Biomedical subjects
C A Wilson
Publications and source records attributed to C A Wilson.
Effect of delequamine (RS15385) on female sexual behaviour in the rat.
The role of alpha 2-adrenoceptors in mediating the noradrenergic control of female sexual behaviour was investigated employing a selective alpha 2-adrenoceptor antagonist, delequamine (RS15385). The drug was given in graded doses of 0.01-30 mg/kg p.o. to ovariectomised plus adrenalectomised rats primed with either 2 micrograms oestradiol benzoate which yielded mainly non-receptive animals or 5 micrograms oestradiol benzoate followed 48 h later by 0.5 mg progesterone, which stimulated a high level of receptivity. Doses between 0.1 and 30 mg/kg significantly increased lordotic activity (receptivity) with an ED50 of 0.32 mg/kg, but had no effect on ear-wiggling or hopping-and-darting (proceptivity). Delequamine had no inhibitory effect in animals displaying high levels of receptivity. Thus we have shown a selective alpha 2-adrenoceptor antagonist, given orally, can stimulate female receptivity in a dose-dependent manner. Bilateral administration into the ventromedial nucleus, but not medial preoptic area, of delequamine (10 micrograms/side/rat) stimulated receptivity and it is suggested that the alpha 2-adrenoceptor may exert its effect by enhancing endogenous noradrenaline release at its active sites.
Hypoxia precedes the development of experimental preretinal neovascularization.
BACKGROUND: Although the mechanism of preretinal neovascular growth in the cell-injected rabbit eye model is not known, it has been proposed that the initial vasodilation and eventual development of neovascularization may be attributable to inflammatory mediators. However, an alternative explanation involving hypoxia has not been considered. The purpose of this study was to measure preretinal oxygen tension prior to the development of preretinal neovascularization in the cell-injected rabbit eye. METHODS: In the rabbit, intravitreous injections of 250,000 homologous dermal fibroblasts were performed on one eye; the fellow (control) eye was injected with vehicle. Preretinal oxygen tension over the myelin wing was measured using 19F-NMR spectroscopy of a 30-microliters droplet of perfluorocarbon previously injected into the preretinal vitreous. RESULTS: Compared to control eyes, fibroblast-injected eyes showed a 1.7-fold decrease in preretinal oxygen tension from the first time studied (1 day after cell injection) through the development of visible neovascularization. Hypoxia occurred without coexisting ophthalmoscopic evidence of vascular occlusion or, on days 1 and 3 after cell injection, retinal detachment. CONCLUSION: This result demonstrates for the first time that preretinal hypoxia precedes the development of preretinal neovascularization in the fibroblast-injected rabbit eye.
Immunohistochemical distribution of basic fibroblast growth factor in experimental retinal ischaemia and reperfusion in the rat.
It has been proposed that basic fibroblast growth factor (basic FGF) mediates the neovascular response in a variety of conditions, including diabetic retinopathy and branch retinal vein occlusion. To test the hypothesis that basic FGF was released from retinal stores as a result of retinal ischaemia, transient retinal ischaemia was induced, followed by 48 h of reperfusion, in the rat by combined central retinal vasculature and optic nerve ligation. The immunolocalization of basic FGF was studied in the retina. We found that basic FGF in the normal retina is present around the deeper retinal vessels and in the neuronal tissue of the outer plexiform layer. In the eyes that had ischaemia followed by reperfusion, there was moderate cellular oedema with retinal swelling, and mitoses in the inner nuclear and plexiform layers. There were no changes evident at the immunohistochemical level either in the intensity or distribution of stores of basic FGF. We conclude from these data that stores of basic FGF are not altered dramatically under the conditions of transient experimental ischaemia and reperfusion in the rat, despite the presence of cellular proliferation.
Absence of detrimental effects of fluoride exposure in diabetic rats.
This study is part of a comprehensive programme to investigate fluoride toxicity and the hypothesis that fluoride ingested by "medically compromised' animals will result in altered physiological function. Its objectives were to monitor fluoride retention, tissue fluoride concentrations and genetic variables in diabetic and control rats chronically exposed to fluoride, and to determine whether or not adverse effects occurred. Male, Zucker fatty diabetic rats and Zucker age-matched lean controls were fed a low-fluoride diet ( < 1.2 parts/10(6) F-) ad libitum and received 0, 5, 15 or 50 parts/10(6) fluoride in their drinking water for 3 or 6 months. Fluoride metabolic balance was determined for 4 days before the end of each study phase. Plasma and urine were analysed for biochemical markers of tissue function, and plasma, urine, faeces and tissues were analysed for fluoride. Bone marrow cells from animals killed after 6 months of treatment were examined for frequency of sister chromatid exchange, a marker of genetic damage. The diabetic rats consumed, excreted and retained significantly greater amounts of fluoride than the controls (p < 0.05). There were dose-related increases in fluoride excretion, retention and tissue concentrations in both classes of animals, which were significantly greater in the diabetic rats. In spite of greater amounts of fluoride in the tissues of diabetic animals, there was no evidence, under these experimental conditions, that any of the fluoride exposures tested caused measurable adverse effects on the physiological, biochemical or genetic variables that were monitored.
Involvement of the 5-HT1A subtype receptor in the neonatal organization of agonistic behaviour in the rat.
5-hydroxytryptamine (5-HT) interacts with testosterone (T) in the development of a number of neuronal systems controlling sexually dimorphic adult behaviours. In this report, we investigated this interaction on the organization of agonistic behaviour in males, females, androgenized females (250 micrograms/pup of T proprionate on the day of birth), and males castrated on the day of birth. We have shown previously that manipulating 5-HT2 activity over the 2nd week of life modulates adult agonistic behaviour, depending on genetic sex and the presence of T. In this report, we investigated the effects seen in adulthood of a 5-HT1A agonist [8-OH-DPAT, 0.25 mg/kg, intraperitoneally (i.p.)] and antagonist (WAY100135, 0.25 mg/kg, i.p.) given over days 8-16 postpartum. The test for agonistic behaviour was carried out in a neutral territory against a matched conspecific, and introductory, offensive and defensive activities were note. Results show that neonatal administration of the 5-HT1A antagonist WAY100135 increases introductory activity and defense in the presence of neonatal T, independent of genetic sex, because these effects were seen in sham-castrated males and androgenized females. Offence followed a similar pattern, in that it was increased by WAY100135, but only in males. In the case of defence, the effects of the antagonist were reinforced by the action of the agonist (8-OH-DPAT) in both males and females, indicating an inhibitory role of 5-HT1A perinatal activity on defence in the presence of malelike levels of circulating T and a facilitatory role when levels of T are low or negligible. These findings indicate that 5-HT1A activity is involved in the development of agonistic behaviour and the effects are influenced by T. The results also show that the offensive and defensive facets of agonistic activity are controlled differently.
Neonatal organizational effects of the 5-HT2 and 5-HT1A subsystems on adult behavior in the rat.
Males, females, neonatally androgenized females, and neonatally castrated males were treated over the second week of life with 0.25 mg/kg of either the 5-HT2 agonist 1-(2,5-dimethoxy-3-iodophenyl)-2-aminopropane HCl (DOI), the 5-HT2 antagonist ritanserin (Rit), the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), or the 5-HT1A antagonist WAY100135 (WAY). Exploration, anxiety, sociosexual preferences, and sexual behavior were measured in adulthood. Agents acting on 5-HT1A receptors do not appear to affect organization of any of the behavioral systems studied. DOI increased exploratory activity but in females only, which suggests that testosterone antagonizes the stimulatory effect of 5-HT2 activity on exploration. Neonatal ritanserin selectively reduced anxiety in females, and DOI had a similar effect in androgenized females. This indicates that neonatal 5-HT2 activity is anxiogenic in normal females, anxiolytic in androgenized females, and has no effect on anxiety in males. Males and androgenized females both showed a preference for the female teaser that was abolished by the 5-HT2 agonist, DOI. These results point out that 5-HT2 activity selectively suppresses heterosexual preference induced in the presence of neonatal testosterone. DOI also reduced both male sexual behavior in males and female sexual behavior in androgenized females. Thus, the 5-HT2 system antagonizes the action of testosterone in stimulating heterosexual orientation and sexual activity, and this is independent of genetic sex.
Behavioral effects of alpha-MSH and MCH after central administration in the female rat.
The behavioral effects of alpha-MSH, MCH, and alpha-MSH + MCH were investigated in the ventromedial nucleus (VMN) and medial preoptic area (MPOA) (bilateral, 100 ng in 0.5 microliter). Infusion of alpha-MSH into the VMN increased aggressive behavior; in the MPOA it reduced exploration and increased anxiety. In both areas it stimulated sexual behavior. MCH also stimulated sexual behavior in the MPOA and VMN and had an anxiogenic effect in the MPOA. The effect of alpha-MSH on aggression and exploration was antagonized by MCH. When given together, the two peptides were mutually antagonistic on anxiety. This study indicates that MCH has central nervous system effects and may be a partial alpha-MSH agonist.
Influence of lamination on the flexural strength of a dental castable glass ceramic.
This study evaluated the effect of veneering Dicor castable ceramic with Vitadur N and Dicor Plus feldspathic porcelains. A biaxial flexure test was conducted on five groups of specimens (Dicor castable ceramic, Vitadur N dentinal porcelain, Dicor Plus dentinal porcelain, Dicor core veneered with Vitadur N and Dicor core veneered with Dicor Plus castable ceramic). Each group consisted of 10 disks of nearly identical dimensions with a 1.98 +/- 0.04 mm thickness and 15.7 +/- 0.35 mm in diameter. Statistical analysis indicated that there was neither significant difference (p > 0.05) between mean flexural strength of Dicor Plus and Vitadur N ceramic or Vitadur N and Dicor/Vitadur N ceramic specimens. The mean flexural strength of Dicor/Vitadur N specimens was significantly lower than the mean flexural strength of Dicor ceramic specimens. Conversely, there was no significant difference between mean flexural strength of Dicor ceramic and Dicor/Dicor Plus ceramic specimens. Scanning electron microscope (SEM) examinations of Dicor/Dicor Plus ceramic specimens suggested better wetting of Dicor core by Dicor Plus ceramic with lower incidence of porosity at the interface. However, Dicor/Vitadur N ceramic specimens exhibited a higher incidence of porosity at the interface. This indicated that lamination of Dicor castable ceramic material with feldspathic porcelain for esthetics could be attained without sacrificing strength of the original material, provided that appropriate veneering material was selected.
BRCA1 protein products: antibody specificity...
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Filamentous organisms in benign and malignant gastric cytology brushings.
Review of 143 gastric brushing specimens from two centres in patients with a subsequent histological diagnosis on biopsy or gastrectomy specimens revealed filamentous organisms (FOs) in a large number of benign and malignant gastric brushings. The presence of FOs in significant numbers of brushings of benign gastric lesions contradicts the previously reported strong association of FOs with only gastric carcinoma, and questions the importance of finding these organisms in gastric brushing and biopsy material.
The Japanese feral mouse Pit1 and Pit2 homologs lack an acidic residue at position 550 but still function as gibbon ape leukemia virus receptors: implications for virus binding motif.
Murine cells are typically resistant to gibbon ape leukemia virus (GALV). MMMol, a Japanese feral mouse cell line, is an exception in that these cells are susceptible to infection by GALV. We show here that MMMol cells are further distinguished by their unusual receptor properties. MMMol cells infected by GALV are resistant to subsequent infection not only by GALV but also by amphotropic murine leukemia virus. This suggests that GALV can enter MMMol via not only the GALV receptor (MolPit1) but also the amphotropic murine leukemia virus receptor (MolPit2). Therefore, MolPit2 was cloned, sequenced, and compared with the previously reported sequence of MolPit1. Earlier studies have shown that a stretch of nine residues (position 550 to 558) in the fourth extracellular domain of Pit1 is crucial for GALV entry and that an acidic residue at position 550 is indispensable. However, MolPit1 has isoleucine at this position and MolPit2 has glutamine at the corresponding position (position 522), thus breaking this consensus. To determine what effect these specific changes in the fourth extracellular domain of MolPit1 and MolPit2 have on GALV receptor function, chimeric receptors were made by substituting the fourth extracellular domain of either MolPit1 or MolPit2 for the same region of Pit2, a nonfunctional receptor for GALV. These chimeras were then tested in MDTF, a cell line that lacks functional GALV receptors and is resistant to GALV. Results show that MDTF expressing these chimeras became susceptible to GALV, whereas cells expressing wild-type Pit2 remained resistant. Further, the MolPit1 chimera was identical to Pit1 in efficiency, but the MolPit2 chimera proved substantially less efficient.
Substitution of a single amino acid residue is sufficient to allow the human amphotropic murine leukemia virus receptor to also function as a gibbon ape leukemia virus receptor.
We have previously reported the unique properties of a receptor for amphotropic murine leukemia viruses (A-MuLVs) expressed on Chinese hamster E36 cells (C.A. Wilson, K.B. Farrell, and M.V. Eiden, J. Virol. 68:7697-7703, 1994). This receptor, HaPiT2 (formerly designated EAR), in contrast to the human form of the A-MuLV receptor (PiT2), functions as a receptor not only for A-MuLVs but also for gibbon ape leukemia virus (GALV). Comparison of the deduced amino acid sequences of the HaPiT2 and PiT2 proteins suggested that differences in the amino acid composition of the extracellular region(s) of the hamster and human proteins account for their functional differences. We substituted extracellular regions of HaPiT2 for those of PiT2 to map the region of the HaPiT2 protein required for GALV receptor function. Only those PiT2-HaPiT2 chimeric receptors containing the fourth and fifth extracellular regions of HaPiT2 functioned as GALV receptors. We have now determined that the substitution of a single amino acid residue, glutamic acid, for the lysine residue at position 522 in the fourth extracellular region of the PiT2 protein is sufficient to render PiT2 functional as a GALV receptor.
Enhanced production of B lymphocytes after castration.
Castration has long been recognized to stimulate thymic growth and augment cellular immunity. We sought to determine whether castration affects B lymphopoiesis by analyzing the phenotype of bone marrow and spleen cells from animals postcastration. In this report, we show that the bone marrow cells from castrated male mice show a sustained, twofold to threefold increase in numbers of B220+/IgM- cells and of newly formed B220+/IgM+ B cells. Most of the expanded B220+/IgM- cell population consisted of small, HSAhi, CD43- cells characteristic of pre-B cells. The castrated animals also showed increased numbers of splenic B cells, primarily consisting of small IgM+, IgDlo, B220lo, HSAhi cells. Taken together, these results show that castration causes dramatic, long-lived enhancement of B lymphopoiesis in bone marrow and increased numbers of mature B cells in the periphery.
Quantitative mapping of ocular oxygenation using magnetic resonance imaging.
Retinal hypoxia is hypothesized to initiate angiogenesis, a leading cause of blindness in developed countries. Attempts to test this hypothesis suffer from the need to use highly invasive oxygen electrodes. In this communication, noninvasive and quantitative mapping of ocular oxygenation using magnetic resonance imaging is demonstrated for the first time.
The cellulase system of the anaerobic rumen fungus Neocallimastix frontalis: studies on the properties of fractions rich in endo-(1-->4)-beta-D-glucanase activity.
Seven fractions rich in endoglucanase activity were separated from the extracellular cellulase system of the anaerobic rumen fungus Neocallimastix frontalis. The fractions (ES1, ES3, ES2U1, ES2U2, ES2U4, ES2U3C1 and ES2U3C2) were separated from each other and from a fraction that could solubilize crystalline cellulose (the so-called crystalline-cellulose-solubilizing component, CCSC) by the sequential use of differential adsorption on the microcrystalline cellulose Avicel, gel filtration and affinity chromatography on concanavalin-A-Sepharose. The molecular masses of the endoglucanase fractions, when determined by gel filtration, were 64, 30, 61, 113, 17, 38 and 93 kDa respectively. Each enzyme degraded carboxymethylcellulose and was rich in activity to cellulose swollen in phosphoric acid to break the hydrogen bonding: cellobiose, cellotriose and cellotetraose were released in differing proportions. Each fraction showed a characteristic gradient when the capacity of each enzyme to increase the fluidity of a solution of carboxymethylcellulose was plotted against the increase in reducing power of the solution. Although neither endoglucanase fraction, acting in isolation, could degrade crystalline cellulose, three of the fractions (ES1, ES3 and ES2U1) could act synergistically with the CCSC fraction in this regard. Remarkably, the same three fractions also acted in synergism with the cellobiohydrolases (CBH I and CBH II) of the aerobic fungus Penicillium pinophilum in degrading crystalline cellulose, but only when both cellobiohydrolase enzymes were present in the solution along with any one of the three endoglucanases. These observations support the conclusion that the mechanism of action of the cellulase system of N. frontalis in degrading crystalline cellulose may be similar to that operating in the aerobic fungi.
Studies on the capacity of the cellulase of the anaerobic rumen fungus Piromonas communis P to degrade hydrogen bond-ordered cellulose.
The anaerobic rumen fungus Piromonas communis, when cultured on cotton fibre as the carbon source, produces an extracellular cellulase that is capable of solubilizing "crystalline" hydrogen-bond-ordered cellulose, in the form of the cotton fibre, at a rate that is greater than that of any other cellulases reported in the literature hitherto. The cell-free culture fluid is also very rich in xylan-degrading enzymes. The activity towards crystalline cellulose resides in a high-molecular-mass (approximately 700-1000 kDa) component (so-called crystalline-cellulose-solubilizing component, CCSC) that comprises endo (1-->4)-beta-D-glucanase (carboxymethylcellulase), beta-D-glucosidase and another enzyme that appears to be important for the breakdown of hydrogen-bond-ordered cellulose. The CCSC is associated with only a small amount of the endo(1-->4)-beta-D-glucanase (1.9%), beta-D-glucosidase (0.7%) and protein (0.5%) found in the crude cell-free cellulase preparation. The CCSC, unlike the bulk of the endo(1-->4)-beta-D-glucanase and beta-D-glucosidase, is very strongly absorbed on the microcrystalline cellulose, Avicel.
Alpha-(4-O-methyl)-D-glucuronidase activity produced by the rumen anaerobic fungus Piromonas communis: a study of selected properties.
The rumen anaerobic fungus Piromonas communis, unlike the rumen anaerobic fungi Neocallimastix frontalis and Neocallimastix patriciarum, produced extracellular alpha-(4-O-methyl)-D-glucuronidase when grown in cultures containing filter-paper, barley straw, birchwood xylan or birchwood sawdust as carbon source. The highest concentration of enzyme was produced in cultures containing birchwood sawdust. The aldobiouronic acid O-alpha-(4-O-methyl-D-glucopyranosyluronic acid)-(1-->2)-D-xylopyranose (MeGlcAXyl) was the best substrate of those tested: the aldotriouronic acid O-alpha-(4-O-methyl-D-glucopyranosyluronic acid (1-->2)-O-beta-D-xylopyranosyl-(1-->4)-D-xylopyranose (MeGlcAXyl2) and the aldotetraouronic acid O-alpha-(4-O-methyl-D-glucopyranosyluronic acid)-(1-->2)-O-beta-D- xylopyranosyl-(1-->4)-O-beta-D-xylopyranosyl-(1-->4)-D-xylopyranose (MeGlcAXyl3) were also attacked but the rate fell as the degree of polymerisation increased. When the same substituted xylo-oligosaccharides were reduced to the corresponding alditols the enzyme activity disappeared. Similarly, p-nitrophenyl-alpha-D-glucuronide was not a substrate. Remarkably, the relative rates of attack shown by the alpha-(4-O-methyl)-D-glucuronidase on the aldouronic acids and on xylans extracted from birchwood, oat spelts and oat straw differed according to the carbon source used to produce the enzyme. The alpha-(4-O-methyl)-D-glucuronidase had a pH optimum of 5.5 and a temperature optimum of 50 degrees C. On gel filtration the enzyme was shown to be associated with proteins covering the range 100-300 kDa, but a major peak of activity in the column effluent appeared to have a molecular mass of 103 kDa.