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Biomedical subjects

N Savage

Publications and source records attributed to N Savage.

At least 55 records · Page 3Linked to original sources
PubMed1988

Ethnic variation in estrogen and progesterone receptor concentration in leiomyoma and normal myometrium.

The total content of 17-beta estradiol and progesterone receptors in human uterine leiomyoma and normal myometrium in a Caucasian population was determined. Estrogen receptor concentrations in leiomyoma and myometrium were not significantly different (p = 0.1401). The concentration of progesterone receptors in leiomyoma was higher than in myometrium (p = 0.0303). Negroid and Caucasian ethnic groups did not differ with respect to estrogen (p = 0.7040) or progesterone (p = 0.8494) receptor concentrations in leiomyoma, but estrogen (p less than 0.005) and progesterone (p less than 0.005) receptor concentrations in normal myometrium were significantly higher in Caucasian than in negroid patients. Leiomyoma in negroid and Caucasian patients appears to be histologically similar, but the biochemical pathway of its pathogenesis seems to differ. Genetic predisposition probably acts as an initiation factor in the myometrium of both ethnic groups, then estrogen receptor levels in negroids and alterations in steroid metabolism in Caucasians promote the growth of leiomyoma.

Adult↗
PubMed1987

Oestrogen and progesterone receptor concentrations in leiomyoma and normal myometrium.

The content of cytoplasmic 17 beta oestradiol and progesterone receptors in human uterine leiomyoma and normal myometrium in the Negroid population was determined. Eighteen women of reproductive age, at various stages of the menstrual cycle, were included in the study. The serum oestrogen and progesterone concentrations were also measured. This is the first report in the literature in which oestrogen and progesterone receptors in leiomyoma are significantly higher than in normal myometrium (P = 0.0002). The steroid dependence of the growth of leiomyomas may be related to the steroid receptor level. The presence of persistently high concentrations of oestrogen and progesterone receptors in leiomyoma should be helpful in the treatment of this benign tumour.

Adult↗
PubMed1987

Characterization of soluble cyclic AMP phosphodiesterases and partial purification of a major form in human leiomyoma of the uterus.

Human leiomyoma of the uterus contained seven forms of cyclic AMP phosphodiesterase in the crude cytosol as revealed by a specific activity stain on non-denaturing polyacrylamide gel electrophoresis. The enzymes from human myometrium and normal uterus showed an identical activity pattern. Ferguson plot analysis showed four different molecular weight species of Mr 229,000 +/- 4,000, 186,000 +/- 4,000, 174,000 +/- 4,000 and 162,000 +/- 4,000. The Mr 174,000 species comprised four differently charged forms. Sucrose density gradient centrifugation of the crude cytosol revealed the presence of three molecular weight species sedimenting at 11.8S, 8.1S and 3.6S. The Michaelis constant (Km) for the band 1 form which displayed linear kinetics was 5 microM and the band 2 form which produced non-linear kinetics had Km values of 5.8 and 37 microM.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Molybdate and the molecular properties of the vervet monkey estrogen receptor.

The Vervet monkey (Cercopithecus aethiops pygerythrus) uterine estrogen receptor was partially characterised. The effect of the molybdate oxyanion on various molecular properties of the receptor was investigated. Molybdate appeared to affect the subunit structure and apparent heterogeneity of the receptor. Anion exchange chromatography of uterine cytosols yielded two ligand binding subunits in a 1:1 ratio in the absence of sodium molybdate, while only a single labelled complex could be demonstrated in cytosols prepared in molybdate containing buffers. Chromatofocussing of the nonstabilized cytosols revealed substantial receptor heterogeneity (7 peaks) while a much simpler pattern (2 peaks) could be observed in the presence of the molybdate. Likewise, iso-electric focussing of labelled cytosols on agarose gels yielded at least 3 high affinity binding components (pI:6.8, 6.2, 5.9) in the absence and only one major band in the presence of sodium molybdate (pI 5.9).

Animals↗
PubMed1986

Acid maltase deficiency: a case study and review of the pathophysiological changes and proposed therapeutic measures.

An adult patient with lysosomal acid alpha-glucosidase deficiency was fully investigated, and then placed on various forms of therapy with favourable response to a high protein, low carbohydrate diet. The rationale for the employment of this therapy, the problem of acid maltase deficiency and the relationship to weakness and glycogenosome formation with accumulation or otherwise of glycogen within the muscle fibres is discussed.

Adult↗
PubMed1985

Characteristics of lipopolysaccharide interaction with human peripheral-blood monocytes.

The interaction between radioiodinated lipopolysaccharide from Escherichia coli 0111:B4 (125I-LPS) and human peripheral-blood monocytes was studied. The association of 125I-LPS with monocytes at 37 degrees C appeared to depend on binding to the cell membrane with subsequent internalization of the molecule, and was not saturable with time (up to 2 h) or 125I-LPS concentration (up to 10 micrograms/ml). There was no apparent difference in the behaviour of unlabelled LPS and 125I-LPS with respect to monocyte association. 125I-LPS association with monocytes was inhibited by LPS and O-polysaccharide from E. coli 0111:B4 and Salmonella typhi 0901, but not by lipid A or polymyxin B. We propose that the mechanism of human monocyte stimulation by LPS involves polysaccharide-dependent binding to the cell membrane followed by internalization of the LPS molecule. We were unable to demonstrate a specific LPS receptor such as that found on murine B-lymphocytes.

Electrophoresis, Polyacrylamide Gel↗
PubMed1985

Dose-dependent reduction of lipopolysaccharide pyrogenicity by polymyxin B.

Lipopolysaccharides (LPS) from Gram-negative bacteria are potent pyrogens in mammals. Polymyxin B (PB), a cationic polypeptide antibiotic, binds lipid A, the active moiety of LPS, with high affinity and abrogates several biological responses to LPS. We studied the effect of PB on pyrogenicity of purified LPS from E. coli 0111:B4 in rabbits. PB reduced the pyrogenic response to LPS in a dose-dependent manner at mass ratios (PB:LPS) from 5:1 to 100:1. Previous reports have suggested that PB is effective only at much higher doses. In our hands, PB itself is pyrogenic, unless previously gamma-irradiated. Our results confirm in vivo the anti-endotoxic action of PB.

Animals↗
PubMed1985

Reversibility of the stabilization effect of sodium molybdate on uterine estrogen and progesterone receptors of the vervet monkey.

Sodium molybdate affected the stability of vervet monkey (Cercopithecus aethiops pygerythrus) uterine estrogen (ER) and progesterone (PR) receptors. Yields of receptors were invariably higher (20-40%) when cytosols were prepared in the presence of 10mM sodium molybdate. No changes were observed in the binding affinities for the natural ligands as reflected in dissociation constants. Receptor-ligand association at 0 degrees C and 20 degrees C was not affected in the presence or absence of molybdate. Stability studies at 37 degrees C indicated both receptors to be more resistant to inactivation in the presence of molybdate. Dissociation of ER and PR was biphasic, indicating the existence of slow (SDC), as well as fast dissociating (FDC) complexes. Rate constants of dissociation were significantly affected by the presence of sodium molybdate. Although no significant changes in the sedimentation coefficients were observed, marked differences in the actual gradient profiles could be illustrated in the presence or absence of sodium molybdate. Observed effects could only be partially reversed in sedimentation dialysis experiments. Proteolytic inhibitors phenylmethylsulfonylfluoride (PMSF) and leupeptin had no inhibitive effect on the molybdate stabilization of ER and PR.

Animals↗
PubMed1983

Respiratory activities of subsarcolemmal and intermyofibrillar mitochondrial populations isolated from denervated and control rat soleus muscles.

Ultraturrax and Nagarse released populations of mitochondria isolated from control and day 21 denervated rat soleus muscle were characterized with respect to their oxidative phosphorylation, ADP translocase and ATPase activities. Both Ultraturrax and Nagarse released mitochondrial populations displayed lower capacities for oxidative phosphorylation; lower ADP translocase activities and higher Mg2+ stimulated ATPase activities than their corresponding controls. For both the denervated and control states, the Nagarse-released mitochondrial populations displayed significantly higher respiratory activities than the Ultraturrax released fractions. The significance of these findings is discussed with regard to the process of mitochondrial respiratory control. In addition the role of mitochondrial dysfunction in denervation muscular atrophy is assessed.

Adenosine Triphosphatases↗
PubMed1981

Ca2+-uptake properties of two populations of mitochondria from normal and denervated rat soleus muscle.

Ultraturrax- and Nagarse-released populations of mitochondria were characterized with respect to their Ca2+-uptake activities (i) by means of the indirect polarographic technique and (ii) directly by the 45Ca Ruthenium Red-quench method of Reed & Bygrave [(1974) Biochem. J. 140, 143-155]. The denervated-muscle subsarcolemmal and intermyofibrillar mitochondrial fractions displayed markedly decreased rates and capacities for Ca2+ uptake compared with their respective controls. The implications of these findings with respect to the process of cell necrosis are discussed.

Animals↗
PubMed1981

Characteristics of sarcoplasmic reticulum from normal and denervated rat skeletal muscle.

Denervation of rat skeletal muscle produces after 14 days a decrease in Ca2+ uptake of a heterogeneous population of sarcoplasmic-reticulum vesicles, when measured in the presence of oxalate. The Mg2+-dependent ATPase (Ca2+-independent) activity increased after the same period and the Ca2+ + Mg2+-dependent ATPase activity decreased. Concomitant with these changes, there was an increase in vesicle size and calcium content. The observations are discussed in terms of changes in altered membrane structure, manifested in the shift of the equilibrium of the ATPase from an enzyme involved in calcium transport to a phosphoenzyme giving rise to an increase in the Mg2+-dependent ATPase activity.

Adenosine Triphosphatases↗
PubMed1981

Increased muscle calcium. A possible cause of mitochondrial dysfunction and cellular necrosis in denervated rat skeletal muscle.

Mitochondrial preparations derived from denervated rat skeletal muscle and paired controls were characterized with respect to their ability to take up externally added Ca2+. The denervated and control muscle homogenates and mitochondrial [Ca2+] were also determined. Our data indicate that the denervated mitochondria are able to take up less Ca2+ than the controls before uncoupling occurs. This defect is associated with elevated [Ca2+] in homogenate and mitochondrial fractions in the denervated state. The causal relationship between Ca2+ overload, mitochondrial functional damage and cell necrosis is discussed.

Animals↗
PubMed1981

Cytosolic oestrogen receptor content of breast cancer tissue in blacks and whites.

We have examined the oestradiol receptor (ER) content of cytosols from 560 Black and White patients. The tumours from the White group contained a significantly lower proportion on ER-negative tumors (35.4%) compared with those from the Black group (46.5%). The proportion of ER-positive tumours is significantly greater in the post- than in th premenopausal White group. The frequencies of ER-positive tumours in the post- and premenopausal Black groups are not significantly different, resembling the situation described by others in Japanese women.

Adult↗
PubMed1980

Racial differences in oestrogen receptor and peroxidase status of human breast cancer tissue.

Cytoplasmic oestradiol receptors and peroxidase from 170 tumours from patients with breast cancer were assayed. The results were analysed in terms of racial groups and menopausal status. It was found that 68% of the receptor-positive tumours were peroxidase-positive, while 59% of the receptor-negative tumours were peroxidase-positive. When results were analysed in terms of racial groups 68% of tumours from White patients were peroxidase-positive and receptor-positive, while only 48% of receptor-negative tumours in this group were peroxidase-positive. This contrasts with the finding of 57% receptor-positive/peroxidase-positive tumours as opposed to 70% receptor-negative/peroxidase-positive tumours in Black patients.

Black People↗