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Biomedical subjects

I R Brown

Publications and source records attributed to I R Brown.

At least 91 records · Page 5Linked to original sources
PubMed1989

Expression of the gene encoding the beta-subunit of S-100 protein in the developing rat brain analyzed by in situ hybridization.

To investigate patterns of expression of the gene encoding the beta-subunit of S-100 protein during development of the rat brain we have used Northern blotting and in situ hybridization histochemistry. During late prenatal development beta-S-100 mRNA was observed first in the germinal zone lining the 4th ventricle. In the postnatal cerebellum this mRNA accumulated primarily in Bergmann glia and astrocytes of the deep white matter. In the hindbrain, expression of S-100 mRNA increased steadily in specific regions during the first postnatal week while levels remained low in more anterior brain regions. By the end of the second postnatal week, a dense punctate signal was distributed throughout the midbrain and hindbrain. Expression in forebrain, first observed at E18, was confined to cells lining the ventricle until the second postnatal week when accumulation of mRNA was observed in specific regions of the hippocampus, neocortex and olfactory bulb. The adult brain pattern of beta-S-100 mRNA distribution is attained during the third postnatal week. These results demonstrate a caudal-rostral gradient in expression of the beta-S-100 gene during rat brain development, as well as pronounced regional differences which may reflect the differentiation of subpopulations of astrocytes.

Aging↗
PubMed1989

Induction of a heat shock gene at the site of tissue injury in the rat brain.

Our objective was to investigate whether localized tissue injury induces expression of a gene encoding the major 70 kd heat shock protein (hsp70) in the mammalian nervous system. A small surgical cut was made in the rat cerebral cortex. By 2 hr postsurgery a dramatic and highly localized induction of hsp70 mRNA was detected at the lesion site using in situ hybridization with labeled riboprobe. By 12 hr the intensity of the signal had diminished, and by 24 hr only a few cells along the walls of the cut demonstrated a high level of hsp70 mRNA. Both neurons and glial cells at the site of the surgical cut responded to tissue injury by induction of hsp70 mRNA. Induction was not observed in other brain regions, nor was the pattern of constitutive expression affected by the surgical procedure.

Animals↗
PubMed1989

Metformin efficacy and tolerance in obese non-insulin dependent diabetics: a comparison of two dosage schedules.

A comparative open study of metformin unit doses of 500 mg and 850 mg was carried out in 64 obese, non-insulin dependent diabetics on 1.5 to 3 g metformin daily. Glycaemic response, blood lactate, plasma metformin concentrations and tolerance for metformin were assessed. On changing from a 500 mg unit dose to an equivalent total dose of metformin using the 850 mg preparation, there were no significant changes in the random blood glucose, glycated haemoglobin, or blood lactate concentrations. Metformin plasma concentrations remained unchanged except for patients transferred from 1.5 to 2.0 g daily to 850 mg twice daily; in these patients plasma concentrations increased from 1.83 +/- 0.87 to 2.50 +/- 0.89 micrograms/l (p less than 0.01). Seven patients (3 asymptomatic and 4 with background symptoms) became intolerant of the 850 mg regimen and required to return to the 500 mg dose regimen. After exclusion of patients intolerant of the 850 mg dose regimen (11%), the remaining patients noted no significant change in symptoms and 28% of all patients transferred to the 850 mg dose unit indicated an overall preference for this regimen.

Adult↗
PubMed1988

Effects of improved glycaemic control on calcium and magnesium homeostasis in type II diabetes.

Poorly controlled type II diabetic patients with hypomagnesaemia, hypermagnesuria, and hypercalciuria were allocated to treatment with either metformin or glipizide, to determine the effects on some indices of mineral metabolism. Despite comparable improvement in glycaemic control, assessed by glucose and haemoglobin A1, there were significant differences between the two groups in the handling of magnesium. Patients receiving metformin showed a reduction in magnesium excretion but remained hypomagnesaemic and hypercalciuric. In contrast, patients receiving glipizide exhibited little change in either magnesium or calcium excretion but showed a significant rise in serum magnesium.

Adult↗
PubMed1987

Atypical nucleosome spacing of rat neuronal identifier elements in non-neuronal chromatin.

Rat neuronal identifier (ID) elements are located in chromatin regions that are organized in nucleosomal structures in both neuronal and non-neuronal cells. A subpopulation of ID sequences in chromatin of liver and kidney cells are relatively resistant to micrococcal nuclease digestion and are organized in nucleosomes exhibiting an atypically short repeat length. Other repetitive elements do not show this organization.

Animals↗
PubMed1987

Rat and mouse identifier sequences are preferentially but not exclusively located in cortical neuronal genes expressed postnatally.

A genetic element called the identifier (ID) sequence, highly repeated in the rat genome, has previously been reported to be located in the introns of some genes transcribed in the adult rat brain by RNA polymerase II (Pol II). We show that nuclear RNA isolated from neurons of cerebral hemispheres (cortex) of 14-day old rats is enriched more than 10-fold in ID sequences compared to nuclear RNA from liver, kidney, cerebellum, or cortical glia. The developmental onset of the difference is during the first 2 weeks after birth. Mouse cortical neuronal nuclear RNA is similarly enriched in an element related but not identical to the rat ID element, and the enrichment also has postnatal onset. The enriched appearance of ID sequences in transcripts whose expression is increased postnatally in cortical neurons correlates developmentally and spatially with the transcription of ID elements by RNA polymerase III (Pol III) and with a change in chromatin structure.

Animals↗
PubMed1987

Altered expression of a heat shock protein in the mammalian nervous system in the presence of agents which affect microtubule stability.

In vitro incubation of the isolated rabbit retina at elevated temperature results in the synthesis of a heat shock protein of M.W. 74,000 (hsp74). Recently we have demonstrated that this protein is associated with preparations of purified retinal microtubules and intermediate filaments. In order to examine the possibility that hsp74 synthesis is related to cytoskeletal stability, the effects of agents known to specifically affect microtubules were examined using an in vitro retinal system. Taxol, an antimitotic agent which stabilizes microtubules, was found to reduce the level of hsp74 synthesized in response to elevated temperature. Colchicine, a potent microtubule de-stabilizing agent, did not induce hsp74 synthesis in the absence of elevated temperature, however, under heat shock conditions, hsp74 synthesis was elevated in the presence of colchicine. Kinetics of microtubule assembly were similar in preparations isolated from cerebral hemispheres of control and hyperthermic animals however, microtubules from the latter were altered in appearance and exhibited a higher degree of crosslinking.

Alkaloids↗
PubMed1987

Effects on in vitro brain protein synthesis of a translational inhibitor isolated from rabbit brain following intravenous administration of LSD.

Inhibition of brain protein synthesis following intravenous administration of d-lysergic acid diethylamide (LSD) is accompanied by generation of a translational inhibitor protein in the postribosomal supernatant of cerebral hemispheres. Addition of an enriched preparation of this factor to a brain cell-free translation system resulted in a selective reduction in the level of phosphorylation of proteins of molecular weight 55K, 41K, and 25K. A similar set of changes was also observed in a brain cell-free system prepared 1 hr subsequent to drug injection. The brain inhibitor reduced the translational capacity of a messenger RNA-dependent reticulocyte lysate programmed with brain polysomes isolated from saline-injected animals however little effect was apparent when polysomes were prepared from LSD-treated animals. The translational inhibitor did not affect the spectrum of translation products from either set of polysomes.

Animals↗
PubMed1987

Selective induction of a heat shock gene in fibre tracts and cerebellar neurons of the rabbit brain detected by in situ hybridization.

In situ hybridization reveals striking regional differences in the expression of constitutive and inducible heat shock genes in the rabbit brain. Fibre tracts throughout the brain show a dramatic induction of heat shock mRNA after hyperthermia, a pattern consistent with a strong glial response to heat shock. While neurons in the cerebellum exhibit a marked induction of heat shock mRNA, neurons of the hippocampus do not. Constitutive expression of a heat shock gene is observed in neuronal laminae of the hippocampus and cerebellum.

Animals↗
PubMed1986

A retinal heat shock protein is associated with elements of the cytoskeleton and binds to calmodulin.

Elevation of body temperature to a level similar to that attained during fever induces a disaggregation of polysomes in the mammalian retina and induction of a 74K heat shock protein (hsp74). Induced retinal hsp74 copurifies with twice cycled microtubules and also with purified intermediate filaments, is precipitated by antibodies prepared against purified Tau proteins and binds to calmodulin.

Animals↗
PubMed1986

Induction of a heat shock protein in the isolated mammalian retina.

The effects of elevated ambient temperature and addition of the psychotropic drug LSD on protein synthesis in the isolated rabbit retina were investigated. Two dimensional gel electrophoresis followed by fluorography of proteins synthesized in vitro demonstrated that synthesis of a heat shock protein of molecular weight 74,000 (74K) was induced by the elevation of temperature and not by the addition of LSD. The appearance of this heat shock protein was shown to be dependent upon the synthesis of new RNA as shown by the addition of actinomycin-D to the incubation medium. The newly synthesized heat shock protein was associated with both nuclear and cytoplasmic fractions.

Animals↗
PubMed1986

Pharmacokinetics of oral ciprofloxacin, 100 mg single dose, in volunteers and elderly patients.

The pharmacokinetics of ciprofloxacin following a single 100 mg oral dose were evaluated in elderly patients (mean age 74 years), laboratory staff (30-40 years) and students (less than 20 years). There were no significant differences in serum Tmax (1.2-1.3 h) or in overall serum elimination half-life (3.7-4.0 h) but Cmax in elderly patients was more than double that in young volunteers (P less than 0.005). The serum AUC value was greater both in fasting students (1.4 mg/h/l) compared with the same subjects after food (1.09: P less than 0.01) and, after food, in elderly patients (1.95) compared with students (0.81: P less than 0.005). Urinary recoveries were greater in fasting subjects and in all categories of volunteers compared with elderly patients. However, in the elderly, urinary ciprofloxacin concentrations (0-6 h mean 66 mg/l: range 17.4-200 mg/l) were more than adequate for the eradication of urinary pathogens.

Administration, Oral↗
PubMed1986

Characterization of a translational inhibitor isolated from rabbit brain following intravenous administration of d-lysergic acid diethylamide.

Intravenous administration of d-lysergic acid diethylamide (LSD) to rabbits results in a transient inhibition of brain protein synthesis in vivo and in vitro. A translational inhibitor that appears in the postribosomal supernatant fraction of cerebral hemispheres following LSD administration was partially purified by gel filtration on Sephadex G-150 and precipitation with 60% ammonium sulfate. This inhibitor, which was proteinaceous, reduced the translational capacity of an initiating cell-free protein synthesis system derived from brain. It also inhibited a messenger RNA-dependent reticulocyte lysate programmed with brain polysomes and a globin-synthesizing reticulocyte lysate system. Addition of the partially purified inhibitor to a brain cell-free protein synthesis system resulted in the decreased formation of ternary complexes as well as 40 and 80S initiation complexes, suggesting that the inhibitor affects an early step in the initiation of protein synthesis in brain.

Animals↗
PubMed1986

Investigation of vitamin A nutrition in pregnant British Asians and their infants.

Plasma retinol and retinol-binding protein (RBP) concentrations were lower in 23 South London Asian women of Indo-Pakistani origin than in 21 non-Asian controls during pregnancy (P less than 0.01 and P less than 0.05 respectively). Cord blood concentrations of retinol and RBP were the same in Asians and non-Asians. Plasma retinol concentration decreased with increasing gestation (P less than 0.01), but RBP concentration did not alter. Retinyl palmitate, 8000 i.u. daily from 30 weeks gestation to term, was given to a group of 14 Asian mothers with low plasma retinol concentrations. This caused a significant increase in maternal plasma retinol concentration at delivery compared with 15 controls, indicating possible deficiency, but did not affect cord blood concentrations. There was no difference in anthropometric measurements of the infants of control or supplemented mothers, nor was there a correlation between the anthropometric measurements and the plasma retinol or RBP concentrations.

Adult↗
PubMed1985

Expression of heat shock genes in fetal and maternal rabbit brain.

Cloned fragments of members of the Drosophila and mouse major heat shock (hsp70) gene family were used to demonstrate that homologous sequences are present in the rabbit genome. After a physiologically relevant increase in body temperature of 3 degrees C, transcription of inducible hsp70 genes is detected in both the fetal and maternal brain and kidney. The induced hsp70 gene transcripts decay rapidly after whole body hyperthermia subsides. Transcripts of constitutively expressed member(s) of the hsp70 gene family, the heat shock cognate genes (hsc70), are detected in unstressed fetal and maternal rabbit tissues.

Animals↗
PubMed1985

Axonal transport of a heat shock protein in the rabbit visual system.

Intraocular injection of [35S]methionine was used to demonstrate the pronounced induction of a 74-kDa heat shock protein in the rabbit retina after a 3 degrees C increase in body temperature was generated by intravenous administration of D-lysergic acid diethylamide. Two-dimensional polyacrylamide gel electrophoresis and fluorography revealed that the induced heat shock protein underwent axonal transport from retinal ganglion cells into the optic nerve and subsequently down the contralateral optic tract to synaptic termini in the visual projection area. Since the heat shock protein took more than 8 days to move down the optic nerve to the superior colliculus, it is transported by slow rather than by fast axonal transport.

Animals↗