some SIVmac-infected rhesus monkeys lyse autologous B lymphoblastoid cell lines infected with a recombinant vaccinia virus that carries the SIVmac gag gene. This lysis is mediated by CD8+ lymphocytes and is MHC class I restricted. Moreover, these effector lymphocytes do not express the NK cell-associated molecules NKH1 or CD16. These cells are, therefore, CTL. In a limited prospective study of SIVmac-infected rhesus monkeys, the presence of the SIVmac gag-specific CTL activity in PBL correlated with both a reduced efficiency in isolating SIVmac from PBL of these monkeys and their extended survival. This method for assessing SIVmac gag-specific cellular immunity in rhesus monkeys will be important not only in investigating the immunopathogenesis of SIVmac-induced disease, but also in evaluating the capacity of candidate AIDS vaccines to elicit a cell-mediated immune response in this animal model.

Animals↗
PubMed1990

Developing a model for the study of quality of life in elderly patients with chronic disease: use of hypertension as an example.

The concept of quality of life (QOL) is multidimensional and complex, especially in regard to chronic disease and old age. The purpose of this study was to explore QOL in a population of elderly patients with hypertension and to suggest a technique for model building. The specific purpose of the study was to test the viability of a model for understanding how the treatment of hypertension affects QOL. Indicators of QOL and determinants of QOL were measured in a group of patients aged 60 years or older with hypertension. Correlation coefficients confirmed the hypothesized model. The confirmed model thus can be used to study other chronic diseases and to assess the QOL effects of treatment of chronic diseases.

Activities of Daily Living↗
PubMed1990

Orthopedic trauma in the elderly.

The bones of elderly individuals fracture easily. The fractures in osteoporotic bones may not be easily identified on plain films. A high level of suspicion will result in more accurate diagnosis and appropriate referral and treatment of these patients.

Aged↗
PubMed1990

Development and characterization of a lyophilized dosage form of IL-1 beta.

The development and characterization of a lyophilized dosage form for recombinant Interleukin-1 beta is described. Included in the evaluation of the drug product are accelerated and long-term stability studies utilizing a number of biophysical techniques (reverse-phase HPLC, SDS-PAGE, isoelectric focusing and ELISA). Data collected with these methods were examined for correlations with biological activity assessments provided by an in-vitro cell culture system (mouse thymocyte proliferation). Results of these studies demonstrate that a lyophilized dosage form of Interleukin-1 beta can be prepared which retains its potency for at least 1 year when stored at ambient temperature. The analytical methodology used to assess the physicochemical integrity of the protein provided a sensitive and reproducible means of predicting changes in biological activity.

Animals↗
PubMed1989

A novel polypeptide secreted by activated human T lymphocytes.

We have identified two cDNA clones, I-309 and G-26, which define genes expressed abundantly in activated human PBMC, but at low or undetectable levels in resting PBMC. Based upon nucleotide sequence analysis, both clones are predicted to encode small, structurally related polypeptides, each containing a hydrophobic leader sequence characteristic of secreted proteins and a motif of four conserved cysteine residues. Further, I-309 and G-26 are structurally related to a growing family of genes that apparently encode small polypeptides whose secretion is induced upon cell activation. I-309 represents a previously undescribed human gene. We have generated an anti-peptide antiserum to the I-309 gene product which recognizes proteins in culture supernatants of an activated T cell clone and of COS cells transfected with the I-309 cDNA, supporting the idea that I-309 encodes a secreted protein. Because I-309 encodes a small protein secreted by activated T cells that displays structural features similar to other cytokines, we believe that it defines a novel cytokine with as yet unknown function.

Amino Acid Sequence↗
PubMed1989

Pathologic bone formation.

The literature on pathologic bone formation is reviewed first on the basis of clinical syndromes and second in relation to newer knowledge of the origin of the bone-forming cells and regulatory molecules. Pathologic bone formation can be categorized into three groups based on the initiating stimulus: trauma, tumors, and idiopathic causes. In the trauma category, the formation of ectopic bone is concerned with major and minor traumatic incidents, surgery, burns, and other causes. In the tumor category, direct and reactive pathologic bone formation is discussed with an emphasis on the different neoplasms capable of ectopic bone formation. The category of idiopathic causes involves the formation of pathologic bone following neurologic injury and in systemic ossification disorders. The origin of the bone-forming cells in all forms of pathologic bone has not been unequivocally determined. However, there is evidence suggesting that these cells may arise from osteogenic stromal elements. Potent bone formation growth-regulating factors have been recently identified, and these molecules must also participate in the formation of pathologic bone. Increased understanding of the processes that control pathologic bone formation will lead to better methods of preventing and treating disorders of ossification.

Bone Marrow Cells↗
PubMed1988

Intrahippocampal injections of gallamine impair learning of a memory task.

Recent evidence has suggested that gallamine may act as an antagonist on presynaptic M2 muscarinic receptors which regulate acetylcholine release. The possibility that gallamine may potentiate learning by enhancing the release of acetylcholine was examined using a behavioral paradigm known to depend on cholinergic activity. Rats were cannulated bilaterally for intrahippocampal (i.h.) injections and adapted to a T-maze before the series of injections was initiated. The effects of bilateral i.h. injections of saline or gallamine (10 micrograms total) were examined on the learning of a win-stay, paired-run task in a T-maze. During the first few sessions, both saline- and gallamine-treated animals achieved below 50% correct responses. Both groups of animals gradually improved performance on the task although, contrary to expectations, gallamine-treated animals did not learn as rapidly as saline-injected animals. To verify the deleterious effects of gallamine on learning, the experiment was repeated using a second group of rats. Similar results were observed; gallamine-treated animals learned to perform the task at a slower rate than the saline-injected controls. The results suggest that treatment strategies with cholinomimetics may impair, rather than enhance performance after long-term administrations.

Animals↗
PubMed1988

Permanent post-traumatic patellar dislocation.

Permanent post-traumatic dislocation of the patella is an extremely rare condition, and is often confused with congenital dislocation. The anatomic abnormalities differ in the two conditions: in the former there is an adaptive flattening of the patella, in the latter there is a propensity for flexion contractures and incongruity of the patella and trochlea. Treatment options include observation, patellar realignment, and patellectomy. In the patient reported, surgical correction appeared to result in patellar alignment.

Accidental Falls↗
PubMed1987

Comparison of dietary intake of urban and rural elderly patients in family practice centers.

To compare dietary intake of urban and rural patients, we interviewed 50 patients over age 64 at each of two family practice centers, one urban and one rural, using the 24-hour dietary recall method for nutrient comparison. A deficiency of calcium was evident in the intake of both elderly populations, but other specific deficiencies were evident in the rural group. We discuss the need for dietary evaluation and intervention in the elderly, with emphasis on the rural population, and offer specific strategies for application by primary care physicians.

Black or African American↗
PubMed1986

A model for assessing health needs of the rural elderly: methodology and results.

The purpose of this health needs assessment of the rural elderly was to determine the actual conditions, opportunities, activities, and attitudes of older citizens living in a rural area and to assess their specific psychological, social, and medical needs. This was accomplished through a survey developed by an interdisciplinary team and distributed to individuals aged 55 years or older in a rural community of Georgia. Survey responses were used to plan and implement a series of four workshops to improve health education in the rural community surveyed. In addition, referrals to health care and social agencies were initiated where indicated.

Activities of Daily Living↗