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Biomedical subjects

S S White

Publications and source records attributed to S S White.

At least 19 recordsLinked to original sources

Tyrosine hydroxylase mRNA is increased in old age and norepinephrine uptake transporter mRNA is decreased in middle age in locus coeruleus of Brown-Norway rats.

In normal aging, cell loss occurs in the locus coeruleus (LC), the major noradrenergic nucleus in the brain. This study examined changes in the LC of aged rats by measuring mRNA expression for tyrosine hydroxylase (TH) and the norepinephrine uptake transporter (NET). TH and NET mRNA expression were measured by in situ hybridization in young, middle-aged and aged rats. It appears that in middle age, the transporter system responds initially to LC cell loss by decreasing NET mRNA expression. Then, with further aging and cell loss, TH mRNA expression increases which may potentially increase NE synthesis in the remaining neurons. These findings suggest that multiple regulatory components are used to maintain stable noradrenergic synaptic levels despite neuronal loss. Published by Elsevier Science B.V.

Aging

Linking service climate and customer perceptions of service quality: test of a causal model.

A set of foundation issues that support employee work and service quality is conceptualized as a necessary but not sufficient cause of a climate for service, which in turn is proposed to be reflected in customer experiences. Climate for service rests on the foundation issues, but in addition it requires policies and practices that focus attention directly on service quality. Data were collected at multiple points in time from employees and customers of 134 branches of a bank and analyzed via structural equation modeling. Results indicated that the model in which the foundation issues yielded a climate for service, and climate for service in turn led to customer perceptions of service quality, fit the data well. However, subsequent cross-lagged analyses revealed the presence of a reciprocal effect for climate and customer perceptions. Implications of these results for theory and research are offered.

Commerce

Effect of pentylenetetrazol on the expression of tyrosine hydroxylase mRNA and norepinephrine and dopamine transporter mRNA.

Seizure activity has been shown to have differential effects on the terminal content of the monoamines, norepinephrine (NE) and dopamine (DA). Induction of seizure activity reduces the terminal content of NE, while DA levels remain unchanged or slightly elevated. This study examined the effect of the chemoconvulsant pentylenetetrazol (PTZ) on the mRNA expression of regulatory proteins which maintain the terminal content of NE and DA (i.e., synthesis and re-uptake). The areas examined were the noradrenergic neurons of the locus coeruleus (LC) and dopaminergic neurons of the substantia nigra pars compacta/ventral tegmentum area (SNpc/VTA) in the rat. In the LC, PTZ increased mRNA expression of the immediate early gene, c-fos, and mRNA expression of the synthesizing enzyme, tyrosine hydroxylase (TH), and the re-uptake protein, norepinephrine transporter (NET). This effect on TH and NET was observed only 1 day after the administration of PTZ. In contrast, PTZ did not alter the expression of c-fos mRNA in the SNpc/VTA, but reduced the expression of the dopamine transporter (DAT) mRNA. This effect was observed only 1 day after the administration of PTZ. TH mRNA expression in dopaminergic neurons was elevated initially in a manner similar to that observed in the LC. However, the effect of PTZ on TH mRNA expression in dopaminergic neurons was more prolonged (still elevated 3 days later). These results indicate that the chemoconvulsant PTZ has differential effects on the mRNA expression of regulatory systems (TH and neurotransporter proteins) in noradrenergic and dopaminergic neurons.

Animals

Alterations in mRNA expression of systems that regulate neurotransmitter synaptic content in seizure-naive genetically epilepsy-prone rat (GEPR): transporter proteins and rate-limiting synthesizing enzymes for norepinephrine, dopamine and serotonin.

Two models of genetically epilepsy-prone rat (GEPR) exist, the GEPR-3 and GEPR-9, GEPR-3 and GEPR-9 share a deficiency in presynaptic norepinephrine (NE) and serotonin (5HT) content in specific regions of the central nervous system (CNS). The presynaptic content of dopamine (DA) does not appear to be altered in either adult GEPR strain compared to Sprague-Dawley (SD) rats, the strain from which the GEPR was derived. Presynaptic content of monoamine neurotransmitters, such as NE, 5HT and DA, are maintained by several regulatory proteins which include: synthesis, re-uptake, release, degradation and vesicular transport. To further characterize the monoamine deficiency observed in the GEPR, the mRNA level of the rate limiting enzymes for the synthesis of NE, 5HT and DA and each of the neurotransporter proteins were measured in seizure-naive GEPR-3, GEPR-9 and SD rats. In the locus coeruleus (LC), the major noradrenergic locus, tyrosine hydroxylase (TH) mRNA level was significantly reduced only in GEPR-9 animals compared to SD rats and GEPR-3, while NE transporter (NET) mRNA was significantly elevated in GEPR-3 compared to SD rats and GEPR-9. TH and DA transporter (DAT) mRNA was measured in the dopaminergic neurons of the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA) and zona incerta (ZI), DAT mRNA level was significantly reduced in all dopaminergic neurons in the GEPR-3 compared to SD rats and GEPR-9, while TH mRNA level was significantly elevated in the SNpc/VTA equally in GEPR-3 and GEPR-9 compared to SD rats. In the ZI, TH mRNA level was significantly reduced in GEPR-3 compared to SD rats and GEPR-9. In the dorsal raphe (DR), a major serotonergic locus, tryptophan hydroxylase (TRH) mRNA level was not significantly different from SD in either strain of GEPR; however, 5HT transporter (SERT) mRNA level was significantly reduced in GEPR-9 in the dorsal and lateral regions of the DR compared in SD rats and GEPR-3. These data indicate that two of the regulatory systems that maintain NE, 5HT and DA content are altered in a differential manner in seizure-naive GEPR-3 compared to seizure-naive GEPR-9, with GEPR-3 showing more alterations in dopaminergic neurons. It is uncertain at the present time how these alterations in mRNA level relate to the enhanced seizure susceptibility of these animals. It was apparent that a straightforward correlation between neurotransmitter loss to transcriptional changes in synthesizing enzymes mRNA or to re-uptake protein mRNA was not observed in noradrenergic and serotonergic neurons. Therefore, the decrease in presynaptic NE and 5HT tissue content in these animals may be due to posttranscriptional modification. In contrast, presynaptic DA tissue content which was unaltered in both strains of GEPR, shows an alteration in TH and DAT mRNA level compared to SD rats in all dopaminergic neurons examined. This indicates a possible involvement of DA in regulating the seizure susceptibility of these animals.

Animals

Hemodynamic patterns in two models of end-to-side vascular graft anastomoses: effects of pulsatility, flow division, Reynolds number, and hood length.

Flow behavior in models of end-to-side vascular graft anastomoses was studied under steady and pulsatile flow conditions. Models were constructed to simulate geometries employed in experimental studies on intimal thickening in a canine model. Reynolds numbers, division of flow in the outflow tracts and the pulsatile waveform employed were taken from measurements obtained in the canine model. Flows in the scaled-up, transparent models were visualized with white, neutrally buoyant particles which were photographed under laser illumination and also recorded on video tape under bright incandescent light. Strong, three-dimensional helical patterns which formed in the anastomotic junction were prominent features of the flow fields. Regions of low wall shear, oscillatory wall shear and long particle residence time were identified from the flow visualization experiments. Comparisons with the limited qualitative data available on intimal thickening in vascular graft anastomoses suggest a relation between localization of vascular intimal thickening and those surfaces experiencing low shear and long particle residence time.

Anastomosis, Surgical

Ophthalmologic screening of adults with mental retardation.

Ophthalmological screening was conducted on 113 clients in a work activity center for adults with mental retardation. Thirty-two percent had abnormalities that were neither refractive nor strabismic. We encountered no instance of neglect of current organic ocular disease. However, 37% of clients had at least one eye that either was not within one diopter of emmetropia or that was not corrected to within one diopter of their retinoscopic findings. Ophthalmologists should consider providing screenings in settings familiar to such clients, where they are more likely to be cooperative.

Adult

Cloning, analysis, and bacterial expression of human farnesyl pyrophosphate synthetase and its regulation in Hep G2 cells.

A partial length cDNA encoding farnesyl pyrophosphate synthetase (hpt807) has been isolated from a human fetal liver cDNA library in lambda gt11. DNA sequence analysis reveals hpt807 is 1115 bp in length and contains an open reading frame coding for 346 amino acids before reaching a stop codon, a polyadenylation addition sequence, and the first 14 residues of a poly(A+) tail. Considerable nucleotide and deduced amino acid sequence homology is observed between hpt807 and previously isolated rat liver cDNAs for farnesyl pyrophosphate synthetase. Comparison with rat cDNAs suggests that hpt807 is about 20 bp short of encoding the initiator methionine of farnesyl pyrophosphate synthetase. The human cDNA was cloned into a prokaryotic expression vector and Escherichia coli strain DH5 alpha F'IQ was transformed. Clones were isolated that express an active fusion protein which can be readily observed on protein gels and specifically stained on immunoblots with an antibody raised against purified chicken farnesyl pyrophosphate phosphate synthetase. These data confirm the identity of hpt807 as encoding farnesyl pyrophosphate synthetase. Slot blot analyses of RNA isolated from Hep G2 cells show that the expression of farnesyl pyrophosphate synthetase mRNA is regulated. Lovastatin increases mRNA levels for farnesyl pyrophosphate synthetase 2.5-fold while mevalonic acid, low-density lipoprotein, and 25-hydroxycholesterol decrease mRNA levels to 40-50% of control values.

Amino Acid Sequence

Effects of acute alcohol administration on maternal calcium metabolism and fetal development in mice.

Pregnant C57Bl/10J mice were treated intraperitoneally with alcohol (Group A) or saline (control) on Day 7 of gestation. On Day 7, at 0 hour and again at 4 hour, Group A received 0.020 ml/GM body weight of 25% (v/v) alcohol, while control mice received 0.020 ml/GM body weight of physiological saline. The injection schedule specified corresponds to a specific stage of fetal development, namely gastrulation. On Day 13 of gestation, all animals were placed in individual metabolic cages to monitor both food and water intake and urinary output. The animals were sacrificed on Day 14. Blood was withdrawn and the serum was used for analyses. In addition, resorption sites within the uterine horns were recorded and fetuses examined. Group A animals had significantly lower serum calcium (Ca) than the controls (6.1 +/- 0.7 mG% versus 9.6 +/- 1.6 mG%, P less than .01). By contrast, the same alcohol injected mice had higher serum phosphate (P) than the controls (18.2 +/- 5.9 mG% versus 12.3 +/- 4.0 mG%, P less than .05). Urinary Ca levels were lower (P less than .05) while urinary P values tended to be higher in alcohol injected mothers. Furthermore, Group A mice had litters which were smaller in size, lower in average fetal body weight and had a higher incidence of resorption (18%) than control mice. Examination of the viable fetuses showed that 53% of those from alcohol treated mothers had facial abnormalities while only 12% of the fetuses from the controls looked abnormal. The results indicate that exposure to acute alcohol in this early stage of pregnancy creates disturbances in maternal Ca metabolism, which may be ultimately related to the observed fetal abnormalities.

Abnormalities, Drug-Induced

Use of electroacupuncture as an analgestic for laparotomies in two dairy cows.

Electroacupuncture was used as the sole analgesic for standing laparotomies on 2 Friesian cows. Needles placed in the lumbosacral space, and second lumbar interspinous space and high in the lumbar fossa were stimulated with an AC current at 15 to 28 Hz. The analgesia produced was similar to that of a paralumbar nerve block.

Abdomen

Peripubertal decline in ovarian LHRH receptor content: characterization and distribution.

In the rat, ovarian LHRH receptor content, as measured by the binding of 125I-D-Ala6, Pro9-LHRH (A-LHRH) to ovarian membranes, decreases markedly during the days preceding the first preovulatory gonadotropin surge. The present study shows that the decrease in LHRH receptor number occurs exclusively in granulosa cells, and that the greatest rate of decline takes place between the juvenile period and the early proestrous phase of puberty. In contrast to granulosa cells, membranes prepared from ovarian tissues after removal of these cells demonstrated no significant change in LHRH binding capacity throughout puberty. Scatchard analysis of competition curves, constructed using membranes from whole ovaries, revealed that receptor affinity remains unchanged (Ka = 9 X 10(9) M-1) as the receptor number decreases. Kinetic binding studies demonstrated that LHRH binding to its receptor reaches equilibrium within 40 min and can be displaced by addition of unlabeled hormone. A kinetic estimate of receptor affinity provided values similar to those obtained by Scatchard analysis. Treatment of ovarian membranes with MgCl2 to uncover occupied binding sites results in more than 70% dissociation of bound labeled ligand. Dissociation of endogenous LHRH using this procedure resulted in some increase in available binding sites only in juvenile rats, but not in first proestrous or first estrous animals in which receptor content was low. The results demonstrate that the decline in ovarian LHRH receptors observed during peripubertal days is confined to granulosa cells, is not due to changes in receptor affinity, and represents a true loss of binding sites.

Animals

Pituitary LHRH receptors during puberty in the female rat: is the proestrous decline in receptor content due to occupancy?

As during the adult estrous cycle, the number of pituitary luteinizing hormone-releasing hormone (LHRH) receptors was found to increase prior to the first preovulatory surge of LH. Receptor content, as measured by the binding of the analog 125I-D-Ala6-Pro9-LHRH to pituitary membranes, declined markedly at the time of the first LH surge, remaining low during the first estrus and first diestrus. When pituitary membranes from animals undergoing an LH surge were incubated with MgCl2 to dissociate endogenously bound hormone, available binding sites were restored to pre-LH surge values. The increase in LHRH binding capacity was not related to an increase in receptor affinity, and it was not demonstrable in other pubertal phases. MgCl2 may have unmasked receptors made cryptic at the time of the LHRH-induced LH surge. Nevertheless, the results are compatible with the view that the proestrous decline in LHRH receptor content is, at least in part, due to occupancy of binding sites by endogenous hormone.

Animals

Changes in ovarian LHRH receptor content during the onset of puberty in the female rat.

LHRH and some of its analogs have been reported to exert inhibitory effects on ovarian function, seemingly following interaction of the neurohormone with specific, high affinity binding sites. The present experiments were undertaken to determine whether LHRH binding sites in the ovary undergo quantitative changes during the onset of puberty in the rat. Changes in LHRH receptor content were assessed by the binding of the stable LHRH analog, [D-Ala6, Pro9]-LHRH to ovarian membrane preparations. LHRH binding in prepubertal rats (anestrus, A) was 166 +/- 11 fmol/mg protein, declined gradually (to 127 +/- 14 fmol/mg protein) during the early proestrous (EP) phase of puberty--a time at which intrauterine fluid begins to accumulate and uterine weight increases more rapidly--and became even lower (75 +/- 4 fmol/mg protein) by 1300 h of the day of first proestrus (LP), prior to the initiation of the first gonadotropin surge. At the time of the surge (1600 h) binding was 70 +/- 3 fmol/mg protein. LHRH binding was minimal on the day of the first estrus (E) and increased slightly on diestrus (D). The results indicate that the ovarian steroidogenic activation that precedes the first surge of gonadotrophins in the rat is associated with a marked loss in ovarian LHRH receptor content and suggest that a reduction in LHRH inhibitory function within the ovary may be a contributing factor to the pubertal enhancement in ovarian secretory activity.

Animals

Activation of growth hormone short loop negative feedback delays puberty in the female rat.

Implantation of GH in the median eminence of the hypothalamus of 23-day-old female rats tonically inhibited serum GH levels throughout prepubertal development (days 23-36) and depressed GH diurnal pulsatile release. Puberty was significantly delayed in GH-deficient animals, a delay associated with a blunted in vitro ovarian steroidal responsiveness to gonadotropins (particularly estradiol) and a marked decrease in prepubertal uterine weight, as evaluated 4, 7, and 13 days after GH implantation. The prepubertal body weight increase was also depressed. Neither ovarian weight nor serum levels of LH, FSH, PRL, or TSH were consistently altered by the GH implant. In addition, evaluation of pulsatile PRL release in 33-day-old rats revealed no difference between control and GH-deficient animals. Ovarian LH receptor content was lower in GH-implanted rats than in controls, suggesting that a decrease in LH receptors may be one of the mechanisms by which a chronic decrease in serum gH depressed the prepubertal ovarian estradiol and, to a lesser extent, the progesterone response to gonadotropins. A direct ovarian site of action for GH was indicated by the results of experiments in which GH was administered to immature hypophysectomized estrogen-treated rats. The in vitro ovarian progesterone response of the GH-treated animals to both hCG and human FSH was distinctly increased by prior in vivo GH treatment. This effect of GH was not reproduced either by the in vivo administration of LH at a dose calculated by RIA to be contaminating the GH preparation or by FSH at a dose that induced a marked increase in aromatase activity in the same ovaries. GH treatment of hypophysectomized rats failed to affect either aromatase activity or hCG-induced estradiol release, indicating that GH does not directly facilitate the production of estradiol by the ovary. The fact that intact rats with GH implants did not actually show a decrease in the ovarian estradiol response to hCG but, rather, failed to show an increased response at the same time as control animals strongly suggests that ovarian maturation was delayed in GH-deficient rats. It is suggested that, in addition to PRL, GH may also play a role in the process of prepubertal reproductive development by enhancing the steroidal response of the ovary to gonadotropins.

Animals

Changes in ovarian luteinizing hormone and follicle-stimulating hormone receptor content and in gonadotropin-induced ornithine decarboxylase activity during prepubertal and pubertal development of the female rat.

Ovarian hCG and FSH receptor content was measured at different postnatal ages (days 4-32), at 4-day intervals, and expressed as counts per min 125I-labeled hormone bound/micrograms DNA. Specific FSH binding was minimal at day 4 and increased to a maximum at day 28, with the greatest rate of increase between day 4 and 16. hCG receptor content increased 6-fold between day 4 and 32, but contrasting with FSH, its greatest rate of increase occurred between day 16 and 28. The effectiveness of in vivo treatment with LH in inducing ovarian ornithine decarboxylase (ODC) activity, measured in 20,000 X g supernatants by the in vitro formation of 14CO2 from labeled ornithine, increased significantly during prepubertal development (days 21-33), paralleling the changes in hCG receptors. Ovarian hCG and FSH receptor content was also measured during the time of puberty. Specific hCG binding increased from anestrus (juvenile 32-day-old animals) to 1300 h of the first proestrus. The levels declined significantly by 1600 h of first proestrus and reached minimal values by the morning of estrus. Specific FSH binding also increased from anestrus to first proestrus, but to a much lesser degree, the levels showing only minor fluctuations during the rest of the cycle. hCG receptors measured in granulosa cells during puberty increased to an even greater extent than in the whole ovary; binding exhibited an 8-fold increase from anestrus to 1300 h of first proestrus and then declined to much lower values on estrus and the first diestrus. The capacity of LH to induce ovarian ODC activity increased markedly between anestrus and first proestrus, declining thereafter, and again paralleled the changes in LH receptor content. Evaluation of the kinetics of binding of hCG and FSH with their respective receptors in ovaries of 28-day-old rats revealed that the binding of hCG reached equilibrium within 4-8 h, whereas the binding of FSH attained equilibrium between 12-24 h. In both cases, however, the labeled hormones were clearly dissociable from their respective receptors by addition of an excess of unlabeled hormone. Moreover, although the ovarian receptor content of both hCG and FSH increased during prepubertal development, the equilibrium association constant of either hormone with its receptor remained unchanged. The results suggest that the infantile increase in FSH receptors may be induced by the high serum FSH levels present at that age and that, as shown by others in hypophysectomized rats, the subsequent increase in hCG receptors is, at least in part, an FSH-dependent phenomenon. The parallel changes in hCG receptors and LH-induced ODC activity during pre- and peripubertal development strongly suggest that an increase in LH binding capacity plays a fundamental role in the process of ovarian growth. It is also suggested that the changes in the steroidogenic ovarian response to hCG previously observed in peripubertal rats are, at least in part, determined by changes in ovarian LH receptor content.

Animals

Delayed puberty induced by chronic suppression of prolactin release in the female rat.

To study the effect of PRL deficiency on the onset of puberty, PRL release was chronically inhibited by treating immature female rats with the dopaminergic receptor agonist, bromoergocriptine (CB-154). The resulting alterations in the time of puberty onset, and in other associated parameters, such as serum levels of pituitary hormones, ovarian responsiveness to gonadotropins and ovarian hCG receptor content were then evaluated. CB-154 was provided in the drinking water from day 22 onward at the concentration of 20 and 100 micrograms/ml. The treatment resulted in almost complete suppression of serum PRL levels throughout the entire period studied (day 22 to first diestrus). In contrast, serum GH, FSH, and LH levels were not depressed. Likewise, pulsatile release of FSH was not affected and only a subtle alteration in pulsatile LH release was apparent. The onset of puberty, as determined by the age at vaginal opening, and at first diestrus after the first estrus and by the presence of corpora lutea at sacrifice (first diestrus), was markedly delayed in the hypoprolactinemic (HPO) rats. This inhibitory effect of CB-154 was completely prevented by concomitant administration of PRL. Ovarian weight was significantly decreased in HPO rats at the three ages studied (27, 32, and 36 days of age). By day 36, 50% of the control animals had already ovulated, as compared with only 9% of the HPO rats. Microscopic examination of ovaries from HPO rats revealed a retarded follicular development. In vitro ovarian progesterone response to hCG studied at day 32 and 36 of age was reduced in the HPO rats. Uterine growth was also depressed in HPO rats, the ovaries of which, when incubated in vitro, failed to show the prepubertal increase in estrogen response to hCG seen in control rats between day 32 ad 36. Aromatase activity, as measured by the in vitro release of estradiol from ovaries incubated in the presence of an excess of androgen substrate, was depressed in HPO rats. hCG receptor content in the ovaries from HPO rats (counts per min [125]hCG bound per micrograms DNA) was also lower than that of control animals at day 32 and 34 but not at day 36. However, at this later time the hCG receptor content per milligram of ovary was still significantly reduced in HPO rats. The results support the view that PRL plays an important role in the process of ovarian development that leads to the onset of puberty in the female rat and that this effect is, at least in part, exerted through a positive influence of PRL on ovarian LH receptor content.

Animals