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Biomedical subjects

M E Stevens

Publications and source records attributed to M E Stevens.

35 records · Page 2Linked to original sources
PubMed1991

Failure of dietary protein and phosphate restriction to retard the rate of progression of chronic renal failure: a prospective, randomized, controlled trial.

Ninety-five patients (63 male, 32 female), age 45 +/- 2 years (mean +/- SEM) with chronic renal failure of varied aetiology were randomized to receive either a conventional low protein diet (0.6 g/kg/day protein, 800 mg phosphate; n = 33), a low phosphate diet (providing approximately 1000 mg phosphate plus an orally administered phosphate binder, minimum protein intake 0.8 g/kg/day; n = 30) or to control (minimum protein intake 0.8 g/kg/day, no phosphate restriction; n = 32). Patients were reviewed for a minimum of 6 months before randomization and were withdrawn from the study if plasma creatinine exceeded 900 mumol/l, plasma phosphate was greater than 2.0 mmol/l or at the onset of uraemic symptoms. Following randomization patients were studied for an average of 19 +/- 3 months. Mean plasma creatinine rose from 398 +/- 33 to 600 +/- 50 mumol/l. Dietary protein intake was estimated at 0.69 +/- 0.02 g/kg/day in the low protein group, 1.02 +/- 0.05 in the low phosphate and 1.14 +/- 0.05 in the controls, phosphate intake was 815 +/- 43, 1000 +/- 47, and 1315 +/- 57 mg/day, respectively. Urinary urea excretion and protein catabolic rates were significantly reduced (p less than 0.01) only in those on protein restriction, at 213 +/- 9 mmol/24 hours and 0.71 g/kg/day, respectively. Phosphate excretion was significantly lower (p less than 0.05) in both the low protein group (17.9 +/- 0.8 mmol/24 hours) and the low phosphate group (18.6 +/- 1.0 mmol/24 hours) compared to controls. Changes in body weight, muscle mass and serum transferrin, albumin and immunoglobulins were comparable between the groups. Mean blood pressure following randomization was 150/89 +/- 3/1 (low protein), 148/87 +/- 3/1 (low phosphate) and 146/87 +/- 3/1 (controls). Progression of renal failure was analysed by rate of all of creatinine clearance (ml/min/1.73 m2/month), by rate of deterioration derived from reciprocal plasma creatinine against time plots (1/mmol/year) and to assess individual patient's response to treatment by two phase linear regression ('breakpoint') analysis of reciprocal plasma creatinine/time plots. Progression was analysed only in patients seen for at least 3 months following randomization. The rate of fall of creatinine clearance was not significantly different between the groups (ANOVA): 0.56 +/- 0.08 ml/min/1.73 m2/month (low protein, n = 28), 0.44 +/- 0.07 (low phosphate, n = 23) and 0.69 +/- 0.11 (control, n = 27).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

In the absence of a downstream element, the apolipoprotein E gene is expressed at high levels in kidneys of transgenic mice.

Human apolipoprotein (apo) E gene constructs with 30 or 5 kilobases of 5'-flanking and 1.5 kilobases of 3'-flanking regions were used to create transgenic mice. High levels of human apoE mRNA were present in the transgenic kidney, but none was detected in the liver, which is normally the major source of apoE. When a construct with 5 kilobases of 5'- and 23 kilobases of 3'-flanking regions was used, only trace levels of human apoE mRNA were detected in the kidney, whereas high levels were found in the liver. These results indicated that regulatory elements downstream of the human apoE gene interacted with the transcription initiation complex to stimulate gene expression in the liver while suppressing expression in the kidney. In each case, human apoE was secreted into the plasma. The source of human apoE in the transgenic kidney was the epithelial cells lining the proximal tubule and Bowman's capsule.

Animals↗
PubMed1989

Expression of a mouse metallothionein-Escherichia coli beta-galactosidase fusion gene (MT-beta gal) in early mouse embryos.

We have microinjected DNA containing the inducible mouse metallothionein-I (MT-I) promoter, coupled to the structural gene for Escherichia coli beta-galactosidase (lacZ), into the pronuclei of one-cell mouse embryos. A qualitative histochemical assay, with 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside (X-Gal) as a substrate, was used to detect expression of lacZ at several preimplantation stages. We observed staining indicative of exogenous beta-galactosidase activity in 5-17% of DNA-injected embryos assayed at preimplantation stages after 16-24 h treatment with ZnSO4. Thus, lacZ can be used as an indicator gene for promoter function during early mouse embryogenesis, and the incorporation of the MT-I promoter into fusion genes can be a useful means of controlling the expression of exogenous genes in preimplantation mouse embryos.

Animals↗
PubMed1988

DNA methylation in the developing marsupial embryo.

Marsupial development differs from early development of placental mammals in that the blastocyst is unilaminar, so that both embryonic and extraembryonic cells are derived from a single layer of cells (protoderm) which faces the blastocyst cavity. Also, all cells in female marsupial conceptuses so far examined show preferential paternal X-inactivation. To test for a possible correlation between cell position, paternal X-inactivation and DNA hypomethylation, marsupial DNA preparations from three regions, embryo, vascular yolk sac and avascular yolk sac, were digested with methyl-specific restriction endonucleases, separated on agarose gels and end-labelled with 32P-dCTP. The size distribution of the fragments obtained indicated three levels of methylation: high methylation of embryonic DNA, intermediate levels of methylation of vascular yolk sac DNA and hypomethylation of avascular yolk sac DNA. The degree of methylation of repeat sequences, observed as discrete bands in end-labelled HpaII digests, was correlated with the overall methylation of tissue DNA. Thus, the difference in methylation in embryonic and extraembryonic DNA was similar to that described for the mouse conceptus, and the outside cell position of marsupial fetal precursor cells did not correlate with hypomethylation. HpaII tiny fragments, which indicate the presence of CpG-rich islands of DNA, were evident in the marsupial digests. In the mouse DNA, these islands are associated with gene transcription and provide one route to cloning of unique gene sequences.

Animals↗
PubMed1986

Disruption of positional fields in apterous imaginal discs of Drosophila.

Certain combinations of alleles at the apterous locus generate wings with extra copies of wing margin structures, some of which are located far from the normal margin. We have examined wing imaginal discs from these mutants, using position-specific antibodies as probes for two-dimensional patterning in the discs. Our results indicate that the adult phenotypes arise from unprecedented disruptions in the two-dimensional pattern of the disc epithelia. Examination of other apterous mutants suggest that pattern alterations may be a general consequence of lesions at this locus.

Animals↗
PubMed1986

Temperature-dependent expression of the apterous phenotype in Drosophila melanogaster.

Mutations at the apterous (ap) locus in Drosophila melanogaster produce a variety of developmental defects, including several classes of wing abnormalities. We describe the wing phenotype produced by homozygotes and hemizygotes of three different temperature-sensitive apterous alleles grown at 16, 18, 20, 22, 25, and 29 degrees. We also describe the phenotype produced by each of these three alleles when heteroallelic with the non-temperature-sensitive apc allele. Constant-temperature and temperature-shift experiments show that each of the heteroallelic genotypes can produce several of the previously described apterous phenotypes and that the length of the temperature-sensitive period for a given phenotype depends on the allelic combinations used to measure it. We suggest that the stage-specific requirements of the tissue for gene product, rather than the time of gene expression per se, determine the temperature-sensitive periods for apterous and other loci. The results support the hypothesis that the various wing phenotypes produced by apterous mutations are due to quantitative reductions in the activity of gene product and that failure to meet specific threshold requirements for gene product can lead to qualitatively different phenotypes.

Alleles↗
PubMed1985

Apparent genetic complexity generated by developmental thresholds: the apterous locus in Drosophila melanogaster.

Mutations at the apterous (ap) locus in Drosophila melanogaster give rise to three distinct phenotypes: aberrant wings, female sterility and precocious adult death. The wing phenotype includes five types of abnormality: blistering, deficiencies, duplications, high-order repetitions and transformation of structures. The mildest phenotype is seen with homozygous apblt animals which have either normal or slightly blistered wings. Most alleles produce, in the homozygote, a deficient wing in which part or all of the wing margin and wing blade is missing, but wing hinge and notum regions are normal. Animals hemizygous for each of 20 ap alleles, as well as apID/apXa heterozygotes, show duplication of parts of the notum associated with complete wing deficiency. Animals heterozygous for apc and the other tested ap alleles show repetitions of parts of the anterior wing margin, an engrailed-like transformation of posterior wing margin into anterior margin or both. Both apblt and apc show similar phenotypes in homozygotes and hemizygotes, yet both produce a less extreme phenotype than that of the other hemizygotes, suggesting that neither mutation causes loss of the entire ap+ function. The 15 alleles that cause precocious death and female sterility occur in six complementation groups based on complementation for these phenotypes. This supports the previous conclusion that the effects of apterous mutations on the wing do not correlate with their effects on viability and fertility. We propose an explanation for the effects of apterous mutations on the wing in which quantitative reductions in the activity of gene product give rise to qualitatively different phenotypes because of different threshold requirements of the ap+ function for critical events in wing disc development.

Alleles↗
PubMed1985

Follow-up prednisolone dosage in rapidly progressive crescentic glomerulonephritis successfully treated with pulse methylprednisolone or plasma exchange.

Of nineteen patients with RPCGN who responded promptly to initial treatment with PMP or PX, and who were subsequently maintained on oral immunosuppression with prednisolone (reducing dosage from 30mg/day) and azathioprine/cyclophosphamide (1-3 mg/kg/day), five showed progressive loss of renal function within one year of responding to treatment. Both the daily dose at four weeks and the cumulative dose of prednisolone at six months were significantly lower (p less than 0.01) in the group whose renal function deteriorated. We suggest that the follow-up dosage of prednisolone may be critical in maintaining continued stable renal function in the first few months after starting PMP or PX.

Adolescent↗
PubMed1983

Aggressive treatment with pulse methylprednisolone or plasma exchange is justified in rapidly progressive glomerulonephritis.

Rapidly progressive crescentic glomerulonephritis (RPGN) carries a poor prognosis, but early immunosuppression may reverse renal impairment. We have given intensive therapy to 27 patients with biopsy proven RPGN from 1977-1981. Fourteen patients received pulse methylprednisolone (PMP) and 13 patients plasma exchange (Px). These patients fared significantly better than 17 patients seen from 1972-1979 who had neither PMP nor Px. Both groups received oral prednisolone and other immunosuppressive agents. PMP and Px were equally effective in prolonging survival without dialysis and had no serious side effects; prognostic factors affecting the outcome of treatment were identified. Early aggressive immunosuppressive therapy is indicated in RPGN.

Adolescent↗
PubMed1967

The effect of the aflatoxins B1, G1, and G2 on protein and nucleic acid synthesis in rat liver.

A comparison has been made of the difference spectra obtained by causing various aflatoxins (B(1), G(1) and G(2)) to interact with calf-thymus DNA. The effect of these toxins on RNA and protein synthesis by rat-liver slices has been measured. The extent of their inhibitory action on the synthetic reactions was proportional to the degree of spectral shift obtained with their interaction with DNA. It is proposed that their toxicity depends on this interaction. It was demonstrated that the RNA polymerase of nucleoli isolated from the livers of aflatoxin B(1)-poisoned rats was inhibited. This finding is in agreement with the proposed mechanism for the hepatotoxic action of aflatoxin.

Aflatoxins↗
PubMedDate not supplied

Differentiation of early subarachnoid hemorrhage from traumatic lumbar puncture.

The problem of early differentiation of "traumatic tap" from subarachnoid hemorrhage (SAH) was studied in the rabbit by determining the changes in percentage of hemolysis and in lactate concentrations in CSF within the first twenty-four hours following induced SAH. The 0.3 to 7% hemolysis which occurred was relatively independent both of the time following SAH and of the number of red blood cells (rbc) in the cerebrospinal fluid (CSF). There was, on the other hand, a significant and time-dependent increase in CSF lactate concentration early after SAH, suggesting the potential clinical value of the detection of increased lactate with a relatively normal lactate/pyruvate ratio in hemorrhagic CSF. Until this can be evaluated in human subjects, however, determination of the rbc counts or total hemoglobin concentrations in serially collected samples of CSF remains the best clinical method.

Animals↗