Critical acceleration of finite-temperature SU(2) gauge simulations.
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Journal Article↗
Biomedical subjects
S Solomon
Publications and source records attributed to S Solomon.
Isolation and characterization of corticostatic peptides from guinea pig bone marrow.
Three corticostatic peptides (GP-CS1, GP-CS2 and GP-CS3) were purified from extracts of guinea pig bone marrow. Each was identified on the basis of their ability to inhibit the secretion of corticosterone by isolated rat adrenal cells stimulated by ACTH. GP-CS1 and GP-CS2 were found to be 31 residues in length, rich in arginine and to have six cysteines typical of the corticostatin/defensin family of peptides previously purified from phagocytic cells of the immune system. GP-CS1 was found to be identical to GP-CS2 except for having a leucine at position 21 instead of isoleucine. GP-CS3 was also found to be rich in arginine and cysteine but structurally distinct from the other peptides. A combination of endoprotease mapping, ion-spray mass spectrometry and gas-phase sequencing revealed that GP-CS3 was a novel homo-dimer consisting of two 13 amino acid residue subunits cross-linked through eight cysteines in an anti-parellel configuration.
Adrenal Glands↗
The effect of HP-1 and related neutrophil granule peptides on DNA synthesis in HL60 cells.
The recently isolated cysteine- and arginine-rich peptides of the neutrophil primary granule and the murine intestinal Paneth cell, named defensins or corticostatins, have a number of distinct biological properties. We report the effects of three of these peptides HP-1, HP-1-56 and HP-4 on the incorporation of [3H]thymidine into the DNA of the leukemic cell line HL60. HP-1 and HP-1-56, but not HP-4, inhibited DNA synthesis at 1-50 nM without causing cell death. At higher concentrations the effect was reversed, resulting in a small, but statistically significant increase in DNA synthesis at 1 microM. In contrast HP-4 had no effect on HL60 cells at nanomolar concentrations but was strongly cytotoxic at micromolar concentrations.
Amino Acid Sequence↗
The isolation and identification of multiple forms of the neutrophil granule peptides from human leukemic cells.
HP-1 is a 30-residue cysteine- and arginine-rich peptide of the human neutrophil primary granule and is the most abundant human representative of the family of peptides variously called defensins and corticostatins. Peptides belonging to this family have many biological activities including the non-oxidative destruction of ingested microorganisms, the inhibition of adrenocorticotropin-stimulated synthesis of glucocorticoids, monocyte chemotaxis, the non-cytolytic inhibition of [3H]thymidine incorporation in HL-60 promyelocyte-like cells and the stimulation of nifedipine-sensitive calcium channels. Using a combination of reversed-phase and size-exclusion high performance liquid chromatography and an HP-1 radio-immunoassay, three immunoreactive peptides were detected and isolated from the promyelocyte-like cell line, HL-60, and from leukocytes of patients with chronic myelogenous and chronic lymphocytic leukemias. One of these peptides was HP-1 itself. A second was identified by gas-phase Edman microsequencing as an amino-terminally extended fragment of the HP-1 precursor which we call HP1-56. The third is likely to arise from enzymatic cleavage of the precursor at a dibasic site. Of the leukemic cells the greatest amount of HP1-56 relative to HP-1 was found in cells from a patient in myeloblastic crisis but overall the richest source of HP1-56 relative to HP-1 was found to be in fetal lung tissue. HP1-56 is difficult to detect in normal peripheral neutrophils and its presence in cells that are actively biosynthesizing primary granule components such as HL-60 may make it useful for studying the biosynthesis of granule polypeptides, their ontogeny, and possibly as a marker protein for leukemic diseases.
Amino Acid Sequence↗
Migraine: current approaches to diagnosis and management.
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Adult↗
Corticostatic peptides cause nifedipine-sensitive volume reduction in jejunal villus enterocytes.
We studied cell-volume changes caused by adding corticostatin (CS) or defensin-like peptides to villus enterocytes isolated in suspension from guinea pig jejunum. Guinea pig CS (10(-9) M) added to villus cells in Na(+)-containing medium reduced volume, but immediate cell swelling was caused by 10(-6) M guinea pig CS. In Na(+)-free N-methyl-D-glucamine-containing medium 10(-9) M guinea pig CS accelerated the initial rate of shrinkage compared with cells in N-methyl-D-glucamine-containing medium alone as well as causing greater cell shrinkage. Guinea pig CS-stimulated cell shrinkage was prevented by a Ca2(+)-channel blocker--5 microM nifedipine, by chelation of extracellular Ca2+ with 100 microM EGTA, or by omega-conotoxin (10(-9) M). The Ca2+ ionophore A23187 (2.5 microM) reduced volume when added to villus cells in N-methyl-D-glucamine-containing medium; this action was prevented by EGTA, or quinine--an inhibitor of K+ conductance, or 9-anthracenecarboxylic acid--a Cl- channel blocker, suggesting that the volume reduction occurred because K+ and Cl- conductances were activated. Guinea pig CS-stimulated volume reduction was also prevented by 100 microM quinine or 9-anthracenecarboxylic acid. We conclude that jejunal villus enterocytes possess a Ca2(+)-activated Cl- conductance and a K+ conductance that need not be stretch-activated. Corticostatic peptides cause volume reduction in villus cells by activating L-type Ca2+ channels; other defensin-like peptides were without effect.
Amino Acid Sequence↗
Corticostatic peptides.
In the last four years corticostatic (anti-ACTH) peptides have been isolated from human, rabbit, guinea pig and rat tissues. These peptides do not act via the cAMP cell signalling system but rather via the inhibition of the binding of ACTH to its receptor most probably through direct competition with the 14-18 sequence of ACTH for receptor binding. ACTH has specific high affinity receptors on adrenal cells but rabbit corticostatin I (CSI) has high capacity, low affinity receptors which are competed for by unlabelled excess CSI but not by excess ACTH. This indicates the presence of specific CSI adrenal cell receptors. The rabbit pituitary, hypothalamus, thalamus, adrenals, lungs and placenta contain sizeable amounts of immunoassayable CSI. Immunochemical localization of CSI indicates that it is present in the large macrophages and in neutrophils in rabbit lung, in macrophages and "supporting" endothelial cells in the spleen and in the adrenals in the cells of the zona reticularis. We have also isolated and identified new peptides which contain 12 cysteines from immune cells of humans, rats and a teleost, the carp. The functions of these peptides are now being determined. This large family of peptides may have many other, yet unidentified functions but at present we can only describe a small number of these.
Adrenal Glands↗
Biochemical evidence of collagenase-mediated collagenolysis as a mechanism of cervical dilatation at parturition in the guinea pig.
Dilatation of the uterine cervix at parturition is accompanied by a remarkable alteration in its biomechanical characteristics leading to a significant reduction in its strength and stiffness. Our previous studies and those of others have suggested the involvement of collagenolysis leading to cervical dilatation. This study provides further evidence for the occurrence of collagenolysis in the dilated guinea pig cervix at birth. The changes in collagenase and collagenase inhibitory activity in vivo in cervices of nonpregnant, pregnant, and postpartum guinea pigs were determined. There were no significant changes in procollagenase, collagenase inhibitory activity, and net procollagenase in animals at 25 and 50 days of gestation compared with nonpregnant animals. At parturition (68 +/- 2 days), there was a 6-fold increase in procollagenase, a 26-fold increase in collagenase inhibitory activity, and a 2-fold increase in net procollagenase activity. Cervices in organ culture obtained at birth produced 2.9-fold more procollagenase, 1.6-fold more collagenase inhibitory activity, and a 10-fold increase in net procollagenase activity when compared to nonpregnant or 25-day pregnant animals. These studies indicate that dilatation of the guinea pig cervix at parturition involves collagenase-mediated degradation of collagen in the cervix.
Animals↗
Retinochoroidal (optociliary) shunt veins, blindness and optic atrophy: a non-specific sign of chronic optic nerve compression.
Fifteen patients are described in whom the triad of blindness, optic disc swelling followed by optic atrophy, and optociliary shunt veins occurred. The causes of the syndrome included spheno-orbital meningioma, optic nerve glioma, meningocele of the optic nerve, and chronic papilloedema. It is postulated that chronic compression of the intraorbital portion of the optic nerve produces gradual obstruction of the central retinal vein, thus preventing the normal passage of venous blood from the retina through the central retinal vein to the cavernous sinus. Optociliary veins are a pre-existing shunt system that allows retinal venous blood to bypass the central retinal vein and exit from the orbit via the choroidal circulation and its anastomoses.
Adolescent↗
Criteria for the diagnosis of migraine in clinical practice.
Criteria for the diagnosis of migraine have evolved from generalized descriptions to specific rules designed to ensure the selection of homogenous groups of patients for research studies. For clinical practice, the former are insufficiently specific and the latter are too complex. For care of headache patients by primary care physicians, we propose that the diagnosis of migraine without aura (common migraine) is warranted if any two of the following symptoms are present: unilateral site, throbbing quality, nausea, photophobia or phonophobia. These criteria are derived from a study comparing the features of 100 patients with migraine without aura and 100 patients with chronic daily headache. The proposed criteria for the diagnosis of migraine without aura were highly sensitive and adequately specific in discriminating groups. These simple criteria should facilitate the diagnosis of migraine by primary care physicians.
Cluster Headache↗
Myocardial ischemia related to ergot alkaloids: a case report and literature review.
Ergotamine tartrate and methysergide are widely used headache treatments with important vasoconstrictive properties. We report a 31-year-old man with cluster headaches who developed severe, prolonged myocardial ischemia following combination therapy with ergotamine tartrate and methysergide. We reviewed the cardiovascular complications of each agent alone and in combination. Given the pharmacologic similarity of these agents, we propose that they may have additive or synergistic cardiac toxicity, at least in vulnerable individuals. We recommend caution when these agents are used together.
Adolescent↗
Headache in HIV-1-related disorders.
To define the causes, clinical significance and characteristics of headaches in HIV-1-related disorders, we studied 49 consecutive HIV-1 infected patients who presented with headache. Work-up included CT scans, cerebrospinal fluid examinations (in the absence of a contraindication) and serologic studies. Overall, 40 of 49 patients (82 percent) had an identifiable serious cause of headache. Cryptococcal meningitis (39 percent) and CNS toxoplasmosis (16 percent) were the leading headache etiologies. Serious causes were more likely in patients diagnosed with AIDS prior to presentation but also occurred in most patients in early stages of infection. Based on this study, we suggest that patients with HIV-1 infection must be managed with a high index of suspicion when they present with new onset headaches.
Adult↗
Immunochemical and immunohistochemical evidence of estrogen-mediated collagenolysis as a mechanism of cervical dilatation in the guinea pig at parturition.
The mechanism of dilatation of the uterine cervix at birth is poorly understood. Several indirect lines of evidence have suggested that cervical ripening is accompanied by collagen degradation. In this study, immunochemical methods have been developed to identify and analyze type I collage degradation in the cervix of the pregnant guinea pig. Using cyanogen bromide-derived peptides of purified guinea pig type I collagen as an immunogen, a polyclonal rabbit antiserum was prepared that recognizes epitopes on the denatured and degraded alpha 2 chain of type I collagen as demonstrated by enzyme-linked immunosorbant assay and immunoblotting. This antibody was used to demonstrate degradation of type I collagen in the extracellular matrix of the dilated cervix at parturition. Moreover, physiological concentrations of 17 beta-estradiol stimulated degradation of type I collagen in the nonpregnant cervix in organ culture. Collagenase degradation products were detected in the extracellular matrix and in the culture media. The effect of 17 beta-estradiol (10(-6) M) was completely blocked by progesterone (10(-4) M). These studies suggest that dilatation of the guinea pig cervix at parturition may be associated with estrogen-mediated degradation of type I collagen.
Animals↗
Hormonal regulation of interstitial collagenase in the uterine cervix of the pregnant guinea pig.
The uterine cervix is a hormonally responsive organ whose function is tightly regulated during pregnancy. Interstitial collagenase is believed to play a key role in the mechanism of cervical dilatation. This study examines the hormonal regulation of procollagenase gene expression in primary monolayer cell cultures derived from cervices of 50-day pregnant guinea pigs. Procollagenase production was constitutive in these cells. Activity was stimulated up to 2-fold by interleukin 1 beta, 17 beta-estradiol, and estrone. The effect of estradiol was completely inhibited by indomethacin and the estrogen antagonist, tamoxifen. The endogenous and the stimulated procollagenase were completely blocked by cycloheximide and by actinomycin D, indicating the need for protein and messenger RNA (mRNA) synthesis, respectively. Progesterone and 17-OH progesterone also stimulated procollagenase production at physiological concentrations (10(-8) M). The stimulatory effect of progesterone was blocked by the antiprogesterone RU38486. Procollagenase mRNA was stimulated by interleukin 1 beta (5 U/ml) and by 17 beta-estradiol (10(-10)-10(-8) M) and progesterone (10(-8) M). But progesterone at 10(-4) M completely blocked the stimulatory effect of 17 beta-estradiol on procollagenase mRNA. Increased availability of prostaglandins by mobilization of arachidonic acid by phospholipase A2 or by the addition of prostaglandin F2 alpha and prostaglandin E2 resulted in a 2-fold increase in procollagenase activity in culture media. These studies demonstrate that procollagenase gene expression is hormonally controlled in the cervix of pregnant guinea pig.
Animals↗
Isolation and characterization of three forms of joining peptide from adult human pituitaries: lack of adrenal androgen-stimulating activity.
Three structural variants of the joining peptide (JP) fragment of POMC have been purified from human pituitaries. Ion exchange and reverse phase tissue extraction procedures were combined with reverse phase HPLC to achieve complete purification of each form of JP. Fragments resulting from tryptic hydrolysis of each form were characterized by amino acid analysis and fast atom bombardment mass spectrometry. The predominant form of human JP, accounting for about 50% of the total purified, was found to be conjugated to glutathione through the lone cysteine residue at position 9. The other two variants were identified as human JP with a free cysteine residue and human JP dimer and accounted for 35% and 15%, respectively, of the total purified. Recently, human JP-(1-18) has been suggested as having adrenal androgen-stimulating activity. None of the three JP variants or their respective 1-20 amino-terminal fragments resulting from tryptic hydrolysis showed any ability to promote the secretion of dehydroepiandrosterone sulfate by cultured human fetal adrenal cells. Similarly, no potentiation of the stimulatory effects of ACTH-(1-39) was observed. The three variants of human JP as well as JP purified from rat, porcine, and bovine pituitaries were tested for their ability to stimulate androgenic steroids from dispersed fetal rabbit adrenal cells. None showed any significant biological activity either in stimulating steroid secretion or in potentiating the action of ACTH-(1-39).
Adrenal Glands↗
Granulins, a novel class of peptide from leukocytes.
We report the isolation and characterization of a novel class of leukocyte peptides with possible cytokine-like activities which we call granulins. They are cystine-rich with molecular weights of approximately 6 Kda, except for granulin D, which appears to be a dimer. We present the sequence of one member of this family, a 56 residue peptide, granulin A, and amino-terminal sequences for three other granulins from human peripheral leukocytes. A fifth related peptide was isolated and partially sequenced from rat bone marrow, suggesting that at least some of the granulin in peripheral leukocytes is preformed in the marrow. Rat granulin, and human granulin A, are closely related, showing that the granulin structures are highly conserved between species.
Amino Acid Sequence↗
Post-translational modification of bovine pro-opiomelanocortin. Tyrosine sulfation and pyroglutamate formation, a mass spectrometric study.
The amino-terminal fragment of beta-lipotropin (i.e. beta-lipotropin (1-40)) and joining peptide portions of pro-opiomelanocortin have been purified from extracts of bovine posterior pituitaries. Peptides were purified using a combination of reversed-phase and ion-exchange batch extraction procedures followed by reversed-phase high performance liquid chromatography. beta-Lipotropin (1-40) was found to consist of four major components while joining peptide was found to consist of two major components. Fast atom bombardment-mass spectrometric analysis of the tryptic fragments of both peptides revealed that the observed heterogeneity could be explained in terms of post-translational modifications. beta-Lipotropin (1-40) was found to be sulfated at tyrosine residue 28 to an extent of about 50%. The tyrosine residue in beta-lipotropin (1-40) is situated within an amino acid sequence with a preponderance of glutamate residues. Sulfation of this amino acid residue is entirely compatible with the known primary structure requirements of the sulfotransferase enzyme located in the trans-Golgi fraction. Both beta-lipotropin (1-40) and joining peptide were found to have pyroglutamate at their amino termini to an extent of about 50%. The cDNA sequence for bovine pro-opiomelanocortin predicts the presence of glutamic acid at position 1 of both peptides. Pyroglutamate is normally formed through the cyclization of glutamine. This reaction is thought to be catalyzed by a pyroglutamate forming enzyme located within the secretory granule fraction. Under certain circumstances peptides with glutamate at their amino termini may act as substrates for this enzyme.
Amino Acid Sequence↗
Arterial stenosis in migraine: spasm or arteriopathy?
Segmental arterial narrowing has rarely been angiographically demonstrated in patients with migraine. One new case is reported and 12 previous cases are reviewed. Though often referred to as vasospasm, arteriographic stenosis may result from edema of the vessel wall, arterial dissection, the effects of puerperium or arteritis. A biphasic course of spasm, similar to the pattern noted with subarachnoid hemorrhage, has been recorded in some migraineurs. The current neurogenic and biochemical concepts of "spasm" developed for subarachnoid hemorrhage are reviewed. Arterial narrowing may be important in several phenomena associated with migraine. It may account for migrainous cerebral infarction or hemorrhage. Vasoconstriction has also been invoked to explain the aura and other features of migraine. But the site of stenosis does not always correlate with the headache or focal neurologic features in location or timing. The angiographic changes are probably an epiphenomena rather than a primary mechanism of migraine. These changes may result from altered sympathetic neuronal activity; factors supporting that concept are reviewed.
Adolescent↗