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F D Miller

Publications and source records attributed to F D Miller.

At least 55 records · Page 3Linked to original sources
PubMed1997

Signal transduction by the neurotrophin receptors.

The neurotrophins signal cell survival, differentiation, growth cessation, and apoptosis through two cell surface receptors, the Trks and p75NTR (p75 neurotrophin receptor). Recent advances indicate that the particular events that are mediated by neurotrophins are dependent upon the cell type and the expression pattern of each neurotrophin receptor. For example, TrkA activation induces cell death of neural tumor cells, and survival and differentiation of neurons. Likewise, p75NTR, when activated in the absence of a strong Trk signal, induces apoptosis of neurons, while in the presence of Trk it enhances responses to neurotrophin. These differing responses point to a complex interplay between neurotrophin-stimulated survival, differentiation, and apoptosis pathways.

Apoptosis↗
PubMed1997

The impact of passive chemotherapy on Schistosoma mansoni prevalence and intensity of infection in the Egyptian Nile Delta.

We investigated the impact of the passive surveillance and treatment program of the Egyptian Ministry of Public Health on the prevalence and intensity of Schistosoma mansoni infection in the northern Nile Delta region of Egypt. The study was based on a large probability sample of the entire rural population of Kafr El Sheikh. Infection and egg counts were determined by examination of stools using the Kato technique. From a sample of 18,777 villagers, 15,017 provided stool specimens. A detailed history of treatment for schistosomiasis was obtained by interview using standardized questions in colloquial Arabic. A positive history of therapy for schistosomiasis was common, with more than 40% of the participating villagers reporting prior treatment. Treatment was further characterized by frequency, dates, type, and where it had been received. In both male and female adults, a positive history of treatment with praziquantel was associated with a significantly reduced prevalence of S. mansoni infection. For example, odds ratios for 20-24-year-old males and females who did not indicate prior treatment were 5.2 (95% confidence interval [CI] = 2.3-7.2) and 6.5 (95% CI = 3.7-9.1), respectively. Geometric mean egg counts (GMECs) were significantly lower by more than two fold (P < 0.01) in both male and female adults who indicated prior treatment. The largest differences in prevalence and GMEC between those with or without a history of prior treatment were seen in the young and middle-aged adults. These results support strengthening programs for encouraging villagers to seek examination and treatment, and strengthen the dissemination and availability of praziquantel in the rural endemic areas of the country.

Adolescent↗
PubMed1996

Comparison of the expression of a T alpha 1:nlacZ transgene and T alpha 1 alpha-tubulin mRNA in the mature central nervous system.

We have previously demonstrated that one member of the alpha-tubulin multigene family, termed T alpha 1 in rats, is a panneuronal gene that is regulated as a function of neuronal growth and regeneration. Moreover, 1.1 kb of the 5' upstream region from this gene is sufficient to direct expression of a marker gene to growing neurons in transgenic mice. In this report, we have characterized the distribution of the T alpha 1:nlacZ transgene in the mature central nervous system in two lines of transgenic mice and have compared its expression to that of the endogenous T alpha 1 alpha-tubulin mRNA. These results demonstrate that the pattern of expression of the T alpha 1:nlacZ transgene is similar to that of T alpha 1 mRNA, with a few notable differences. Furthermore, expression of the transgene and the mRNA within the mature brain is panneuronal and, in many cases, is highest in those populations of neurons that show some capacity for morphological growth. These results, together with our previous studies on mature regenerating neurons (Gloster et al. [1994] J. Neurosci. 14:7319-7330; Wu et al. [1994] Soc. Neurosci. Abstr. 20:542) suggest that the T alpha 1:nlacZ transgene will provide a useful marker of growth-associated gene expression in the mature nervous system.

Animals↗
PubMed1996

Selective upregulation of T alpha 1 alpha-tubulin and neuropeptide Y mRNAs after intermittent excitatory stimulation in adult rat hippocampus in vivo.

Adult central neurons exhibit significant structural and molecular changes in epilepsy. We have examined changes in two markers of morphological and physiological plasticity, T alpha 1 alpha-tubulin (T alpha 1) and neuropeptide Y (NPY) mRNAs, in response to intermittent (20 Hz, 10 seconds, 1 minute-1) stimulation of the rat perforant path in vivo. Stimulus trains elicited brief (0.5-3 seconds) afterdischarges in the ipsilateral dentate gyrus (DG). Four hours of stimulation caused no significant loss of inhibition in the DG 40-48 hours after stimulation ceased. However, it did lead to an increase in NPY mRNA in neurons of the ipsilateral and, to a lesser extent, contralateral DGs and Ammon's Horn. Many of these were presumably interneurons that normally express NPY. However, dentate granule cells (DGCs), which do not normally express this peptide, also expressed robust levels of NPY mRNA bilaterally. NPY mRNA levels peaked at 4-24 hours and returned to baseline by 48 hours poststimulation. Although 24 hours of stimulation induced a similar increase in interneurons, DGCs showed no detectable NPY mRNA. Afterdischarges were necessary to elevate NPY mRNA expression. Four hours of stimulation elevated T alpha 1 mRNA expression in both ipsilateral and, to a lesser extent, contralateral DGCs; this elevation peaked at 24 hours poststimulation and declined to baseline by 72 hours. Stimulation for 24 hours caused broader changes in T alpha 1 mRNA expression, with increases in DGCs and in CA3 pyramidal cells bilaterally. Acute denervation of the DG did not affect T alpha 1 mRNA level in the hippocampal formation. Elevated synaptic input resulting in afterdischarges, but not necessarily in excitability changes in the DG, led to alterations in the expression of molecular markers of plasticity. These changes may reflect adaptive responses to physiological activation.

Animals↗
PubMed1996

Retinoblastoma gene in mouse neural development.

The retinoblastoma gene (Rb) was the first tumor suppressor gene to be cloned [Dryja et al., 1986; Friend et al., 1986; Lee et al., 1987], and, as a consequence, has been studied intensively within the context of cell cycle regulation and oncogenesis. However, a number of recent findings indicate that the retinoblastoma gene product (pRb) likely plays an essential role not only in controlling entry into the cell cycle, but also in the terminal differentiation of a number of different cell types [Lee et al., 1994; Gu et al., 1993]. In particular, the phenotype of the Rb nullizygous mice, created by a number of groups using homologous recombination [Jacks et al., 1992: Clarke et al., 1992; Lee et al., 1992], indicates that pRb is essential for normal development of the nervous and hematopoietic systems and may even function to regulate apoptosis [Haas-Kogan et al., 1995]. Although this paper briefly reviews the traditional role of pRB in regulation of cellular proliferation, we focus on the role of pRB in neuronal development and apoptosis. Recent reviews have been published on the role of pRb in cell cycle and transcriptional regulation [Hamel et al., 1992; Cobrinik et al., 1992; Kouzarides, 1993; Hollingsworth et al., 1993; Helin and Harlow, 1993; Sherr, 1994], as well as the relationship between pRb and p53 [Picksley and Lane, 1994; White, 1994].

Animals↗
PubMed1996

Viral vectors for modulating gene expression in neurons.

The inability to reliably express foreign proteins in postmitotic neurons has hampered numerous studies in the field of neurobiology. Within the past several years, a number of viral vectors that overcome this problem under controlled conditions in vitro have been developed. In particular, recombinant adenoviruses have proved to be efficient, non-cytotoxic vectors for manipulating neurons in dissociated and organotypic cultures, when used at low viral titres. In contrast, vectors derived from herpes simplex virus 1 still suffer from concerns regarding cellular cytotoxicity, in spite of several generations of vector development; however, recent advances in amplicon technology may solve this problem. Finally, several new-generation vectors, including those generated from adeno-associated virus, show great promise as neuronal gene-transfer vectors in vivo.

Adenoviridae↗
PubMed1996

Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons.

Programmed cell death is an ongoing process in both the developing and the mature nervous system. The tumor suppressor gene, p53, can induce apoptosis in a number of different cell types. Recently, the enhanced expression of p53 has been observed during acute neurological disease. To determine whether p53 overexpression could influence neuronal survival, we used a recombinant adenovirus vector carrying wild type p53 to transduce postmitotic neurons. A control consisting of the same adenovirus vector background but carrying the lacZ reporter expression cassette was used to establish working parameters for the effective genetic manipulation of sympathetic neurons. We have found that recombinant adenovirus can be used at titers sufficiently high (10 to 50 multiplicity of infection) to transduce the majority of the neuronal population without perturbing survival, electrophysiological function, or cytoarchitecture. Moreover, we demonstrate that overexpression of wild type p53 is sufficient to induce programmed cell death in neurons. The observation that p53 is capable of inducing apoptosis in postmitotic neurons has major implications for the mechanisms of cell death in the traumatized mature nervous system.

Adenoviridae↗
PubMed1995

Seroepidemiology of hepatitis E virus in the Egyptian Nile Delta.

The seroendemicity of hepatitis E virus (HEV) in an entire village population located in the Egyptain Nile Delta is described. Serum specimens were obtained from 68% of the total population of 1,850 villagers. The lack of serum specimen was greatest in the youngest age group (< 5). Commercially available enzyme immunoassays (EIA) for antibody to hepatitis A virus (anti-HAV), to hepatitis B virus core antigen (anti-HBc), to second-generation hepatitis C virus (anti-HCV) core and nonstructural antigen, and to hepatitis E virus (HEV) were used. Only repeated reactive sera were coded as positive. Stool specimens were examined for Schistosoma mansoni by the Kato method and standard methods for the examination of the liver and spleen by ultrasonography were used. Unadjusted for nonrespone, the seroprevalence of anti-HEV was 17.2% (SE +/- 1.1). Anti-HEV seroprevalence increased by age and was not associated statistically with any of the other viral markers including HCV. Anti-HAV seroprevalence was consistently > 95%, even in the youngest age group (< 5). The overall sero-endemicity of HEV was higher than reported elsewhere and appears not to have been introduced into the village population recently.

Adolescent↗
PubMed1995

Estrogen stimulates oxytocin gene expression in human chorio-decidua.

We have recently shown that oxytocin (OT) is synthesized within human amnion, chorion, and decidua during late gestation. The levels of OT messenger ribonucleic acid (mRNA) increased around the time of parturition, suggesting that locally produced OT may play a role in this poorly understood process. In this report, we present results from investigations into the effects of estrogen and progesterone on the synthesis of OT by human chorio-decidua. Using an in vitro incubation system, estradiol at physiological concentrations more than doubled the concentration of OT mRNA. This was reflected by an increase in the amount of OT peptide secreted into the medium. The increase in OT mRNA was antagonized by tamoxifen, suggesting that the effects were estrogen receptor mediated. Progesterone had no effect on OT mRNA synthesis. Using ribonuclease protection assays, mRNAs for estrogen receptor (ER) and progesterone receptor (PR) were detected in all tissues examined. The highest levels were found in decidua, with lower amounts in chorion and very small amounts in amnion and placenta. This is the same relative tissue distribution that we previously demonstrated for OT mRNA. A single transcript was present for ER, and two transcripts were protected for PR. The concentrations of ER mRNA in chorio-decidua were 3-fold higher in tissues obtained after spontaneous labor onset than in tissues obtained from cesarean section at a similar gestational age but before labor onset. Levels of PR did not change significantly. We conclude that synthesis of OT in human chorio-decidua may be regulated in part by estrogen, and that regulation of ER levels may be an important factor modulating this effect. These data support the hypothesis of a paracrine network within human fetal membranes and decidua that may participate in regulating the timing of human birth.

Chorion↗
PubMed1995

Schistosoma mansoni in the Nile Delta, Egypt. A large scale epidemiological study in Kafr El Sheikh Governorate.

This is an early descriptive report of the 'Epidemiology 123' project in Egypt which makes use of large probability sampling methods. These results focus on Schistosoma mansoni infection in the northern Nile Delta Governorate of Kafr El Sheikh. A probability sample of 18,777 persons, representing the rural population of the entire Governorate, was drawn. The sample was designed not to exclude villages based on location or presence of health care facilities and to include representation of the smaller ezbas or hamlets. The objective was to obtain detailed estimates on age and sex specific patterns of S. mansoni infection, and to provide a baseline for prospective studies. Stool specimens were examined by the Kato method. The estimated prevalence of S. monsoni infection in the rural population was 39.3% (SE +/- 3.3) in 44 villages and ezbas after weighing for the effects of the sample design. The estimated geometric mean egg count per gram stool (GMEC) was 72.9 (SE +/- 7.3). Prevalence and GMEC varied considerably by village and ezba, with ezbas having a significantly higher prevalence. Villages and ezba specific prevalence was strongly associated with GMEC (r2 = 0.61, p < 0.001). The prevalence of S. mansoni infection increased by age to 55.4% (SE +/- 3.2) at age 16, without significant change in the adult ages. There was no gender difference until age six, after which males were consistently higher until middle age, when the differences converged. The age and sex specific pattern of GMEC varied widely, however, when the GMEC data were collapsed into five year age groups, GMEC peaked at 81.5 (SE / + - 12.1) epg in the 10 to 14 year age group. These estimates provide the basis for evaluating control measures for reducing prevalence, intensity of infection, and transmission.

Adolescent↗
PubMed1995

Impact of population-based selective chemotherapy on prevalence and intensity of Schistosoma mansoni infections in the Nile Delta: Kafr El Sheikh.

The impact of selective treatment with praziquantel (40 mg/kg) on Schistosoma mansoni prevalence and intensity of infection in two annual follow-up examinations was measured. The target population was the entire rural area of the northern Nile Delta Governorate, Kafr El Sheikh, from which a probability sample was drawn. The sample included 44 villages and hamlets (ezba). Baseline prevalence was determined by the examination of stool by two Kato slides and all infected persons treated and reexamined one year later. Those found infected in the second round were treated and examined again one year later. The prevalence and geometric mean egg count declined across all ages in each follow-up (prevalence: 39.3% (SE +/- 3.3), 28.4% (SE +/- 2.6), and 22.4% (SE +/- 2.3), respectively; and GMEC: 72.9 (SE +/- 7.3), 52.5 (SE +/- 4.5), and 41.9 (SE +/- 2.4), respectively). Reduction in prevalence varied considerably by village and ezba and was strongly related to the proportion of the village or ezba population that was infected and treated (r2 = 0.29). This latter observation provides a rationale for the maximum application of chemotherapy in the endemic Nile Delta community.

Adolescent↗
PubMed1995

Patterns of infection, incidence and reinfection with Schistosoma mansoni in Nile Delta Governorate: Kafr El Sheikh.

Two annual follow-up measures of incidence, reinfection after treatment and reversion rates were estimated in a large prospective study of Schistosoma mansoni located in the northern Nile Delta of Kafr El Sheikh. Rates were estimated in a cohort established from a probability sample of the entire rural area of Kafr El Sheikh. Infection was determined by the examination of two Kato stool slides. The weighted first and second annual overall incidence rates were 20.4%, SE +/- 1.4 and 15.9%, SE +/- 1.4, respectively. Geometric mean egg counts in incident cases were 35.6 epg, SE +/- 1.2 and 31.0, SE +/- 1.6 in the first and second follow-ups. Incidence was strongly associated with first round prevalence (r2 = 0.34). Reinfection rates were higher: 33.4%, SE +/- 3.1 and 31.0%, SE +/- 2.1. Reinfection was associated with incidence (r2 = 0.32). Reversion rates were highest in children 0 to 4 years old (61.2%, SE +/- 18.1 and 78.5%, SE +/- 7.0, respectively) and increased from the first to second follow-up: 37.2%, SE +/- 3.4 and 47.0%, SE +/- 3.7, respectively. Patterns of these rates by village community, age and sex are also given over both follow-up examinations and comparison with limited data on rates of S. mansoni infection from previous studies, suggests a stable pattern of transmission over time in the Nile Delta.

Adolescent↗
PubMed1994

Nerve growth factor derived from terminals selectively increases the ratio of p75 to trkA NGF receptors on mature sympathetic neurons.

Exposure of neuronal terminals to target-derived NGF has been hypothesized to regulate cell body responses at a distance. To test this hypothesis and, more specifically, to determine whether NGF distally regulates the synthesis of its two characterized receptors, we developed the following paradigm. Sympathetic neurons of the superior cervical ganglion (SCG) that project either to the eye or to the ear were labeled, in adult animals, with the retrograde tracers Fast Blue and Fluoro-Gold, respectively. NGF was then injected daily into the anterior chamber of one eye, exposing the terminals of the ipsilateral eye neurons to increased NGF. To control for systemic and/or localized injury effects, cytochrome C or PBS were injected into the contralateral eye of the same animals. In situ hybridization and image analysis were then used to determine neuronal levels of p75 NGF receptor, trkA, and T alpha 1 alpha-tubulin mRNAs, with the latter providing a correlative measure of neuronal sprouting. Morphological measurements revealed that exogenous, terminally-derived NGF increased the mean cross-sectional area of eye neurons by 37%. Grain counts for p75 NGF receptor mRNA increased from 2- to 6-fold in the NGF-treated neurons, and grain densities, which accounted for neuronal hypertrophy, also increased significantly. In contrast, grain counts for trkA mRNA were not significantly increased by this treatment, while T alpha 1 alpha-tubulin mRNA levels increased only 1.5- to 2-fold. No increase in grain density was detected for either of these mRNAs. The NGF-induced increased in p75 NGF receptor mRNA levels was accompanied by terminal sprouting and by an increase in the density of p75 NGF receptors on terminal neurites, as indicated by IgG-192 immunostaining of the NGF-treated iris. These data therefore suggest that, in addition to promoting local sprouting, increased target-derived NGF increases the levels of p75 NGF receptor relative to trkA on terminal neurites, by differentially regulating receptor synthesis. Such a direct regulatory feedback loop may well play an integral role in precisely modulating neuronal responses as a function of the amount of available trophic support and/or target tissue.

Animals↗
PubMed1994

Disruption of fast axonal transport in vivo leads to alterations in Schwann cell gene expression.

Following nerve injury, Schwann cells distal to the site of injury down-regulate genes associated with myelination. We hypothesized that at least some of these alterations were due to the loss of ongoing axon:Schwann cell homeostatic signals, as opposed to loss of physical contact and/or inflammatory responses. To directly test this hypothesis, we perturbed axonal physiology by selectively blocking fast axonal transport via locally cooling the sciatic nerve to 5-8 degrees C (a cold block). Immunostaining with the monoclonal antibody ED1, which recognizes mononuclear phagocytic cells, demonstrated that macrophages did not invade the cold-blocked nerve, indicating the lack of an inflammatory response. Morphological studies demonstrated that the nerve distal to the cold block showed no signs of Wallerian degeneration, with maintenance of normal axon and myelin profiles, and confirmed the absence of invading macrophages. Thus, any effects of a cold-block treatment were not likely due to inflammatory responses or to loss of physical contact between axons and Schwann cells. To determine whether this treatment affected Schwann cell phenotype, we examined expression of the major myelin protein P0, and p75 NGF receptor, both of which are regulated as a function of axon:Schwann cell interactions. Levels of p75 NGF receptor mRNA were unaffected by the cold block, while p75 NGF receptor protein levels were increased in the region of the nerve immediately adjacent to the cold block, presumably reflecting protein accumulation as a consequence of the block to fast axonal transport. In contrast, levels of P0 mRNA were decreased in the distal nerve in a fashion that indicated modulation of Schwann cell phenotype as a function of local axonal microenvironment. These data therefore suggest that P0 and p75 NGF receptor are regulated as a function of two different aspects of Schwann cell:axon communication. Furthermore, these data demonstrate that the presence of axon:Schwann cell contact alone is insufficient to maintain Po gene expression and indicate that at least some myelin-specific Schwann cell responses are dependent upon ongoing biochemical signals generated by the axon and maintained by fast axonal transport.

Animals↗
PubMed1994

The epidemiology of Schistosoma mansoni, hepatitis B and hepatitis C infection in Egypt.

There appears to be no epidemiological association between Schistosoma mansoni infection, the intensity of S. mansoni infection or S. mansoni infection complicated by schistosome hepatic fibrosis and the presence of antibody to hepatitis B virus core antigen (anti-HBc), hepatitis B surface antigen (HBsAg), antibody to hepatitis C virus (anti-HCV) or antibody to both agents. This was the main conclusion of a population-based study of an entire village in the northern Egyptian Nile Delta. All 1850 villagers were invited to participate and serological, parasitological and ultrasound examinations were completed on a high proportion of the total population (68% provided sera and higher percentages provided stool specimens and were subjected to ultrasound examinations). Testing with dual Kato slides indicated a high prevalence of S. mansoni infection in the village (49.1%), typical of the area. Hepatitis B virus (HBV) markers (presence of either anti-HBc and/or HBsAg) and anti-HCV were also found to be prevalent, present in 24% and 15.9% of the villagers, respectively. The age-adjusted odds ratios (OR) for infection with S. mansoni and HBV [1.13; 95% confidence interval (CI) = 0.87-1.48], HBsAg (1.11; CI = 0.47-2.58), or anti-HCV (1.02; CI = 0.7-1.37) were not significantly greater than unity. Similarly low and non-significant OR estimates were observed with those positive for both HBV and anti-HCV. No other outcome measures of S. mansoni infection (i.e. intensity of infection or ultrasonographically-determined schistosomal hepatic fibrosis) were found to be associated with HBV, HBsAg or anti-HCV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗