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Biomedical subjects

A E Miller

Publications and source records attributed to A E Miller.

At least 37 records · Page 2Linked to original sources
PubMed1985

Establishment of a line of human fetal glial cells that supports JC virus multiplication.

Primary cultures of human fetal brain cells were transfected with plasmid DNA pMK16, containing an origin-defective mutant of simian virus 40 (SV40). Several weeks after DNA treatment, proliferation of glial cells was evident in the culture, allowing passage of the cells at low split ratios. Initially, only 10% of the cells demonstrated nuclear fluorescence staining using a hamster tumor antibody to the SV40 T protein. By the sixth passage, however, 100% of the cells reacted positively to the same antibody. During these early passages, the cells designated SVG began growing very rapidly and acquired a homogeneous morphology. Cell division required only low serum concentrations, was not contact-inhibited, and remained anchorage dependent. These characteristics of the SVG cells have been stable through 25 passages or approximately equal to 80 cell generations. The SV40 T protein is continuously produced in the cells and can direct the replication of DNA inserts in the pSV2 vector, determined by in situ hybridization using biotin-labeled DNA probes, which contains the SV40 replication origin. More importantly, SVG cells support the multiplication of the human papovavirus JCV at levels comparable to primary cultures of human fetal glial cells, producing infectious virus as early as 1 week after viral adsorption. Their brain-cell derivation has been established as astroglial, based on their reactivity with a monoclonal antibody to glial fibrillary acid protein and lack of activity with an anti-galactocerebroside antibody, which identifies oligodendroglial cells. The SVG cells represent a unique line of continuous rapidly growing human fetal astroglial cells that synthesizes a replication-proficient SV40 T protein. Their susceptibility to JC virus (JCV) infection obviates a host restriction barrier that limited JCV studies to primary cultures of human fetal brain and thus should allow for more detailed molecular studies of human brain cells and JCV that infects them.

Antigens, Polyomavirus Transforming↗
PubMed1985

Progesterone and luteinizing hormone secretion following stress-induced interruption of constant estrus in aged rats.

Concentrations of progesterone and luteinizing hormone (LH) were measured during the first diestrus and subsequent proestrus after constant estrous was interrupted by restraint stress. Stress stimulated an acute increase in serum progesterone. Although stress resulted in changes in vaginal cytology characteristic of normal estrous cycles, stress-treated constant estrous (CE) rats had no midcycle (diestrous day 1) elevation of progesterone and markedly lower LH and progesterone during the afternoon of proestrous than age-matched normally cycling controls. The majority of the treated rats resumed CE without completing a cycle. In a separate experiment, progesterone injection during proestrous resulted in increased LH secretion in aging rats with normal estrous cycles. These data indicate that decreased proestrous progesterone secretion may contribute to the decrease in neuro-endocrine stimulation of proestrous gonadotropin secretion in the aged rat and may be associated with the initiation of CE.

Aging↗
PubMed1985

Cessation of stuttering with progressive multiple sclerosis.

Two patients stuttered severely into adult years. Stuttering ceased as signs of progressive MS developed. Both patients had clinical evidence of bilateral cerebellar dysfunction, and other forms of speech impairment appeared as the stuttering abated. The cerebellar lesions may have been responsible for the abolition of stuttering.

Adult↗
PubMed1983

In vitro transcription of Drosophila actin and 70,000-dalton heat shock protein genes.

Drosophila genomic DNAs containing a chromosomal locus 87C1 70,000-dalton heat shock protein gene, the locus 79B actin gene, and the 88F actin gene have been used as templates in an in vitro HeLa transcription system. RNA polymerase II-dependent transcription initiates from specific sites on the heat shock protein gene and the 79B actin gene. The locations of the transcription start sites were determined by two types of experiments: sizing of RNA runoff transcripts and S1 nuclease mapping of the 5' terminus of the in vitro transcripts. Transcription initiates at or near the in vivo initiation site of the heat shock protein gene and initiates at or near a site 14 nucleotides downstream of the in vivo start site of the 79B actin gene. The addition of the 79B actin, 88F actin, or heat shock protein templates to a HeLa extract transcription reaction precluded the transcription of a second template subsequently added. The exclusion occurs rapidly, within 15 s, is not dependent on transcription, and is only partially resistant to high concentrations of the second added template. We propose that stable protein-promoter complexes play an important role in maintaining exclusive transcription of the first template added in vitro.

Actins↗
PubMed1982

Immune regulation in myasthenia gravis: evidence for an increased suppressor T-cell population.

The production of anti-acetylcholine receptor antibodies in myasthenia gravis represents a persistent and unexplained break in self-tolerance. The studies reported here demonstrate an altered regulatory T-cell population with an increase in the percentage of circulating T-suppressor cells as defined by two independently developed murine monoclonal antibody markers. Leu 2a- and OKT8a-positive cells were significantly increased within the T-cell population in myasthenia gravis (25.0 +/- 6.4% versus 20.7 +/- 2.9% and 34.9 +/- 7.0% versus 26.0 +/- 3.2%, respectively) compared to an age- and sex-equivalent group. In addition, the circulating total T-cell population was reduced in myasthenia gravis. Patients with symptomatically uncontrolled disease (with or without immunosuppression) demonstrated significantly altered ratios of helper to suppressor T-cells, while patients whose myasthenia symptoms were controlled did not differ from normal subjects.

Adolescent↗
PubMed1982

Temporal patterns of serum luteinizing hormone and testosterone and endocrine response to luteinizing hormone releasing hormone in aging male rats.

Temporal patterns of serum testosterone and luteinizing hormone (LH) concentration and responsiveness to luteinizing hormone releasing hormone (LHRH) were measured in young (2 to 3 months), middle-aged (12 to 13 months), and aged (22 to 26 months) male rats. Average testosterone and LH concentrations, as well as individual sample variations, were higher in young than in middle-aged and aged rats and higher in middle-aged than in aged groups. In addition, the young group showed a diurnal pattern of serum testosterone concentration and greater ranges of LH and testosterone concentrations in individual blood samples. Young male rats showed greater increases in serum LH and testosterone than middle-aged and aged groups after intravenous LHRH, 1 and 5 ng/g of body weight. These data indicate that LH and testosterone secretion are progressively reduced in the aged male rat and suggest alterations in neuroendocrine control of pituitary gonadotropin secretion as the most important alteration in the gonadal control system in these animals.

Aging↗
PubMed1982

Endogenous and interferon-augmented natural killer cell activity of human peripheral blood mononuclear cells in vitro. Studies of patients with multiple sclerosis, systemic lupus erythematosus or rheumatoid arthritis.

Peripheral blood mononuclear cells (PBMC) of normal human donors are spontaneously cytotoxic for certain tumour-derived and virus-infected target cells. This so-called natural killing (NK) can be augmented by the action of interferons (IFN) and by IFN-inducers. In this study, we have compared both endogenous and augmented NK activity of normal donors with that of patients suffering from either multiple sclerosis (MS), systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Endogenous NK was assayed using an NK susceptible target cell (K562), and augmented NK using a target cell (WI-L2) which is lysed only by NK effector cells that have been pre-stimulated by IFN or IFN-inducers. While NK function appeared normal in RA patients, this study confirms previous reports of defective endogenous NK in many MS and SLE patients. In addition, anomalous IFN-augmented NK was also detected in many patients with these two diseases, indicating that defective NK function cannot always be corrected by IFN treatment in vitro. Analysis of IFN production, endogenous NK and IFN-augmented NK by individual patients with MS or SLE showed the defects in their IFN-NK systems to be highly selective, suggesting that individual components of this system may operate independently.

Adult↗
PubMed1981

Immunological studies in senile dementia of the Alzheimer type: evidence for enhanced suppressor cell activity.

To examine immunological variables in senile dementia of the Alzheimer type (SDAT), we compared SDAT patients with elderly and young controls with regard to concanavalin A (Con A)-induced suppression, lymphocyte proliferation, interferon production, and serum immunoglobulin levels. The results showed exaggerated Con A suppression and reduced lymphocyte proliferation in SDAT patients compared to elderly control subjects. Interferon production after stimulation by Con A and immunoglobulin levels did not differ between SDAT and elderly control subjects. The results suggest impaired immunoregulatory mechanisms in patients with SDAT that may be related to the cause or course of SDAT. Alternatively, these immunological changes may be secondary to pathological changes in the central nervous system.

Adult↗
PubMed1981

Interferon responses of leukocytes in multiple sclerosis.

In vitro interferon (IFN) responses of peripheral blood leukocytes to measles virus and to other IFN inducers were determined for multiple sclerosis patients and normal donors. The group mean IFN response to measles virus was significantly lower in patients (15 units) than in normal donors (100 units), and a greater proportion of the patients failed to exhibit a significant IFN response. This defect was not specific for measles virus and was also observed consistently in response to Newcastle disease virus, Poly(I).Poly(C), and concanavalin A. The level of IFN response was not related to the clinical stage of disease.

Adult↗
PubMed1980

Selective decline in cellular immune response to varicella-zoster in the elderly.

The incidence of herpes zoster rises markedly in the aged. We evaluated the hypothesis that cellular immunity to varicella-zoster (VZ) viral antigens may be impaired in aged subjects. We found that the lymphocyte proliferation to VZ antigen was less in older asymptomatic individuals than in normal young controls. In contrast, responses to other antigens did not differ. Antibody titers to VZ were similar in both young and old subjects. Impairment of cellular immunity to VZ, on a population basis, may contribute to the increased risk of herpes zoster in the elderly.

Aged↗
PubMed1979

The effect of age on reproduction in repeatedly mated female rats.

The effects of age and repeated pregnancies on reproduction were studied in Long-Evans rats. Indices of reproduction measured included estrous cycles, successful mating, numbers of rats producing litters, average litter size, average pup weight and serum LH-from a 4 pm proestrous blood sample. There were no differences in these reproductive parameters between rats with serial pregnancies initiated at 2 or 9 mo of age. The percentage of rats producing normal litters was reduced much faster than the percentage of successfully mated rats with normal ovarian cycles. Although 60% of the rats still had normal ovarian cycles and were mated at 17 mo of age, only one rat (4%) produced a litter. Increasing age and multiple pregnancies did not significantly affect the LH concentration of the proestrous blood sample or the average litter size or pup weight of the rats with successful pregnancies. These data suggest post-ovulatory loss of reproduction in the aging rat.

Animals↗