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Biomedical subjects

A J Eisenfeld

Publications and source records attributed to A J Eisenfeld.

At least 19 recordsLinked to original sources
PubMed1998

Perflenapent emulsion: a US contrast agent for diagnostic radiology--multicenter, double-blind comparison with a placebo. EchoGen Contrast Ultrasound Study Group.

PURPOSE: To evaluate perflenapent emulsion as a contrast agent for ultrasound (US) of the liver, kidneys, and vasculature. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, multicenter trial of 151 patients was performed. Investigators and blinded readers compared sonograms obtained after intravenous administration of perflenapent emulsion (0.05 mL/kg) and of a placebo with baseline sonograms. RESULTS: Contrast enhancement occurred in 140 of 149 patients (94%) after perflenapent administration and in 12 patients (8%) after placebo administration (P < .001). Enhancement lasted 5.0-15.4 minutes with perflenapent and 0.1-1.7 minutes with the placebo (P < .001). Perflenapent enhanced or facilitated visualization of blood flow, abnormal structures, masses, and lesions in 138 of 147 patients (94%) versus 12 of 147 (8%) for the placebo (P < .001). Improved visualization assisted in the diagnosis in 105 of 143 perflenapent studies (73%) compared with five of 143 placebo studies (3%) (P < .001). Diagnostic information affected case management in 71 of 148 patients (48%) after perflenapent administration and in nine of 148 patients (6%) after placebo administration (P < .001). Adverse effects associated with perflenapent were few and mostly mild, occurred within 30 minutes, and resolved without treatment. CONCLUSION: Perflenapent emulsion is a safe and effective contrast agent for US of the liver, kidneys, and vasculature.

Adult↗
PubMed1997

Safety assessment of the use of perflenapent emulsion for contrast enhancement of echocardiography and diagnostic radiology ultrasound studies.

PURPOSE: The studies were undertaken to assess the safety of the use of perflenapent emulsion (EchoGen, SONUS Pharmaceuticals, Bothell, Wash.) for contrast enhancement of echocardiography and radiology ultrasound studies. MATERIALS AND METHODS: In all, 1,001 patients or subjects were enrolled in 21 clinical studies. Clinical laboratory test, pulse oximetry, vital signs, and electrocardiograms (ECGs) were obtained in 818 patients before and after administration of perflenapent emulsion and active control [5% sonicated human albumin, (Albunex, Molecular Biosystems, Inc., San Diego, Calif.)] or placebo (saline) to determine mean changes from baseline. Adverse event rates were monitored following administration of perflenapent emulsion in 743 patients and placebo in 151 patients. RESULTS: No clinically significant abnormalities in clinical laboratory, pulse oximetry, vital signs, or ECG evaluations were observed. Values following administration of perflenapent emulsion were comparable with those following placebo or active control. Perflenapent emulsion (50/743; 6.7%) was comparable with placebo (4/151; 2.6%) in the overall incidence of adverse events considered related to the test article. Adverse events that occurred with a frequency of > or = 1% within 30 min after perflenapent emulsion administration were vasodilation and taste aberration. Adverse events which were mostly mild to moderate in intensity, began within 10 to 20 min after administration, and resolved spontaneously within 10 to 20 min. CONCLUSION: Perflenapent emulsion is generally well tolerated in patients undergoing echocardiography and ultrasound of other target organs.

Adolescent↗
PubMed1987

Estrogen receptors and androgen receptors in the mammalian liver.

An estrogen receptor and an androgen receptor are present in the mammalian liver. In the liver of the rat, the estrogen receptor concentration increases markedly at puberty and this change correlates with enhanced estrogen stimulation of plasma renin substrate synthesis. High doses of estrogen are required for nuclear binding in liver when compared to doses for the uterus. The high dose requirement appears to be predominantly due to extensive metabolism in the hepatocyte of the estrogen to inactive derivatives. Furthermore, estradiol is much weaker than ethinyl estradiol for promoting nuclear binding in the liver. This is due to extremely rapid and extensive metabolism of estradiol. In human liver the concentration of estrogen receptor is low. An androgen receptor is present in high concentration in rabbit liver and is located predominantly in the nucleus after androgen administration. High concentrations of a putative androgen receptor are also present in human liver cytosol. Preliminary studies indicate that synthetic progestins can attach to the human liver androgen receptor. To date, a progesterone receptor has not been found in the mammalian liver. Thus, it appears that extensive steroid metabolism in liver preferentially diminishes sex steroid interaction with liver receptors and that androgen receptors may mediate progestin effects in liver. These observations provide a scientific basis for improved safety of oral contraceptives. Lowering the estrogen and progestin doses in oral contraceptives will decrease the major side-effects, which are liver mediated, and still maintain the desired effects at the hypothalamic-pituitary axis and uterus. Furthermore, it is likely that by selecting which estrogen, progestin or androgen is administered as well as by utilizing a parenteral route of administration that sex steroid effects on the liver could be minimized.

Animals↗
PubMed1987

Uveoretinitis in rabbits following immunization with interphotoreceptor retinoid-binding protein.

Interphotoreceptor retinoid-binding protein (IRBP) is a glycoprotein found in the interphotoreceptor matrix between the neurosensory retina and the retinal pigment epithelium and is thought to shuttle retinol among cells that border the interphotoreceptor space. Immunization of rabbits with bovine IRBP caused subsequent photoreceptor degeneration, as documented by light- and electron microscopy. Beginning on post-injection day 18, scattered regions had photoreceptor outer segments that were disorganized and shortened or absent. Macrophages were found between the retinal pigment epithelium and neurosensory retina and within choroidal interstitium and blood vessels. Labeling of these cells with a marker specific for monocytic macrophages (RAM11) and absence of labeling with a marker for retinal pigment epithelium (rabbit anti-bovine cellular retinaldehyde-binding protein) suggest that these macrophages were hematogenous in origin. Staining of retinas with fluorescein isothiocyanate (FITC)-conjugated sheep anti-rabbit IgG revealed leakage of rabbit IgG into the interphotoreceptor matrix on and after day 18 in experimental animals but not in controls, suggesting breakdown of the outer blood-retinal barrier. Indirect immunofluorescence with anti-glial fibrillary acidic protein revealed labeling of Müller cells in experimental retinas on and after day 18, but not in control or shorter survival experimental retinas. There were foci of increased cellularity in the choroid on days 18, 26 and 39. From days 26 through 67, the retinal pathology became more widespread. Varying degrees of outer-segment degeneration were present in all parts of the retina and in many areas there was total loss of outer segments and loss of some photoreceptor-cell bodies. The inner retina appeared unaffected in all experimental and control retinas. These results demonstrate that injection of rabbits with bovine IRBP causes retinal photoreceptor degeneration as anti-IRBP titers increase and breakdown of the outer blood-retinal barrier ensues. Further studies will be required to elucidate factor(s) that control accessibility of the neurosensory retina to circulating antibodies against IRBP and other intrinsic retinal proteins.

Animals↗
PubMed1986

Preservation of steroid receptors in frozen brain and pituitary tissue: use of the cryoprotective agent, dimethylsulfoxide.

This paper examines the effects of freezing and thawing on steroid receptor concentrations in the brain and pituitary of the rat. Storage at -70 degrees C for 1-2 weeks had no detectable effect on levels of cytoplasmic estrogen receptors. However, freezing and thawing resulted in measurable losses of cytoplasmic androgen, progestin and glucocorticoid receptors. Cell nuclear receptors were measured by exchange assay after in vivo administration of non-radioactive steroids. Nuclear estrogen, androgen and progestin receptor concentrations were all reduced by freezing compared to the levels in fresh tissue. In all cases except that of cytoplasmic glucocorticoid receptors, these losses could be prevented by freezing the tissue in 10% aqueous dimethylsulfoxide.

Animals↗
PubMed1985

Synthesis of estradiol fatty acid esters by human breast tumors: fatty acid composition and comparison to estrogen and progesterone receptor content.

The estradiol-17 beta-fatty acid esters are non-polar metabolites of estradiol, formed in many tissues, including human breast tumors. It has been shown in the rat that the synthesis of these esters is greatest in those tissues that respond to estrogen stimulation. Thus the possibility was explored that the biosynthesis of the estradiol esters in human breast tumors occurs mainly in those tumors that are estrogen sensitive; and thus that the synthesis of this family of non-polar metabolites of estradiol could be used as an additional marker for the identification of hormonally dependent tumors. However, the conversion of estradiol to the esters did not correlate with other indicators of estrogen responsiveness, the progesterone or estrogen receptors. Interestingly, the composition of the fatty acids in the estradiol-17-esters synthesized in the human tumors was markedly different from those originally identified in the bovine uterus. In the bovine uterus, the esters were predominantly unsaturated, 85%, while in this study the saturated esters were the major component. Since after systemic administration the saturated estradiol-17-esters have been found to be much longer-lived than the unsaturated esters, the biosynthesis of the relatively high proportion of saturated esters by human breast tumors may indicate a significantly prolonged duration for the estrogenic signal produced by endogenously formed estradiol esters. These esters formed and sequestered within the tumor cell, may serve as a preformed store of estradiol, which after enzymatic hydrolysis, can locally stimulate growth of tumors that are estrogen responsive.

Breast Neoplasms↗
PubMed1985

Localization of retinoid-binding proteins in developing rat retina.

Antibodies to cellular retinol-binding protein (CRBP) and cellular retinal-binding protein (CRALBP) were obtained from rabbits immunized with antigens purified from bovine retina. Antigens were localized on frozen sections of rat retina using indirect FITC immunofluorescence. In the retinal pigment epithelium of rats from postnatal day 1 (the day of birth) to postnatal day 32, specific staining with anti-CRBP was restricted to the cytoplasm; the nuclei were unstained. In the neurosensory retina, Muller cell endfeet were stained with anti-CRBP at all ages examined. No CRBP reactivity was found in the pigment epithelium of the ciliary body at any age examined. On postnatal days 14 and 32, in addition to Muller cell endfeet and radial processes, two fine laminae in the inner plexiform layer were faintly positive for CRBP. Anti-CRALBP stained the cytoplasm of the RPE and Muller cells in the adult rat. In developing rat retina, in addition to Muller cells and the retinal pigment epithelium, the ciliary body pigment epithelium and the outer epithelium of the iris were stained with anti-CRALBP in the first postnatal week. The intensity of staining of the ciliary body pigment epithelium decreased gradually from postnatal day 8 until postnatal day 14, at which point a clear line of demarcation was found between the positively stained retinal pigment epithelium and the adjacent, lightly stained, pigment epithelial cells of the ciliary body.

Aging↗
PubMed1985

Autoradiographic localization of tritiated dihydrotestosterone in the flank organ of the albino hamster.

In the hamster flank organ, the growth of hair and growth of sebaceous glands are androgen-dependent functions. Although dihydrotestosterone (DHT) is known to be a potent stimulator of flank organ growth, there is no information about localization of DHT receptor sites in this organ. The purpose of this study was to use steroid autoradiography to localize DHT receptors in the hamster flank organ. Because steroid hormones are functional when translocated to nuclear receptors, nuclear localization by autoradiography defines receptor sites. In order to be able to visualize autoradiographic grains from radiolabeled androgens around hair follicles, albino hamsters were studied to avoid confusion between the grains and pigment granules which are abundant in the more common Golden Syrian hamster. Mature male hamsters castrated 24 hours earlier were given tritium-labeled dihydrotestosterone ( [3H]DHT). Using the technique of thaw-mount steroid autoradiography, 4-micron unfixed frozen sections were mounted in the dark onto emulsion-coated glass slides and allowed to develop for 4-6 months. [3H]DHT was found to be concentrated over sebocyte nuclei. The label was present peripherally as well as in differentiating sebocytes. There was no nuclear localization of [3H]DHT in animals pretreated with excessive quantities of unlabeled DHT. Steroid metabolites of [3H] DHT were assessed by thin-layer chromatography in paired tissue samples. Most of the label remained with DHT. Uptake was inhibited in the flank organ of hamsters pretreated with unlabeled DHT. Specific DHT receptors in the albino hamster flank organ are located in peripheral and differentiating sebocytes. Steroid autoradiography is a useful tool to study androgen interaction in the skin.

Animals↗
PubMed1985

Androgen receptor in the rabbit liver and apparent translocation to the nucleus in vivo.

The present study demonstrates that the liver of a mammal, the rabbit, contains an androgen receptor. Rabbit liver cytosol or purified nuclei were incubated with the radioactive androgen R-1881 (methyltrienolone). The cytosol of adult female rabbit liver contained androgen-binding sites of high affinity, Kd 0.9 nM, and a capacity of 7000 fmol/g liver or 79 fmol/mg cytosol protein. After partial purification by 35% ammonium sulfate precipitation (AS cytosol), the binding specificity pattern was consistent with that of androgen receptor. Apparent translocation from cytosol to nucleus was examined by administering 100 micrograms nonradioactive R-1881 in vivo. One hour later, almost all of the receptor was detected in liver nuclei. The receptor concentration in purified nuclei, as determined by an exchange procedure, was 2100 fmol/g liver, which is an increase of 6-fold relative to the low levels in nuclei of untreated rabbits. The binding affinity, specificity pattern, and protease sensitivity for the sites in the nucleus after in vivo androgen in general resembled those as AS cytosol binding in untreated liver. Androgen receptors were also present in AS cytosol of the immature female rabbit liver and, in lower concentration, of the intact adult male rabbit. The properties of liver androgen binding are quite different from those of testosterone binding protein present in serum. Accordingly, an androgen binding protein with high affinity and specificity and capable of translocation to the nucleus in vivo has been detected in mammalian liver. An androgen receptor in the mammalian liver may mediate androgen effects on liver function, including modulation of synthesis of selective plasma proteins.

Animals↗
PubMed1985

Cysteamine causes reduction of prolactin monomers followed by aggregation in the rat pituitary gland.

Storage forms of PRL were studied in control and cysteamine-treated cultures of estradiol-induced tumors in Fischer 344 rats and in secretory granules isolated from these tumors to further investigate the mechanism of action of cysteamine on PRL. The two major bands visible when protein is stained after electrophoresis of isolated granules migrate to the position of PRL and GH monomers. Electrophoresis under reducing conditions changes the position, but does not noticeably increase the amount of each band. [3H]PRL in cells labeled for 8 h with [3H]leucine also exists predominantly as monomer. Immunoreactivity of PRL in cell lysates or isolated granules is not affected by incubation with reducing agents beta-mercaptoethanol or glutathione at concentrations up to 5 mM, but cysteamine decreases PRL immunoreactivity in isolated granules at concentrations of 3 mM and higher. Electrophoresis of isolated granules after incubation with 25 mM cysteamine for 1 h demonstrates that cysteamine converts PRL to the reduced form. After 4 h, or after dilution of the granules before solubilization, the amount of reduced monomer is decreased, and larger molecular weight species appear. The reduced monomer can be recovered by electrophoresis under reducing conditions. The fully immunoreactive form can be recovered by incubation for 1 h with dithiothreitol at concentrations of 0.3 mM-3 mM. These data indicate that: PRL exists predominantly in monomeric form in the rat pituitary gland, and cysteamine reduces PRL, and formation of disulfide-linked aggregates of PRL occurs subsequently under some conditions.

Animals↗
PubMed1985

Immunocytochemical localization of retinoid-binding proteins in developing normal and RCS rats.

Interstitial retinol-binding protein (IRBP), cellular retinol-binding protein (CRBP), and cellular retinal-binding protein (CRALBP) were localized in developing normal and RCS rat retinas. IRBP is found in the presumptive interphotoreceptor space in normal and RCS rats on P1. It reaches adult levels on P18. In the RCS rat, the level of IRBP decreases after P18 until there is only a small amount of staining on P38. CRBP and CRALBP are localized in the retinal pigment epithelium from P1 to adult. CRALBP is also found in the ciliary body pigment epithelium and in the outer epithelium of the iris during the first week, but decreases during the second week to a very low level as found in the adult. The significance of the early presence of IRBP and the transient appearance of CRALBP in the ciliary body and iris epithelia is discussed.

Age Factors↗
PubMed1985

Immunocytochemical localization of interphotoreceptor retinoid-binding protein in developing normal and RCS rat retinas.

Interphotoreceptor retinoid-binding protein (IRBP) was localized immunocytochemically in developing normal and RCS rat retinas. IRBP was present in normal and RCS neural retinas on the day after birth (postnatal day 2, P2) to P8 in the space between the neuroblastic layer and the retinal pigment epithelium (RPE). The presence of IRBP prior to the development of outer segments (OS) suggests that OS formation is not linked temporally with IRBP secretion. On P10, staining was confined to the interphotoreceptor space with an intense band of label adjacent to the RPE. This staining pattern persisted in normal rats throughout development and until P18 in RCS rats. On P18, anti-IRBP staining in the RCS was spread evenly throughout the OS layer with no intense band of label adjacent to the RPE and after P18, there was decreased staining with anti-IRBP. On P45 and later, no staining of the RCS retina was found with anti-IRBP. Immunoblots of normal and RCS retinas corroborated the results from immunocytochemical staining. These findings suggest that IRBP may be synthesized in the photoreceptors, but is not abnormal in amount or distribution prior to onset of retinal degeneration in the RCS rat.

Animals↗
PubMed1984

Assessment of possible transneuronal changes in the retina of rats with inherited retinal dystrophy: cell size, number, synapses, and axonal transport by retinal ganglion cells.

In pigmented RCS rats with inherited retinal dystrophy, most photoreceptor cells disappear between postnatal days 20 and 100. We have examined the time course of the degeneration of photoreceptor nuclei and synapses and determined whether transneuronal changes occur in the inner nuclear layer (INL), inner plexiform layer (IPL), and retinal ganglion cells following loss of photoreceptor cells in these animals. Electron microscopic photomontages of the entire thickness of the IPL of dystrophic (RCS-p+) and control (RCS-rdy+ p+) rats 334 to 515 days old were prepared, and synapses were counted and identified as either conventional (amacrine) or ribbon (bipolar) types. Neither the incidence of synapses in the IPL nor the ratio of conventional to ribbon synapses differed in the dystrophic and control retinas. Ganglion cell diameter, perimeter, area, and density were measured from drawings of wholemount preparations of dystrophic and control rats 105 days and older. Diameter, perimeter, area and number of ganglion cells were not significantly different in the two genotypes. Anterograde axonal transport was measured by studying the displacement of labeled material as it traveled along ganglion cell axons and accumulated in the superior colliculus. The normal and dystrophic rats showed no significant difference in (1) the rates of rapidly moving components (approximately 110-180 mm/day) and slowly moving components (1.7-2.5 mm/day) or (2) the amount of radioactive material transported to the superior colliculus. The absence of transneuronal changes in retinal ganglion cells of RCS rats contrasts with results obtained earlier in rd mice (Graftstein et al., '72). Unlike the RCS rat, retinal degeneration in rd mice occurs before the maturation of the retina. We hypothesize that the ganglion cells may be more affected by loss of input early in development, and, therefore, ganglion cells of retinal dystrophic rats are less affected despite little or no synaptic input for several months. Furthermore, any reduction in the electrical activity of retinal ganglion cells that might follow loss of photoreceptor cells does not result in a significantly decreased rate of axonal transport.

Aging↗
PubMed1984

Müller cell expression of glial fibrillary acidic protein after genetic and experimental photoreceptor degeneration in the rat retina.

Glial fibrillary acidic protein (GFAP) is normally found in astrocytes. In the normal rat retina at all ages, only astrocytes stain for GFAP. This staining pattern is also found in RCS rats with inherited retinal dystrophy younger than 38 days. Beginning on day 38, when about 61% of the photoreceptors have degenerated, a few GFAP-positive fibers span the retina from the inner limiting membrane to the external limiting membrane. By day 41 and at all later ages examined, the radial fibers of Müller cells is a response to photoreceptor necrosis or might be a direct effect of the mutant gene, we induced photoreceptor degeneration in normal, adult Sprague-Dawley rats by exposing them to constant light for variable periods of time. After 3 days in constant light, there is a 20% reduction in the number of photoreceptors and many Müller cells are positive for GFAP. Immunoblot studies confirmed that the anti-GFAP reacted with a single protein from retina that corresponded in molecular weight and Triton-insolubility to GFAP. The immunoblots also corroborated the results from anti-GFAP immunostaining of control and experimental retinas. These results indicate that Müller cells express GFAP immunoreactivity in response to experimentally as well as genetically induced photoreceptor degeneration.

Animals↗
PubMed1984

Antiproliferative actions of tamoxifen to human ovarian carcinomas in vitro.

The cytosolic estrogen receptor (ERc) and progestin receptor (PRc) levels were measured in 56 human epithelial ovarian tumors. The maximum ERc content in a tumor sample was 163 fmol/mg cytosolic protein. Forty-six of the tumor samples were evaluable for clonogenic growth in soft agar, and 19 samples produced 15 or more colonies per 10(5) cells plated. Four of the samples that grew had ERc levels of greater than 30 fmol/mg cytosolic protein. No correlation, however, between growth in soft agar and ERc or PRc content was observed. The antiproliferative properties of the antiestrogen, tamoxifen, were studied. Although no decrease in colony formation was observed after a 1-hr exposure to 0.2 or 2 microM tamoxifen, continuous exposure of cells to 2 microM tamoxifen reduced clonogenicity in 8 of 18 solid ovarian carcinomas examined. The maximum diminution in colony formation was approximately 50% of that of the control and was seen in 2 tumor samples. Both tumors that displayed the maximum response to continuous tamoxifen treatment had ERc and PRc levels greater than 30 fmol/mg cytosolic protein. None of the 14 tumors with ERc levels less than or equal to 30 fmol/mg cytosolic protein exhibited a decrease in colony formation of more than 50%. Exposure of cells for 1 hr to the combination of doxorubicin and tamoxifen produced a significant antagonism of the individual doxorubicin or tamoxifen antiproliferative effects in 7 of 9 samples examined. These data suggest that in a subset of human ovarian epithelial carcinomas tamoxifen alone can have some direct antiproliferative action on the clonogenic cells. The maximum antiproliferative effect of tamoxifen observed was related to ERc content in ovarian tumors.

Adult↗
PubMed1983

Differences in breast cancer risk factors according to the estrogen receptor level of the tumor.

One hundred and forty-eight postmenopausal breast cancer cases and 585 postmenopausal controls were included in an investigation of whether various risk factors for breast cancer are associated with the level of estrogen (E) receptor (ER) protein in the tumor. In an intracase analysis, the tumor ER level was positively associated with nulliparity, late age at first live birth, a history of benign breast disease, and having breast-fed at least 1 child and was negatively associated with previous use of E replacement therapy. A case-control analysis suggested that the first three variables, established risk factors for breast cancer, are associated with an increased risk for malignant breast tumors that are ER-positive but not for those that are ER-negative. This analysis did not provide a clear interpretation of the findings in the intracase comparisons with regard to prior breast-feeding and the use of E replacement therapy.

Aged↗
PubMed1982

Separation of steroidal estrogens and their major unconjugated metabolites by high performance liquid chromatography.

A high performance liquid chromatographic method is described for the rapid, non-destructive separation of a number of physiologically important steroidal estrogens, including the labile catechol estrogens. This procedures uses a "Diol" column and gradient elution to separate in a single run, estrogens ranging from 2-methoxy estrone, one of the least polar C18 steroids, to estriol, one of the most polar. Simpler, isocratic conditions, are provided for the separation of estrogens of similar polarity. A semi-preparative column of similar composition was used for the purification of samples containing 25 to 50 mg of individual steroids.

Chromatography, High Pressure Liquid↗