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Biomedical subjects

P C May

Publications and source records attributed to P C May.

At least 19 recordsLinked to original sources
PubMed1992

Sulfated glycoprotein 2: new relationships of this multifunctional protein to neurodegeneration.

Sulfated glycoprotein 2 (SGP-2) from rat, and similar molecules from cow, dog, human, pig, ram and quail are known by 11 or more acronyms. SGP-2 is associated with the responses of brain and other tissues to injury; it and related molecules are also normally secreted by the adrenal gland, the liver and the testes. The mRNA of this protein is found in increased levels in Alzheimer's disease. In rats, after perforant path or excitotoxin lesions, levels of the protein or mRNA are elevated in astrocytes, and also in neurons. In rats, brain SGP-2 is regulated by gonadal and adrenal steroids. However, these increases after brain lesions may relate to a function that is associated with the human protein, namely that of inhibiting complement-mediated cell lysis. Other activities suggested for SGP-2 are lipid transport and cell-cell interactions, which are consistent with sequence data that predict binding of dinucleotides, heparin and lipids. The emerging neurobiology of SGP-2 encompasses the subjects of cell death, synaptic remodelling, neuroendocrinology and neurodegenerative diseases.

Animals↗
PubMed1992

Sulfated glycoprotein-2 expression increases in rodent brain after transient global ischemia.

Sulfated glycoprotein-2 (SGP-2) is emerging as a prominent marker of neurodegeneration in mammalian brain. Regulation of brain SGP-2 was studied in adult male Wistar rats subjected to 30 min of forebrain ischemia by four vessel occlusion. By 3 days after the ischemic insult, SGP-2 RNA levels were increased two fold in caudate nucleus and hippocampus. SGP-2 protein levels assessed by immunoblots were markedly increased in both brain regions following ischemia. GFAP RNA levels also increased over 5 fold in caudate nucleus and hippocampus following the ischemic insult. Despite significant elevations in GFAP RNA, protein levels of GFAP assessed by immunoblot were only marginally affected. The elevated expression of SGP-2 in rodent brain following this and other experimental lesion paradigms (e.g., excitotoxic lesions, deafferentation) suggest some general involvement of SGP-2 in neurodegeneration and remodelling following neuronal injury.

Animals↗
PubMed1992

Dopa accumulates in the hypothalamic-hypophysial portal vessels and is taken into the anterior pituitary of NSD-1015-treated rodents.

DOPA was measured in the anterior pituitary and hypothalamic-hypophysial portal blood after treatment with NSD-1015, a DOPA decarboxylase inhibitor. NSD-1015 caused DOPA to accumulate in the anterior pituitary of mice and rats, and increased DOPA in the hypothalamic-hypophysial portal blood of rat. Serum prolactin was also increased. Interruption of the anterior pituitary blood supply from the hypothalamic-hypophysial system by cannulation of the entire pituitary stalk eliminated the NSD-1015-induced DOPA accumulation in the rat pituitary. We conclude that DOPA can be taken into the anterior pituitary from the portal blood of NSD-1015-treated rodents and that the anterior pituitary lacks tyrosine hydroxylase activity in both mice and rats.

Animals↗
PubMed1991

Sulfated glycoprotein-2 is increased in rat hippocampus following entorhinal cortex lesioning.

Thios study showed responses of sulfated glycoprotein-2 (SGP-2) in the rat hippocampus after deafferenting lesion. SGP-2 is a plasma protein that also occurs in many peripheral tissues. In some circumstances, elevations of SGP-2 mRNA are associated with cell degeneration and responses to injury. This study used entorhinal cortex lesions (ECL) to partially deafferent the hippocampus by damaging the perforant path and to induce synaptic remodeling. SGP-2 mRNA is increased in hippocampal astrocytes after ECL. Western blot analysis of soluble hippocampal proteins identified 3 major forms of rat SGP-2 protein: a precursor (61 kDa) and 2 reduced subunits at 39.5 and 35 kDa. These forms increased at 4 days post ECL ipsilaterally to the lesion. By immunocytochemistry (ICC), SGP-2 showed an increased immunoreactivity on the lesioned side by 2 days post ECL that continued through 14 days post ECL. Besides immunopositive astrocytes, punctate immunochemical reaction products occurred among the degenerating fibers of the perforant path. We conclude that changes of SGP-2 protein in the hippocampus after ECL occur roughly in parallel with increases of SGP-2 mRNA. The punctate immuno-deposits could represent secreted SGP-2 and may be useful as a marker for degenerating pathways.

Animals↗
PubMed1991

Cloning of hippocampal poly(A) RNA sequences that increase after entorhinal cortex lesion in adult rat.

Evidence is given for altered gene expression in the hippocampus in response to entorhinal cortex lesioning. Three RNA markers encoding glial fibrillary acidic protein, apolipoprotein E and alpha-tubulin were isolated from a rat hippocampal cDNA library by differential screening with cDNA probes from entorhinal cortex lesioned and control rat hippocampus RNA. By Northern blot analysis, mRNA for apolipoprotein E and alpha-tubulin increased to peak around 6 days after the lesion and returned to near control level at 30 days. The increased synthesis of both mRNAs coincides with the acute phase of synaptogenesis, protein synthesis, and polyribosomes accumulation in the deafferented hippocampal area.

Animals↗
PubMed1991

Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning.

Entorhinal cortex lesions (ECL) that damage the perforant path to the hippocampus induce rapid increases of apolipoprotein E (apo E) mRNA in the hippocampus. Apo E mRNA was localized in astrocytes by in situ hybridization in combination with immunocytochemistry for glial fibrillary acidic protein (GFAP). Unilateral ECL also increased hippocampal GFAP mRNA, with increases preceding those of apo E mRNA. The apo E mRNA and GFAP mRNA responses were transiently bilateral in non-denervated zones. The timing of response in apo E mRNA to deafferentation supports suggestions that apo E has roles in membrane remodelling during responses to neuron injury.

Animals↗
PubMed1990

Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer's disease and in response to experimental lesions in rat.

A hippocampal poly(A) RNA, pADHC-9, was cloned by differential screening of a human hippocampal cDNA library. By RNA blot analysis, pADHC-9 was elevated 2-fold in Alzheimer's disease hippocampus. In situ analyses identified pADHC-9 expression in pyramidal and non-pyramidal cells of the hippocampus and entorhinal cortex. Nucleotide sequence analysis identified pADHC-9 as a potential human homolog of rat sulfated glycoprotein 2 (SGP-2). SGP-2 expression increased in rat hippocampus following experimental lesions that mimic intrinsic neuronal loss and/or deafferentation. The function of pADHC-9 in brain has not been defined, but in serum, a similar protein inhibits complement-dependent cytolysis. Increased expression of pADHC-9 in Alzheimer's disease hippocampus may be a compensatory response mounted to retard a complement-driven neurodegenerative cascade.

Alzheimer Disease↗
PubMed1990

Selective alterations of RNA in rat hippocampus after entorhinal cortex lesioning.

In vitro translation products from RNA of rat hippocampus after deafferentation by entorhinal cortex lesions were analyzed by two-dimensional gel electrophoresis. Although hippocampal total RNA yield was not affected 14 days after the lesion, analysis of the gels showed reproducible changes in the steady-state level of several transcripts. Glial fibrillary acidic protein RNA increased 2-fold over control hippocampi RNA. Moreover, seven other transcripts of unknown identity had increased prevalence in the denervated hippocampus. The changes, which ranged from 2- to 20-fold, involved mRNA encoding small slightly acidic polypeptides: 12 kDa (pI 5.6), 13 kDa (pI 6.1), 20 kDa (pI 5.8), 31 kDa (pI 5.7), 33 kDa (pI 5.7), 35 kDa (pI 5.6), and 53 kDa (pI 5.4). These results suggest new molecular markers for analyzing the complex mechanisms of synaptic reorganization in the dentate gyrus after deafferentation.

Actins↗
PubMed1990

The Bath bike for walking rehabilitation.

We describe a new rehabilitation aid for walking and its role in traumatology, discussing its advantages over current aids. Wider applications are suggested in the fields of neurology, rheumatology and spinal injury.

Early Ambulation↗
PubMed1989

The Bath bridge angle-guide.

A device is described which facilitates the accurate location of a guide-pin for the placement of the sliding lag screw when treating fractures of the subtrochanteric zone of the femur with any of the modern sliding hip screw plates.

Equipment Design↗
PubMed1989

Altered gene expression in Alzheimer's disease brain tissue.

We review the evidence for altered gene expression in Alzheimer's disease brain and identify alternative molecular approaches for isolating additional novel markers. One marker, pADHC-9, was isolated from a human hippocampal cDNA library by differential screening with AD and control cDNA probes. This clone hybridizes to a 2 Kb RNA which is increased 2 fold in AD hippocampus. The deduced amino acid sequence of pADHC-9 codes for a 52 kDAL protein similar to a testicular sulfated glycoprotein secreted by rat Sertoli cells. The normal function of this protein in brain and whether that function is altered in Alzheimer's disease is unknown.

Alzheimer Disease↗
PubMed1989

Oral administration of estradiol to young C57BL/6J mice induces age-like neuroendocrine dysfunctions in the regulation of estrous cycles.

Exogenous estradiol (E2) can accelerate the onset of acyclicity and other age-related neuroendocrine changes in rodents. The present study demonstrates that chronic oral administration of E2 (850 micrograms/kg body wt/day) induces premature acyclicity in intact C57BL/6J mice. After 6 wk of E2, mice regained cyclicity but ceased cycling prematurely, whereas 12 wk of E2 caused permanent acyclicity in all mice. The acyclicity after 12 wk of E2 was not reversed by ovarian replacement from young donors, which implies extra-ovarian (neuroendocrine) lesions. The above studies with intact mice can not identify the contributions from exogenous E2 and endogenous ovarian sections and the possible impact of oral E2 on the ovary. Therefore, mice were ovariectomized (OVX) to remove ovarian contributions, treated for 12 wk with oral E2, and then were given young ovarian grafts and assayed for neuroendocrine functions. Approximately 50% of the E2-treated and grafted mice were permanently acyclic, whereas controls cycled well. Thus, oral E2 causes irreversible neuroendocrine damage. However, the presence of the ovary during E2 treatment increases the loss of cyclicity, implying a dose effect. We conclude that the induction of acyclicity is dependent on the dose and duration of E2 exposure.

Administration, Oral↗
PubMed1989

Corticosterone-induced responses in rat brain RNA are also evoked in hippocampus by acute vibratory stress.

Corticosterone (CORT) induces responses in brain cells that are mediated by glucocorticoid receptors through regulation of gene activity. We previously found rapid increases in select poly(A)-containing RNAs in rat hippocampus following treatment with CORT that are mediated by low-affinity glucocorticoid receptors. To determine if these responses are hippocampal specific, we examined RNA responses to glucocorticoids in several brain regions, myocardium, and cultured astrocytes by two-dimensional gel electrophoretic resolution of 35S-methionine labelled, in vitro translation products. RNAs coding for similar 35-, 33-, and 20-kdalton polypeptides are induced after 3 days of CORT treatment (40 mg/kg/day) in hippocampus, hypothalamus, cortex, striatum, cerebellum, and myocardium. Primary astrocyte cultures (neonatal rat), however, showed increases after hydrocortisone (1 microgram/ml) in only the 20- and 33-kdalton translation products, while the 35-kdalton polypeptide was not detected. The hippocampal responses were maintained for up to 3 months during chronic daily CORT treatment. To determine if an increase in endogenous CORT levels would also evoke the RNA responses, we subjected rats to 2 h vibratory stress and analyzed the in vitro translation products. RNAs coding for the 35- and 20-kdalton polypeptides were increased 3- to 5-fold in the hippocampus after acute stress in intact rats, but not in stressed adrenalectomized rats. These results suggest a new class of molecular stress responses in brain cells that is glucocorticoid dependent under physiological conditions.

Animals↗
PubMed1989

N-methyl-aspartic acid lesions of the arcuate nucleus in adult C57BL/6J mice: a new model for age-related lengthening of the estrous cycle.

We report a new effect of the excitotoxin N-methyl-aspartic acid (NMA) on adult mice. Besides confirming cell loss in the arcuate nucleus of animals treated as adults, we also observed lengthened estrous cycles. Cycling female C57BL/6J mice were treated with subcutaneous injections of NMA and estrous cycles monitored for 30 days. NMA treatment lengthened average estrous cycle length by 1 day, to 5.6 days. The elongated cycles were due to an increase in the frequency of 5- and 6-day cycles at the expense of 4-day cycles. This effect was observed in mice aged 4 and 7 months; however, 10-month-old mice had irregular cycles and a higher mortality rate following NMA, which precluded cycle analysis. NMA caused a region-specific 30-45% cell loss in the rostral portions of the arcuate nucleus; no cell loss was detected in the adjacent ventromedial nucleus. Possible neuronal substates for NMA lesions, as analyzed by in vitro receptor autoradiography for glutamate receptor subtypes, include a high density of kainate receptors in the arcuate nucleus; there was little specific binding of ligands to NMDA and quisqualate receptors. Consistent with the regional pattern of cell loss, little specific binding of any glutamatergic ligand was observed in the VMN. NMA caused weight gain in all age groups. Serum LH and PRL were unaffected by NMA. The transition from 4-day to 5- and 6-day estrous cycles produced by NMA treatment mimics the early age-related changes in estrous cycle patterns in rodents. This new model will be useful in analyzing the contributions of neuroendocrine changes in the arcuate nucleus to reproductive senescence.

Aging↗