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A Bateman

Publications and source records attributed to A Bateman.

At least 73 records · Page 4Linked to original sources
PubMed1996

Structural and functional analysis of a promoter of the human granulin/epithelin gene.

Granulins (grns) or epithelins (epis) are peptides with molecular masses of approx. 6 kDa that modulate the growth of cells. The precursor for the grns/epis, which might itself be biologically active, is a secreted glycoprotein containing multiple repeats of the grn/epi motif. Grn/epi mRNA occurs widely in vivo, particularly in tissues rich in epithelial and haematopoietic cells. To understand better the role of the gene products for grn/epi it is important to determine the patterns of grn/epi gene expression and how this is regulated. To assist in this we have obtained the 5' sequence of the human grn/epi gene, and using chimaeras of the grn/epi -5' sequence and the chloramphenicol acetyltransferase gene we have shown a strong promoter activity associated with the 5' sequence of the human grn/epi gene. We have further delineated regions of the 5' sequence that confer high-level expression on the chimaeric gene.

Animals↗
PubMed1996

The isolation and characterization of a novel corticostatin/defensin-like peptide from the kidney.

We report the isolation and characterization of RK-1, a novel peptide found in the kidney. RK-1 is related to the corticostatin/defensins and has the sequence MPC-SCKKYCDPWEVIDGSCGLFNSKYCCREK but differs from the very cationic corticostatins/defensins in having only one arginine and a calculated charge at pH 7 of +1. Like some myeloid corticostatin/defensins RK-1 inhibits the growth of Escherichia coli. Since corticostatin/defensins effect ion flux in responsive epithelia we used volume changes in villus enterocytes as a model system to study the effects of RK-1 on ion channels in epithelial cells. At concentrations > or = 10(-9) M RK-1 decreased enterocyte volume in a dose-dependent manner through a pathway that requires extracellular calcium and is inhibited by niguldipine, a dihydropyridine-sensitive "L"-type Ca(2+)-channel blocker. In other assay systems for corticostatin-defensins, such as the inhibition of adrenocorticotropin-stimulated steroidogenesis, or cell lysis, RK-1 was inactive or only weakly active. These results demonstrate the existence of a novel system of biologically active peptides in the kidney represented by RK-1 which is antimicrobial and can activate epithelial ion channels in vitro.

Adrenal Cortex Hormones↗
PubMed1996

Corticostatins/defensins inhibit in vitro NK activity and cytokine production by human peripheral blood mononuclear cells.

Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytotic cells of the myeloid lineage. Natural killer (NK) cells are spontaneously cytotoxic large granular lymphocytes that are involved in immunosurveillance against cancer and infections. Their activity is modulated by hormones of the hypothalamic-pituitary-adrenal axis. We wished to determine whether two human corticostatins/defensins, HP-1 and HP-4, are able to change in vitro the spontaneous NK activity of human peripheral blood mononuclear cells (PBMC) and the responses either to the stimulatory cytokines immune interferon (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory hormone cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay with K562 cells as a target. HP-1 and HP-4 (10 (-8) -10 (-9) M) significantly inhibited the spontaneous and cytokine-inducible NK activity, and increased the cortisol-dependent inhibition. Radioimmunoassay of HPLC purified fractions obtained from sonicated NK cells showed HP-1 in the two cell preparations examined. We also evaluated the effects of HP-1 and HP-4 (10 (-8) M -10(-9) M) upo IFN-gamma and interleukin 6 (IL-6) production by PBMC stimulated with phytohemagglutinin (PHA) or concanavalin A (ConA). IFN-gamma was titrated with the biological assay using WISH cells as indicators and vescicular stomatitis virus (VSV) as the challenge virus. IL-6 was measured using an enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that corticostatins/defensins are novel modulators of lymphocyte functions in vitro. Their immunodepressing properties could add complexity and plasticity to hypothalamic-pituitary-adrenal-cytokine circuits in vivo.

Adrenal Glands↗
PubMed1996

Members of the immunoglobulin superfamily in bacteria.

We report a prediction that two prokaryotic proteins contain immunoglobulin superfamily domains. Immunoglobulin-like folds have been identified previously in prokaryotic proteins, but these share no recognizable sequence similarity with eukaryotic immunoglobulin superfamily (IgSF) folds, and may be the result of the physics and chemistry of proteins favoring certain common folds. In contrast, the prokaryotic proteins identified have sequences whose match to the immunoglobulin superfamily can be detected by hidden Markov modeling, BLASTP matches, key residue analysis, and secondary structure predictions. We propose that these prokaryotic immunoglobulin-like domains are almost certain to be related by divergence from a common ancestor to eukaryotic immunoglobulin superfamily domains.

Amino Acid Sequence↗
PubMed1996

Active minimisation of radiation scatter during breast radiotherapy: management implications for young patients with good-prognosis primary neoplasms.

BACKGROUND AND PURPOSE: Radiotherapy is used to reverse or prevent local tumour growth but is also a carcinogen in its own right. A recent audit of post-radiotherapy second malignancies in this institution revealed a striking preponderance of tumours originating near the outside edge of the treatment field. Since this finding suggests the existence of a critical subtherapeutic dose range predisposing to tumourigenesis, we attempted to define and reduce this radiation scatter dose. MATERIALS AND METHODS: We undertook a dosimetric review of 6 MV scatter from a linear accelerator in sites matching the putative tumourigenic region, and then extended this analysis to patients and tissue phantoms. RESULTS: A wide range of radiation scatter doses was confirmed-for example, doses 3 cm from the field edge varied from 1.7 to 22% of the therapeutic dose depending upon the field parameters. Scatter doses were then assessed in a sample of eight patients undergoing standard breast radiotherapy. Contralateral breast sites 4-12 cm from the midline received 4-10% of the therapeutic dose, or 200-500 cGy for a 50 Gy treatment, approximating historical estimates of the tumourigenic range. The deep component of this scatter dose from medial field breast irradiation was reduced 19% simply by replacing the 15 degrees medial tangential field wedge with a 30 degrees lateral wedge. Other manoeuvres which reduced contralateral breast dose by up to 46% included making the posterior field edges co-planar and shielding the breast during medial field irradiation. CONCLUSIONS: These results suggest that the risk of radiogenic second malignancies could be significantly decreased by careful attention to the treatment details. Greater awareness of these measures may prove particularly relevant to the conservative management of young patients with good-prognosis breast neoplasms such as ductal carcinoma in situ.

Breast↗
PubMed1996

Impact of Medicaid managed care on child and adolescent emergency mental health screening in Massachusetts.

OBJECTIVE: The study evaluated the impact of Medicaid managed care on decision making during emergency mental health screening and the outcomes of such screening for children and adolescents. METHODS: Data on client attributes and on system characteristics (payer, referral source, and disposition) were available for 297 Medicaid and non-Medicaid episodes of emergency mental health screening that occurred one year before the implementation of a statewide managed Medicaid program in Massachusetts and 393 episodes that occurred one year after implementation. Outcomes included changes in the volume of service provided and in the pattern of dispositions, particularly inpatient admissions. RESULTS: Although the total volume of child and adolescent emergency screening episodes significantly increased after implementation of Medicaid managed care, inpatient admissions decreased significantly. Among episodes not covered by Medicaid, no significant changes were noted after implementation on any variables. In the Medicaid group, significant differences were found in client attributes and system characteristics. After implementation the volume of emergency screening episodes for Medicaid clients increased significantly, and inpatient admissions decreased significantly. The pattern of dispositions changed significantly, with increased use of newly available crisis stabilization services. CONCLUSIONS: Although implementation of Medicaid managed care achieved the short-term goal of a decrease in hospitalizations, and probably concomitant savings, issues of quality of care for children and adolescents, and savings over the longer term, remain to be addressed.

Adolescent↗
PubMed1995

Outline structures for the extracellular domains of the fibroblast growth factor receptors.

Fibroblast growth factor receptors (FGFRs) have three extracellular domains that belong to the immunoglobulin superfamily. We have determined the outline structures for these domains on the basis of their homology to the I set molecule telokin. The outline structures describe the relative positions of residues in each domain; their major secondary structures, and the extent to which residues are accessible to the solvent. They also provide the basis of a coherent description of the change in recognition properties that occur when the IIIb and IIIc exons are switched and of the effects of mutations in FGFRs that cause genetic diseases.

Amino Acid Sequence↗
PubMed1995

Factors associated with admission to public and private hospitals from a psychiatric emergency screening site.

OBJECTIVE: The study examined factors associated with admission to public and private hospitals from a mental health care emergency screening system operating under a longstanding mandate to maximize use of private inpatient treatment. METHODS: For 206 patients evaluated at the mental health emergency screening site over a two-and-a-half-month period, data were collected on demographic and clinical characteristics, admission history, services received during the emergency encounter, system variables such as time the patient spent at the emergency screening site, number of admission sites asked to accept the patient, and all reasons cited by providers for refusing to admit the patient. Logistic regression was used to develop a model of factors most likely and least likely to be associated with private hospitalization. RESULTS: Overall, 60 percent of the sample was refused admission by one or more providers, and 55 percent, who were not accepted by and private hospital, became public patients. Private hospital admission was associated with patient or family involvement in referral and disposition, private or Medicaid insurance, a presenting problem of depression or suicidality, and longer time spent at the emergency screening site. Public admission was associated with no insurance, a past history of major public hospitalization, current or past history of assaultiveness, a presenting problem of aggression, and lack of any discharge site. CONCLUSIONS: Private providers are reluctant to admit patients who have characteristics associated with public hospitalization. In the restructuring of health care, a more fully privatized system will likely be called on to absorb such patients. Their care, treatment, and impact on the system should be carefully monitored and evaluated.

Adult↗
PubMed1994

Cost-effectiveness of recruitment methods in a population-based epidemiological study: the Melbourne Visual Impairment Project.

The cost-effectiveness of five recruitment methods was evaluated to determine the best method of encouraging eligible persons to participate in the Melbourne Visual Impairment Project (a population-based epidemiological study). The evaluation was divided into two phases. Phase 1 included one of two types of initial contact, by direct personal contact or by telephone. Phase 2 involved recruiting residents after an attempt had been made by either the telephone or the doorstep approach, and included a second attempt by a field interviewer, subsequent attempts by senior field staff, and finally, financial incentives. The cost-effectiveness of each method was determined by dividing the approach's cost by the effectiveness ratio. We identified 269 eligible households with 356 eligible residents. An 89 per cent response rate was achieved at the examination centre, comprising 61 per cent from Phase 1 and 28 per cent from Phase 2. Although both recruitment methods in Phase 1 were equally cost-effective, there was a significant difference in the effectiveness of each method in actually recruiting residents. The doorstep method was more costly per attender but was far more effective at 76 per cent recruitment than the telephone method at 47 per cent (P < 0.001). We have demonstrated a practical two-stage approach (the doorstep method in Phase 1 and follow-up strategies in Phase 2) to population-based recruitment involving the middle to elderly age group that should be relevant to many epidemiological studies.

Adult↗
PubMed1993

Aspartimide formation in the joining peptide sequence of porcine and mouse pro-opiomelanocortin.

The joining peptide (JP) portion of pro-opiomelanocortin extracted from mouse pituitary glands has previously been shown to exist in one major and several distinct minor forms (Bennett, H. P. J. (1986) Peptides 7, 614-622). We now confirm the heterogeneous nature of JP extracted from mouse neurointermediate pituitary glands and show that similar forms of JP are also to be found in extracts of porcine pituitary glands. Three forms of porcine JP (pJP-A, pJP-B, and pJP-C) were purified from whole porcine pituitary glands using reversed-phase high performance liquid chromatography methods. The three structural variants constitute approximately 10, 75, and 15%, respectively, of the total JP observed. Mass spectrometric analysis revealed that pJP-C was 18 mass units smaller than pJP-B, which is consistent with the formation of a succinimide structure at the aspartyl 16-glycine 17 peptide bond. Such symmetrical imide structures are known to hydrolyze at physiological pH to yield a mixture of the original alpha-aspartyl peptides and isomerized isoaspartyl peptides. We were able to show that pJP-A was the isomerized isoaspartyl form by demonstrating that pJP-A but not pJP-B was a substrate for the protein carboxyl methyltransferase enzyme (L-isoaspartyl/D-aspartyl protein methyltransferase; EC 2.1.1.77) purified from bovine erythrocytes. This cytosolic enzyme is known to preferentially methylate L-isoaspartyl residues within model substrates. Control experiments in which JP was incubated in the acidic medium used to extract the pituitary tissue showed that the isoforms of pJP are not artifacts of peptide purification. Furthermore, we have isolated the isoforms of pJP at levels which are 100 times greater than would be expected for a spontaneous reaction. We conclude that the formation of the aspartimide form of JP appears to be a facilitated process, possibly occurring as a result of conformation constraints dictated by the structure of pro-opiomelanocortin, or an as yet uncharacterized post-translational event.

Adrenocorticotropic Hormone↗
PubMed1993

The complementary deoxyribonucleic acid sequence, tissue distribution, and cellular localization of the rat granulin precursor.

Granulins (grns; also called epithelins) are cysteine-rich polypeptides with pleiotropic effects on epithelial cell growth in vitro. The grn/epi gene is widely expressed in epithelial cell lines, many of which respond to the gene product, raising the possibility of autocrine or paracrine regulation. In vitro the grn gene is expressed in cell types of diverse lineages, including epithelial cells, lymphoid and myeloid cells, and fibroblasts, but it is not known which cells express the gene in vivo. To understand the physiological role of the grn gene products it is necessary to know the context of grn gene expression in vivo. We have isolated the rat grn precursor complementary DNA and determined, by Northern blot analysis and in situ hybridization, the tissue distribution and cellular localization of grn gene expression. The complementary DNA predicts a 589-amino acid protein of M(r) 63,500 with seven and one-half grn repeats arranged in tandem and shows an overall identity of 75% with human progrn. The grn gene is expressed in a variety of tissues derived from all three embryonic germ layers but is most abundant in the spleen and several tissues of endocrine significance including the adrenal glands, epididymis, placenta, and ovary. Although widely expressed in tissues, gene expression is restricted to specific cell types. For example in the kidney, grn messenger RNA was detected in epithelial cells of the proximal and distal convoluted tubules and Bowman's capsule but not in medullary epithelia. In the spleen, grn messenger RNA expression was localized in lymphocytes, whereas hybridization signals were detected over scattered hepatocytes in the liver. Thus, although the grn gene is widely expressed in tissues and cell lines of many lineages in vitro, its expression in situ is restricted to hematopoietic and some epithelial cells. The restricted cell distribution suggests that the expression of the grn gene is more closely regulated in vivo than in cell cultures. Its localization to epithelial cells in situ supports an autocrine or paracrine role for these factors.

Amino Acid Sequence↗
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↗