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A Bateman

Publications and source records attributed to A Bateman.

At least 19 recordsLinked to original sources
PubMed1992

Structure and chromosomal location of the human granulin gene.

Granulins are a family of cysteine rich polypeptides some of which have growth modulatory activity. We showed previously that the granulins are encoded within the same precursor consisting of seven granulin domains arranged in tandem. Here we report the chromosomal location and structural organization of the protein coding region of the granulin gene. The granulin gene was assigned to chromosome 17 using DNA from human-hamster somatic cell hybrids. The protein-coding region of the granulin gene was shown to comprise 12 exons covering about 3700 bp. Each tandem granulin repeat is encoded by two non-equivalent exons, a configuration unique to the granulins that would permit the formation of hybrid granulin-like proteins by alternate splicing.

Alternative Splicing↗
PubMed1992

Purification of cationic cystine-rich peptides from rat bone marrow. Primary structures and biological activity of the rat corticostatin family of peptides.

Seven cationic, cystine-rich peptides of 29 to 32 amino acid residues have been purified from extracts of rat bone marrow (R-1, R-1a, R-1b, R-2, R-3, R-4 and R-5). Structural analysis clearly indicated that all seven peptides belong to the corticostatin/defensin family of leukocyte-derived peptides known to participate in oxygen-independent killing of phagocytosed bacteria. For R-1 to R-5, six cysteine residues were found at characteristic and highly conserved positions. R-1a and R-1b were partially characterized and appear to be structural variants of R-1. Aside from the conserved cysteines, there is a remarkable degree of structural diversity evident within the sequences of those members of the corticostatin/defensin family characterized so far. The structures of the peptides that we have purified can be compared directly with the sequences obtained for rat defensins isolated from extracts of peritoneal neutrophils (Lehrer, Ganz and Selsted, Cell, 64 (1991) 229-230). Some discrepancies are apparent which can be explained in terms of proteolytic cleavage of several of these peptides at both amino- and carboxyl-termini. The corticostatins owe their bioactivity to their ability to compete with corticotropin for occupancy of the corticotropin receptor (Zhu, Hu, Mulay, Esch, Shimasaki and Solomon, Proc. Natl. Acad. Sci. USA, 85 (1988) 592-596). The potency of these peptides can be expressed in terms of their capacity to inhibit the steroidogenic response of isolated rat adrenocrotical cells half-maximally stimulated by corticotropin (i.e., at the ED50 concentration for corticotropin in this assay, namely 33 pM). In this assay, the rat peptides R-1, R-2 and R-3 were shown to be inactive. In contrast, the more cationic peptides R-4 and R-5 were found to inhibit steroidogenesis. R-4 was somewhat less active than rabbit corticostatin (IC50 25 nM) showing an IC50 value of 50 nM. R-5 appeared to be significantly less potent than R-4. The lower yield of R-5 precluded an accurate estimate of the corticostatic potency of this peptide. R-4 differs in structure from R-5 in having an arginine to serine substitution at position 7. It can be concluded that an arginine at this position accounts, at least in part, for the corticostatic activity of R-4.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains.

Granulins are candidate growth factors recently discovered in human and rat inflammatory leukocytes and bone marrow. Two granulin homologs, epithelin 1 and 2, occur in the rat kidney. Epithelin 1, which is probably identical to rat leukocyte granulin, exhibits proliferative and antiproliferative effects on epithelial cells in vitro. Here we show by cDNA analysis that the prepropeptide for the human granulins is a 593-residue glycoprotein, containing seven tandem repeats of the 12-cysteine granulin domain. By Northern blot analysis, gene expression was seen in myelogenous leukemic cell lines of promonocytic, promyelocytic, and proerythroid lineage, in fibroblasts and was seen very strongly in epithelial cell lines. Some epithelial cell lines respond to the mature peptide and express the gene. Among tissues examined, the kidney had the highest levels of granulin mRNA.

Amino Acid Sequence↗
PubMed1992

Dysfunctional grieving.

Dysfunctional grieving represents a failure to follow the predictable course of normal grieving to resolution (Lindemann, 1944). When the process deviates from the norm, the individual becomes overwhelmed and resorts to maladaptive coping. The process implies movement toward assimilation to or accommodation of the loss, resulting in progression toward social, psychological, and medical morbidity. Nurses will better assess the needs of the client with adequate information about the client's recent losses and perception of those losses. Such an assessment, in conjunction with an understanding of the signs, symptoms, and predisposing factors of complicated bereavement, will enable the nurse to develop a plan of effective intervention. Both case examples illustrate unresolved grief. In Case Example 1, the patient denied the importance of the relationship, which became masked with displaced anger and therefore delayed the grieving process. In Case Example 2, the patient's attempts at grieving over the loss of her son were complicated by her long-standing struggle with her husband's infidelity at the time of her pregnancy. The revelation of secondary loss is common in dysfunctional grieving. Resolution of grief encompasses not only accommodation to object loss, but also change in the pathological behaviors incorporated into the patient's self-image as a result of the loss (Lazare, 1979). The maladaptive operations employed by these patients to preserve self-image were discarded as the grief resolved. The focus of therapy included the loss of those behaviors as they were relinquished to prevent the patient from experiencing further anxiety and sense of loss (Zisook, 1987).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

Bacterial siderophores: structures of pyoverdins Pt, siderophores of Pseudomonas tolaasii NCPPB 2192, and pyoverdins Pf, siderophores of Pseudomonas fluorescens CCM 2798. Identification of an unusual natural amino acid.

Pyoverdins were isolated and characterized respectively from the cultures of Pseudomonas tolaasii NCPPB 2192 (pyoverdins Pt, Pt A, and Pt B) and Pseudomonas fluorescens CCM 2798 (Pyoverdins Pf/1, Pf/2, Pf, Pf/3/1, and Pf/3/2) each grown in iron-deficient conditions. Their structures were established by using FAB-MS, NMR, and CD techniques. These siderophores are chromopeptides, and all but one (pyoverdin Pf/3/3) possess at the N-terminal end of their peptide chain the same chromophore that has been reported in pyoverdin Pa from Pseudomonas aeruginosa ATCC 15692 [Wendenbaum, S., Demange, P., Dell, A., Meyer, J. M., & Abdallah, M. A. (1983) Tetrahedron Lett. 24, 4877-4880] and pseudobactin B 10 from Pseudomonas B10 [Teintze, M., Hossain, M. B., Barnes, C. L., Leong, J., & Van der Helm, D. (1981) Biochemistry 20, 6446-6457] which is derived from 2,3-diamino-6,7-dihydroxyquinoline. In pyoverdins Pt this chromophore is bound to a linear peptide chain D-Ser-L-Lys-L-Ser-D-Ser-L-Thr-D-Ser-L-OHOrn-L-Thr-D-Ser-D-OHOrn (cyclic) which has its C-terminal end blocked by cyclic D-N delta-hydroxyornithine. In pyoverdins Pf, the peptide chain is also linear, SerCTHPMD-Gly-L-Ser-D-threo-OHAsp-L-Ala-Gly-D-Ala-Gly-L-O HOrn(cyclic), and contains an unusual natural amino acid which is the result of the condensation of 1 mol of serine and 1 mol of 2,4-diaminobutyric acid, forming a cyclic amidine. The pyoverdins Pt differ only in substituent bound to the nitrogen on C-3 of the chromophore, which is succinic acid in pyoverdin Pt A, succinamide in pyoverdin Pt, and alpha-ketoglutaric acid bound to the chromophore by its C-5 carbon atom in pyoverdin Pt B. Similarly, pyoverdin Pf/1, pyoverdin Pf/2, pyoverdin Pf (the major compound), and pyoverdin Pf/3/2 are substituted respectively by L-malic acid, succinic acid, L-malic amide, and succinamide. Pyoverdin Pf/3/3 has the same chromophore as azotobactin, the peptidic siderophore of Azotobacter vinelandii. These pyoverdins are very similar to pseudobactin B 10, the siderophore of Pseudomonas B10: they are linear peptides containing three bidentate groups strongly chelating Fe(III) and blocked at their N-terminal end by the catecholic chromophore and at their C-terminal end by cyclic N delta-hydroxyornithine. They differ therefore from other pyoverdins such as those from P. aeruginosa ATCC 15692 which contain a partly cyclic peptide [Briskot, G., Taraz, K., & Budzikiewicz, H. (1989) Liebigs Ann. Chem., 375-384].

Amino Acid Sequence↗
PubMed1989

Isolation and biological activity of corticostatic peptides (anti-ACTH).

Corticostatins (CS's) are a family of low molecular weight peptides, rich in arginine and cysteine with the ability to inhibit ACTH stimulated adrenocortical steroidogenesis. They show a high degree of specificity in that they do not inhibit the action of angiotensin II in the adrenal cortex. Four corticostatins have been isolated from rabbit lung extracts and peritoneal neutrophil extracts and one from human neutrophils. Among them corticostatin I, CSI, is the most potent with an I.D.50 of 25 nM. Corticostatin activity is different from other published inhibitory factors such as TGF-B and ANF, which inhibit basal and angiotensin II stimulated steroidogenesis. Other factors such as macrophage secreted products, and septic shock plasma factors which have not been fully characterized also have suppressive activity on ACTH induced adrenocortical steroidogenesis in vitro. It is not yet clear whether there is any relationship between corticostatins and these macrophage products and shock plasma factor. Corticostatins do not inhibit dbcAMP induced steroidogenesis, however they do inhibit the accumulation of cAMP in response to ACTH in rat adrenal cell suspensions. Binding studies show that CSI is a competitive inhibitor of ACTH, probably acting by blocking, the address recognition site of the receptor. There is wide variation in the potency of the corticostatins ranging from an ID50 of 100 ng/ml for CSI to a completely inactive analog, HP1. In this paper we will describe the purification of the corticostatins and some recent results obtained on their mechanism of action.

Adrenal Glands↗
PubMed1988

Structure of a novel human granulocyte peptide with anti-ACTH activity.

We report the purification, structure and biological properties of a peptide of novel sequence from human granulocytes that inhibits ACTH stimulated synthesis of corticosterone in rat adrenal cell suspensions. The peptide HP-4 is homologous to a previously described human granulocyte peptide HP-1 that has no anti-ACTH activity.

Adrenal Glands↗
PubMed1987

The corticostatic (anti-ACTH) and cytotoxic activity of peptides isolated from fetal, adult and tumor-bearing lung.

The possibility that corticosteroids influence lung maturation was suggested in 1968 by Buckingham et al. and supported by studies mounted in humans and in rabbits by Liggins and Howie and by a collaborative study from the N.I.H. To our knowledge no reverse process, i.e. the regulation of adrenal function by the lung, has been postulated. In attempting to isolate ACTH from fetal lung we found peptides which depressed corticosterone production. Eventually, we isolated a group of peptides from rabbit fetal lung which showed potent inhibition of corticosterone production in rat adrenal cell suspensions. Using high-resolution reverse-phase HPLC and high-sensitivity gas-phase sequencing techniques the primary structure of one of these peptides has been determined and it was called corticostatin. The adult rabbit lung contains a large quantity of a very similar peptide, which elutes close to corticostatin but whose amino acid composition differs by a single glycine and possibly a serine. This peptide is also potently corticostatic. We have isolated homologous human peptides but these show no apparent corticostatic activity in rat adrenal cell suspensions. They do, however, show interesting effects on in vitro growth of lung cell lines.

Adrenal Glands↗
PubMed1986

The actions of N-terminal fragments of corticotrophin on steroidogenesis in dispersed rat adrenal cells in vitro.

The finding that the rat adrenal zona glomerulosa cell shows specific sensitivity to stimulation by alpha-MSH and related peptides has been confirmed both in vivo and in vitro, raising the possibility that alpha-MSH may have a physiological role in the control of glomerulosa function and aldosterone secretion. To define more closely the structural features which confer teh specificity of the glomerulosa response, other ACTH derived peptides have been tested for their specificity of actions on rat adrenal cells in vitro. The peptides tested were ACTH(5-24), ACTH(1-12), ACTH(1-14), ACTH(1-15), ACTH(1-16) and ACTH(1-17). Their actions were compared with those of alpha-MSH and ACTH(1-24). All of the ACTH-derived peptides stimulated glomerulosa corticosterone production with sensitivities similar to that of alpha-MSH; minimum effective concentration was 10 nmol/l. Also, like alpha-MSH, the shorter ACTH peptides stimulated aldosterone production only relatively weakly in these cells from animals on normal sodium intake. Only ACTH(5-24), ACTH(1-16) and ACTH(1-17) stimulated fasciculata/reticularis cells at concentrations up to 1 mumol/1. The actions of all of the shorter peptides were thus unlike those of ACTH(1-24) which stimulates both cell types with approximately equal sensitivity, and which furthermore strongly stimulates aldosterone production. The data suggest that the 18-24 region of the ACTH molecule contains the signal for a fasciculata/reticularis response, and the region 1-13 that for glomerulosa specificity. They confirm the view that, in the rat, alpha-MSH itself may be the specific pituitary glomerulosa-stimulating agent which much experimental work has predicted. They also indicate that synthetic ACTH(1-17) analogues should be used with caution.

Adrenal Cortex↗
PubMed1985

Postsynaptic block of a glutamatergic synapse by low molecular weight fractions of spider venom.

Fractions of low molecular weight (ca. 600-1000 dalton) isolated by high performance liquid chromatography (HPLC) and thin layer chromatography (TLC) from the venoms of the New-World spiders, Argiope trifasciata and Araneus gemma block transmission at glutamatergic nerve-muscle junctions in the locust, Schistocerca gregaria. These fractions are probably small peptides containing phenolic or indolic residues. Their effects on the neurally evoked twitch contraction, the junctional potential to glutamate ionophoresis and the voltage-clamped excitatory postsynaptic current of locust muscle indicate uncompetitive antagonism of the glutamate receptor channel complex through open channel block. In view of their slow reversibility of action they should make useful tools for future biochemical studies of locust glutamate receptors.

Animals↗