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S L Rogers

Publications and source records attributed to S L Rogers.

At least 37 records · Page 2Linked to original sources
PubMed1998

Perspectives in the management of Alzheimer's disease: clinical profile of donepezil.

Donepezil HCI is a piperidine-based reversible acetylcholinesterase (AChE) inhibitor, chemically distinct from other cholinesterase (ChE) inhibitors and rationally designed to treat the symptoms of Alzheimer's disease (AD). It is highly selective for AChE in the central nervous system (CNS), with little or no affinity for butyrylcholinesterase (BuChE). In preclinical studies in animals, donepezil produced increased CNS acetylcholine. The resultant enhancement of cholinergic activity gave rise to improved performance by rats on tests of learning and memory, with no evidence of hepatic or renal toxicity. In subsequent phase I clinical evaluations in healthy volunteers, donepezil demonstrated favorable pharmacokinetic, pharmacodynamic and safety profiles. Its long terminal disposition half-life supported once-daily administration, with no requirement for dose modification in the elderly or in patients with renal or hepatic impairment. A 14-week, phase II dose-finding study in patients with mild to moderate AD (Clinical Dementia Rating [CDR], 1-2; Mini-Mental State Examination [MMSE], 10-26) showed that donepezil at a dose of 5 mg/day produced highly significant improvements in cognition (as measured by the Alzheimer's Disease Assessment Scale, cognitive subscale [ADAS-cog]). Subsequently, two pivotal parallel-group, placebo-controlled phase III trials (of 15 and 30 weeks' duration) showed highly statistically significant improvements in ADAS-cog, MMSE, Clinician's Interview-Based Impression of Change with caregiver input (CIBIC plus) and CDR-SB (Sum of the Boxes) scores, compared with placebo, in mild to moderate AD patients treated with either 5 or 10 mg/day donepezil. Adverse events in the phase II and III trials were mild and transient and resolved with continued donepezil administration. The donepezil clinical trials program has shown that this drug is a clinically effective and well-tolerated once-daily treatment for the symptoms of mild to moderate AD.

Alzheimer Disease↗
PubMed1998

A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group.

The efficacy and safety of donepezil as a treatment for patients with mild to moderate Alzheimer's disease (AD) was investigated in a multicenter, double-blind study. Patients were randomly assigned to treatment with placebo (n = 162), 5 mg/d donepezil (n = 154), or 10 mg/d donepezil (n = 157) for 24 weeks followed by a 6-week, single-blind placebo washout. The primary efficacy measures were the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Clinician's Interview Based Assessment of Change-Plus (CIBIC plus), with the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB), and patient rated Quality of Life (QoL) used as secondary measures. Cognitive function, as measured by the ADAS-cog, was significantly improved in the 5- and 10-mg/d donepezil groups as compared with the placebo group at weeks 12, 18, and 24. Clinician's global ratings on the CIBIC plus also improved in both the 5- and 10-mg/d donepezil groups relative to placebo. At the end of the 6-week placebo washout phase, ADAS-cog scores and CIBIC plus ratings were not significantly different for the three groups. Significant treatment benefits were also observed consistently in both the 5- and 10-mg/d groups on the MMSE and the CDR-SB, but there was no consistent effect on the patient-rated QoL. Cholinergic side effects (primarily diarrhea, nausea, and vomiting) were reported more often in the 10-mg/d group than either the 5-mg/d or placebo groups. Side effects were transient and generally mild in severity. These data indicate that donepezil is a well-tolerated drug that improves cognition and global function in patients with mild to moderate AD.

Aged↗
PubMed1997

Regulated bidirectional motility of melanophore pigment granules along microtubules in vitro.

Although many types of membrane-bound organelles rely upon microtubule-based transport for their proper placement within the cytoplasm, the molecular mechanisms that regulate intracellular motility remain largely unknown. To address this problem, we have studied the microtubule-dependent dispersion and aggregation of pigment granules from an immortalized Xenopus melanophore cell line. We have reconstituted pigment granule motility along bovine brain microtubules in vitro using a microscope-based motility assay. Pigment granules, or melanosomes, move along single microtubules bidirectionally; however, analysis of the polarities of this movement shows that melanosomes that have been purified from dispersed cells exhibit mostly plus end-directed motility, while movement of organelles from aggregating cells is biased toward the minus end. Removal of all soluble proteins from the melanosome fractions by density gradient centrifugation does not diminish organelle motility, demonstrating that all the components required for transport have a stable association with the melanosome membranes. Western blotting shows the presence of the plus end-directed motor, kinesin-II, and the minus end-directed motor, cytoplasmic dynein in highly purified melanosomes. Therefore, purified melanosomes retain their ability to move along microtubules as well as their regulated state. Direct biochemical comparison of melanosomes from aggregated and dispersed cells may elucidate the molecular mechanisms that regulate organelle transport in melanophores.

Animals↗
PubMed1994

Transforming growth factor-beta 1 differentially regulates proliferation, morphology, and extracellular matrix expression by three neural crest-derived neuroblastoma cell lines.

We reported previously (S. L. Rogers, P. J. Gegick, S. M. Alexander, and P. G. McGuire, Dev. Biol. 151, 191-203, 1992) that transforming growth factor-beta 1 (TGF beta 1) inhibited proliferation, up-regulated fibronectin synthesis, and suppressed melanogenesis in a population of quail neural crest cells in vitro. Here, we report that cell lines derived from the parent SK-N-SH neuroblastoma line (R. A. Ross, B. A. Spengler, and J. L. Biedler, J. Natl. Cancer Inst. 71, 741-747, 1983) respond differentially to TGF beta 1, and their responses provide further insights into the actions of this growth factor on neural crest subpopulations. The SH-EP cell line exhibits primarily nonneuronal traits and responded to TGF beta 1 with increased thymidine uptake after 6 days of culture, increased expression of fibronectin mRNA and protein, and decreased laminin synthesis. Many SH-EP cells also acquired a dramatically elongated morphology, reminiscent of Schwann cells in culture. Thymidine uptake by the neuronal SY5Y cell line was not substantially altered. Neither fibronectin mRNA nor protein was detectable in either TGF beta 1-treated or untreated cultures, although laminin synthesis was upregulated by the growth factor. In TGF beta 1-treated cultures of the intermediate SH-IN cell line, which has been reported to display both neuronal and nonneuronal characteristics, there was marked flattening of many cells, a steady decrease in thymidine uptake, and increased expression of both fibronectin and laminin. The observed responses of SH-IN cells mimic those observed in primary neural crest cultures and appear to represent similar differentiation toward a mesenchymal phenotype. These results substantiate the idea that closely related but diverging neural crest-derived cell types respond selectively to TGF beta 1 and demonstrate that these SK-N-SH-derived cell lines will be useful in experimental approaches that will allow us to infer mechanisms underlying regulation of neural crest differentiation.

Cell Differentiation↗
PubMed1992

Transforming growth factor-beta alters differentiation in cultures of avian neural crest-derived cells: effects on cell morphology, proliferation, fibronectin expression, and melanogenesis.

Neural crest cell differentiation is responsive to a variety of extrinsic signals that include extracellular matrix (ECM) molecules and growth factors. Transforming growth factor-beta (TGF-beta) has diverse, cell type-specific effects, many of which involve regulation of synthesis of ECM molecules and their cell surface receptors. We are studying both separate and potentially interrelated influences of ECM and growth factors on crest differentiation and report here that TGF-beta alters several aspects of crest cell behavior in vitro. Clusters of quail neural crest cells were cultured in the presence and absence of 400 pM TGF-beta 1 and examined at 1, 3, and 5 days. When examined at 5 days, there was a dramatic decrease in the number of melanocytes in treated cultures, regardless of the onset or duration of TGF-beta treatment. With continuous TGF-beta treatment, or with treatment only during crest cluster formation on explanted neural tubes, many cells increased in area, becoming extremely flat. These changes were evident beginning on Day 3. While quantitative analyses of video images documented the size increase, several aspects of motility were relatively unchanged. Synthesis of fibronectin (FN) by approximately 11% of cells on Day 3 and 31% of cells on Day 5 was demonstrated by immunocytochemistry and was associated with a sixfold increase in FN mRNA by Day 5. Experiments which correlated FN immunoreactivity with incorporation of bromodeoxyuridine suggested that the population of large, flat, FN-positive cells did not proliferate selectively and that there was a slower rate of proliferation in TGF-beta-treated cultures than in untreated cultures. The large FN-immunoreactive cells resemble cells derived from cephalic neural crest and raise interesting questions concerning potential roles for TGF-beta in regulating crest differentiation in vivo.

Animals↗
PubMed1992

Comparative purification of recombinant HIV-1 and HIV-2 reverse transcriptase: preparation of heterodimeric enzyme devoid of unprocessed gene product.

A procedure for producing and purifying recombinant HIV-1 and HIV-2 reverse transcriptase (RT) is described. These enzymes are produced by Escherichia coli-transformed with a plasmid containing the gene encoding for either the human immunodeficiency virus type 1 (HIV-1) or HIV-2 RT protein. Both proteins are partially processed by host cell proteases giving rise to a mixture of heterodimeric and nonheterodimeric products, which are subsequently resolved to near homogeneity by chromatography on phosphocellulose, Q-Sepharose, and hydrophobic interaction HPLC. Both HIV-1 (66/51 kDa) and HIV-2 (68/54 kDa) heterodimeric enzymes devoid of excess unprocessed (p66 or p68) precursors are isolated, enabling comparative enzymatic characterization of the fully active (and biologically relevant) heterodimeric forms. Homogenous HIV-1 and HIV-2 RT purified by this methodology exhibit near equivalent polymerase and RNase H activities.

Amino Acid Sequence↗
PubMed1992

Neurotoxic effects of platinum compounds in cultured dorsal root ganglion cells.

The neurotoxic cancer chemotherapeutic agent cis-diamminedichloroplatinum (II) (cis-platin) was tested in a model system of cultured embryonic chick dorsal root ganglion cells, in order to investigate cellular mechanisms of toxicity. At 7.5 ug/ml, the drug caused mild toxicity. At doses of 75 ug/ml, cis-platin was toxic to cultures in 6 hours, in both neuronal and non-neuronal cell populations. After 24 hours of incubation with 75 ug/ml cis-platin, there was extensive cell death. The trans isomer of the drug, trans-platin, was less toxic than cis-platin at similar doses, causing less severe damage to the cells as well as less cell death. With both drugs, abnormalities in patterns of nuclear staining were prominent, whereas neuronal cell membrane staining patterns were less affected. Both drugs seemed to affect non-neuronal cells to a greater extent than neurons. Ultrastructural findings with both drugs included nucleolar segregation; mitochondrial changes were nonspecific. In this in vitro system, both cis- and trans-platin are toxic. The toxicity appears to predominantly affect the nucleus, and to preferentially involve non-neuronal cells.

Animals↗
PubMed1991

Immunological correlates of seasonal fluctuations in mood and behavior and their relationship to phototherapy.

Immunological parameters were studied before and after phototherapy, with bright and dim light, in 38 individuals with a range of retrospectively reported seasonal changes in mood and behavior. There was a significant negative correlation between the degree of mood and behavioral difficulties in fall and winter (seasonality) and the total number of circulating natural killer cells. Changes in the numbers of circulating helper T cells correlated significantly with changes in mood following phototherapy. Moreover, mitogen-induced lymphocyte blastogenesis increased significantly after phototherapy, but there was no significant difference between the bright and dim light treatments. The results suggest that cellular immune function is associated with both seasonality and response to phototherapy.

Adult↗
PubMed1990

Substratum effects on cell dispersal, morphology, and differentiation in cultures of avian neural crest cells.

Adhesive extracellular matrix (ECM) molecules appear to play roles in the migration of neural crest cells, and may also provide cues for differentiation of these cells into a variety of phenotypes. We are studying the influences of specific ECM components on crest differentiation at the levels of both individual cells and cell populations. We report here that the glycoproteins fibronectin and laminin differentially affect melanogenesis in cultures of avian neural crest-derived cells. Clusters of neural crest cells were allowed to form on explanted neural tubes for 24 and 48 hr, and then subcultured on uncoated glass coverslips or coverslips coated with fibronectin or laminin. The morphology of cells varied on the three substrata, as did patterns of cell dispersal. Crest cells dispersed most rapidly and extensively on fibronectin. In contrast, cells on laminin dispersed initially, but then assumed a stellate morphology and rapidly formed small aggregates. Cell dispersal was minimal on glass substrata, resulting in a uniformly dense distribution. These patterns of dispersal were similar in subcultures of both 24- and 48-hr clusters, although dispersal of cells from older clusters was less extensive. The rate and extent of melanogenesis correlated with patterns of cell dispersal. Cell from 24-hr clusters underwent melanogenesis significantly more slowly on fibronectin than on the other two substrata. Pigment cells began to differentiate by 2 days of subculture in the cell aggregates on laminin and in the dense centers of cultures on untreated glass. By 5 days, there was significantly more melanogenesis in cultures on laminin and glass than on fibronectin substrata. Melanogenesis in cultures of 48-hr clusters was more rapid and extensive on control (glass) substrata than on fibronectin or laminin, correlating with reduced cell dispersal. We conclude that fibronectin and laminin, which are found along neural crest migratory pathways in vivo, can affect melanogenesis in vitro by regulating patterns of cell dispersal.

Animals↗
PubMed1990

The effects of phototherapy in the general population.

Patients with recurrent winter depression and its subsyndromal form have been reported to benefit from bright full-spectrum light (phototherapy). In order to determine whether this treatment (2 h in the morning) during winter is effective in a random sample of the general population we investigated the responses of 20 subjects with varying degrees of winter difficulties. A control group (n = 20) matched for the degree of seasonality, age, and sex was treated with dim light. Individuals were selected from a larger survey sample of the Montgomery County population (MD, U.S.A.) and were comparable to the latter in their degree of winter difficulties. Enhancement of environmental light does not, on the basis of the present study, appear to be indicated for the public at large, but rather for a subgroup of individuals with histories of winter difficulties.

Adult↗
PubMed1989

Phototherapy in individuals with and without subsyndromal seasonal affective disorder.

Antidepressant and energizing effects of bright light exposure (phototherapy) have been widely reported to occur in patients with seasonal affective disorder. We have attempted to evaluate whether other segments of the population might benefit from phototherapy, most notably individuals with subsyndromal seasonal affective disorder, as well as healthy individuals with no winter difficulties (controls). We have studied 20 subjects in each of these two categories and have found that bright artificial light did not alter mood and behavior in controls. In contrast, individuals with subsyndromal seasonal affective disorder responded favorably to treatment with bright environmental light. A dose of 5 hours of bright light exposure, divided between morning and evening, was more effective than 2 hours of exposure. This finding may have practical implications for establishing optimal environmental lighting conditions for those individuals whose winter difficulties do not meet criteria for seasonal affective disorder.

Adult↗
PubMed1988

Phototherapy in subsyndromal seasonal affective disorder (S-SAD) and "diagnosed" controls.

Antidepressant and energizing effects of bright light exposure have been widely reported to occur in patients with seasonal affective disorder (SAD). In order to evaluate whether other segments of the population might also benefit from this treatment, we studied 20 normal individuals with mild SAD-like symptoms (subsyndromal SAD, S-SAD) and 20 with no reported seasonal difficulties (non-S-SAD). Whereas S-SAD individuals benefited from phototherapy, non-S-SAD normals did not. This finding raises the questions of whether a history of seasonal problems might be a marker of vulnerability to affective episodes and if S-SAD individuals might be considered as a high risk population in this regard.

Adult↗
PubMed1987

Selective interaction of peripheral and central nervous system cells with two distinct cell-binding domains of fibronectin.

Mechanisms of cell interaction with fibronectin have been studied with proteolytic fibronectin fragments that have well-defined ligand binding properties. Results of a previous study (Rogers, S. L., J. B. McCarthy, S. L. Palm, L. T. Furcht, and P. C. Letourneau, 1985, J. Neurosci., 5:369-378) demonstrated that (a) central (CNS) and peripheral (PNS) nervous system neurons adhere to, and extend neurites on a 33-kD carboxyl terminal fibronectin fragment that also binds heparin, and (b) neurons from the PNS, but not the CNS, have stable interactions with a 75-kD cell-binding fragment and with intact fibronectin. In the present study domain-specific reagents were used in inhibition assays to further differentiate cell surface interactions with the two fibronectin domains, and to define the significance of these domains to cell interactions with the intact fibronectin molecule. These reagents are (a) a soluble synthetic tetrapeptide Arg-Gly-Asp-Ser (RGDS; Pierschbacher, M. D., and E. Ruoslahti, 1984, Nature (Lond.), 309:30-33) representing a cell-binding determinant in the 75-kD fragment, and (b) an antibody raised against the 33-kD fragment that binds specifically to that fragment. Initial cell attachment to, and neurite extension upon, fibronectin and the two different fragments was evaluated in the presence and absence of the two reagents. Attachment of both PNS and CNS cells to intact fibronectin was reduced in the presence of RGDS, the former more so than the latter. In contrast, the antibody to the 33-kD fragment did not affect attachment of PNS cells to fibronectin, but significantly decreased attachment of CNS cells to the molecule. RGDS inhibited attachment of CNS cells to the molecule. RGDS inhibited attachment of both cell types to the 75-kD fragment to a greater degree than it did attachment to the intact molecule. Cell interaction with the 33-kD fragment was not affected by RGDS. Reduction of neurite lengths (determined after 24 h of culture) by the domain-specific reagents paralleled the reduction in initial adhesion to each substratum. Therefore, it appears that (a) both PNS and CNS cells have receptors for each cell-binding domain of fibronectin, (b) the receptor(s) for the two domains are distinct, with attachment to the 33-kD fragment being independent of RGDS, and (c) the relative importance of each domain to cell interaction with intact fibronectin is different for CNS and PNS cells.

Animals↗
PubMed1986

Distribution of laminin in the developing peripheral nervous system of the chick.

During axonal elongation in the developing peripheral nervous system, the temporal and spatial distribution of adhesive molecules in extracellular matrices and on neighboring cell surfaces may provide "choices" of pathways for growth cone migration. The extracellular matrix glycoprotein laminin appears in early embryos and mediates neuronal adhesion and neurite extension in vitro. In this study, we have examined the distribution of laminin at early periods of peripheral nervous system development. The distribution of laminin, demonstrated by immunostaining frozen sections of chick embryos, was compared to the distribution of fibronectin and of early peripheral neurites as revealed with an antibody to a neurofilament-associated protein. Laminin is present in the neural tube basement membrane, in early ganglia, and in developing dorsal and ventral roots, where the laminin staining pattern parallels that of neurofilaments. In early ganglia and nerve roots, laminin immunostaining defines loose "meshworks" rather than basement membranes, which seem to form slightly later in these structures. In contrast, fibronectin is absent in neural tube basement membrane, ganglia, and nerve roots, although it is present along neural crest migratory pathways and in intersomitic spaces. Our observations of laminin distribution are consistent with the possibility that laminin provides an adhesive surface for neurite extension at some stages of early peripheral nervous system development.

Age Factors↗
PubMed1986

Seasonal affective disorder in children and adolescents.

The authors studied seven children with symptoms of seasonal affective disorder. During the winter months the children regularly experienced irritability, fatigue, school difficulties, sadness, and sleep changes as well as other symptoms of seasonal affective disorder found in adults. An open trial of bright environmental light reversed many of these symptoms and improved mood and psychosocial functioning in the winter months. School counselors and therapists should consider seasonal affective disorder in the differential diagnosis of children with school difficulties that are most prominent in the fall-winter semester.

Adolescent↗