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S Stone

Publications and source records attributed to S Stone.

At least 19 recordsLinked to original sources
PubMed1992

Carrier detection of deletions in female relatives of X-linked disorders by non-isotopic in situ hybridisation.

Recent studies suggest that a non-isotopic in situ hybridisation (NISH) approach can be successfully employed to investigate the carrier status of female relatives in families of selected patients with Duchenne muscular dystrophy (DMD) or Hunter syndrome, whose diseases are due to a specific X chromosome deletion. Whilst the majority of metaphase spreads from normal females show specific hybridisation signals on both X chromosomes when tested with either dystrophin or Hunter gene-derived probes, only one X chromosome in each metaphase spread will show the relevant hybridisation complex in female carriers of deletions involving the dystrophin or Hunter gene. Thus, the NISH method can be a valuable diagnostic tool for the detection of the carrier status of female relatives of patients with X chromosome deletions.

Chromosome Deletion↗
PubMed1992

Carrier detection of deletions of the Hunter gene by in situ hybridization.

Deficiency of the lysosomal enzyme alpha-iduronate sulphate sulphatase (IDS) causes the clinical manifestations of Hunter syndrome, an X-linked condition. In about 30% of male patients, the disease is due to a major deletion. Using a non-isotopic in situ hybridization (NISH) method, and a yeast artificial chromosome (YAC) probe, the Hunter gene was mapped to the terminal region of the human X chromosome, close to the Xq28 band. The NISH procedure was then applied to investigate the carrier status of female relatives of a Hunter patient known to have a deletion of the IDS gene. Unequivocal evidence that two female relatives were carriers of the deletion was obtained, demonstrating that the NISH method is a valuable diagnostic tool in genetic counselling of families with Hunter patients.

Chromosome Deletion↗
PubMed1992

Proteolytic modification of prolactin by the female rat brain.

Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analyses we have identified immunoreactive prolactin (PRL) proteins with molecular weights of 24 and 16 kD in the female rat brain. Because PRL target tissues have been shown to contain enzymes which, in vitro, cleave PRL into a 16-kD PRL fragment, studies were performed to characterize PRL proteolysis in the female rat brain. In vitro proteolysis of PRL was examined by incubating [125]I-PRL with 25,000 g subcellular fractions followed by SDS-PAGE under reducing conditions. At acidic pHs, incubation of PRL with 25,000 g hypothalamic fractions consistently resulted in the generation of a 16-kD fragment. The generation of the 16-kD fragment was time and tissue concentration dependent. Enzyme inhibitor analysis indicated that PRL proteolysis could be blocked by aspartate and serine protease inhibitors, but not sulfhydryl, metalloenzyme or trypsin protease inhibitors. Subcellular localization of hypothalamic PRL proteolytic activity by equilibrium density centrifugation revealed a bimodal distribution of proteolytic activity with modal densities of 1.12 and 1.24 g/ml. Homogenization of the tissue in a hypo-osmotic medium disrupted the high density peak resulting in a single low-density peak at the top of the gradient. These data indicate that subcellular fractions of the rat brain contain enzymes which can cleave PRL into a 16-kD fragment under acidic conditions. The majority of the enzymatic activity is localized in membrane-bound particles with a density similar to subcellular particles which contain PRL.

Animals↗
PubMed1992

Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid, and the brain.

T4 is bound to transthyretin (TTR; 75%) and albumin (Alb; 25%) in rat serum and only to TTR in cerebrospinal fluid (CSF). In addition to the liver, TTR is synthesized in large amounts in the choroid plexus and then secreted into the CSF, suggesting that serum T4 could be transported to the CSF and brain via the choroid plexus. We determined whether serum T4 bound to TTR is transported into the choroid plexus and CSF. N-Bromoacetyl-L-[125I]T4, a derivative of T4 that binds covalently to TTR, was used as the affinity label for the T4-binding site on TTR. Rats were injected with [125I]T4, acetyl-[125I]T4 covalently bound to human TTR ([125I]T4Ac.human hTTR), or acetyl-[125I]T4 covalently bound to human Alb ([125I]T4Ac.hAlb). The quantities of [125I]T4Ac.hTTR and [125I]T4Ac.hAlb present in the choroid plexus, CSF, and brain 90 min later were barely detectable. In contrast, [125I]T4 injected as the unbound form accumulated in the choroid plexus and CSF to levels 6-11 times higher than with [125I]T4Ac.hTTR (P less than 0.005). We then used a synthetic flavonoid (EMD) that competitively inhibits binding of T4 to serum TTR and transiently increases serum free T4 to determine the role of choroid plexus TTR and CSF TTR in the transport of T4 from serum to brain. Rats were given 110 microCi [125I]T4 15 min after the injection of vehicle, a low (0.3 mumol/100 g BW) or high dose of EMD (2.0 mumol/100 g BW). Rats were killed 60 min later. In serum, the percentage of [125I]T4 bound to TTR decreased and free T4 increased similarly in the low and high dose EMD-treated rats. In contrast, the percentage of [125I]T4 bound to TTR in choroid plexus and, subsequently, CSF was significantly decreased in rats given the high dose of EMD, but was not affected by the low dose of EMD, suggesting that in high doses, EMD crossed from serum to choroid plexus and CSF and occupied TTR-binding sites for T4. There was a significant decrease (P less than 0.05) in the percentage of injected [125I]T4 in the high dose vs. the low dose EMD-treated rats in total choroid plexus (61%), 1 ml CSF (94%), and 1 g cerebral cortex (46%) and cerebellum (46%).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Prolactin-stimulated mitogenesis of cultured astrocytes.

PRL has been reported to activate cell cycle-specific enzyme markers in nonreproductive tissues. To determine if PRL stimulates cell cycle-specific markers and cell growth in the central nervous system, the effect of PRL on cellular proliferation was examined in cultured astrocytes. Astrocytes from confluent cultures were plated onto glass slides at a density of 2 x 10(4) cell/ml 24 h before use. In some experiments, cells were serum deprived for 24 h (Go-arrested) after plating. Cell proliferation was examined directly by an increase in cell number and in individual cells by immunofluorescent detection of proliferating cell nuclear antigen (PCNA) and the incorporation of 5-bromo-2'-deoxyuridine (BrUd). When incubated with 1% serum, a small percentage (less than 5%) of the cells expressed PCNA. In cells cultured with rat PRL (10(-10)-10(-7) M) for 18 h, staining of PCNA increased in a dose-dependent manner, with maximal expression occurring at 10(-9) M PRL. At concentrations above 10(-9) M, PCNA staining decreased. To examine the specificity of the PRL-induced increase in PCNA, cells were incubated in the presences of 10(-9) M rat (r) or bovine (b) GH. Whereas incubation of astrocytes with rPRL and bPRL activated PCNA, cells incubated with either rGH or bGH showed only a slight increase in the number of cells expressing PCNA. Further, incubation of astrocytes with 1 nM PRL in the presence of 100 nM cyclosporine, an immunosuppressive agent that specifically displaces PRL from its receptor, decreased the percentage of nuclei stained for PCNA to that observed in non-PRL-stimulated controls. Transient exposure of cells to 10(-9) M PRL for 30 min resulted in an increase in the number of cells expressing PCNA when cultured for 18 h in the presence of 1% serum. In the presence of 1% serum, 10(-9) M PRL increased the incorporation of BrUd and resulted in a 3-fold increase in the doubling rate. In cells incubated in serum-free medium, only a few PCNA-positive cells could be detected. Treatment of Go-arrested astrocytes with PRL (10(-10)-10(-7) M) for 18 h resulted in a dose-dependent increase in the expression of PCNA. PCNA-positive cells were detected in cultures incubated with 10(-11) M PRL, with maximal expression at 10(-9) M.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Effect of in vivo administration of recombinant acidic fibroblast growth factor on thyroid function in the rat: induction of colloid goiter.

We have recently demonstrated that the iv administration of 0.6-60 micrograms/kg.day of acidic fibroblast growth factor (acidic FGF) increases thyroid weight in male and female rats. Interestingly, measurement of serum TSH and thyroid hormones in rats treated with 6 micrograms/kg.day acidic FGF for 30 days revealed only a slight increase in serum T4 and reverse T3 concentrations. Since thyroid function was only examined 24 h after the 30th daily treatment, we performed a series of experiments to evaluate the effects of acidic FGF on thyroid function following single and 6 multiple injections of acidic FGF. There was a small increase in the serum TSH concentrations at 2, 4, 8, and 24 h after a single high dose iv injection of acidic FGF (60 micrograms/kg). In contrast, serum T3 concentrations were slightly decreased at 2, 4, and 8 h after acidic FGF administration. There was no effect of a single injection of acidic FGF on serum T4, reverse T3, or thyroglobulin concentrations. After 6 days of treatment, there was a 34% increase in the thyroid weights of rats treated with acidic FGF. Analysis of serum hormones revealed a slight increase in serum TSH, T3, and T4 concentrations in acidic FGF-treated rats, but no change in serum reverse T3 or thyroglobulin concentrations. There was no effect of acidic FGF administration on thyroid radioiodine uptake, the intrathyroidal metabolism of radioiodine, or the relative amounts of thyroidal thyroglobulin or peroxidase messenger RNAs, or on liver 5'-deiodinase activity. In hypophysectomized rats, with no detectable levels of serum TSH, acidic FGF failed to increase thyroid weight. These data suggest that FGFs may participate with TSH in the regulation of thyroid weight and colloid accumulation, and that autocrine or paracrine growth factors may be involved in the pathogenesis of colloid goiter.

Animals↗
PubMed1992

Effects of selenium deficiency on thyroid hormone economy in rats.

In selenium-deficient rats, peripheral T4 to T3 conversion is markedly decreased due to the loss of the selenoprotein, type I iodothyronine 5'-deiodinase (5'D-I). Despite the marked increase in circulating T4 that results from this loss of 5'D-I, serum T3 concentrations in selenium-deficient rats remain in the normal range. To determine the physiological mechanism(s) that maintains circulating T3 when peripheral T4 to T3 conversion is impaired, we examined the interrelationships between selenium intake and the metabolism of T3 and T4 in the rat. In euthyroid rats, selenium deficiency caused the expected loss of 5'D-I, with a 52% increase in serum T4, which paralleled an increase in the T4 biological half-life. Consistent with the prolonged t1/2 of T4, short term thyroidectomy (48 h) in selenium-deficient rats failed to decrease serum T4 concentrations to the levels observed in short term thyroidectomized, selenium-supplemented rats. Short term thyroidectomy also caused an expected 33% decrease in liver 5'D-I and a 44% increase in brain type II iodothyronine 5'-deiodinase (5'D-II) activities in selenium-supplemented rats. However, in selenium-deficient rats, short term thyroidectomy did not affect 5'D-I or 5'D-II activities. In contrast to the selenium-dependent changes in circulating T4 levels, little or no change in circulating T3 concentrations occurred. There was a 20% increase in the T3 half-life in selenium-deficient rats. The serum T3 sulfate concentration was increased, and T3 deiodination was reciprocally decreased in the selenium-deficient rats. These data suggest that increased T3 sulfate generation in selenium-deficient rats may lead to greater T3 availability through enterohepatic recycling of the iodothyronine and may explain why there are only minor changes in serum T3 concentrations in selenium-deficient rats.

Animals↗
PubMed1992

Estradiol increases prolactin synthesis and prolactin messenger ribonucleic acid in selected brain regions in the hypophysectomized female rat.

Immunoreactive PRL which is not of pituitary origin, has been identified in many regions of the rat brain. We have previously demonstrated that estradiol increases hypothalamic immunoreactive PRL content in hypophysectomized female rats. To determine if estradiol stimulates PRL synthesis, we examined the effect of estradiol on the in vivo production of PRL, and on the expression of PRL messenger RNA (mRNA) in the hypothalamus, pons, and cerebral cortex. To examine the effect of estradiol on the in vivo production of PRL, [35S] methionine was injected into the lateral ventricle and its incorporation into immunoprecipitable PRL was determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In estradiol, but not vehicle-treated hypophysectomized rats, a 24,000 M(r) immunoprecipitable PRL protein was detected in the hypothalamus and pons-medulla, 2 and 4 h after methionine administration. No immunoprecipitable PRL proteins were detected in the amygdala, hippocampus, cortex, or serum at either time point. In addition, in the hypothalamus, but not the pons-medulla, a second PRL band was detected with an apparent mol wt of 16,000K. To determine if estradiol increased the expression of PRL mRNA, copy DNA was obtained by reverse transcription of poly(A+) mRNA prepared from intact and vehicle or estradiol-treated hypophysectomized rats and analyzed by polymerase chain reaction amplification. In tissues from hypophysectomized rats, there was little, or no, detectable levels of PRL mRNA. In contrast, in estradiol-treated hypophysectomized rats PRL mRNA was easily detected in the hypothalamus and pons-medulla by polymerase chain reaction amplification. These data suggest that estradiol increases the PRL content in the hypothalamus and pons-medulla by increasing PRL gene expression, in a manner similar to that reported in the pituitary.

Animals↗
PubMed1991

Prolactin stimulation of protein kinase C activity in the rat hypothalamus.

Stimulation of cultured hypothalamic slices with PRL causes a rapid translocation of a Ca2+/phospholipid dependent protein kinase from the cytosol to the membrane fraction. The translocation of PKC from the cytosol to the membrane occurred at physiological concentrations of PRL with a maximal response occurring at 10(-10) M. At concentrations above this, there was less PKC activity translocated from the cytosol to the membrane. When injected into the medial preoptic area of the hypothalamus, PRL resulted in a similar translocation of PKC activity. These data clearly indicate that PRL can activate PKC in the rat hypothalamus, and suggest that PKC may be one of the transmembrane signaling mechanisms involved in the regulation of brain function by prolactin.

Animals↗
PubMed1991

Physiological and morphological properties of off- and on-center bipolar cells in the Xenopus retina: effects of glycine and GABA.

We studied the morphology and center-surround organization of Lucifer Yellow injected OFF- and ON-center bipolar cells in the light-adapted Xenopus retina and the effects of glycine and GABA on their cone-mediated light responses. In both classes of cell, prominent antagonistic surround responses up to 20 mV in amplitude could be evoked without first suppressing the center responses with steady illumination. An additional feature of the light-evoked bipolar cell response was a pronounced (up to -24 mV) delayed hyperpolarizing after potential (DHAP) which followed the depolarizing responses of both classes of bipolar cell. The morphological features of dye-injected bipolar cells conformed to the general idea of segregation of ON and OFF pathways in the inner and outer interplexiform layer, however, the morphology of axonal arborizations was different for both classes. OFF-center cells ramified symmetrically around the primary branchpoint, whereas ON-center cells had a strongly asymmetrical arrangement of their axonal tree. The center and surround responses were differentially sensitive to glycine and GABA. Glycine eliminated the antagonistic surround responses in both OFF and ON cells; the center responses were reduced to some extent but were not eliminated. In contrast, GABA affected the hyperpolarizing responses much more strongly than the depolarizing response components. That is, the amplitude of the center response in the OFF cell and the surround response in the ON cell was reduced 80-90% during exposure to GABA, whereas the surround and center depolarizations of OFF and ON cells, respectively, were reduced only 0-10%. Our findings implicate a role for GABAergic and glycinergic pathways in the center-surround organization of bipolar cells in Xenopus retina. In addition, the results suggest that the pathways mediating center-surround antagonism may be different in OFF-bipolar cells vs. ON-bipolar cells.

Animals↗
PubMed1991

Stimulation of hypothalamic prolactin release by veratridine and angiotensin II in the female rat: effect of ovariectomy and estradiol administration.

In the female rat immunoreactive prolactin (IR-PRL) has been identified in the hypothalamus and in other brain regions. Brain IR-PRL is not of pituitary origin and, based on polyacrylamide gel electrophoresis and peptide mapping, shares a high degree of sequence homology with its pituitary counterpart. We have previously shown that hypothalamic tissue can release IR-PRL in vitro when depolarized by potassium. In this study, we examined the release of IR-PRL from hypothalami obtained from intact and ovariectomized rats and incubated in the presence of veratridine (an alkaloid which depolarizes excitable membranes), angiotensin II, or thyrotropin-releasing hormone. Hypothalamic tissue spontaneously released IR-PRL, and this release was significantly increased by veratridine or angiotensin II in a dose-dependent manner. The specificity of the angiotensin-II-evoked IR-PRL release was demonstrated by the inhibitory effect of saralasin, an angiotensin II receptor antagonist, on hypothalamic IR-PRL release. Thyrotropin-releasing hormone (100 microM) had no effect on hypothalamic IR-PRL release. Ovariectomy decreased hypothalamic IR-PRL content and IR-PRL release in response to veratridine and angiotensin II. The effect of estradiol on hypothalamic IR-PRL content and release was also examined by obtaining hypothalami from ovariectomized rats injected with estradiol (1 microgram/day) or vehicle for 5 days. When compared with vehicle injected rats, administration of estradiol significantly increased the hypothalamic IR-PRL content (46 +/- 4 vs. 81 +/- 16 ng/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1990

A chromatic horizontal cell in the Xenopus retina: intracellular staining and synaptic pharmacology.

1. We identified a chromatic-type horizontal cell (C-cell) in the Xenopus retina by intracellular dye injection with Lucifer yellow or horseradish peroxidase (HRP). C-cells hyperpolarized in response to blue light and depolarized in response to red light. 2. In either photopic or mesopic states, moderate-intensity blue and red stimuli evoked responses that were inverted with respect to each other but of similar waveform and latency. In the presence of a bright green adapting field, the maximal voltage (Vmax) of the hyperpolarizing and depolarizing response component approached 30 mV; the kinetics of both waveforms were fast, and the hyperpolarizing response was followed by a small depolarizing overshoot at light OFF. Thus the blue-sensitive photoreceptor is capable of initiating large visual signals under photopic conditions when transmission from green-sensitive rods is suppressed. Under mesopic conditions (no adapting field) the kinetics of both waveforms were slower. The Vmax of the hyperpolarizing response reached 30-40 mV, whereas the cone-mediated depolarization saturated at 15 mV. 3. Both response components of the C-cell showed large receptive fields with no center-surround antagonism. 4. The C-cell perikaryon was located in the distal inner nuclear layer. It emitted four to seven long, tapering processes that ran horizontally for 90-100 microns. Two kinds of terminal dendrites, short and long, extended from the tapering processes toward the layer of photoreceptor bases. 5. Glycine (5-10 mM) completely eliminated the depolarizing response of the C-cell, whereas the hyperpolarizing component was unaffected. In contrast, gamma-aminobutyric acid (GABA; 5-10 mM) had no obvious effect on either component. 6. The C-cell light response was modified in two stages by cis-2,3-piperidine dicarboxylic acid (cis-PDA; 0.5-5 mM): first the depolarizing response disappeared; then the membrane potential hyperpolarized concomitant with a large reduction or elimination of the hyperpolarizing light response. In contrast, DL-2-amino-4-phosphonobutyric acid (APB) had no obvious effect on either response component or the membrane potential of the cell. 7. Our pharmacological findings are consistent with the view that the hyperpolarizing response in the C-cell is mediated by direct synaptic input from a blue-sensitive photoreceptor. The depolarizing response mediated by the red-sensitive cone could be explained by a direct synapse from the red cone or an indirect pathway involving luminosity (L-type) horizontal cells.

Adaptation, Ocular↗
PubMed1990

Diphtheritic polyneuritis in an elderly woman: clinical and neurophysiological follow-up.

A 71-year-old English lady initially presented with a bulbar paralysis and, six weeks later, developed a generalised sensori-motor neuropathy. Corynebacterium diphtheriae mitis was cultured from her throat swab. Despite a good clinical recovery at one month, nerve conduction velocity was at its lowest. As far as the authors are aware, this is one of the few cases of neurophysiological and clinical follow-up in a British subject with diphtheritic peripheral neuropathy. This case emphasises the importance of giving antitoxin early.

Adrenocorticotropic Hormone↗
PubMed1979

Long-term results of pulmonary autograft for aortic valve replacement.

Eighty-five survivors who left hospital after pulmonary autograft replacement for severe aortic regurgitation have been followed critically. Five patients died in the first five years and 80 were followed for six to 11 years. Important aortic regurgitation occurred only early and was always related to technical malpositioning of one autograft cusp. Seven patients with fascial pulmonary valves had problems, requiring removal in four. There was a small (2%) morbidity from the right sided homograft and six were removed five to seven years later for progressive calcification; three of these had been irradiated. Despite a high incidence of trivial diastolic murmurs this valve replacement is still preferred for young patients without dilated aortic roots since the survivors remain well, with excellent, maintained relief of outflow obstruction, without problems from haemolysis and thromboembolism, and without deteriorating autograft function or need for anticoagulants. Histology of five autografts examined up to seven years after operation has shown normal living architecture.

Adolescent↗
PubMed1978

Spatial deficit in familial left-handed children.

This study was designed to evaluate the hypothesis that familial left-handed children who presumably have bilateral representation of language ability should show an impairment in spatial ability. Children, whose average age was 8 yr. and of whom 22 were right-handed, 11 familial left-handed, and 11 non-familial left-handed, were tested on verbal subtests of the Wechsler Intelligence Scale for Children--Revised, i.e., Vocabulary and Similarities and on spatial subtests, i.e., Block Design and Object Assembly. The results did not support the hypothesis that the spatial ability of familial left-handed children would be worse than their verbal ability. However, there was modest support for the hypothesis that familial left-handers were worse in spatial ability than right-handers.

Adolescent↗
PubMed1976

Hormonal dependency in Darier disease.

Variation in the severity of keratosis follicularis relative to states of homonal change was noted in eight women with the disease. Observations included frequent onset near puberty, puberty, exacerbation during menses, and improvement while patients are pregnant or on oral contraceptive agents. It is proposed that states of relative estrogen excess are associated with quiescence of this skin disorder. In support of this hypothesis, three postpubertal women with Darier desease were observed to undergo significant improvement with the use of estrogen-dominant birth control pills.

Adolescent↗