Electron correlation in doubly excited states of the hydrogen molecule.
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Journal Article↗
Biomedical subjects
S Lee
Publications and source records attributed to S Lee.
The minCD locus of Bacillus subtilis lacks the minE determinant that provides topological specificity to cell division.
A key event of the sporulation process in Bacillus subtilis is the asymmetric cell division that divides the developing cell into two unequal compartments. To examine the function of vegetative cell division genes in this developmental division, we isolated and characterized the B. subtilis counterpart to the Escherichia coli minicell operon minB, which governs correct placement of the division septum. Starting from the closely linked spoIVF locus, we used walking methods to isolate the region of the B. subtilis chromosome proximate to the divIVB minicell locus. DNA sequence analysis found two open reading frames whose predicted products had significant identity to the E. coli MinC cell division inhibitor and the MinD ATPase activator of MinC, and disruption of minCD function generated a minicell phenotype in B. subtilis. Notably, no homologue to the E. coli MinE topological specificity element was found in the B. subtilis minCD region. The B. subtilis min genes were part of an operon transcribed from a major promoter more than 2.5 kb upstream from minC. An internal promoter immediately upstream from minC was dependent on RNA polymerase containing sigma-H and was active at the onset of sporulation. However, neither minC nor minD function was absolutely required for sporulation and, by implication, for asymmetric septum formation.
Adenosine Triphosphatases↗
Open evaluation of a new non-preserved artificial tear.
In an open, one-eye controlled study the efficacy of a new, non-preserved artificial tear (sodium chloride 0.34% W/W, hydroxyethylcellulose 0.44% W/W), stored in single-use disposable units (Minims, Smith and Nephew) was compared to a variety of other tear substitutes in 30 patients who were currently applying artificial tears to both eyes. It was found that the new drop was tolerated well by the majority of patients with 19 subjects (63%) preferring them to their existing medication. There was a significant reduction in the overall rose bengal staining pattern and also in the stain uptake of the medial conjunctiva between the first and second visits in the Minims treated eyes, but not in the eyes treated with the other drops (P < 0.05). There was also a significant improvement in the patients' subjective feelings of dryness and grittiness in the Minims treated eyes, but not in the other eyes (P < 0.05).
Adult↗
Prenatal alcohol exposure blunts interleukin-1-induced ACTH and beta-endorphin secretion by immature rats.
The functional relationship between the immune and the hypothalamic-pituitary-adrenal (HPA) axis [and in particular the release of pro-opiomelanocortin (POMC)-related peptides and corticosteroids induced by interleukins (ILs)] is essential for coordinating the appropriate immune responses to pathogens. Exposure of pregnant mammalian females to alcohol results in abnormal immune functions in the offspring, as well as in altered HPA axis activity. We therefore tested the hypothesis that prenatal alcohol exposure might modify the stimulatory action of ILs on the HPA axis of the pups, thus providing a mechanisms through which this treatment results in increased rate of infectious or inflammatory processes. Pregnant dams were fed a liquid alcohol diet throughout gestation. Dams with free access to food (ad libitum group), or dams fed an isocaloric diet in which sucrose replaced alcohol (pair-feeding), were also included. At 22-24 days of age, the pups were injected intraperitoneally with IL-1 beta, corticotropin-releasing factor (CRF), or the vehicle. Blood samples obtained 1-2 hr later indicated that the alcohol diet resulted in significantly blunted adrenocorticotropic hormone (ACTH) and beta-endorphin, but not corticosterone release, in response to IL-1 beta. Pair-fed pups also showed some decrease in their pituitary response, although to a lesser degree. In contrast, there was no measurable difference in the ability of CRF to increase plasma ACTH levels. These results suggest that prenatal exposure to alcohol interferes with the stimulatory action of IL-1 beta on the secretion of POMC-related peptides, a phenomenon probably not caused by decreased pituitary responsiveness to CRF.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
Effect of exposure to an alcohol diet for 10 days on the ability of interleukin-1 beta to release ACTH and corticosterone in the adult ovariectomized female rat.
Adult ovariectomized female rats were fed an alcohol diet for 10 days. Animals fed ad libitum, or fed an isocaloric diet (pair-fed), were also included in all experiments. The intravenous injection of interleukin-1 beta caused dose-related increases in plasma adrenocorticotropic hormone (ACTH) levels in all three groups of rats. However, alcohol-fed animals showed a significant blunting of their ACTH, but not corticosterone response, in comparison with rats fed ad libitum or pair-fed. In contrast, corticotropin-releasing factor (CRF) injection caused overall statistically comparable ACTH secretory rates in all animals, although small differences were observed in some cases. Exposure to mild electroshocks for 30 min significantly increased ACTH values in all animals, but alcohol-fed rats again showed blunted release. In this paradigm, pair-fed animals exhibited a response that was intermediate between that of the ad libitum and alcohol-fed groups. We conclude that chronic alcohol consumption decreases the response of the hypothalamic-pituitary axis to cytokines and mild footshocks. This suggests that the activity of both CRF nerve terminals in the median eminence, and of CRF perikarya in the hypothalamus, is inhibited by this treatment, although pituitary responsiveness to CRF appears unchanged.
Adrenocorticotropic Hormone↗
[An outbreak of Pseudomonas sepsis associated with nosocomial infection in a pediatric ward].
A five-year old girl, diagnosed with fever of unknown origin (FUO), was transferred to our hospital due to a deterioration in her general condition. Pseudomonas cepacia (P. cepacia) was detected in her blood culture and she soon recovered after imipenem cilastatin (IPM/CS) administration. When the former hospital was informed of the results of her blood cultures, we learned that five other cases of FUO had occurred there within the previous two weeks in noncompromised children. Except for one case, Pseudomonas species was detected in their blood cultures. P. cepacia was found in one case, Pseudomonas aeruginosa (P. aeruginosa) was detected in two other cases, and both P. cepacia and P. aeruginosa were demonstrated in the other patient. Although the origin of the bacteria is unknown, it may have spread to the children through a contaminated liquid reservoir or medical devices.
Bacteremia↗
Estimating the growth rate of slowly growing marine bacteria from RNA content.
In past studies of enteric bacteria such as Escherichia coli, various measures of cellular RNA content have been shown to be strongly correlated with growth rate. We examined this correlation for four marine bacterial isolates. Isolates were grown in chemostats at four or five dilution rates, yielding growth rates that spanned the range typically determined for marine bacterial communities in nature (mu = 0.01 to 0.25 h). All measures of RNA content (RNA cell, RNA:biovolume ratio, RNA:DNA ratio, RNA:DNA:biovolume ratio) were significantly different among isolates. Normalizing RNA content to cell volume substantially reduced, but did not eliminate, these differences. On average, the correlation between mu and the RNA:DNA ratio accounted for 94% of variance when isolates were considered individually. For data pooled across isolates (analogous to an average measurement for a community), the ratio of RNA:DNA mum (cell volume) accounted for nearly half of variance in mu (r = 0.47). The maximum RNA:DNA ratio for each isolate was extrapolated from regressions. The regression of (RNA:DNA)/(RNA:DNA)(max) on mu was highly significant (r = 0.76 for data pooled across four isolates) and virtually identical for three of the four isolates, perhaps reflecting an underlying common relationship between RNA content and growth rate. The dissimilar isolate was the only one derived from sediment. Cellular RNA content is likely to be a useful predictor of growth rate for slowly growing marine bacteria but in practice may be most successful when applied at the level of individual species.
Journal Article↗
Conditional silencing: the HMRE mating-type silencer exerts a rapidly reversible position effect on the yeast HSP82 heat shock gene.
The HMRE silencer of Saccharomyces cerevisiae has been previously shown to transcriptionally repress class II and class III genes integrated within the HMR silent mating-type locus up to 2.6 kb away. Here we study the ability of this element to repress at an ectopic position, independent of sequences normally associated with it. When integrated 750 bp upstream of the HSP82 heat shock gene, the silencer represses basal-level transcription approximately 5-fold but has no effect on chemical- or heat-shock-induced expression. Such conditional silencing is also seen when the HMRE/HSP82 allele is carried on a centromeric episome or when the entire HMRa domain is transplaced 2.7 kb upstream of HSP82. Notably, the a1 promoter within the immigrant HMRa locus remains fully repressed at the same time HSP82 is derepressed. The position effect mediated by the E silencer is absolutely dependent on the presence of a functional SIR4 gene product, is lost within 1 min following stress induction, and is fully reestablished within 15 min following a return to nonstressful conditions. Similar kinetics of reestablishment are seen in HMRE/HSP82 and HMRa/HSP82 strains, indicating that complete repression can be mediated over thousands of base pairs within minutes. DNase I chromatin mapping reveals that the ABF1, RAP1, and autonomously replicating sequence factor binding sites within the silencer are constitutively occupied in chromatin, unaltered by heat shock or the presence of SIR4. Similarly, the heat shock factor binding site upstream of HSP82 remains occupied under such conditions, suggesting concurrent occupancy of silencer and activator binding sites. Our results are consistent with a model in which silencing at the HMRE/HSP82 allele is mediated by direct or indirect contacts between the silencer protein complex and heat shock factor.
Alleles↗
Hepatitis C virus antibodies in patients with chronic liver disease: ELISA and RIBA HCV strip immunoblot assay results.
In a study using the current first generation Ortho ELISA, a second generation Ortho ELISA, and the RIBA HCV strip immunoblot assay, all patients who were strongly positive for antihepatitis C virus (HCV) on ELISAs (OD490 > 3) were reactive to RIBA for multiple bands. While all ELISA false positive samples had low or intermediate OD490 values, RIBA confirmed HCV reactivity in 50% of the patients reactive to ELISA with a low suspicion of HCV infection, thus suggesting that RIBA HCV strip immunoblot assay will be most useful for patients who react weakly positive or intermediate to ELISA.
Chronic Disease↗
Is weight phobia always necessary for a diagnosis of anorexia nervosa?
Several reviews of the history of anorexia nervosa have concluded that weight phobia, a basic diagnostic criterion for the disorder, did not emerge as a predominant motive for food refusal until around 1930. In addition, investigators have reported cases of self-starvation without apparent weight phobia in non-Western cultures. Three explanations have been proposed for these findings: 1) patients who do not demonstrate a definite weight phobia are in fact suffering from an eating disorder not otherwise specified, 2) weight phobia has been overlooked or concealed, and 3) there has been a transformation in the content of anorexia nervosa in the West and an analogous situation may be occurring in the developing countries. The authors conclude that a change in the core features of anorexia nervosa in Western cultures since 1930 can be demonstrated. They explore the question of whether anorexia nervosa would be the same illness if the criterion of weight phobia were not required and conclude that anorexia nervosa may be conceptualized in several different ways without including the phenomenon of weight phobia or body image disturbance. Finally, they recommend that because the desire for thinness appears to be culture-bound, anorexia nervosa is the best disorder to use in examining the influence of culture on psychopathology. Therefore, cases of self-starvation in non-Western cultures should be studied carefully because they may clarify the core features of anorexia nervosa.
Anorexia Nervosa↗
Localization of S1 and elongation factor-1 alpha mRNA in rat brain and liver by non-radioactive in situ hybridization.
Elongation factor-1 alpha (EF-1 alpha) is a ubiquitous, highly conserved protein that functions in peptide elongation during mRNA translation. We recently reported that, as do lower species, mammals also contain a second EF-1 alpha-like gene (S1). Unlike EF-1 alpha, which is present in all tissues, S1 mRNA is detected only in brain, heart, and muscle by Northern analysis and RNAse protection assays. In this report we present the identification of S1 and EF-1 alpha messages by non-radioactive in situ hybridization in brain and liver. We show that with this technique we can detected S1 mRNA only in certain cells in brain, mostly neurons; on the other hand, EF-1 alpha is present in all cell types that we have studied so far. We demonstrate that although EF-1 alpha mRNA can be detected in S1-negative cells it is also present in high abundance in S1-positive cells. The results presented here correlate with our previous finding that mammalian species contain a tissue-specific EF-1 alpha-like gene, S1. The presence of a second EF-1 alpha-like transcript within fully differentiated cells suggests a novel cell type-specific gene expression whose function may be related to the permanent growth-arrested state of cells in brain, heart, and muscle.
Animals↗
Simple schizophrenia--a forgotten diagnosis.
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Adult↗
Gastric emptying and bloating in anorexia nervosa.
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Adult↗
d-fenfluramine and cognitive therapy in bulimia nervosa.
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Body Weight↗
Multicenter phase II trial of mitoxantrone in patients with advanced nasopharyngeal carcinoma in Southeast Asia: an Asian-Oceanian Clinical Oncology Association Group study.
PURPOSE: Patients with advanced nasopharyngeal carcinoma (NPC) have a high incidence of recurrence and often develop distant metastases despite local control. This prospective multicenter phase II trial was conducted to evaluate the safety and efficacy of Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ) in the therapy of patients with advanced NPC. PATIENTS AND METHODS: One hundred eight patients with advanced NPC, namely, those with recurrent or persistent disease following primary radiotherapy, or newly diagnosed metastatic disease, were treated with mitoxantrone. Mitoxantrone was administered intravenously at an initial dose of 12 mg/m2 and repeated every 3 weeks, with dose escalation to a maximum of 14 mg/m2. The distribution of histologic subtypes was representative of NPC, with the majority being (61%) undifferentiated (or anaplastic) carcinoma. RESULTS: The overall response rate (complete response [CR] and partial response [PR]) was 25% (95% confidence interval, 17% to 33%). The median response duration, time to treatment failure, and survival duration were 140, 82, and 394 days, respectively. Histology (poorly differentiated squamous cell) was found to be the only important factor in predicting response (P = .04) based on a multivariate analysis of nine pretreatment characteristics. The major dose-limiting toxicity was leukopenia. The incidences of nausea/vomiting, alopecia, and stomatitis/mucositis were 34%, 6%, and 3%, respectively. None were severe. Two patients had asymptomatic, moderate Alexander-grade cardiotoxicity. CONCLUSION: This study represents a large, controlled multicenter trial of single-agent mitoxantrone in the treatment of advanced NPC. Mitoxantrone was well tolerated and produced an overall response rate comparable to that of other single-agent therapies used in the treatment of advanced head and neck cancer. Combination trials with mitoxantrone for advanced disease should be considered.
Adult↗
The chronic intracerebroventricular infusion of interleukin-1 beta alters the activity of the hypothalamic-pituitary-gonadal axis of cycling rats. I. Effect on LHRH and gonadotropin biosynthesis and secretion.
We have previously reported that the acute injection of interleukin-1 beta (IL-1 beta) into the brain ventricles of intact female rats promptly decreases LHRH release and inhibits gene expression of this peptide in the medial preoptic area (MPOA). The present studies were therefore designed to determine whether continuous exposure to the cytokine would disrupt the estrous cycle. IL-1 beta was injected intracerebroventricularly for 4-6 days at a rate of 4 ng/h. Daily vaginal smears were obtained to follow the cycle; pituitary LH and FSH secretion were measured at regular intervals. Steady state levels of LH and FSH messenger RNA (mRNA) in the pituitary, and LHRH gene expression in the MPOA, were measured at the end of the treatment. Infusion of IL-1 beta caused a total disruption of the estrous cycle, characterized by persistent smears indicative of the diestrus stage. When compared to animals treated with the vehicle, rats infused with IL-1 beta showed a significant decrease in circulating LH concentrations, which was accompanied by lowered mRNA levels in the pituitary. This statistical difference (P < 0.01) persisted even when treated rats were compared to control in a similar stage of the cycle (i.e. diestrus). Plasma FSH levels remained low at all times after IL-1 beta infusion but showed the expected cyclic changes in control animals. At the end of treatment, LHRH gene expression was also markedly suppressed in LHRH neurons distributed between the rostral preoptic area/organum vasculosum of the lamina terminalis and the MPOA of these animals. These results indicate that prolonged infusion of IL-1 beta into brain ventricles disrupts the estrous cycle, an event accompanied by decreased biosynthesis/release of LHRH and gonadotropins. We report in a related study that IL-1-treated rats also show increased plasma progesterone levels. However, it is improbable that this change was responsible for the interruption of the cycle described here; indeed we have previously observed that the central administration of IL-1 beta to intact rats resulted in an immediate blockade of the spontaneous activity of LHRH perikarya during the afternoon of proestrus and significantly decreased LHRH mRNA levels in gonadectomized animals. Taken together, these data suggest that the primary effect of IL-1 beta is at the level of LHRH perikarya, and that the resulting interruption of the cycle is caused by altered LHRH neuronal activity and blunted gonadotropin secretion.
Animals↗
Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells.
The endocrine pancreas consists of several differentiated cell types that are distinguished by their selective expression of peptide hormones such as insulin, glucagon, and somatostatin. Although a number of homeobox-type factors have been proposed as key regulators of individual peptide genes in the pancreas, their cellular distribution and relative abundance remain uncharacterized. Also, their overlapping DNA binding specificities have further obscured the regulatory functions these factors perform during development. In this report we characterize a novel homeobox-type somatostatin transactivating factor termed STF-1, which is uniformly expressed in cells of the endocrine pancreas and small intestine. The 283-amino acid STF-1 protein binds to tissue-specific elements within the somatostatin promoter and stimulates somatostatin gene expression both in vivo and in vitro. Remarkably, STF-1 comprises the predominant tissue-specific element-binding activity in nuclear extracts from somatostatin-producing pancreatic islet cells, suggesting that this protein may have a primary role in regulating peptide hormone expression and specifying endocrine cell lineage in the developing gut.
Amino Acid Sequence↗
Corticotropin-releasing factor activates c-fos, NGFI-B, and corticotropin-releasing factor gene expression within the paraventricular nucleus of the rat hypothalamus.
Studies examining the regulation of hypothalamic CRF biosynthesis have provided substantial information regarding the relevance of this peptide in neuroendocrine homeostasis. However, the consequences of elevated CRF levels within the mammalian central nervous system on regulation of CRF production within the paraventricular nucleus (PVN) of the hypothalamus remain unclear. The expression of the immediate early gene c-fos has been used and validated as a marker for neural systems activated by a variety of extracellular stimuli and has been especially useful when examining activation of central neuroendocrine systems such as those involved in the response to stressful stimuli. The present study investigates the effects of injecting CRF into the lateral ventricle of conscious rats, firstly on the expression of two separate immediate early genes, c-fos and NGFI-B within the hypothalamic PVN, and secondly on the expression of CRF mRNA itself, as determined by quantitative in situ hybridization. Expression of Fos protein was also examined by immunohistochemical techniques. Intracerebroventricular (icv) injection of CRF increased the gene expression of both c-fos and NGFI-B in the parvocellular division of the PVN 30 min after injection. Fos immunoreactivity increased in this same region between 30-60 min, whereas expression of the CRF gene itself increased 2-fold 60 min after injection and remained elevated 2 h after treatment. A positive hybridization signal for CRF was observed over Fos-immunoreactive neurons within the parvocellular division of the PVN. Finally, we observed that all CRF-induced changes in gene expression were abolished by pretreatment with the competitive CRF antagonist alpha-helical CRF-(9-41). The time-related changes in expression of the genes measured imply that the expression of both c-fos and NGFI-B occurs before a significant increase in the expression of CRF. The results also suggest that CRF may act in a positive manner to regulate its own biosynthesis.
Animals↗