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Biomedical subjects

S Garrison

Publications and source records attributed to S Garrison.

13 recordsLinked to original sources

Functional characterization of Pactolus, a beta-integrin-like protein preferentially expressed by neutrophils.

Murine Pactolus is a beta-integrin-like molecule expressed exclusively on the surface of granulocytes. Cell surface expression of Pactolus is dramatically increased following activation of bone marrow neutrophils with known agonists, and cross-linking of cell surface Pactolus, suggesting the bulk of the protein is in intracellular stores. The mature protein is found in two forms depending upon the extent of N-linked glycosylation. There is no evidence to suggest that Pactolus requires an associated alpha chain for expression. In some mouse strains, a truncated form of the protein is predicted based upon alternative splicing: this form, however, is unstable and rapidly degraded after synthesis. Differences in the quantities of these Pactolus mRNA isoforms have defined two alleles. BALB/c and C3H/HeJ mice possess allele B and preferentially express the truncated, unstable product, whereas C57BL/6 mice possess allele A and only produce the membrane-bound form. Sequence analysis has shown the difference between these two alleles is due to a single base pair difference at the splice acceptor site for the truncated product. The increased expression of the membrane form of Pactolus by granulocytes of C57BL/6 mice suggests a compensatory adhesion function that is reduced in cells from the low producing strains.

Alternative Splicing↗

Genomic organization, chromosomal localization, and transcriptional variants of the murine Pactolus gene.

The Pactolus gene encodes a cell surface protein similar to that of the beta integrin subunit family. The murine Pactolus gene is comprised of 16 exons that encompass 24 kb of the genome. The genomic organization of the Pactolus gene is very similar to that described for the human beta2 integrin gene (and deduced for murine beta2 integrin), including a separate exon containing only 5' untranslated sequences. The Pactolus gene was mapped to a terminal region of murine Chromosome (Chr) 16, distinct from the previously mapped site of the beta2 integrin gene on murine Chr 10. The Pactolus gene encodes three distinct transcripts via alternative splicing. The Pactolus A transcript encodes the full-length protein including transmembrane and cytoplasmic domains, while the Pactolus B transcript truncates translation before reaching these membrane-anchoring sequences. A newly discovered form, Pactolus C, is found in neonatal samples (along with Pactolus A) and would also encode a prematurely terminated protein. This form is derived from an alternative splicing event that skips part of exon 11, deletes exon 12, and uses an alternative acceptor site upstream of exon 13. The formation of the Pactolus B and C forms is thus governed by a complex alternative splicing mechanism that is affected by the developmental status of the animal.

5' Untranslated Regions↗

Identification of pactolus, an integrin beta subunit-like cell-surface protein preferentially expressed by cells of the bone marrow.

We have sought to develop methodologies to identify genes that are preferentially expressed during the differentiation of mast cells from their hematopoietic stem cell precursors. By using a modified differential display protocol, we compared a subset of transcripts expressed in bone marrow cells differentiated into immature mast cells with the exogenous addition of stem cell factor (SCF) or interleukin 3. One gene was identified that was preferentially expressed in the SCF-derived cells and encodes a novel murine integrin beta subunit-like molecule, dubbed Pactolus-1 (Pactolus). Two distinct forms of Pactolus mRNA were detected which, via alternative splicing, are predicted to encode a membrane-bound form and truncated version of the protein. The full-length Pactolus gene product is very similar to a number of beta subunit integrin chains, particularly beta2, with the notable exceptions of the apparent deletion of the metal-binding site within the putative metal ion-dependent adhesion site-like domain of the Pactolus gene product and a cytoplasmic domain that shares no obvious homology to similar domains of the other beta subunit integrin proteins. Although the Pactolus sequence was first identified in immature mast cell samples, screening of murine tissues indicated the highest level of Pactolus expression was found in the bone marrow, suggesting that the expression of Pactolus is confined to immature and maturing bone marrow-derived cells, and that the SCF-derived mast cells are more representative of this state than are the interleukin 3-derived mast cells. Immunoprecipitation of Pactolus revealed a cell-surface protein with an apparent molecular mass of about 95 kDa. Surprisingly, no associating alpha integrin subunit could be identified suggesting that either Pactolus does not associate with another integrin subunit or the association is too weak to be identified. These data suggest that Pactolus represents a gene and gene product related to those of the integrin beta subunits but whose function(s) may be quite distinct from those of the integrin beta subunits.

Alternative Splicing↗

Using the Quetelet body mass index as a mortality indicator for patients starting renal replacement therapy.

OBJECTIVE: The purpose of this study was to compare clinical profiles and mortality risk of patients starting renal replacement therapy (RRT) across three Quetelet body mass index (BMI) classifications: lean, normal, and obese. SAMPLE/SETTING: All patients applying for dialysis services using Health Care Financing Administration (HCFA) from 2728-U4 were sampled during the period of April 1, 1995 through June 30, 1995 in two end-stage renal disease (ESRD) Networks. These two ESRD networks encompassed 7 states and provided 846 patients for this analysis. DESIGN: A descriptive survival study was used with a follow-up period of 18 months. METHODS: The Quetelet BMI was calculated based on dividing the predialysis (i.e. before the first dialysis) weight in kilograms by the height in meters squared (kg/m2). Lean, normal, and obese groups were established by quartiles for each gender. A normal BMI consisted of all patients in which the observed BMI was greater than the 25th percentile or less than the 75th percentile. RESULTS: The lean risk group had more health problems than either the normal or obese group, most notably, a higher prevalence of chronic obstructive pulmonary disease (n = 35, 16.99%) [p = 0.007] and peripheral vascular disease (n = 51, 24.76%) [p = 0.005]. CONCLUSIONS: Death risk was higher in the lean group compared to the normal group after adjusting for age, sex, diabetes, coronary artery disease (CAD), and albumin ratio levels. Based on the simplicity of this technique, recommendations for using the Quetelet BMI as a part of routine patient screening is advocated. Obtaining height and weight are necessary assessment parameters for patients starting dialysis therapy. Using the Quetelet BMI will help nurses to identify those patients who are at nutritional risk.

Aged↗

Limited availability of medications for cancer patients.

We surveyed both chain and independent pharmacies within 10 counties of central South Carolina to determine the availability of certain medications that are often prescribed for patients during cancer treatment. One hundred twenty (59%) of the 202 surveys distributed were returned. Results indicate that many of the 65 products included in the survey are not stocked on a regular basis by the majority of the pharmacies that responded. Limited availability of these medications not only may prevent a patient from receiving timely drug therapy, but may exacerbate the anxieties and frustrations experienced by patients as they deal with their disease as well. This limited accessibility to medications could directly influence patient compliance. Therefore, patients need to be informed that availability is often limited, and that prescribed medications may require special ordering by their pharmacist. Awareness of this potential problem and increased communication among physicians, nurses, pharmacists, and patients could alleviate delays in drug therapy and improve the continuity of patient care.

Analgesics↗

Inner ear damage secondary to diabetes mellitus. I. Changes in adolescent SHR/N-cp rats.

The association between diabetes mellitus and hearing impairment has been debated in many previous studies. The spontaneous hypertensive/NIH-corpulent (SHR/N-cp) rat has been shown to be a unique genetic model for non-insulin-dependent diabetes mellitus. Seventeen diabetic and 17 control young male rats were divided into groups according to diet and phenotype. The rats were fed either 54% of sucrose or 54% starch diets for 3.5 months and killed at 5 months. The cochleas were fixed, decalcified, dissected, and stained for hair cell counting. A significant loss of outer hair cells was noted in the diabetic obese (SHR/N-cp) animals when compared with the control obese (LA/N-cp) animals in every group. Although no significant difference was noted between the diabetic obese (SHR/N-cp) animals receiving the starch and sugar diets, the diabetic obese (SHR/N-cp) animals were more severely affected than the nondiabetic lean (SHR/N-cp) rats.

Animals↗

Developmental differences in Bender-Gestalt recall of children with learning and behavior problems.

To investigate the visual-memory ability of children referred for psychological evaluations of academic and/or behavior problems, 135 children were administered the Bender-Gestalt and then asked to reproduce as many designs from memory as they could. Analysis indicated that the number of designs recalled increased with age and Performance IQ but not Full Scale IQ. Results were discussed in terms of the importance of considering developmental level when evaluating children and the establishment of rough cut-off scores on recall of the Bender-Gestalt designs.

Adolescent↗

NAD-dependent ADP-ribosylation of arginine and proteins by Escherichia coli heat-labile enterotoxin.

Escherichia coli heat-labile enterotoxin (labile toxin, LT) catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide and the ADP-ribosylation of arginine (Moss, J., and Richardson, S.H. (1978) J. Clin. Invest. 62, 281-285). Analysis of the product of the ADP-ribosylation of arginine by nuclear magnetic resonance spectroscopy indicated that the reaction was stereospecific and resulted in the formation of alpha-ADP-ribosyl-L-arginine. This reaction product rapidly anomerized to yield a mixture of the alpha and beta forms. In the presence of [adenine-U-14C]NAD, E. coli enterotoxin catalyzed the transfer of the radiolabel to proteins; the ADP-ribosylation of proteins was inhibited by arginine methyl ester, an alternative substrate. Digestion of the 14C-protein with snake venom phosphodiesterase released predominantly 5'-AMP. No product was obtained with a mobility similar to that of 2'-(5''-phosphoribosyl)-5'-AMP. This result is consistent with the covalent attachment by the enterotoxin of ADP-ribose rather than poly(ADP-ribose) to protein. Thus, LT is catalytically equivalent to choleragen, an enterotoxin of Vibrio cholerae, and activates adenylate cyclase through a similar stereospecific ADP-ribosylation reaction.

Adenosine Diphosphate Sugars↗

Gangliosides sensitize unresponsive fibroblasts to Escherichia coli heat-labile enterotoxin.

Chemically transformed mouse fibroblasts did not raise their cyclic AMP level in response to Escherichia coli heat-labile enterotoxin. These fibroblasts did, however, incorporate exogenous mono-, di-, and trisialogangliosides. After the uptake of monosialoganglioside galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GM1), the cells responded to E. coli heat-labile enterotoxin. The di- and trisialogangliosides were considerably less effective. GM1, the putative cholera toxin (choleragen) receptor, has been implicated previously as the receptor for E. coli heat-labile enterotoxin based on the ability of the free ganglioside to inhibit the effects of toxin. This investigation establishes that the ganglioside, when incorporated into fibroblasts, serves a functional role in mediating the responsiveness to the toxin.

Animals↗