Urinary 6-hydroxymelatonin in menstruating women.
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Adult↗
Biomedical subjects
J A Hamilton
Publications and source records attributed to J A Hamilton.
Premenstrual symptom changes and plasma beta-endorphin/beta-lipotropin throughout the menstrual cycle.
The beta-endorphin (BE) hypothesis of premenstrual symptomatology was assessed in 15 healthy, drug-free normally cycling women. Cycle-phase assignment was aided by measurement of basal body temperature and plasma progesterone. For the entire group, peripheral plasma BE concentrations by radioimmunoassay (with substantial beta-lipotropin (BL) cross-reactivity) were generally unvarying across the menstrual cycle. High and low symptom subgroups were defined by retrospective and prospective daily self-reports of premenstrual changes. For the cycle studied, moderate to extreme symptom severity was defined according to premenstrual increases in impaired concentration, water retention and negative affect. No between-groups difference was observed for any cycle-phase for absolute values of beta-endorphin (BE/BL). When difference scores were examined, there was a positive time-lag correlation between follicular-to-periovulatory changes in BE/BL and the subsequent luteal increase in impaired concentration over the periovulatory baseline (rs = 0.82); considering the number of comparisons, however, the correlation fails to reach significance. The salience of various types of stressors on mood was assessed; there was a trend for "task-demands" to account for a greater percentage of negative attributions premenstrually compared to post-menstrually, for the entire group. The relative inconsistency in plasma BE/BL from cycle to cycle may be related in part, to the lack of stability in certain cycle characteristics from month to month. Future studies of BE/BL across the menstrual cycle may benefit from a demanding task in a provocative stress-paradigm.
Adult↗
Activation and proliferation signals in murine macrophages: synergistic interactions between the hematopoietic growth factors and with phorbol ester for DNA synthesis.
There has been recent interest in the synergistic interactions between the growth factors involved in the in vitro control of hematopoiesis and other cell lineages. As a convenient model system, such interactions governing the DNA synthesis in murine bone marrow-derived macrophages (BMMs) were studied. By themselves, murine colony-stimulating factor-1 (CSF-1) and recombinant murine granulocyte-macrophage CSF (GM-CSF) were stimulators of DNA synthesis in quiescent or noncycling BMMs, whereas recombinant murine interleukin-3 (IL-3) and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), were weak mitogens. On the other hand, murine granulocyte CSF (G-CSF), concanavalin A (Con A), and lipopolysaccharide (LPS) were inactive on their own. When the quiescent BMMs were exposed to combinations of the CSFs, there were striking synergistic effects for both GM-CSF and IL-3 with suboptimal doses of CSF-1, with a smaller effect for GM-CSF with IL-3 and little or no effect for CSF-1 with G-CSF. CSF-1, GM-CSF, and IL-3 could also synergize with TPA; CSF-1 cooperated with 1-oleoyl-2-acetylglycerol (OAG), both sets of results pointing to an interaction with protein kinase C. LPS completely abolished the CSF-1-mediated stimulation of DNA synthesis. We propose that BMMs are suitable normal cells in which to examine in depth the various mechanistic possibilities for these interactions.
Animals↗
The menstrual cycle in context, I: Affective syndromes associated with reproductive hormonal changes.
In some women, mood and behavioral changes appear to be linked to the menstrual cycle. New basic science data on steroid-brain interactions have renewed interest in the menstrual cycle as a naturalistic model for assessing gonadal steroid-induced mental and behavioral changes. The authors investigate similarities and differences in affective symptoms associated with reproductive-related gonadal steroid changes that span the life cycle of women, including the menstrual cycle, oral contraceptive use, pregnancy, the postpartum period, and perimenopause. Recommendations for reporting of symptoms and implications for future research are discussed.
Aging↗
The menstrual cycle in context, II: Human gonadal steroid hormone variability.
Menstrual cycle-related mood or behavior changes are best understood in the context of the hormonal variability that occurs in men as well as in women over different periods of time. This paper reexamines what is known and what is not known about the clinical correlates of fluctuations in gonadal and adrenal steroid hormones. The authors highlight the need for a more gender-comparative approach to the psychoneuroendocrinology of endogenous cycles.
Adrenal Cortex Hormones↗
Stimulation of human synovial fibroblast DNA synthesis by recombinant human cytokines.
The pronounced synovial hyperplasia often found in rheumatoid joints can be explained at least partially, by the interaction of monocyte-macrophage polypeptides (monokines) and lymphocyte polypeptides (lymphokines) with synovial fibroblast-like cells. We now report that purified recombinant human cytokines, interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor alpha, tumor necrosis factor beta (or lymphotoxin) and, to a variable extent, interferon-gamma, stimulate the DNA synthesis of human synovial fibroblast-like cells cultured in low (i.e., 1%) fetal bovine serum. With the exception of interferon-gamma, the effects of the cytokines were generally elevated by indomethacin, suggesting inhibition of the DNA synthesis by an endogenously produced cyclooxygenase product(s). Consistent with this suggestion, exogenous prostaglandin E2 suppressed cytokine induced DNA synthesis. All of the cytokines studied might play a role in the synovial hyperplasia present in rheumatoid disease.
Cells, Cultured↗
Carbon 13 NMR studies of saturated fatty acids bound to bovine serum albumin. I. The filling of individual fatty acid binding sites.
13C NMR chemical shift and intensity results for a series of carboxyl 13C-enriched saturated fatty acids (8-18 carbons) bound to bovine serum albumin (BSA) are presented as a function of increasing fatty acid (FA)/BSA mole ratio. Spectra for long-chain (greater than or equal to 12 carbons) FA X BSA complexes exhibited up to five FA carboxyl resonances, designated a, b, b', c, and d. Only three resonances (peaks b, b', and d) were observed below 3:1 FA X BSA mole ratio, and at greater than or equal to 3:1 mole ratio, two additional resonances were observed (peaks c and a). In a spectrum of 5:1 stearic acid X BSA complexes, peaks b, b', and d each represented approximately one-fifth, and peak c approximately two-fifths, of the total FA carboxyl intensity. Plots of total carboxyl/carbonyl intensity ratio as a function of FA X BSA mole ratio were linear up to 7-9 mole ratio. Deviation from linearity at mole ratios greater than or equal to 7 was accompanied by the detection of crystalline unbound FA (as 1:1 acid/soap) by X-ray diffraction. In contrast to long-chain FA X BSA complexes, 13C NMR spectra of octanoic acid X BSA complexes yielded only one FA carboxyl resonance (peak c) at FA X BSA mole ratios between 1 and 20. We conclude: peaks b, b', and d represent FA bound to three individual high affinity (primary) long-chain FA binding sites on BSA; peak c represents FA bound to several secondary long-chain (or primary short-chain) FA binding sites on BSA; peak a represents long-chain FA bound to an additional lower affinity binding site. We present a model that correlates the observed 13C NMR resonances with individual binding site locations predicted by a recent three-dimensional model of BSA.
Binding Sites↗
Carbon 13 NMR studies of saturated fatty acids bound to bovine serum albumin. II. Electrostatic interactions in individual fatty acid binding sites.
13C NMR chemical shift results as a function of pH for a series of carboxyl 13C-enriched saturated fatty acids (8-18 carbons) bound to bovine serum albumin (BSA) are presented. For octanoic acid bound to BSA (6:1, mol/mol), the chemical shift of the only FA carboxyl resonance (designated as peak c), plotted as a function of pH, exhibited a complete sigmoidal titration curve that deviated in shape from a corresponding theoretical Henderson-Hasselbach curve. However, FA carboxyl chemical shift plotted as a function of added HCl yielded a linear titration curve analogous to those obtained for protein-free monomeric fatty acid (FA) in water. The apparent pK of BSA-bound octanoic acid was 4.3 +/- 0.2. However, the intrinsic pK (corrected for electrostatic effects resulting from the net positive charge on BSA) was approximately 4.8, a value identical to that obtained for monomeric octanoic acid in water in the absence of protein. For long-chain FA (greater than or equal to 12 carbons) bound to BSA (6:1, mol/mol), chemical shift titration curves for peak c were similar to those obtained for octanoic acid/BSA. However, the four additional FA carboxyl resonances observed (designated as peaks a, b, b', and d) exhibited no change in chemical shift between pH 8 and 3. For C14.0 X BSA complexes (3:1 and 6:1, mol/mol) peaks b' and a exhibited chemical shift changes between pH 8.8 and 11.5 concomitant with chemical shift changes in the epsilon-carbon (lysine) resonance. In contrast, peaks c and d exhibited no change and peak b only a slight change in chemical shift over the same pH range. We conclude: the carboxyl groups of bound FA represented by peaks a, b, b', and d were involved in ion pair electrostatic interactions with positively charged amino acyl residues on BSA; the carboxyl groups of bound FA represented by peak c were not involved in electrostatic interactions with BSA; the similarity of the titration curves of peak c for BSA-bound octanoic acid and long-chain FA suggested that short-chain and long-chain FA represented by peak c were bound to the same binding site(s) on BSA; bound FA represented by peaks b' and a (but not d or b) were directly adjacent to BSA lysine residues. We present a model which correlates NMR peaks b, b', and d with the putative locations of three individual high-affinity binding sites in a three-dimensional model of BSA.
Binding Sites↗
Transbilayer movement of bile acids in model membranes.
The ability of bile acids to traverse membranes has important implications for their reabsorption from the gut, recirculation to and uptake into the liver, and resecretion into bile. The rate constant for transbilayer movement, or "flip-flop", of three common, unconjugated bile acids was determined by 13C nuclear magnetic resonance spectroscopy. At high pH, the sodium salts of the bile acids did not appreciably traverse the bilayer; however, upon protonation a rapid equilibration between the inner and outer monolayers occurred. The rate of flip-flop of each bile acid at 37 degrees C was found to be dependent on both number and location of hydroxyl groups but not on concentration in the bilayer over the range studied (2-4 wt%) nor on the presence of a different bile acid in the same bilayer.
Bile Acids and Salts↗
Interleukin-1 beta and interleukin-1 alpha stimulate the plasminogen activator activity and prostaglandin E2 levels of human synovial cells.
Monocyte-macrophage polypeptides (monokines) cause synovial cells to increase the levels of putative mediators of destruction and inflammation. This interaction may account for some of the properties of rheumatoid pannus. We report here that samples of purified human interleukin-1 beta (IL-1 beta) and recombinant IL-1 alpha stimulate both the plasminogen activator activity and prostaglandin E2 levels of human synovial fibroblast-like cells. The same holds true for purified pig IL-1 (catabolin) and recombinant murine IL-1. The elevation in plasminogen activator activity was inhibited by indomethacin, and this suggests that endogenous prostanoids are important in the IL-1-mediated stimulation of proteinase activity.
Dinoprostone↗
Diverse morphological responses of normal human synovial fibroblasts to mononuclear leukocyte products: relationship to prostaglandin production and plasminogen activator activities, and comparison with the effects of purified interleukin 1.
Supernatant media from cultured human mononuclear blood leukocytes (MCCM) induced morphological changes in normal human synovial fibroblasts in culture, including the formation of cells with a dendritic or stellate morphology and, less frequently, cells with a striking fenestrated appearance. These changes were fully reversed within 1 h of removing the MCCM. They were inhibited by indomethacin, the glucocorticoids hydrocortisone, prednisolone and dexamethasone, and by colcemid, but not by actinomycin D and only weakly by cycloheximide. The morphological responses to MCCM could be reproduced by MCCM fractions containing interleukin 1-like activity and by purified forms of human interleukin 1 (IL-1), including monocyte-derived IL-1 beta and recombinant IL-1 alpha. These responses were also inhibited by indomethacin, indicating a link with prostanoid production. However, the morphological responses were not related to the stimulation of plasminogen activator activity due to MCCM, MCCM fractions, or IL-1.
Cells, Cultured↗
Interleukin-1 beta and interleukin-1 alpha stimulate the N-acetyl-beta-glucosaminidase activity of human synovial cells.
The properties of synovial cells are altered in vitro by monocyte-macrophage polypeptides (monokines), and these changes could explain some of the properties of the inflamed synovium in rheumatoid disease. Purified monokines have become available only recently for testing on the target synovial cells. We report here that purified human interleukin (IL)-1 beta and recombinant human IL-1 alpha stimulate the extracellular activity of the lysosomal hydrolase, N-acetyl-beta-glucosaminidase (NAG), of human synovial fibroblast-like cells. In contrast, another monokine, synovial activator, does not increase the NAG activity. Thus NAG is another cellular activity which can be modulated by interleukin-1.
Acetylglucosaminidase↗
Effect of bromocriptine on affect and libido in hyperprolactinemia.
Six women with primary hyperprolactinemia (mean prolactin level, 50 ng/ml) were matched with six normal women on eight factors influencing life style. Observers blind to endocrine status followed the subjects weekly for 10 weeks. Patients took bromocriptine, 2.5 mg twice daily, or placebo in a randomized double-blind sequence with crossover at 5 weeks. The mean Hamilton score for the patients was compatible with mild depression and higher than that for normal subjects during placebo but not during bromocriptine treatment. Libido was similar in both groups during placebo and bromocriptine. The mean number of orgasms reported per day was lower in patients than in normal subjects during both treatment conditions, although one patient reported orgasms during drug treatment only. Hyperprolactinemia in women may be associated with mild depression and a decrease in orgasmic frequency.
Adult↗
Effects of auranofin and other antirheumatic drugs on human myelopoiesis in vitro.
Leukopenia is one of the more serious side effects of auranofin (AF) therapy for rheumatoid arthritis. AF and its deacetylated form inhibited the development of macrophage and granulocytic colonies from progenitor cells in human bone marrow even at concentrations less than or equal to 10(-9)M. The disease suppressive activity of AF could result in part from the reduction of cell numbers in arthritic lesions and our findings provide a mechanism for this possibility. In contrast, other slow acting antirheumatic drugs, sulfasalazine, chloroquine and hydroxychloroquine, show partial inhibition of colony development but at concentrations of the order of 10(-5)M.
Anti-Inflammatory Agents↗
Potentiation of delayed-type hypersensitivity by pertussigen or cyclophosphamide with release of different lymphokines.
The effects of lymphokine production of two agents known to potentiate delayed-type hypersensitivity (DTH), pertussigen (pertussis toxin) (PT) and cyclophosphamide (CY) have been investigated. These two agents were administered to immunized mice. Subsequently, lymph nodes and spleen cells were exposed to specific antigen in vitro. The resulting culture supernatants were assayed for the presence of lymphokines. Only supernatants of cells from the mice given PT contained appreciable quantities of interferon-gamma (IFN-gamma) and stimulated cells of the monocyte-like WEHI-265 cell line to produce procoagulant activator and plasminogen activator. On the other hand, CY was more effective than PT on the production of interleukin-3 (IL-3). Both adjuvants had small enhancing effects on the production of interleukin-2 (IL-2). With either adjuvant, the cell populations induced had a similarly enhanced capacity to transfer DTH. These results demonstrate that the capacity of cells to transfer DTH does not necessarily correlate with their release of particular lymphokines. The potentiation of DTH by cyclophosphamide did not depend on significantly enhanced generation of IFN-gamma, procoagulant activator, or plasminogen activator. The amount of IFN-gamma in the culture supernatants correlated with their capacity to produce procoagulant activator and plasminogen activator, whereas the amount of IL-2 and IL-3 did not.
Adjuvants, Immunologic↗
Temperature-dependent molecular motions and phase behavior of cholesteryl ester analogues.
The phase behavior and temperature-dependent molecular motions of three cholesteryl ethers (caproyl, myristyl, oleyl) and a cholesteryl carbonate (oleyl) were characterized. The properties of each ether were qualitatively similar to, but quantitatively different from, those of the corresponding cholesteryl ester. For example, cholesteryl oleyl ether exhibited the same phase transitions as cholesteryl oleate, but at much lower temperatures (e.g., the ether isotropic liquid to cholesteric transition is at 29 degrees C). 13C NMR spectra of ethers in the isotropic liquid and liquid crystalline phases were similar to those of the ester analogue. However, near the liquid to liquid crystalline transition, the steroid ring C3 and C6 linewidths, the C3/C6 linewidth ratio, and the steroid ring rotational correlation times tau rx and tau rz calculated from the linewidths were larger for the ether than the ester analogue. The oleyl carbonate had qualitatively different properties from its analogues (e.g., stable vs. metastable cholesteric and smectic phases). Quantitative results (e.g., relatively long tau rx and tau rz in the isotropic liquid phase) for the carbonate were also distinct from those of both the ester and ether analogues. A comparison of analogues in which the polar linkage is the only structural variable yielded insights into the intermolecular interactions which influence phase behavior.
Chemical Phenomena↗
Partial synthesis and properties of a series of N-acyl sphingomyelins.
A series of sphingomyelins (SM) with different chain length fatty acids (C14:0, C16:0, C18:0, C20:0, C22:0, and C24:0) N-linked to the primary amino group of sphingosine have been synthesized starting with bovine brain SM. Two different acid hydrolysis procedures, butanolic HCl (H. Kaller, 1961. Biochem. Z. 334: 451-456) and methanolic HCl (R.C. Gaver and C.C. Sweeley. 1965. J. Am. Oil Chem. Soc. 42: 294-298), were used and the resultant sphingosylphosphocholine (SPC) was converted to SM using two acylation methods: using fatty acid imidazolide to yield the O-acyl, N-acyl SPC, followed by mild alkaline hydrolysis for selective deacylation at the O-acyl linkage, and selective acylation at the amino group of SPC using the free fatty acid in the presence of dicyclohexylcarbodimide. Following chromatographic purification, N-acyl SM were obtained in high yield (80-90%), and were characterized by a combination of thin-layer chromatography, high performance liquid chromatography, chemical analysis, optical rotation, circular dichroism, infrared spectroscopy, 13C NMR, and sphingosine base analysis. The N-acyl SM were chemically homogeneous with respect to fatty acid composition and the sphingosine base composition resembled that of the starting bovine brain SM. However, as a consequence of the epimerization at C-3 of SPC in both acid hydrolysis procedures, the resulting N-acyl SM consisted of mixtures of D-erythro and L-threo sphingomyelins. By differential scanning calorimetry hydrated C14:0 to C24:0 SM exhibited gel-liquid crystal transitions in the range 30-50 degrees C but the chain length dependence was complex.(ABSTRACT TRUNCATED AT 250 WORDS)
Acylation↗
Pertussigen in vivo enhances antigen-specific production in vitro of lymphokine that stimulates macrophage procoagulant activity and plasminogen activator.
Pertussigen is a protein toxin of Bordetella pertussis that acts as a powerful stimulator of the intensity and duration of delayed-type hypersensitivity (DTH) in mice. This study describes the potent in vivo effect of pertussigen on the levels of antigen-specific macrophage-activating lymphokine(s); lymphokine(s) was measured by the stimulation of macrophage procoagulant activity (mPCA), or plasminogen activator (PA) activity. Lymphoid cells were removed from immunized animals and cultured with specific antigen, keyhole limpet hemocyanin, ovalbumin, or human gamma-globulin. The culture supernatants were then incubated with the monocyte-like cell line WEHI-265 to measure mPCA or with WEHI-265 or resident peritoneal macrophages to measure PA activity. Mice were given pertussigen at the time of immunization, and the subsequent generation by lymphocyte supernatants of both of these macrophage activities proved to be greatly enhanced; the effect of pertussigen was antigen specific. Pertussigen thus induces an increase in lymphokine(s) production responsible for the in vitro increase in macrophage mPCA and PA activity and which may be responsible for some of the potent immune effects of this agent in vivo.
Animals↗