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S Cheung

Publications and source records attributed to S Cheung.

At least 37 records · Page 2Linked to original sources

Gonadal steroid hormone-dependence of beta-endorphin-like immunoreactivity in the medial preoptic area of the rat.

Gonadal steroid hormones are known to alter the expression of proopiomelanocortin (POMC) mRNA in neurons of the arcuate nucleus (ARC). These neurons send projections to the medial preoptic area (MPOA), wherein mu-opiate receptor density is cyclical and gonadal steroid hormone-dependent. Although beta-endorphin-(beta-Endo) content in the MPOA is known to vary across the estrous cycle, the effect of gonadal hormones on the distribution and density of beta-Endo-like immunoreactive (IR) fiber density in the preoptic area is unknown. In the present study, immunohistochemical staining was used to investigate the effects of gonadal steroid hormone treatment on beta-Endo-like IR fibers in the MPOA of ovariectomized (OVX) female rats. The density of beta-Endo-like IR fibers was low in the MPOA of OVX rats, but increased slightly following treatment with 17 beta-estradiol (E2) or 3 h after subsequent progesterone (P) injection. However, beta-Endo-like IR fiber density increased significantly 27 h after E2P treatment, and remained elevated 51 h after E2P treatment in the periventricular zone and in the medial portion of the medial preoptic nucleus, although the general distribution of fibers was unchanged. These results suggest that the density of MPOA beta-Endo innervation is normally gonadal steroid hormone-dependent and that the medial MPOA contains greater opioid tone than the lateral MPOA regardless of the hormonal state. Furthermore, since beta-Endo-like IR fiber density remained elevated even though gonadal hormone levels decreased, additional factors might modulate the release or turnover of beta-Endo in the MPOA during normal estrous cycling.

Animals↗

Gonadal steroid hormone regulation of proopiomelanocortin gene expression in arcuate neurons that innervate the medial preoptic area of the rat.

The density of beta-endorphin (beta-endo)-like immunoreactive (IR) fibers in the medial preoptic area (MPOA) has been shown to vary across the estrous cycle and is gonadal steroid hormone-dependent. These beta-endo-containing fibers are presumably projections of proopiomelanocortin (POMC) neurons which are located in the arcuate nucleus (ARC). POMC mRNA level varies across the estrous cycle in the ARC and its expression is differentially altered by gonadal steroid hormones. However, it is unclear how gonadal steroids regulate POMC gene expression in ARC neurons that innervate the MPOA. Therefore, combined fluorogold (FG) retrograde neuronal labeling and in situ hybridization histochemistry were used to investigate the effects of gonadal steroid hormone treatment on POMC gene expression in ARC neurons supplying the MPOA of ovariectomized (OVX) female rats. POMC-expressing cells were located in the ARC and median eminence (ME), wherein such neurons were significantly larger than unlabeled cells that surround them. A relatively greater number of ARC POMC neurons were observed to innervate the medial portion of the medial preoptic nucleus (MPN) than the lateral portion of the MPN. Estradiol (E2) and progesterone (P) treatment before FG injection did not affect the number of FG and POMC double-labeled neurons in the ARC, which suggests that hormone treatment did not alter the number of POMC-expressing neurons projecting to the MPN. In OVX animals, ARC POMC mRNA labeling was relatively low, and increased significantly in neurons of the most rostral ARC region 48 h after E2 treatment. P administration enhanced and prolonged the effect of E2 in this group of ARC neurons. E2P treatment significantly increased POMC mRNA expression beginning 13 h after P injection in all but the most caudal ARC POMC neurons. Thereafter, E2P treatment gradually increased POMC mRNA expression for at least 1 additional day. Gonadal steroid hormone treatment apparently affects POMC mRNA expression uniformly in neurons of the same ARC subdivision without regard to their efferent targets. Diurnal variation of POMC mRNA expression is present only in the most rostral ARC region, which contains a population of E2-sensitive POMC neurons. The results suggest that the relatively greater beta-endo-like IR fiber density in the medial MPN is due to a greater number of POMC neurons innervating this region. The pattern of innervation of the MPN by POMC neurons is unaffected by gonadal steroid hormone treatment, which appears to induce POMC expression in ARC neurons, and eventually to stimulate the synthesis and transport of beta-endo in POMC neuronal axons which project to the MPOA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

End-tidal carbon monoxide in newborn infants: observations during the 1st week of life.

Serial end-tidal carbon monoxide corrected for ambient CO (ETCOc) levels were measured in an ethnically diverse population of 87 normal newborn infants during the first 5 days of life. The results demonstrate a progressive reduction in ETCOc from 1.6 +/- 0.4 to 0.8 +/- 0.2 ppm. These levels were unrelated to ethnicity, but were inversely related to serum bilirubin levels. We conclude that ETCOc is not a useful indicator for predicting the course of transitional hyperbilirubinemia in the normal newborn infant.

Asian People↗

Gonadal steroid hormones and hypothalamic opioid circuitry.

Endogenous opioid peptides derived from several gene families are localized within hypothalamic regions known to be involved in the regulation of reproduction. For example, the proenkephalin gene products, met- and leu-enkephalin, and the proopiomelanocortin (POMC) gene product, beta-endorphin, are found in the rat medial preoptic area (MPOA). Moreover, the expression of these peptides and their receptors varies across the estrous cycle in the female rat. We have examined the gonadal steroid regulation of mu-opiate receptors and opioid peptides in the MPOA, and POMC mRNA expression in neurons that innervate the MPOA. mu-Opiate receptors in the MPOA are sexually dimorphic and gonadal steroid hormone-dependent. Hormonal priming of ovariectomized rats with estrogen and progesterone (P) upregulates MPOA mu-receptors 27, but not 3, hr after P treatment. Inhibition of protein synthesis during the first 6 hr after P prevents receptor upregulation. The density of beta-endorphin fibers in the MPOA also increases following hormone treatment, and POMC mRNA expression in neurons that innervate the MPOA is induced by hormone treatment beginning 13 hr after P treatment. This delayed response might be ubiquitous among POMC neurons, as those innervating the median eminence also exhibit increased POMC mRNA expression along a similar time course. The results suggest that hormonal feedback regulates opioid peptides which act at mu-receptors in the MPOA to influence reproductive behavior and cyclicity. These opioid functions represent an important component in the complex regulatory processes which control reproduction.

Animals↗

Anti-imipramine antibodies recognize endogenous serotonin uptake and imipramine binding inhibitors.

Calf brain and human platelet extracts purified by Bio-Gel P2 column chromatography contained substances that inhibited serotonin uptake and 3H-imipramine binding. Some of these endogenous substances were also recognized by rabbit antibodies produced against imipramine. The data suggest the possible existence of endogenous serotonin uptake modulators, which may possess a partial molecular structure similar to that identified by the antibodies.

Animals↗

Human islet xenograft survival in diabetic rats. A functional and immunohistochemical study.

Prolonged survival of human islet xenografts under the kidney capsule of diabetic rats was achieved. Human islet xenograft survival time for the nonimmunosuppressed and single-dose antithymocyte serum-treated rats were 3.7 +/- 0.33 days (mean +/- SE, n = 6) and 4.2 +/- 0.63 (n = 4), respectively. In the recipients given 5 doses of ATS after islet transplantation, the graft survival time was significantly prolonged to 18.2 +/- 1.9 days (n = 6). An intravenous glucose tolerance test was performed on 3 recipients with a functional graft 12 days after xenotransplantation. The mean K rate was 1.44 +/- 0.43 (n = 3) compared with that of 2.1 +/- 0.14 (n = 5) found in normal control rats. Human C-peptide was present in the rat recipients following islet transplantation. In addition all 3 recipients showed significant basal human C-peptide values posttransplant and achieved levels of above 2.4 ng/ml during IVGTT. Morphologic and immunohistochemical examination of the islet grafts show that in recipients without immunosuppression or with a single dose of ATS, there was marked degree of fibrosis with little endocrine tissue left in the graft area by day 5. In contrast, the xenograft from recipients treated with 5 doses of ATS still contained well-preserved islet tissue with many insulin and glucagon containing cells on the day of graft removal when blood glucose had returned to the hyperglycemic level. Infiltration of the graft area with lymphoid cells (OX1+, OX8+, and W3/25+) was prominent, but they were not detected within the islets. Staining with monoclonal antibody clone L243 did not detect any expression of human class II antigen on the human pancreatic endocrine cells undergoing rejection by the host. This study has shown that with adequate immunosuppression human islet xenograft can normalize the blood glucose with prolonged survival time in diabetic rat recipients. The discordant xenotransplantation model used in this study would be useful for future xenotransplantation studies.

Animals↗

Solution conformations of DNAs containing binding sites of the catabolite gene activator protein and lac repressor protein: characterization by Raman spectroscopy.

Raman spectra from three subfragments of the Escherichia coli lactose promoter region were obtained in 0.1 M NaCl. The three DNAs are 21, 40, and 62 bp in length. The 21 and 62 bp DNAs contain the binding site for the catabolite gene activator protein (CAP). The 40 bp DNA contains the binding site for the lac repressor. A quantitative analysis of Raman band characteristics indicates an overall B-type conformation for these gene regulatory sites. Bands which correspond to A-family (807 cm-1) and B-family (834 cm-1) deoxyribose phosphate vibrations have the same intensities as bands found in heterogeneous DNAs. The spectra of the 21 bp CAP site have, however, a small band at 867 cm-1 and several other small differences similar to some characteristics observed in C-DNA spectra. Several dG nucleosides in the CAP site appear to be altered from the conventional C2'-endo/anti conformation. At 45 degrees C, well below the melting region of these DNAs, small changes occur in the spectra of the 40 bp lac repressor site which are not observed in the other DNAs. A weak band occurs at 705 cm-1, and intensity changes are observed at 497, 682, and 792 cm-1. The changes suggest that the conformations of several dG nucleosides are altered and that a small region may exist with characteristics of an A-family backbone. This conformational change at 45 degrees C coincides with previous NMR observations indicating an enhanced imino proton exchange rate at a GTG sequence within the lac operator site.

Binding Sites↗

A recurrent DNA sequence at sites of protein interaction.

Variation in the observed spin lattice relaxation rate (Robs) interpreted as proton exchange dominated in sequences corresponding to part of promoters where RNA polymerase initiates mRNA synthesis has been observed by both Patel et al. and Reid and co-workers. A higher Robs was also seen in the TA pair of the GTG/CAC in the sequence corresponding to the lambda phage cro repressor binding site by Kyogoku et al. As we pointed out in the introduction, the one case where a three-dimensional structure for a turn of a helix is known shows clear structural heterogeneity which has led to detailed consideration of geometry of regulatory regions. Nussinov and collaborators have generalized the details of the Dickerson dodecomer to note potential similarities in operators including the lac system and the enhancer sequences described above. Like the steric considerations of Calladine and Dickerson and nearest neighbor structure analysis of Bubienko et al., the focus is on the geometry of a sequence leading to base tilt angles and potential overlap since they are measurable parameters. With the observation that the DNA molecule is both structurally and dynamically flexible, there will no doubt be many new variables that can be made as a function of DNA sequence. Biophysical chemists in some ways are like the intoxicated person searching for a lost key at a site different from where it was lost because that is where the light is best. Thus, each physical method has its most convenient observable. It is hoped that the above discussion illustrates that a very large and diverse set of biochemical results are awaiting detailed explanation in molecular terms using the illumination of high resolution physical techniques.

Antibodies↗

Correlation of lac operator DNA imino proton exchange kinetics with its function.

The kinetics for imino hydrogen exchange, at individual base pairs in the DNA sequence corresponding to the lactose operon operator of Escherichia coli, has been examined by NMR saturation recovery measurements as a function of temperature. Three 17-base-pair subsections of the lac operator DNA were chemically synthesized for these studies. The results support our previous observations in the 36-base-pair complete lac operator DNA fragment that has been used in our previous NMR studies. The results indicate faster opening kinetics at a GTG/CAC that is also the site of operator mutations leading to the highest level of constitutive beta-galactosidase synthesis. The GTG/CAC sequence occurs frequently and often symmetrically in prokaryotic and eukaryotic DNA sites where one anticipates specific protein interaction for gene regulation or recombination.

DNA, Bacterial↗

Possible molecular detent in the DNA structure at regulatory sequences.

A common feature that appears in a number of DNA sites where proteins interact is the sequence GTG/CAC. In the lac operator this sequence leads to a region with a higher imino proton exchange rate well below the optical melting temperature. It is suggested that this reflects a structural feature recognized by proteins that bind specific sites on the DNA molecule.

Base Sequence↗

An automated verbal medical history system.

Computer-based automated medical history acquisition systems have not been as widely utilized as originally anticipated. The high cost, limited accessibility and alien nature of the computer terminal equipment have all been cited as important factors in the limited acceptance. A system has been developed that makes it possible to use a standard household telephone as the computer input and output terminal in obtaining medical history data. Patient acceptance is excellent, and medical information gathered using this technique is as accurate as that obtained by self-administered questionnaires or personal interviews. This system maintains the advantages of the terminal-based automated history program while eliminating many of its deficiencies.

Computers↗

Analysis of the bradykinin response in dogs and its antagonism by analgesic drugs.

Dogs respond to bradykinin (triacetate) by struggling, vocalizing, and/or biting. In 128 dogs used twice, the threshold dose of the peptide increased more than 2-fold, while its onset and duration of action were unchanged. In both trials, the frequency distribution of the threshold dose was not normal; struggling occurred alone or with vocalization and/or biting in 95% of the animals in the first trial and in 96% of the animals in the second trial. In assaying analgesic drugs for antibradykinin activity, multiples of the threshold dose of the peptide were given after oral administration to compensate for tachphylaxis. The oral ED50 values (95% confidence limits) were 0.80 (0.50--1.06) mg/kg for d-amphetamine, 1.20 (0.63--2.57) mg/kg for indomethacin, 1.90 (0.50--6.48) mg/kg for methadone, 15.0 (8.0--30.9) mg/kg for phenylbutazone and 50.0 (20.0--120.0) mg/kg for acetylsalicylic acid. ED50 values for d-proproxyphene, codeine, meperidine, pentazocine and ethoheptaxine by the oral route could not be determined. The intravenous ED50 (95% confidence limits) of meperidine was 0.80 (0.30--1.90 mg/kg. The antibradykinin model in dogs is sensitive to orally administered acetylsalicylic acid-type analgesic compounds which may be a reflection of their prostaglandinsynthetase inhibiting properties.

Analgesics↗