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Biomedical subjects

R D Saunders

Publications and source records attributed to R D Saunders.

At least 55 records · Page 3Linked to original sources
PubMed1992

Prenatal irradiation and spatial memory in mice: investigation of critical period.

Pregnant CD1 mice were exposed on various gestational or postnatal days to 1 Gy of 250 kV X-rays. Ten adult, male offspring from each exposure condition were tested in a radial arm maze. Compared to sham-exposed control mice, acquisition of spatial information was unimpaired in animals exposed on gestational days 13 or 15, or on postnatal day 10, but animals exposed on gestational day 18 or postnatal day 1 showed sustained deficits in acquisition. These results appear consistent with the known time-course for the proliferation and migration of the dentate granule cells of the hippocampus in the mouse, and are discussed in relation to the dependence on hippocampal integrity of the acquisition and use of spatial information. The results suggest that comparable deficits in mental function might be expected in humans similarly exposed to ionizing radiation during periods of proliferation and migration of the dentate granule cells.

Animals↗
PubMed1991

Low-resolution genome map of the malaria mosquito Anopheles gambiae.

We have microdissected divisions of the Anopheles gambiae polytene chromosomes, digested the DNAs with a restriction enzyme, and PCR-amplified the DNA fragments to generate a set of pooled probes, each corresponding to approximately 2% of the mosquito genome. These divisional probes were shown to have high complexity. Except for those derived from near the centromeres, they hybridize specifically with their chromosomal sites of origin. Thus, they can be used to map cloned DNAs by a dot blot procedure, which is much more convenient than in situ hybridization to polytene chromosomes. We discuss additional potential uses of these probes, such as easier isolation of molecular markers and genes, including those that cross-hybridize with clones available from other insects. It is expected that the probes will substantially accelerate molecular genetic analysis of this most important malaria vector.

Animals↗
PubMed1991

Integrated maps of the Drosophila genome: progress and prospects.

A physical map of the Drosophila melanogaster genome is being assembled, consisting of ordered overlapping cosmid clones. The map is constructed in steps, separately for each chromosomal division. Gaps in this map are to be bridged with yeast artificial chromosome clones. Hybridization to previously cloned genes and extensive use of in situ hybridization to polytene chromosomes ensure that the cosmid map is firmly anchored to the wealth of available genetic and cytogenetic information. The intention is to make the physical map widely available as part of an overall, integrated genetic resource for the Drosophila research community.

Animals↗
PubMed1990

Towards a physical map of the Drosophila melanogaster genome: mapping of cosmid clones within defined genomic divisions.

A physical map of the D. melanogaster genome is being constructed, in the form of overlapping cosmid clones that are assigned to specific polytene chromosome sites. A master library of ca. 20,000 cosmids is screened with probes that correspond to numbered chromosomal divisions (ca. 1% of the genome); these probes are prepared by microdissection and PCR-amplification of individual chromosomes. The 120 to 250 cosmids selected by each probe are fingerprinted by Hinfl digestion and gel electrophoresis, and overlaps are detected by computer analysis of the fingerprints, permitting us to assemble sets of contiguous clones (contigs). Selected cosmids, both from contigs and unattached, are then localized by in situ hybridization to polytene chromosomes. Crosshybridization analysis using end probes links some contigs, and hybridization to previously cloned genes relates the physical to the genetic map. This approach has been used to construct a physical map of the 3.8 megabase DNA in the three distal divisions of the x chromosome. The map is represented by 181 canonical cosmids, of which 108 clones in contigs and 32 unattached clones have been mapped individually by in situ hybridization to chromosomes. Our current database of in situ hybridization results also includes the beginning of a physical map for the rest of the genome: 162 cosmids have been assigned by in situ hybridization to 129 chromosomal subdivisions elsewhere in the genome, representing 5 to 6 megabases of additional mapped DNA.

Animals↗
PubMed1990

Dominant lethal studies in male mice after exposure to a 50-Hz electric field.

Male C3H/He mice were sham-exposed or exposed continuously for 2 weeks to a vertical, 50-Hz, electric field at 20 kV/m rms. Densities of currents induced in the testes are estimated to be near 100 microA/m2. After the exposure, each male was mated with two different female mice each week during a period of 8 weeks. By this schedule, female mice were impregnated with sperm that had been exposed to the electric field at different stages of the spermatogenic cycle. No significant differences as a function of exposure condition were observed in pregnancy rates or in survival of embryos before or after implantation. The absence of effects was not due to insensitivity of assays; other mice that were exposed to X-rays (dose to testes = 1.5 Gy) presented reliable evidence of mutagenesis.

Animals↗
PubMed1990

Major depression, panic disorder, and mitral valve prolapse in patients who complain of chest pain.

PURPOSE: Patients with chest pain but without angiographic evidence of significant atherosclerotic coronary artery disease (CAD) are often found to have other medical or psychiatric disorders, including mitral valve prolapse, panic disorder (PD), and major depressive disorder (MDD). The purpose of this study was to determine the degree of comorbidity between MDD/PD and mitral valve prolapse in a group of patients with non-CAD chest pain. PATIENTS AND METHODS: Patients referred for cardiac catheterization and coronary angiography for suspected CAD who were 70 years of age or younger and without other significant medical illnesses or cardiac complications were eligible for study. The first 100 patients who agreed to a psychiatric diagnostic interview were recruited. RESULTS: Forty-eight of the 100 patients were found to be without significant CAD. Forty-two percent of these patients, compared to 19% of the patients with significant CAD, were found to have either MDD, PD, or both. Eighty percent of the patients without CAD who had mitral valve prolapse also had either MDD or PD (p less than 0.006). CONCLUSIONS: The finding that mitral valve prolapse was significantly associated with MDD/PD has implications for the diagnosis and treatment of patients with non-CAD chest pain, and may explain why these patients complain of symptoms.

Cardiac Catheterization↗
PubMed1990

Lack of acute effects of 20 mT, 50 Hz magnetic fields on murine haemopoiesis.

Some epidemiological studies have drawn attention to a possible association between exposure to extremely low-frequency (ELF) electromagnetic fields and the development of acute myeloid leukaemia (AML) in adults. At present there is no experimental evidence for such an association. We have investigated the acute effects of power frequency magnetic fields on haemopoiesis in CBA/H mice known to be susceptible to the induction of AML after exposure to ionizing radiation. Up to 19 days after exposure to 50 Hz fields at 20 mT for 7 days no significant effects on peripheral blood characteristics were observed. Assays of the bone marrow stem cells and myelomonocytic progenitor cells also failed to reveal significant effects. Our experiments cannot, however, rule out subtle effects on cell population dynamics, and further investigations, including long-term studies, are required to establish the extent to which ELF magnetic fields might affect the haemopoietic system.

Animals↗
PubMed1990

Mutations at the asp locus of Drosophila lead to multiple free centrosomes in syncytial embryos, but restrict centrosome duplication in larval neuroblasts.

Mutations at abnormal spindle result in abnormally long and wavy microtubules in the meiotic spindles of males. Some of these spindles have a single pole and take the form of unopposed hemi-spindles. Unfertilised eggs produced by homozygous asp females may have either no nuclei, or a small number of large nuclei, consistent with there also being an effect upon female meiosis. Such eggs also display free centrosomes and independent arrays of microtubules. Embryos that have this phenotype are also present among the progeny of fertilised homozygous asp females, together with embryos that undergo varying degrees of aberrant morphogenesis, developing a variety of abnormal cuticle patterns. This latter category shows asynchronous mitoses prior to cellularisation, and has abnormal arrays of spindle microtubules. Such embryos can develop large areas that are either devoid of or have a reduced number of nuclei, in which there are centrosomes that have dissociated from the mitotic spindles. Neuroblasts in the brains of homozygous asp larvae display a high mitotic index, and have condensed chromosomes aligned as if blocked at metaphase. Immunostaining reveals that many cells contain a single centrosome connected to the metaphase chromosomes by microtubules in a hemi-spindle-like structure.

Alleles↗
PubMed1989

PCR amplification of DNA microdissected from a single polytene chromosome band: a comparison with conventional microcloning.

A novel alternative to microcloning for the production of region specific chromosomal DNA is described. In this method, 'microamplification', single bands are dissected from polytene chromosomes and digested with Sau3A. Oligonucleotide adaptors are ligated to these fragments to provide convenient priming sites for polymerase chain reaction amplification. In this way, as much as 1 microgram of DNA can be amplified from a single band. Probes made from PCR amplified DNA from two such dissections have been used to probe cloned DNA form a 100 kb chromosome walk. Whereas conventional microcloning has generated cloned EcoRI fragments corresponding to 3-4 kb of the walk, the PCR probes cover greater than 90% of this chromosomal region. Thus microamplification is significantly more effective than microcloning in providing probes for establishing chromosomal walks.

Animals↗
PubMed1989

Role of intracellular pH in the axolemma- and myelin-induced proliferation of Schwann cells.

In order to provide additional information on the biochemical events that interact to cause Schwann cells to proliferate, we have monitored the intracellular pH of Schwann cells that have been stimulated to divide with myelin-enriched fractions (MEF) or axolemma-enriched fractions (AEF). The intracellular pH of Schwann cells was monitored using 2',7'-bis(carboxymethyl)-5(6)-carboxyfluorescein (BCECF), which displays an increase in fluorescence upon alkalinization. Both AEF and MEF caused dose-dependent increases in the intracellular fluorescence of the Schwann cell cultures. At their maximum doses, AEF and MEF stimulation resulted in a 260 and 300% increase in intracellular fluorescence, respectively. The increase in intracellular fluorescence was abolished when cells were stimulated in Na+-free media, suggesting a role for the Na+/H+ exchanger. Mitotic stimulation required integrity of the Na+/H+ exchanger, as inhibition of the Na+/H+ exchanger for periods up to 1 h after addition of mitogen caused a significant inhibition of subsequent mitosis. Phorbol esters, which can potentiate AEF- and MEF-induced Schwann cell proliferation, increased intracellular fluorescence fivefold, an effect which was also dependent upon the presence of Na+ in the culture media. The specificity of the increase in intracellular pH for AEF and MEF was tested by incubating Schwann cells with liver microsomes and a biologically inactive phorbol alcohol, neither of which is significantly mitogenic for Schwann cells. Neither liver microsomes nor phorbol alcohol had a significant effect on intracellular pH. The implications of the increase in intracellular pH in Schwann cells with respect to inositol phospholipid metabolism, protein kinase C activation, and cellular proliferation are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1988

Studies of the induction of dominant lethals and translocations in male mice after chronic exposure to microwave radiation.

Male C3H mice were exposed to 100 W m-2 of 2.45 GHz continuous-wave microwave radiation for 6 h per day for a total of 120 h over an 8-week period. The exposure level was chosen so that the specific energy absorption rate (SAR) would be approximately equal to the level of 4 W kg-1 which is considered by a number of organizations to be a threshold for adverse biological effects. At the end of the treatment period the mice were mated with a different group of (C3H x 101) F1 hybrid females each week for the following 8 weeks. There was no significant reduction in pregnancy rate, preimplantation survival or postimplantation survival in the exposed group compared to sham-exposed controls. At the end of the mating period a cytogenetic analysis was carried out of meiotic chromosome preparations of testicular tissue, thus sampling cells that were stem cell spermatogonia during the treatment regime. The results showed no difference in the frequency of reciprocal translocations between the sham and treated groups, or in the frequency of cells with autosome or sex chromosome univalents. Low levels of fragments and exchanges were found in both groups. It is concluded that there is no evidence in this experiment to show that chronic exposure of male mice to 2.45 GHz microwave radiation induces a mutagenic response in male germ cells. This conclusion is in agreement with the observations of Berman et al. (1980), who reported a lack of male germ cell mutagenesis after repetitive or chronic exposure of rats to 2.45 GHz.

Animals↗
PubMed1988

1-oleoyl-2-acetylglycerol and A23187 potentiate axolemma- and myelin-induced Schwann cell proliferation.

The effects of 1-oleoyl-2-acetylglycerol (OAG) and the calcium ionophore A23187 on the proliferation of Schwann cells stimulated with either a myelin-enriched membrane fraction (MEF) or an axolemma-enriched membrane fraction (AEF) have been examined. Using incorporation of [3H]thymidine as an index of proliferation, 16% of the cells became labeled after incubation with MEF (20 micrograms protein/ml) and AEF (40 micrograms protein/ml) for 72 h. Only 0.5% of the cells became labeled in cultures which were not exposed to the membrane fractions. Addition of OAG (10-500 microM) or A23187 (1.9-190 nM) in the absence of the membrane mitogens had no effect on the proliferative response of quiescent cultures of Schwann cells. When added simultaneously, however, OAG and A23187 were able to induce proliferation of the cells, although the response was only 30% of the response achieved with maximal doses of either AEF or MEF. Both OAG and A23187 were able to potentiate the mitogenicity of AEF or MEF, but only when AEF and MEF were added at submaximal concentrations. When Schwann cells were prelabeled with [3H]glycerol and then stimulated to proliferate with AEF or MEF, the amount of [3H]diacylglycerol was increased two- to threefold above that in control cultures for time periods up to 1 h. These results suggest that the proliferation of Schwann cells induced by either AEF or MEF is partially mediated through the combined effects of diacylglycerol and an increase in intracellular calcium.

Animals↗
PubMed1988

Schwann cell proliferation is accompanied by enhanced inositol phospholipid metabolism.

Inositol phospholipid metabolism during mitogen-induced Schwann cell proliferation has been examined. Addition of axolemma- and myelin-enriched membrane fractions (AXL and MYE, respectively) to cultured Schwann cells stimulated 32P incorporation into phosphatidylinositol 4-monophosphate [PtdIns(4)P] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. During the first 5 min of incubation with the mitogens, the amount of 32P incorporated into PtdIns(4)P and PtdIns(4,5)P2 was four- to fivefold above control values. The phosphorylation of the inositol phospholipids was dependent on the concentration of membrane mitogens and was maximal within 1 h. Schwann cells that were prelabeled with [3H]glycerol and then stimulated with AXL and MYE displayed a 30-70% increase in the amounts of [3H]PtdIns(4)P and [3H]PtdIns(4,5)P2 and a 60-80% increase in the amount of [3H]phosphatidic acid. A concomitant 20% decrease in the content of [3H]PtdIns was observed after stimulation. These results suggest that the increased metabolism of PtdIns, PtdIns(4)P, and PtdIns(4,5)P2 may be one of the initial molecular events in the transduction of the mitogenic signal across the Schwann cell plasma membrane.

Animals↗
PubMed1987

Identification of a female-sterile mutation affecting yolk protein 2 in Drosophila melanogaster.

The three yolk proteins (YP1, YP2 and YP3) of Drosophila melanogaster are synthesised in the fat body and ovarian follicle cells and selectively accumulated in the developing oocytes to provide a nutrient source for embryogenesis. We have described the phenotype of a temperature-sensitive female-sterile mutant, fs (1) K313, nad characterised its yolk proteins. This mutation affects the secretion of YP2 and is the first mutation affecting YP2 to be described. Using genetic and molecular tests we argue that the female-sterile phenotype results, at least in part, from the abnormal secretion of YP2 perturbing the follicle cell secretory pathway in general and thus causing defects in chorion protein secretion. The gene coding for YP2 in fs (1) K313 has been cloned and sequenced. Two amino acid substitutions have been found which probably cause the abnormal secretion of YP2 and the resulting female-sterile phenotype.

Animals↗
PubMed1987

Early membrane lipid changes in laminectomized and traumatized cat spinal cord.

The effects of surgical exposure (laminectomy) and compression trauma on various aspects of membrane lipid metabolism in the feline spinal cord were determined in this study. Tissue samples were frozen in situ and grossly dissected into gray and white portions prior to lipid analyses. Laminectomy alone resulted in measurable changes in spinal cord lipid metabolism, including increases in gray matter free fatty acids, diacylglycerols, and eicosanoids. A 90-min recovery period greatly reduced the levels of these compounds. Compression of the spinal cord with a 170-g weight (following a 90-min recovery period) caused very large increases in gray matter free fatty acids, diacylglycerols, and eicosanoids, and decreases in cholesterol and ethanolamine plasmalogens. Similar, but time delayed changes in these compounds were also observed in white matter.

Animals↗