In situ hybridization for showing hormone effects on oxytocin mRNA in specific populations of hypothalamic neurons and their possible participation in multiplicative hormonal responses.
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Biomedical subjects
Publications and source records attributed to S K Chung.
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Antisense RNA targeted against the major capsid protein (MCP) of Lactococcus lactis subsp. cremoris bacteriophage F4-1 reduced bacteriophage replication by up to 50%. The region containing the mcp gene was oriented to transcribe the antisense strand using a L. lactis subsp. cremoris Wg2 promoter. The size of the mcp insert transcribed affected the level of bacteriophage inhibition and the greatest level of inhibition was achieved using a 301-bp fragment from the 5' end of the mcp. Antisense mcp RNA constructs were stable and did not alter the endogenous plasmid profile in the host, L. lactis subsp. cremoris F4-1. There were, however, some adverse effects on the host during the stationary phase as exhibited by a decline in cell density.
Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) was used to differentiate recurrent or residual malignant disease from the effects of cancer treatment. Transaxial images were obtained after injection of 5-10 mCi (185-370 MBq) of F-18 FDG in 68 patients (including 33 with brain tumors) whose posttreatment computed tomographic (CT) or magnetic resonance (MR) imaging findings had been suggestive of malignant disease. PET findings were correlated with surgical results in 18 patients and with the outcomes of CT, MR imaging, clinical, and laboratory 9-month follow-up studies in 50 patients. There was good agreement between F-18 FDG uptake and presence or absence of malignant disease except in four cases of brain tumors in which histologic findings could not be correlated with biologic behavior. The putative sensitivity and specificity in the 33 cases of brain tumors were 80% and 94%, respectively. The authors conclude that PET with F-18 FDG is useful in detection of previously treated metabolically active tumors but is limited in diagnosis of recurrent microscopic or metabolically inactive tumors.
This paper deals with the problem of improving the capability of the medical decision support system (MDSS) for diagnosing nasal allergy by integrating the previously developed expert system with the neural network approach. Three knowledge acquisition methods were used to develop the expert system: statistical, rule-based, and the combined approach. Among the three, a combined approach showed the best prediction rate based on discriminant analysis. Using the results of a combined approach as input values, the neural network was developed using back-propagation method. Unlike the expert system, the neural network system provides the resulting allergy status in probabilistic terms. Managerial as well as legal issues were also discussed in this paper.
Modulation of the activity of potassium and other ion channels is an essential feature of nervous system function. The open probability of a large conductance Ca(2+)-activated K+ channel from rat brain, incorporated into planar lipid bilayers, is increased by the addition of adenosine triphosphate (ATP) to the cytoplasmic side of the channel. This modulation takes place without the addition of protein kinase, requires Mg2+, and is mimicked by an ATP analog that serves as a substrate for protein kinases but not by a nonhydrolyzable ATP analog. Addition of protein phosphatase 1 reverses the modulation by MgATP. Thus, there may be an endogenous protein kinase activity firmly associated with this K+ channel. Some ion channels may exist in a complex that contains regulatory protein kinases and phosphatases.
Possible estrogen influences on oxytocin mRNA expression were studied in preoptic and anterior hypothalamic regions as might be important for behavioral as well as neuroendocrine controls. In situ hybridization for oxytocin mRNA determination was supported by immunocytochemical identification and was compared with vasopressin mRNA in situ hybridization. With these techniques, oxytocin-expressing neurons were identified in medial preoptic, anterior commissural, periventricular, paraventricular, supraoptic, and perifornical nuclei as well as the bed nucleus of the stria terminalis and intersupraopticoparaventricular (internuclear) islands. Distribution and number of oxytocin mRNA-containing neurons and oxytocin mRNA levels were compared between ovariectomized control rats given cholesterol implants and ovariectomized rats given short-term (2 days) or long-term (2 months) estradiol treatment (10% estradiol, subcutaneous silastic implants). Effectiveness of long-term estrogen treatment was confirmed behaviorally. While there was a trend in several cell groups for a larger number of oxytocin-mRNA-containing neurons to be observed following 2 days of estrogen treatment, this was not statistically significant. Moreover, additional oxytocin-mRNA containing cell groups were not seen after short or long estradiol treatment. With computer-aided analysis, mean pixels per oxytocin-mRNA expressing neuron (reflecting oxytocin mRNA content) were compared between groups: In the supraoptic nucleus and the anterior commissural nucleus, these were increased both by 2 days and 2 months of estradiol treatment. These differences may be important in modulating female reproductive behavior. Present findings also suggest that estradiol can affect the oxytocinergic system via an indirect route since the cell groups influenced here by estradiol do not contain estrogen receptors. Oxytocinergic neurons may serve as a good system to compare direct transcriptional with indirect effects of hormones.
A preparation for the study of sexual function in anesthetized spinal male and female rats is discussed. Urethral stimulation in males elicited penile erection, ejaculation, and rhythmic contractions of the striated perineal muscles. In females, vaginal and uterine contractions and rhythmic contractions of the perineal muscles were elicited. These responses show many similarities to responses seen during sexual climax in unanesthetized humans and animals. This response, which we refer to as the urethrogenital reflex, is unaffected in either sex by gonadectomy. We determined that the urethrogenital reflex is produced by a spinal pattern generator and is under tonic descending inhibition from the brain stem. We conclude that this preparation may be a valuable model for experimental study of the neural mechanisms of sexual function in both sexes.
A case report is presented in which there were computed tomographic (CT) findings of struma ovarii (SO) simulating a teratodermoid cyst. The patient was a 73-year-old woman with a painful mass in the lower abdomen. CT revealed a large complex mass with multiple cystic and solid components. One of the cysts had fat-fluid level and minor calcification in the wall. The histological findings were struma ovarii. To our knowledge, these CT findings have not been described previously. Our case demonstrates the importance of including struma ovarii in the CT differential diagnosis of teratodermoid cysts.
Ventromedial hypothalamic projections to the midbrain central gray may be involved in the mediation of female reproductive behavior. In order to demonstrate and examine projections of the ventromedial nucleus in the midbrain central gray, in the rat, electrolytic lesions were placed in the ventromedial nucleus and the midbrain central gray was examined for ultrastructural signs of degeneration at various intervals, i.e. 27.5 h and two, four, six and eight days following the lesions. The fine structure of the midbrain central gray of unlesioned animals was also examined to characterize its normal morphology and to establish a baseline with which to compare the effects of the lesion. In unlesioned animals, the neuropil of midbrain central gray contained several synaptic types, with axodendritic synapses appearing to be the most predominant. Dendrites contained well-preserved microtubules. Synaptic endings contained many clear, round vesicles and some contained dense-cored vesicles as well. Neuropil synapses were both asymmetric and symmetric. Cell bodies were characterized by light cytoplasm and had asymmetric and symmetric synapses on their surface. Following electrolytic lesions in the ventromedial nucleus, various types of degenerative patterns were seen in the midbrain central gray, including electron-dense, flocculent, watery, and pinocytotic degeneration. Specific characteristics of degeneration included shrunken, dense axons and endings, clumped synaptic vesicles, abnormally large, dark mitochondria, membranous sacs of various sizes, swollen endings with reduced numbers of synaptic vesicles, and endings and processes containing large numbers of coated vesicles. Some of these signs were already evident at 27.5 h following the lesion. In addition, degenerating postsynaptic processes and cell bodies were seen in the midbrain central gray. At 27.5 h survival time, degenerating dendritic processes often appeared swollen, devoid of microtubules, and contained enlarged mitochondria. At longer survival times neuronal degeneration was observed in the midbrain central gray, characterized by electron-dense cell bodies and pycnotic nuclei. Both degenerating pre- and postsynaptic elements appeared to be engulfed by glial processes. Control lesions in non-hypothalamic regions which project to the midbrain central gray, i.e. nucleus gigantocellularis and pontine reticular formation and in a non-projecting region, i.e. parietal cortex, were performed.(ABSTRACT TRUNCATED AT 400 WORDS)
In the preceding experiments with electrolytic lesions of the ventromedial nucleus of the hypothalamus, we showed pre- and postsynaptic degeneration in the midbrain central gray of the rat. The postsynaptic degeneration seen may indicate a transneuronal effect of the ventromedial nucleus on the midbrain central gray. Electrolytic lesions, however, destroy afferent endings and fibers in passage, so that the postsynaptic degeneration seen in the midbrain central gray may be due to retrograde degeneration of midbrain central gray afferents to the ventromedial nucleus or due to degeneration of fibers in passage. In order to distinguish among these possibilities, chemical, i.e. kainic acid and N-methyl aspartate, lesions were made in the ventromedial nucleus and the ultrastructure of the midbrain central gray and cerebral cortex was examined at various intervals following the lesions. Both of these excitotoxins have been shown to destroy neurons, sparing afferent terminals and fibers in passage. Animals receiving kainic acid lesions in the right ventromedial nucleus were allowed to survive for one week, and animals receiving N-methyl aspartate lesions in the right ventromedial nucleus were permitted to survive for four, eight, and 20 days. Midbrain central gray tissue of unlesioned animals served as a control for both kainic acid and N-methyl aspartate lesions. In addition, other control animals received injections of the same amount of N-methyl aspartate in the right parietal cortex and were permitted to survive for four and eight days. For each of the above injection and survival conditions, the left cortex and subdivisions of the midbrain central gray were removed and processed for electron microscopy. Animals receiving ventromedial hypothalamic lesions with both kainic acid and N-methyl aspartate showed signs of pre- and postsynaptic degeneration. A quantitative analysis (General Linear Model Procedure) of degeneration was performed on the cortex and midbrain central gray of animals receiving N-methyl aspartate lesions in the ventromedial nucleus and cortex, and several parameters were measured. Animals receiving ventromedial hypothalamic lesions and surviving for eight and 20 days show significantly higher ratios of degenerating presynaptic elements to total presynaptic elements, degenerating postsynaptic elements to total postsynaptic elements, and degenerating total elements to total elements, in the midbrain central gray than in the cortex. Furthermore, the ratio of degenerating postsynaptic elements to total postsynaptic elements is larger than the other ratios.(ABSTRACT TRUNCATED AT 400 WORDS)
A novel preparation for the study of male and female sexual function in anesthetized, acutely spinalized rats is reported. In both sexes, the coitus reflex (the neuromuscular concomitants of sexual climax) could be elicited by mechanical stimulation of the distal urethra. It is concluded that the spinal sexual circuitry is essentially similar in both sexes and that the coitus reflex is generated by a hormone-insensitive spinal pattern generator and is triggered by a simple peripheral stimulus.
Axons of ventromedial hypothalamic (VMH) neurons have been previously shown to terminate in the midbrain central gray (MCG) (Chung et al. 1984, 1986). Since VMH synapses in this region may be involved in the mediation of estrogen-induced lordosis behavior, we examined the effect of estrogen on the morphology of synapses in the MCG. Ovariectomized adult female rats were given daily subcutaneous injections of estradiol benzoate (10 micrograms) or the vehicle control and after 20 days of injection, only the estrogen-treated rats showed the lordosis response. A quantitative analysis of MCG tissue from these animals demonstrates morphological changes in various synaptic parameters with estrogen treatment including: 1) an increase in the mean number of dense-cored vesicles and an increase in the number of terminals containing dense-cored vesicles, 2) an increase in the length of postsynaptic densities (PSDs), 3) an increase in the number of PSDs showing perforations, 4) an increase in the number of synapses, and 5) an increase in the number of synapses with positive synaptic curvature. No alterations in the number of subjunctional bodies were observed. The dense-cored vesicles may contain an estrogen-induced trophic factor which may function in maintaining the integrity of postsynaptic processes and cells in the MCG with which VMN endings contact (Chung et al. submitted) and/or which induces morphological changes in postsynaptic structures which facilitate the effects of estrogen on lordosis behavior.
Automated data processing and quality control of radioimmunoassays offer not only increased speed but also a more thorough and statistically rigorous analysis of results. An external quality assessment scheme for serum thyroxine, triiodothyronine and thyroid stimulating hormone (TSH) assays was performed in five nuclear medicine laboratories in Korea to compare with the assay performances of the World Health Organization Radioimmunoassay Program. The required radioimmunoassay kits were supplied through the International Atomic Energy Agency (IAEA). We have determined the weighted root mean squared error, and variance ratio as the indices of standard curve and also the average batch coefficient of variation (ABCV) as the parameters of response error relationship curve and precision profile. There was a good fit for the triiodothyronine assay, but 3 of 5 laboratories showed possible bad fit in the T4 and TSH assay systems. The ABCV was less than 5 percent for the T3 and T4 assay system, however for the TSH system, only 1 laboratory showed the ABCV value of less than 5 percent. We have also calculated the within batch variation (drift) and between laboratory variations.
An extensive taxonomic investigation identified strain SK&F-AAJ-271 as a new species, designated Actinomadura parvosata. Fermentations of this organism produce a complex of acidic, lipophilic glycopeptide antibiotics, the parvodicins. Structures for seven of the isolated components were derived from a combination of mass spectral, high-field NMR and chemical techniques. The O-acetyl functionality present in two of the isolated components is a structural feature unique among the known members of this class of antibiotics. The parvodicins are active in vitro against a range of Gram-positive bacteria. The most active parvodicin, C1, produces high serum levels in vivo and has the potential for a long duration of action.
The informational gains obtained by the use of pinhole collimator scintigraphy (PCS) have been well documented. The present study has been undertaken to prospectively investigate its efficacy in diagnosing several commonly occurring spinal diseases. Patient material consisted of metastatic cancer (39 vertebrae), compression fractures (33 vertebrae), tuberculous spondylitis (17 vertebrae), and pyogenic spondylitis (six vertebrae). PCS findings were characterized in terms of localization, appearance, and homogeneity of abnormal radionuclide accumulation. Thus, metastatic cancer manifested as diffusely or focally homogeneous accumulation within the vertebral body or as a typical short-segmental accumulation along the end-plate, whereas compression fracture manifested as characteristic board-like accumulation along the entire length of end-plates. Tuberculous spondylitis, on the other hand, revealed homogeneous accumulation throughout the vertebral body, and pyogenic spondylitis revealed accumulation at the end-zone of opposing vertebral bodies giving sandwich-like appearance. The disk space at the affected level was not narrowed in the former two diseases but it was narrowed in the latter two. It was concluded that PCS may be useful in differentiating metastatic cancer, compression fracture, tuberculous spondylitis, and pyogenic spondylitis.
Biosynthetic feeding experiments with 14C and 13C-labeled precursors in Kibdelosporangium aridum have established the biosynthetic origins of the heptapeptide aglycone of the aridicin antibiotics, and the tentative sequence of the later stage biosynthetic transformations. The aglycone moiety has been found to be derived from tyrosine, sodium acetate and L-methionine. It is suggested that the preformed aglycone is first mannosylated and then followed by the attachment of the glycolipid. The sugar oxidation to the glucuronic acid level was found to take place as a terminal step of the biosynthesis.
In connection with the biosynthetic studies of the aridicin antibiotics in Kibdelosporangium aridum, various microorganisms, known to produce related glycopeptide antibiotics, have been examined for their glycosylating activity. A number of strains were found to mannosylate the aridicin aglycone, while Actinoplanes teichomyceticus was found to have deacylating activity as well. A protoplast system of K. aridum was developed and was found to possess novel glycosylating activity in addition to the mannosylating activity which was also present in the whole cells. Effects on the glycosylating activity by various membrane solubilizing agents have been discussed.
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