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Biomedical subjects

R G Smith

Publications and source records attributed to R G Smith.

At least 19 recordsLinked to original sources
PubMed1979

Estrogen-binding proteins in the human postmenopausal uterus.

Two intracellular high-affinity, low-capacity estrogen-binding proteins, which have the characteristics of receptors, with equilibrium dissociation constants of 10(-10)M and 10(-9)M, have been observed in the human uterus. The higher-affinity protein (10(-10)M) appears to play the main role in activating end-organ response to estrogen stimulation. The role of the lower-affinity protein (10(-9)M) is uncertain. In a human postmenopausal uterine system without estrogen stimulation, Scatchard analysis of uterine cytosol partially purified by ammonium sulfate fractionation and incubated at 4 degrees C for 18 hours revealed only the higher-affinity receptor component (10(-10)M). In a post menopausal uterine system with estrogen priming (and in the premenopausal uterus) both the high- and low-affinity components were observed. Competition studies indicated that the receptors were specific for estradiol. The clinical significance of these findings is discussed.

Adult↗
PubMed1979

Isolation and purification of a hen nuclear oestrogen receptor and its effect on transcription of chick chromatin.

An oestrogen receptor was isolated, characterized and purified from the nuclear fraction of the hen oviduct. The receptor sediments at 4.6 S on glycerol gradients, has an equilibrium dissociation constant (Kd) of 1.1 X 10(-10)M, an association constant (ka) of 1.4 X 10(-6) M-1.S-1, and a dissociation constant (kd) of 5 x 10(-5) s-1. The receptor chromatographed from DEAE-cellulose as a single peak at 0.15 M-KCl and was not retained by phosphocellulose. Polyacrylamide-gel electrophoresis of the receptor in the presence of sodium dodecyl sulphate demonstrated two subunits with apparent mol.wts. of 74000 and 80000. The overall purification achieved was 90000-fold by using a combination of cell fractionation, (NH4)2SO4 fractionation and affinity chromatography. This represents the first separation, isolation and purification of the highest-affinity binding component (Kd 10(-10)M) of two high-affinity oestrogen-binding proteins present in both chick and hen oviduct cytosol and nuclei. To examine directly the effect of the purified receptor on transcription a reconstituted cell-free system was used, which contained the receptor--oestradiol complex, Escherichia coli RNA polymerase, rifampicin and chromatin prepared from hormone-withdrawn chick tissue. The receptor-hormone complex at a concentration of 0.1 nM stimulated transcription of oviduct chromatin by promoting an increase of 14000 sites for RNA-chain initiation, which is similar to the number of additional sites measured in the oviducts of diethylstilboestrol-stimulated immature chicks [Tsai, Schwartz, Tsai & O'Malley (1975) J. Biol. Chem. 250, 5165-5174]. Oestradiol alone had no effect on transcription. Thus the data demonstrate that the purified nuclear oestradiol-receptor complex can regulate gene transcription in vitro in a manner similar to that observed in target cells in vivo.

Animals↗
PubMed1979

Contribution from geriatric medicine within acute medical wards.

In 1977 a scheme of attachment to acute medical wards of consultants in geriatric medicine and associated junior medical staff was instituted in a large Edinburgh teaching hospital. The effect on admissions of patients aged 65 and over was examined for comparable periods before and during this arrangement. Mean and median stays were reduced for both sexes but more noticeably for women. The mean stay for all women aged over 65 was reduced from 25 to 16 days and for women aged over 85 from 50 to 19 days. The proportion staying under two weeks was significantly increased in both sexes, and the proportion discharged home also increased, correspondingly fewer patients being transferred to convalescent wards. These changes were not accompanied by increased transfers to the geriatric department, and probably the skills and extra resources available to the geriatric service were the factors mainly responsible for the changes in performance.

Acute Disease↗
PubMed1979

Inhibition of gonadotropin by delta9-tetrahydrocannabinol:mediation by steroid receptors?

Competition assays for estradiol receptors in cytosol preparations of uteri from rhesus monkeys and humans showed that delta9-tetrahydrocannabinol (THC) does not compete with estradiol for intracellular estrogen recptors. Although isotopically labeled THC bound to macromolecules in uterine cytosol from the rhesus monkey, the binding was not displaced by unlabeled THC, diethylstilbestrol, estradiol, progesterone, cortisol, or 5 alpha-dihydrostestosterone. Scatchard analyses indicated that high-affinity saturable binding of THC to cytosol did not occur. Thus the inhibitory effect of THC on gonadotropin and steroid secretion in primates is not mediated by the interaction of THC with intracellular steroid hormone receptors.

Animals↗
PubMed1979

Identification of lymphoblastic lymphoma cells using a dual assay for T cell differentiation markers.

An assay that simultaneously detects two differentiation markers found in thymocytes is described. There markers include the membrane receptor for sheep erythrocytes (E) and the nuclear enzyme, terminal deoxynucleotidyl transferase (TdT). Cells are incubated with E, pelleted onto slides and then stained for TdT by an indirect immunofluorescence technique. The E-positive, TdT-positive phenotype is characteristic of the tumor cells in many cases of lymphoblastic lymphoma. Cells of this dual phenotype were not found in the peripheral blood or bone marrow of individuals without neoplastic disease. An 8-year-old-girl with lymphoblastic lymphoma is described whose peripheral blood and bone marrow smears were thought to be morphologically normal at the time of diagnosis. However, 3% of her peripheral blood and about 1% or her bone marrow mononuclear leukocytes were identified as E-positive, TdT-positive. These cells disappeared from both sites five weeks after institution of therapy, and her peripheral blood remains free of such cells nine months after diagnosis. This dual assay for E-rosette formation and TdT is a more sensitive technique than conventional morphology for the detection of tumor cells of this type. The assay may be useful in monitoring the therapy of patients with this tumor.

Bone Marrow↗
PubMed1979

Presence of lymphocyte membrane surface markers on "small cells" in a pineal germinoma.

A 16-year-old boy was operated on via an occipital transtentorial craniotomy for a pineal tumor. Routine histological examination of the tissue revealed it to be a germinoma, as characterized by the presence of two cell populations: large cells and small, lymphoid-appearing cells. The cells were evaluated in a single-cell suspension for the presence of lymphocyte membrane surface markers; small cells exclusively were found to have such markers. A T-lymphocyte membrane marker was present in 51% of the small cells, whereas 15 to 18% of the small cells had a B-lymphocyte membrane marker.

Adolescent↗
PubMed1979

Characterization of a type-C virus produced by co-cultures of human leukemic bone-marrow and fetal canine thymus cells.

The putative human helper virus SKA-21/A204V, isolated by Nooter et al. in 1977 from human leukemic bone-marrow cells following co-culture with normal fetal canine thymus cells, Cf2th, has been characterized with respect to its major viral core protein, reverse transcriptase, and nucleic acid sequences. The results of these analyses show that this virus is not distinguishable from the woolly monkey type-C virus, SSAV-1, by the techniques employed.

Animals↗
PubMed1979

Prolactin receptors in the ovary.

The binding of prolactin (PRL) to the plasma membranes of bovine and human ovaries was investigated using both homologous and heterologous 125I-prolactin. Saturation and Scatchard analysis demonstrated that human prolactin binds to human ovarian membranes with a Kd of 2 x 10(-10) M; to bovine ovarian membranes with a Kd of 1.9 x 10(-10) M; and to bovine corpora lutea membranes with a Kd of 1.9 x 10(-10) M. The concentrations of binding sites in bovine and human ovaries were 2.9 x 10(-15) moles/mg of protein and 2.0 x 10(-15) moles/mg of protein, respectively. The number of bindings sites in the bovine corpora lutea was 1.5 x 15(-15) moles/mg of protein. Specificity studies with bovine PRL, ovine PRL, human luteinizing hormone, human follicle-stimulating hormone, and bovine growth hormone showed this binding to be specific. Comparison of binding of PRL to membranes of other target and nontarget tissues suggests that the ovary is one of the primary target tissues. These data suggest that prolactin plays a role in the ovarian cycle.

Animals↗
PubMed1979

Effect of tetrahydrocannabinol on the hypothalamic-pituitary axis in the ovariectomized rhesus monkey.

Single doses of delta9-tetrahydrocannabinol (THC) (5.0, 2.5, 1.25, or 0.625 mg/kg) can decrease the levels of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the ovariectomized rhesus monkey. The inhibition of gonadotropins (50% to 88%) lasts for 6 to 24 hours depending upon the dose of THC. There are no great differences in the responses of the two gonadotropins to THC. The inhibition of gonadotropin levels by THC appears to be at the level of the hypothalamus, since both LH and FSH are released from the pituitary gland in response to LH- releasing factor in the presence of THC.

Animals↗
PubMed1979

Saliva as a matrix for measuring free androgens: comparison with serum androgens in polycystic ovarian disease.

We report a simple and direct procedure for the measurement of circulating free testosterone concentrations by using saliva as a matrix rather than serum. There is a close correlation between saliva testosterone values measured by radioimmunoassay, calculated values of free testosterone, and free testosterone estimated by equilibrium dialysis. Our method is direct and has the advantage that the biologic fluid can be obtained routinely by noninvasive techniques outside the clinic during a course of therapy. We also show that a single saliva value is of greater diagnostic use than any of the currently used androgen assays. Testosterone was found to be elevated in the saliva of 17 infertility patients diagnosed as having polycystic ovarian syndrome, 14 of these patients were hirsute.

Androstenedione↗
PubMed1979

An evaluation of the leading patent equivalents services.

Patent equivalent services are useful tools for identifying patent families. A patent family consists of a group of patents in various countries which cover the same invention. The patent equivalents services provided by the three leading suppliers--Chemical Abstracts Service, Derwent Publications Ltd., and INPADOC--have been tested and evaluated for coverage, recall, and accuracy. Results are reported for a test sample consisting of 75 pharmaceutical patent families.

Drug Industry↗
PubMed1979

Evidence for the epoxide-diol pathway in the biotransformation of mephenytoin.

A dihydrodiol metabolite of mephenytoin (5-dihydroxycyclohexadienyl)-5-ethyl-3-methylhydantoin and other mono- and dihydroxylated and N-demethylated metabolites were identified in urine from a male epileptic patient receiving therapy with mephenytoin (300 mg/day). Metabolites, extracted from urine before and after enzymatic hydrolysis, were derivatized with a trimethylsilyl reagent and analyzed by combined gas chromatography and mass spectrometry. Two previously unreported metabolites were characterized: 5-ethyl-5-(di-hydroxyphenyl)-3-methylhydantoin and 5-ethyl-5-(hydroxy-methoxy-phenyl)-3-methylhydantoin. The structures of several other metabolites were confirmed: N-demethylmephenytoin, 5-ethyl-5-hydroxyphenylhydantoin, 5-ethyl-5-hydroxyphenyl-3-methylhydantoin and mephenytoin dihyrodiol. The dihydrodiol metabolite was of special interest since it was probably produced via an epoxide intermediate, 5-(epoxy-cyclohexadienyl)-5-ethyl-3-methylhydantoin. Previous reports have demonstrated that epoxides of this structural class are extremely reactive compounds, capable of alkylating biologic macromolecules. Covalent binding of the mephenytoin epoxide to macromolecules may be an important factor in the production of adverse and sometimes fatal side effects observed in patients receiving long-term therapy with mephenytoin.

Adult↗
PubMed1979

An immunologic approach for the detection of tumor cells in the peripheral blood of patients with malignant lymphoma; implications for the diagnosis of minimal disease.

Lymphocytes were isolated from infiltrated lymph nodes and blood of eight patients with malignant lymphocytic lymphoma. All patients had normal numbers of circulating lymphocytes with normal morphology. None of the patients had serum paraproteins. The isolated lymphocytes from patients and controls were stained with affinity purified antibody specific for kappa- or lambda-light chains and analyzed by using a fluorescence activated cell sorter. Cells from infiltrated nodes stained for only one light chain type at high levels of fluorescence intensity. An increase in the number of brightly stained cells bearing the light chain type found in the involved node was readily detected in the peripheral blood of all but one of the patients with lymphoma. Similar changes in the ratio of kappa+- to lambda+-cells were not observed in 41 samples from nomral individuals and patients with other diseases.

Cell Transformation, Neoplastic↗