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Biomedical subjects

A Riggs

Publications and source records attributed to A Riggs.

At least 19 recordsLinked to original sources
PubMed2005

Multipotent progenitor cells isolated from adult human pancreatic tissue.

The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus.

Adult↗
PubMed2000

Chromatin fine structure profiles for a developmentally regulated gene: reorganization of the lysozyme locus before trans-activator binding and gene expression.

The chicken lysozyme locus is activated in a stepwise fashion during myeloid differentiation. We have used this locus as a model to study at high resolution changes in chromatin structure both in chicken cell lines representing various stages of macrophage differentiation and in primary cells from transgenic mice. In this study we have addressed the question of whether chromatin rearrangements can be detected in myeloid precursor cells at a stage well before overt transcription of the lysozyme gene begins. In addition to restriction enzyme accessibility assays and DMS footprinting, we have applied new, very sensitive techniques to assay for chromatin changes. Particularly informative was UV photofootprinting, using terminal transferase-dependent PCR and nonradioactive detection. We find that the basic chromatin structure in lysozyme nonexpressing hematopoietic precursor cells is highly similar to the pattern found in fully differentiated lysozyme-expressing cells. In addition, we find that only in nonexpressing cells are dimethylsulfate footprints and UV photofootprints affected by trichostatin, an inhibitor of histone deacetylation. These results are interpreted to mean that most chromatin pattern formation is complete before the binding of end-stage trans-activators, supporting the notion that heritable chromatin structure is central to the stable epigenetic programs that guide development.

Animals↗
PubMed1996

Mitochondrial glycerol-3-phosphate dehydrogenase. Cloning of an alternatively spliced human islet-cell cDNA, tissue distribution, physical mapping, and identification of a polymorphic genetic marker.

Pancreatic beta-cell mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) plays a major role in glucose-induced insulin secretion. Decreased activity of this enzyme has thus been proposed to play a role in the pathogenesis of NIDDM. Cloning of human insulinoma mGPDH cDNAs disclosed the existence of two variant transcripts with different 5' ends. Reverse transcription polymerase chain reaction (PCR) confirmed the presence of both mGPDH mRNAs in purified native human pancreatic islets and other tissues. A major 6.5-Kb mGPDH transcript was detected by Northern blot analysis in RNA from human and rat pancreatic islets, with distinctly lower levels in other human tissues, indicating that previously reported high mGPDH enzymatic activity in beta-cells is determined by high transcript levels. The mGPDH gene was mapped to chromosome 2 by PCR analysis of genomic DNA from human/rodent somatic cell hybrids, and five independent overlapping yeast artificial chromosome (YAC) clones containing the mGPDH sequence were identified from the Centre d'Etude du Polymorphisme Humain YAC library. Analysis of these YAC clones identified a highly polymorphic chromosome 2q21-q33 dinucleotide repeat genetic marker (D2S141) physically linked to the mGPDH gene. These studies provide the means to investigate the role of the human mGPDH gene in the pathogenesis of NIDDM and illustrate the value of a novel strategy to identify genetic markers for diabetes candidate genes.

Alternative Splicing↗
PubMed1993

Quality of care in nursing homes: from the resident's perspective.

This paper derives from a study conducted by the Deakin Institute of Nursing Research between 1988 and 1990, whose major objective was to determine the impact of staffing mix on nursing resident's quality of care and life. Resident satisfaction with life in the nursing home is a key element in determining the quality of care and quality of life provided. Both the literature review and the study objectives supported the view that resident outcome can be collected through assessing the quality of care and the quality of life, through assessment by informed observers using instruments derived from explicitly stated standards, and through eliciting the perceptions of residents themselves. A schedule designed to measure satisfaction with care was developed and resident interviews were undertaken using this measure and the Life Satisfaction Index (A). The majority of responses to the resident satisfaction schedule were positive. The high percentage of positive responses did not correlate with the observations of the research assistants and there was some concern that while residents were able to assess care they were reluctant to criticize the staff or their behaviour.

Aged↗
PubMed1993

Staff in Australian nursing homes: their qualifications, experience and attitudes.

This paper is based upon findings from a study carried out by the Institute of Nursing Research between 1989 and 1990. The major objective of the study was to determine the impact of staffing mix on nursing home residents' quality of care and life as measured against the standards set out in 'Living in a Nursing Home'. An additional objective was to identify if there are any factors which may constrain or influence optimality. 'Skills mix' is sometimes used to describe the ratio of different levels of staff in terms of qualifications. The literature suggests, however, that such factors are only one dimension of skills mix in terms of the skills which people bring into their work in nursing homes. Other factors include the numbers of staff; the mix of staff in terms of level of qualification; the life experience of staff; and the educational experience of staff. This paper examines the findings of the study in the light of staff characteristics based on the criteria identified.

Attitude of Health Personnel↗
PubMed1992

Gene mapping studies confirm the homology between the platypus X and echidna X1 chromosomes and identify a conserved ancestral monotreme X chromosome.

The identification of the sex chromosomes in the three extant species of Prototherian mammals (the monotremes) is complicated by their involvement in a multivalent translocation chain at the first division of male meiosis. The platypus X chromosome, identified by the presence of two copies in females and one in males, has been found to possess a suite of genes that have been mapped to the X chromosomes of all eutherian and metatherian mammals. We have extended gene mapping studies to a member of the only other extant monotreme family, the echidna, which has a G-band equivalent X1 chromosome, as well as a smaller X2. We find that the five human X-linked genes (G6PD, GDX, F9, AR and MCF2) map to the echidna X1 chromosome in locations equivalent to those on the platypus X. These results confirm that the echidna X1 is the original X chromosome in this species, and identify a conserved ancestral monotreme X chromosome.

Animals↗
PubMed1992

Skills mix in Australian nursing homes.

This study investigated the relationships between skills mix, resident dependency and the quality of care and life of residents in a stratified random sample of 200 non-government homes in four Australian states. The study considered various measures of skills mix including the qualifications of the staff (staffing mix), the exposure of staff to in-service training and the leadership style of the director of nursing. The only relationships found between staffing mix (that is, the proportion of qualified and unqualified staff) related to the positive effect of therapy staff on the variety of experience of residents. Significant relationships between a number of other components of skills mix and the outcomes of care were found. Specifically, exposure to in-service training of staff and the leadership style of the director of nursing affected quality of care. State enrolled nurses were found to be significantly less satisfied with their work than registered nurses or untrained nurse assistants. Further studies are suggested in these areas and a review of skills mix in relation to them is recommended.

Activities of Daily Living↗
PubMed1992

Management and leadership in Australian nursing homes.

This paper is based on the outcomes of a study undertaken by Deakin Institute of Nursing Research for the Department of Community Services and Health between 1988 and 1990 (1). The study, which looked at the relationship between skills mix and resident outcomes, involved gathering data from 200 nursing homes in four Australian states using questionnaires and a case study approach. One of the major findings related to the importance of the management and leadership style on the outcome of quality of care and life within the nursing home. The pivotal role of the senior nurse (ie the director of nursing or charge nurse) in affecting high quality is consistently reported in the literature and this was confirmed by the study. Factors drawn from the quantitative and qualitative parts of the study, which make an important contribution to the quality of care experienced by residents, included the director of nursing's attitude, commitment and interpersonal skills. Also important were the ideology of the staff, team cohesiveness and positive attitude and an overall staffing environment which adheres to an agreed philosophy and is stable, satisfied and friendly. All of these were found to be influenced by the senior nurse.

Aged↗
PubMed1988

Carcinogenicity and haemoglobin synthesis induction by cytidine analogues.

We investigated 5-azacytidine and five of its analogues for: (1) carcinogenicity, in the male Fischer rat; (2) toxicities using changes in rat weights in vivo and a cytotoxicity assay in vitro; and (3) haemoglobin gene expression, using minor haemoglobin synthesis in sheep, mice and rats. 5-Azacytidine was found to be a complete carcinogen. It increased the incidence of testicular tumours as well as non-testicular tumours in rats treated for 12 months. 5-Azacytidine also had hepatic tumour promoting properties and was able to induce transplacental carcinogenesis when administered to pregnant rats on day 21 of timed pregnancies. None of the other 5 analogues that were tested appeared to be carcinogenic in small experiments. All the analogues which are known to have hypomethylating activity were found to be cytotoxic in vitro; the most potent being 5-azacytidine. As judged by decreased rat weight compared to untreated controls, the fluorinated cytidine analogues and 5'-deoxyazacytidine were more toxic than 5-azacytidine. Altered haemoglobin synthesis was seen in rats and DBA/2J mice, but not in sheep. In mice, where the clearest haemoglobin changes were noted, an increase in minor haemoglobin synthesis was found using both high and low doses of 5-azacytidine, and with 5,6-dihydro-5-azacytidine and 5-aza-2'-deoxycytidine. These last two analogues appear to be relatively non-toxic, noncarcinogenic in these experiments, and retain haemoglobin activating properties with a potency similar to that of 5-azacytidine.

Animals↗
PubMed1984

The tumorigenicity of 5-azacytidine in the male Fischer rat.

5-Azacytidine was administered to young adult male Fischer rats. Tumors were found in 31 out of 70 rats that had received 5-azacytidine and survived 18 months from the start of the experiment. Several rats had multiple primary tumors. In the rats that were tested for complete carcinogenicity a variety of tumor types was found. These included acute leukemia and malignant reticuloendotheliosis, and tumors of the testis, skin, and bronchus. No hepatic tumors were found in the group that was tested for hepatic tumor initiation. Hepatocellular carcinomas were found only in the group that was examined for hepatic tumor promotion by receiving a prior initiating dose of diethylnitrosamine. No tumors were found in the age controls. Thus, in these initial experiments, 5-azacytidine appeared to be a complete carcinogen, inducing tumors in several organs, and a tumor promoter but not a complete carcinogen for the liver.

Animals↗
PubMed1980

Hemoglobins of the tadpole of the bullfrog, Rana catesbeiana. Amino acid sequence of the alpha chain of a major component.

The complete amino acid sequence has been determined for the alpha chain of component III of the hemoglobin of the tadpole of the bullfrog, Rana catesbeiana. The chain comprises 141 residues of which 80 (57%) are identical to those in the corresponding positions of the human chain. Almost the same extent of similarity exists in the comparison with the sequenced part of the alpha chain of the adult bullfrog. The major features of this chain are: 1) each residue which is common to all other alpha chains of known sequence is also found in this alpha chain; 2) an acetylated NH2 terminus prevents formation of one of the salt bridges found in human hemoglobin which is responsible for part of the alkaline Bohr effect in mammalian hemoglobins; and 3) a prolyl residue at alpha 99 (G6) must distort the G helix.

Amino Acid Sequence↗
PubMed1980

Hemoglobins of the tadpole of the bullfrog, Rana catesbeiana. Amino acid sequence of the beta chain of a major component.

The amino acid sequence of the beta chain of component III of the hemoglobin of the tadpole of the bullfrog. Rana catesbeiana, has been determined. Comparison of this sequence with the 117 identified residues of the beta chain in the adult bullfrog shows that 50% (59 of 117) of the residues are identical; 55% (81 of 146) are identical in the comparison with the human beta chain. Tadpole hemoglobin lacks most of the residues believed responsible for the alkaline Bohr effect in human hemoglobin: the NH2 terminus is acetylated and histidine H5 (alpha 122) in the human alpha chain is replaced by glutamine in the tadpole. Although the tadpole beta chain has a COOH-terminal histidine, the hydrogen bond responsible in human hemoglobin for about one-half the normal alkaline Bohr effect cannot form, because asparagine rather than aspartate is present at position 94. However, histidyl residue H21 (beta 143), invoked to explain the reversed "acid" Bohr effect in human hemoglobin, is present in the tadpole chain and is adjacent to a seryl residue (beta 144) rather than lysyl residue, so that the pK of the beta 143 histidine should be higher than in human hemoglobin. This could explain the substantial acid Bohr effect in tadpole hemoglobin.

Amino Acid Sequence↗
PubMed1978

The kinetics and equilibria of squirrel-fish hemoglobin. A Root effect hemoglobin complicated by large subunit heterogeneity.

The functional properties of squirrel-fish hemoglobin have been measured by studying ligand binding equilibria and kinetics. The results show that squirrel-fish hemoglobin has a Root effect with a corresponding stabilization of the low affinity state. The properties of this state are pH dependent even in the absence of cooperativity. The effect of ATP shifts the overall ligant affinity towards the low affinity state and is characteristic of the allosteric effect caused by organic phosphates. Under pH and ATP conditions favoring the low affinity conformational state, a 10-fold difference in the binding kinetics of carbon monoxide to the alpha and beta subunits is observed.

Adenosine Triphosphate↗
PubMed1978

The hemoglobin of the common sting-ray, Dasyatis sabina: structural and functional properties.

1. The hemoglobin of the sting-ray, Dasyatis sabina, is both polymorphic and heterogeneous; three components predominate. 2. One major component has two kinds of polypeptide chain, of which one, presumably an alpha-chain, has a blocked NH2-terminus and an arginyl COOH-terminus, whereas carboxypeptidases A and B release tyrosine and histidine from the COOH-terminus of the beta-chain. 3. The amino acid sequence of the beginning NH2-terminal segment of the beta-chain of the major component has been determined. 4. The hemoglobin of the sting-ray, Dasyatis sabina, is highly resistant to urea and does not dissociate readily into subunits. 5. Oxygen binding by the hemoglobin is not affected by organic phosphates or high concentrations of either NaCl or urea. 6. The hemoglobin does not polymerize beyond tetramers. 7. Cooperativity, as monitored by n in the Hill equation, is pH-dependent and maximal between pH 8.5 and 9.0. 8. The hemoglobin has a large Bohr effect; the oxygen affinity is 16 times higher at pH 10 than at pH 6.5.

Animals↗