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Biomedical subjects

R L Davis

Publications and source records attributed to R L Davis.

At least 199 records · Page 11Linked to original sources
PubMed1992

Diffuse leptomeningeal involvement by a ganglioglioma in a child. Case report.

Gangliogliomas are tumors composed of neuronal and glial elements that typically grow slowly by expansion only. This report describes a 20-month-old girl with a ganglioglioma that extensively involved the subarachnoid space; microscopic foci of tumor were found in the brain and spinal cord. Despite chemotherapy and radiation therapy, the child died 5 months after diagnosis. Molecular genetic analysis showed loss of chromosome 17p DNA sequences in the tumor tissue.

Brain Neoplasms↗
PubMed1992

Resection of dominant opercular gliosis in refractory partial epilepsy. Report of two cases.

Frontal opercular gliosis in the dominant hemisphere caused medically refractory partial epilepsy in two patients. Both patients were aphasic during their seizures, but otherwise had normal speech. Magnetic resonance images showed well-demarcated lesions resembling tumors in each patient; on heavily T2-weighted images, the lesions were hyperintense compared with normal brain. Cortical mapping with subdural grids localized speech to the area of the lesions; therefore, the resections were performed under local anesthesia and speech was tested throughout the procedure. Postoperatively, both patients were seizure-free and had no new neurological deficits. Well-demarcated lesions, even in the dominant operculum, can be safely removed in patients with medically refractory partial epilepsy.

Adolescent↗
PubMed1991

Characterization of the memory gene dunce of Drosophila melanogaster.

The dunce (dnc) gene of Drosophila melanogaster encodes cAMP phosphodiesterase (PDEase) and is required for learning/memory and female fertility. The gene is structurally complex, demonstrated in part by Northern blotting experiments which detected multiple RNAs ranging in size from 4.2 to 9.6 kb (1 kb = 10(3) bases or base-pairs). To characterize these RNAs and to understand their sequence heterogeneity, we isolated and analyzed 29 new and independent cDNA clones representing the dnc RNAs. Restriction mapping, hybridization analysis and sequence determination of these cDNA clones and the corresponding genomic exons resolved these into six different classes. Exons defined by the cDNA clones are distributed over more than 148 kb of genomic DNA, with some exons being used alternatively among the RNAs. The RNAs are transcribed from at least three initiation sites: two of these were mapped by parallel S1-nuclease and primer extension experiments. In addition, some of the heterogeneity is generated by using varying lengths of a 3'-untranslated trailer sequence. Altogether, the results indicate that the size and sequence heterogeneity of dnc transcripts results from transcription initiation at multiple sites, alternative splicing, and processes which generate different 3' ends. The existence of multiple protein products is suggested by the alternative use of exons which code for portions of the open reading frame. The protein variation potentially includes N-terminal differences coded for by transcript-specific 5' exons and internal differences arising from the optional inclusion of a 39 base-pair exon and from the alternative use of two 3' splice sites separated by six base-pairs. Expression of a cDNA clone in yeast containing a large portion of the open reading frame produced cAMP PDEase activity identical in properties to the Drosophila enzyme affected by the dnc mutation. The results suggest that the remarkable structural complexity of dnc may reflect an intricate control of the spatial and/or temporal expression of various isoforms of cAMP PDEase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo.

In this report we provide four lines of evidence indicating that E12/E47-like proteins interact in vivo with the myogenic HLH proteins MyoD and myogenin. First, cotransfection of MyoD and E47 in COS cells indicates that these factors synergistically enhance transcription of a reporter gene containing an oligomerized MyoD-binding site. Second, mobility-shift assays of muscle cell nuclear extracts, "double shifted" with specific antisera, have identified complexes binding to the MEF1 site that contain either MyoD or myogenin in association with E12/E47-like proteins. Third, association with E47 alters the phosphorylation state of MyoD. Fourth, C3H10T1/2 cells expressing antisense E2A transcripts contain low levels of E2A gene products and display less terminal muscle differentiation when infected with retroviral MyoD or when challenged to differentiate with 5-azacytidine treatment. In addition we demonstrate that MyoD, in conjunction with E12/E47-like proteins, is functioning as a regulatory nodal point for activation of several other downstream muscle regulators.

Adenovirus Early Proteins↗
PubMed1991

The Drosophila dunce locus: learning and memory genes in the fly.

The dunce gene, one of several genes critical for normal learning and memory in Drosophila, is organized in a complex and bizarre way, with enormous introns containing several other unrelated genes. Recent studies have focused on the spatial expression pattern of the product, cAMP phosphodiesterase, and have provisionally identified the mushroom bodies as important sites of action of dunce within adult brain. In addition, the recent cloning and characterization of dunce counterparts from mammals has revealed that these too may participate in animal behavior and, in particular, in the regulation of mood.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Low-dose craniospinal radiation therapy for medulloblastoma.

At the University of California, San Francisco, 65 children with medulloblastoma of the posterior fossa were treated postoperatively with craniospinal irradiation; the dose to the posterior fossa was 54 Gy. The 26 children initially treated had only radiation therapy, receiving 30 to 40 Gy to the spine and 40 to 50 Gy to the brain. Subsequently, 39 children were treated with low-dose craniospinal irradiation and chemotherapy; 24 to 30 Gy was directed to the whole brain and 24 to 26 Gy to the spinal axis. Chemotherapy generally consisted of procarbazine just before, and hydroxyurea during, radiation therapy. Poor-risk and good-risk patients (defined by tumor resection less than 75% or greater than 75%, positive or negative myelogram, positive or negative cerebrospinal fluid analysis, age less than or greater than 2 years, respectively) were evenly distributed between the low-dose and high-dose craniospinal radiation therapy groups. Median follow-up was 51 months (range, 24 to 228 months). Kaplan-Meier actuarial survival for all patients was 73% at 5 years, 70% at 10 years. Freedom from disease progression was 68% at 5 years, 65% at 10 years. Whereas poor-risk patients treated with low-dose craniospinal irradiation and chemotherapy had a 5-year survival of 58% and a 5-year freedom from disease progression of 39%, those figures in the comparable good-risk patients were 83% and 77%, respectively. For both good-risk and poor-risk patients, the posterior fossa was the primary site of recurrence. Tumors recurred in the frontal region, probably under blocks, in three patients receiving low-dose irradiation and in two receiving the higher dose. Reducing the dose of whole-brain and spinal irradiation and giving chemotherapy did not result in a higher rate of recurrence in the brain or spinal cord. Intellectual and social function appeared better in patients receiving the lower dose. We did not study whether chemotherapy benefitted good-risk patients. Craniospinal axis irradiation at a lower dose than conventionally used does not compromise local control or survival in patients with medulloblastoma, and may reduce toxicity.

Adolescent↗
PubMed1991

Evaluation of bromodeoxyuridine in glioblastoma multiforme: a Northern California Cancer Center Phase II study.

In a study activated in 1983 and closed in 1987, the Brain Tumor Research Center of the University of California and the Northern California Cancer Center evaluated the effect of bromodeoxyuridine in the treatment of glioblastoma multiforme. A total of 160 patients were evaluable of 173 entered. Patients were to receive a bromodeoxyuridine infusion of 0.8 g/m2 daily over 24 hours for 4 days of each of 6 weeks of radiotherapy directed to the tumor plus a margin delivering a total of 60 Gy. Eligibility requirements included Karnofsky performance status greater than or equal to 70, biopsy or resection and central pathology review by one of the authors. Following radiotherapy patients were to receive chemotherapy with procarbazine, CCNU, and vincristine for 1 year. Median survival was 55.7 weeks and time to failure, 34.5 weeks for the evaluable group of 160 patients. In a univariate analysis the variables that influence survival and time to failure were: age, Karnofsky performance status, bromodeoxyuridine dose and the delivery of at least one procarbazine, CCNU, and vincristine cycle following radiotherapy. In multivariate analysis, age, Karnofsky performance status, and bromodeoxyuridine dose remain significant for time to failure; age and Karnofsky performance status remain significant for survival.

Adult↗
PubMed1991

The cyclic AMP phosphodiesterase encoded by the Drosophila dunce gene is concentrated in the mushroom body neuropil.

Drosophila dunce (dnc) flies are defective in learning and memory as a result of lesions in the gene that codes for a cAMP-specific phosphodiesterase (PDE). Antibodies to the dnc PDE showed that the most intensely stained regions in the adult brain were the mushroom body neuropil--areas previously implicated in learning and memory. In situ hybridization demonstrated that dnc RNA was enriched in the mushroom body perikarya. The mushroom bodies of third instar larval brains were also stained intensely by the antibody, suggesting that the dnc PDE plays an important role in these neurons throughout their development. The role of the dnc PDE in mushroom body physiology is discussed, and a circuit model describing a possible role of the mushroom bodies in mediating olfactory learning and memory is presented.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Amikacin pharmacokinetics in patients receiving high-dose cancer chemotherapy.

We retrospectively analyzed amikacin pharmacokinetics in 28 patients (mean age, 47.4 +/- 13.6 years) who received high-dose chemotherapy during a neutropenic febrile episode. Patients received an experimental protocol of high-dose anticancer chemotherapy. Amikacin pharmacokinetic parameters were calculated from two or more concentrations in serum around a single dose by the method of Sawchuck and Zaske (J. Pharmacokinet. Biopharm. 4:183-195, 1976). Predicted parameters were calculated by using standard methods. The observed amikacin volume of distribution and clearance were significantly greater and the elimination half-life was longer than predicted (0.38 +/- 0.13 versus 0.25 liter/kg [P = 0.0001], 1.51 +/- 0.92 versus 1.17 +/- 0.38 liters/h/kg [P = 0.012], and 3.8 +/- 2.4 versus 2.9 +/- 1.1 h [P = 0.011], respectively). Multivariate analysis revealed that albumin correlated negatively and creatinine correlated positively with the volume of distribution and the elimination half-life. Creatinine and the percentage below the ideal body weight correlated negatively and hematocrit correlated positively with clearance. Administration of dosage regimens based on predicted pharmacokinetic parameters yielded subtherapeutic amikacin concentrations in serum in our patients. Because of the increased dosage requirements and the need for adequate antibiotic treatment in this population, we suggest guidelines for empiric dosing for patients with advanced cancer receiving intensive chemotherapy.

Adolescent↗
PubMed1991

Physical compatibility and chemical stability of amphotericin B in combination with magnesium sulfate in 5% dextrose injection.

The physical compatibility and chemical stability of amphotericin B for injection USP (AB) admixed with magnesium sulfate injection USP (MS) in 5% dextrose injection USP (D5W) was evaluated. AB (final concentration of either 40 or 80 micrograms/mL of solution) and MS (final concentration of 0, 2, or 4 mg/mL of solution) were mixed in glass volumetric flasks containing D5W. AB concentration, as quantitated by high-performance liquid chromatography, and visible admixture clarity were monitored at zero, three, and six hours after combining with MS. At the three-hour observation, visible admixture clarity appeared to decrease in all multiple drug combinations and a clear supernatant began to develop as particulates settled to the bottom of the container. MS (final concentration of 4 or 8 mg/mL of solution) and AB (final concentration of 80 micrograms/mL of solution) were prepared in two separate intravenous polyvinyl chloride bags of D5W. The solutions were manually set to infuse via gravity for six hours and mix at the y-site of an intravenous administration set. Samples of the mixture were collected from the terminal end of a primary intravenous administration set at zero, two, four, and six hours after beginning the infusions. Each sample appeared visibly clear and maintained an AB concentration of at least 100 percent of the initial admixture concentration. MS and AB mixed in the same container appeared to be physically incompatible. The same admixture appeared to be physically compatible and chemically stable, in terms of AB, when infused as separate solutions mixed at a y-site of an intravenous administration set.

Amphotericin B↗
PubMed1991

Gemistocytic astrocytomas: a reappraisal.

Although gemistocytic astrocytomas are considered slow-growing astrocytomas, they often behave aggressively. To clarify the biological and clinical behavior of these rare tumors, the authors retrospectively identified 59 patients with gemistocytic astrocytoma whose tumors were diagnosed and treated between June, 1976, and July, 1989. Three patients who were lost to follow-up review were excluded, as were two whose original slides could not be obtained and three whose tumors were diagnosed at recurrence or at autopsy. The pathological material of the remaining 51 patients was reviewed using two sets of histological criteria. Thirteen patients (Group A) had "pure" gemistocytic astrocytoma, defined as a glial tumor with more than 60% gemistocytes/high-power field and a background of fibrillary astrocytes. Fifteen patients (Group B) had "mixed" gemistocytic astrocytoma, defined as a glial tumor with 20% to 60% gemistocytes/high-power field and a background of anaplastic astrocytes. Twenty-three tumors did not meet these criteria and were excluded from analysis. The median age of the patients was 48.5 years in Group A and 38.3 years in Group B (p less than 0.05). In both groups, the median Karnofsky Performance Scale score was greater than 90%. All patients underwent surgical procedures (four total and 19 partial resections, and five biopsies) and postoperative radiation therapy. The majority also had interstitial brachytherapy, chemotherapy, or both. Ten patients had one reoperation for tumor recurrence and one had two reoperations; other treatments for recurrence included brachytherapy, chemotherapy, and repeat irradiation. All four patients who originally underwent gross total resection are still alive; all five who had a biopsy have died. There was no significant difference in median survival times between groups: 136.5 weeks in Group A (range 10 to 310+ weeks) and 135.6 weeks in Group B (range 31 to 460+ weeks). Analysis of all 28 patients showed a better prognosis for patients less than 50 years of age (185 vs. 36 weeks survival time; p less than 0.001), patients with preoperative symptoms lasting for more than 6 months (228.1 vs. 110.2 weeks survival time; p less than 0.05), and patients with seizures as the first symptom (185.7 vs. 80 weeks survival time; p less than 0.01). Survival time did not correlate with the presence of perivascular lymphocytic infiltration. The authors conclude that the presence of at least 20% gemistocytes in a glial neoplasm is a poor prognostic sign, irrespective of the pathological background. It is proposed that gemistocytic astrocytomas be classified with anaplastic astrocytomas and treated accordingly.

Adult↗
PubMed1991

Intradural chordoma of the tentorium cerebelli. Case report.

A rare case of intradural chordoma is described. The literature contains seven examples of intradural extraosseous chordoma, all reported in a ventral location. This is the first reported case of a primary intradural chordoma distant from the clivus and involving both the supra- and infratentorial compartments.

Cerebellum↗
PubMed1991

Metastatic juvenile pilocytic astrocytoma. Case report.

The authors report the case of a metastatic juvenile pilocytic astrocytoma of the hypothalamic region in a 10-year-old boy. Eight years after craniotomy and radiation therapy, the tumor spread via cerebrospinal fluid pathways to the left cerebellar tonsil and the lumbosacral region. Histological evaluation of both the original hypothalamic and the new lumbosacral masses showed features of a slow-growing juvenile pilocytic astrocytoma with no evidence of malignant transformation. The clinical implications and possible mechanisms of metastatic spread are discussed.

Astrocytoma↗
PubMed1991

Cigarette smoking during pregnancy and mother's occupation.

The association between mother's occupation and cigarette smoking prevalence during pregnancy was analyzed in over 350,000 Washington State births during the years 1984 through 1988. Smoking prevalence during pregnancy varied markedly by maternal age, race, marital status, and social class, with higher smoking rates found in unmarried women, women 25 through 29 years old, native Americans and whites, and women in low socioeconomic classes. Women who worked in traditionally male occupations or in occupations where alcohol was served had the highest smoking rates. Occupational groups with exposure to toxic or carcinogenic substances (including second-hand smoke) also had elevated smoking rates. These data could be useful in planning intervention strategies, in studies of occupational morbidity and mortality, and in analysis of the reproductive effects of maternal occupational exposures.

Adolescent↗
PubMed1990

Cloning and expression in Escherichia coli of a hypoxanthine-guanine phosphoribosyltransferase-encoding cDNA from Plasmodium falciparum.

The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) of Plasmodium falciparum plays a key role in the salvage of preformed purine nucleotides from parasite-infected erythrocytes. Since P. falciparum cannot synthesize purines de novo, development of inhibitors specific for the parasite HGPRT should be an effective method of chemotherapy. To provide sufficient amounts of HGPRT for biochemical and crystallographic analysis, we have isolated the P. falciparum HPRT cDNA sequence and expressed it in an Escherichia coli strain deficient for both de novo purine synthesis and guanine utilization (strain GP120). GP120 cells containing the P. falciparum HPRT plasmid vector (pRD500), when grown in the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG) which induces the tac promoter of the expression vector, produce a novel protein of 26 kDa, which is in agreement with the predicted Mr deduced from the HPRT cDNA open reading frame. In addition, we have demonstrated significant HGPRT activity in cell-free extracts of GP120[pRD500] cultures grown in minimal medium containing xanthine, as the sole source of purines, and IPTG.

Amino Acid Sequence↗
PubMed1990

Cell proliferation inhibited by MyoD1 independently of myogenic differentiation.

Cell growth and differentiation are usually mutually exclusive. Transformation of myoblasts by retroviruses containing the myc oncogene inhibits differentiation, preventing cells from withdrawing from the cell cycle. If cell-cycle withdrawal is a prerequisite for myoblast differentiation, it is probably an early event in terminal cell differentiation, but this has not yet been established. MyoD1 regulates myogenesis. It is expressed only in skeletal muscle, but can convert other cells to muscle cells. The MyoD1 protein, a nuclear phosphoprotein in part similar to the myc family of proteins, is a DNA-binding protein binding to the enhancer sequences of the muscle-specific creatine phosphokinase gene. Thus, introduction of MyoD1 into cells provides a simple approach to study the effect of induction of differentiation on cell growth. In cultured NIH 3T3 cells, inhibition of cell proliferation occurs within 18 hours, and expression of myosin starts after 72 hours. Furthermore, injection of MyoD1 into quiescent NIH 3T3 cells inhibit cell proliferation independently of induction of differentiation. Deletion of the myc-like domain in the MyoD1 gene eliminates the inhibition of DNA synthesis, but substitution of the basic domain with the analogous domain from the E12 transcription factor inhibits growth yet fails to induce differentiation. Inhibition of DNA synthesis, therefore, seems to be controlled separately from myogenic differentiation.

Animals↗