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Biomedical subjects

D Hume

Publications and source records attributed to D Hume.

At least 19 recordsLinked to original sources
PubMed2002

Seasonal changes in morphology and function of the gastrointestinal tract of free-living alpine marmots ( Marmota marmota).

The gastrointestinal tracts of 76 free-living alpine marmots ( Marmota marmota) shot during a population control program in Switzerland were collected and analysed for patterns of change in morphology and function over the period from emergence from hibernation in April to just before re-entry into hibernation in September. Between first emergence and mid-summer (July) the fresh tissue mass of the stomach increased by 105%, the small intestine by 259% (among the largest recorded for a mammal), caecum by 185%, proximal colon by 138%, and distal colon by 144%. Mitotic activity was greatest in the small intestine; the mitotic index was high (40%) compared with indexes in the stomach and hindgut (approximately 4%) even at emergence, and increased to approximately 60% by mid-summer. Microbial activity in the caecum was also significant at emergence. The stomach (length) and caecum (length and fresh mass) increased in response to ingested food earlier than did the small intestine. Between mid-summer and September there were decreases in small intestinal tissue mass and mitotic activity. It is concluded that the gastrointestinal tract of alpine marmots probably continues to function throughout hibernation at a low level, with a mid-winter trough as part of an endogenous circannual rhythm. However, after emergence in spring, increases in size and activity of the tract appear to be a response to ingested food rather than to an endogenous signal. The early signs of down-regulation of the small intestine before re-entry into hibernation, together with its delayed up-regulation in response to food in spring, are consistent with the high costs of maintaining this section of the digestive system.

Animals↗
PubMed2000

Co-operative induction of pro-inflammatory signaling by Toll-like receptors.

Toll-like receptors (TLRs) mediate detection of a broad range of pathogens and pathogen-derived products including LPS, peptidoglycan, bacterial lipopeptides, and lipoteichoic acid. Recent evidence indicates that the broad specificity of TLRs may be a consequence of the interactions between different TLRs. In this report, we demonstrate that while a constitutively active TLR4 homodimer can induce the production of pro-inflammatory cytokines, homodimers of TLR2 and TLR6 cannot. However, when co-expressed in the same cell, constitutively active TLR2 and TLR6 strongly induce cytokine production, indicating that these TLRs require partners to productively signal. Since TLR4 signals as a homodimer, while TLR2 and TLR6 do not, it is clear that, despite the conservation of their cytoplasmic signaling domains, the mechanisms by which they initiate signaling are different. We have localized the region of TLR4 that mediates its ability to signal as a homodimer to the membrane-proximal half of the cytoplasmic tail of the receptor.

Animals↗
PubMed1999

Crystal structure of mammalian purple acid phosphatase.

BACKGROUND: Mammalian purple acid phosphatases are highly conserved binuclear metal-containing enzymes produced by osteoclasts, the cells that resorb bone. The enzyme is a target for drug design because there is strong evidence that it is involved in bone resorption. RESULTS: The 1.55 A resolution structure of pig purple acid phosphatase has been solved by multiple isomorphous replacement. The enzyme comprises two sandwiched beta sheets flanked by alpha-helical segments. The molecule shows internal symmetry, with the metal ions bound at the interface between the two halves. CONCLUSIONS: Despite less than 15% sequence identity, the protein fold resembles that of the catalytic domain of plant purple acid phosphatase and some serine/threonine protein phosphatases. The active-site regions of the mammalian and plant purple acid phosphatases differ significantly, however. The internal symmetry suggests that the binuclear centre evolved as a result of the combination of mononuclear ancestors. The structure of the mammalian enzyme provides a basis for antiosteoporotic drug design.

Acid Phosphatase↗
PubMed1999

Crystallization and preliminary X-ray diffraction studies of mammalian purple acid phosphatase.

The oxidized form of purple acid phosphatase from pig allantoic fluid has been crystallized in the presence of phosphate using the hanging-drop technique. The crystals belong to the space group P2(1)2(1)2(1) and have unit-cell parameters a = 66.8, b = 70.3, c = 78.7 A. Diffraction data collected from a cryocooled crystal using a conventional X-ray source extend to 1.55 A resolution. A knowledge of the three-dimensional structure of mammalian purple acid phosphatase will aid in understanding the substrate specificity of the enzyme and will be important in the rational design of inhibitors, with potential in the treatment of bone diseases.

Acid Phosphatase↗
PubMed1997

Recombinant human and mouse purple acid phosphatases: expression and characterization.

The mammalian purple acid phosphatases (also called tartrate-resistant acid phosphatases) are expressed primarily in actively resorbing osteoclasts and activated macrophages. The enzymes are characterized by the presence of a binuclear iron center at the active site. Recent studies on transgenic mice lacking purple acid phosphatase implicate the osteoclast enzyme in both bone resorption and bone mineralization. To characterize the mammalian enzymes in more detail, particularly with respect to their substrate specificity at the low pH of the osteoclastic resorptive space (2.5-3), we have purified the recombinant human and mouse enzymes from baculovirus-infected insect cells. The properties of the recombinant mouse enzyme are compared with those of the nonrecombinant enzyme isolated from mouse spleen. The kinetics of hydrolysis of the substrates p-nitrophenyl phosphate, phosphotyrosine, and pyrophosphate and a phosphotyrosyl peptide by the recombinant human and mouse enzymes and the nonrecombinant mouse and pig enzymes were analyzed. For all the enzymes the ratio k(cat)/Km was typically approximately 10(6) M(-1) s(-1) and was higher at pH 2.5 than at 4.9. The increase was attributable to a large decrease in Km at the lower pH value. The results indicate that the enzyme exhibits high catalytic efficiency toward substrates such as pyrophosphate and acidic phosphotyrosine-containing peptides, particularly at low pH values typical of the bone resorptive space. The implications of the results for the physiological function of the enzyme are discussed.

Acid Phosphatase↗
PubMed1991

Phasing the conformational unit of spectrin.

Many proteins contain a repetitive sequence motif, which implies that they contain a repetitive structural motif. Spectrin and the related proteins dystrophin and alpha-actinin consist largely of repeated motifs of 100-120 residues. But the repeating motif is degenerate and it has been difficult to define the boundaries of the repeating sequence unit or its corresponding structural unit. We have determined at which residues the structural units that correspond to spectrin's repeating 106-amino acid motifs begin and end. Drosophila alpha-spectrin cDNAs were expressed in bacteria to show that single segments (106 amino acids) and pairs of segments encoded by selected regions of spectrin cDNA can fold into stable conformations whose biophysical and biochemical properties are similar to those of native spectrin. Because such folding was critically dependent on the phasing of the expressed sequence with respect to the apparent boundaries of the repeating motifs, our data provide experimental evidence that relates the boundaries of the folded, conformational unit to the chemical sequence of repeating motifs.

Amino Acid Sequence↗
PubMed1990

Acute administration of ethanol suppresses pentylenetetrazole-induced c-fos expression in rat brain.

The effect of acute ethanol administration on pentylenetetrazole-induced c-fos expression in rat brain was studied. Pentylenetetrazole induced the rapid and transient expression of c-fos mRNA in rat brain. Maximal induction at a dose of 30 mg/kg was detected within 30 min and persisted for 60 min. Thereafter c-fos gene expression decreased to control levels by 180 min. No increase in c-fos mRNA was evident at doses of pentylenetetrazole less than or equal to 20 mg/kg, whereas maximal elevation was seen at 30 to 40 mg/kg. This action was inhibited by acute ethanol treatment (blood alcohol level greater than or equal to 100 mg/dl). Acute ethanol treatment alone had no effect on c-fos gene expression.

Actins↗
PubMed1989

Turn losses into gains: the bad debt audit.

The post-bad debt audit is the ideal time to review the policies and procedures that affect patient accounts. Review the Hill-Burton procedures if appropriate; review the manner in which accounts are processed for public assistance or welfare. Investigate unconfirmed third-party coverage and other areas of potential slippage. The bad debt audit is an excellent management tool to gain insight into the entire patient accounting processing cycle. It is an extremely efficient and cost-effective resource if properly conducted and if recommendations for improvement are properly implemented and monitored.

Accounting↗
PubMed1987

Selective resistance of bone marrow-derived hemopoietic progenitor cells to gliotoxin.

The fungal metabolite gliotoxin at low concentrations prevents mitogen stimulation of mature lymphocytes as a result of gliotoxin-induced genomic DNA degradation. Bone marrow, on the other hand, contains a subpopulation of cells resistant to gliotoxin at similar concentrations. This population includes the hemopoietic progenitor cells that grow in vitro in response to appropriate colony-stimulating factors and cells that form colonies in the spleens of lethally irradiated recipients. Gliotoxin treatment of lymph node cell-enriched bone marrow significantly delayed the onset of graft-versus-host disease in fully allogeneic bone marrow chimeras.

Animals↗
PubMed1985

Studies of peritoneal macrophage function in murine systemic lupus erythematosus. 2. Nature of elevated resident peritoneal cells in NZB and (NZB x NZW)F1 mice.

The numbers of resident peritoneal cells recovered from NZB and (NZB X NZW)F1 hybrid mice, which develop systemic lupus erythematosus (SLE), increased strikingly with age as compared with cells recovered from normal mice. The rise paralleled the onset of anti-DNA antibodies, occurring earlier in females than in males. The increased number of cells was due to an accumulation of medium-sized cells with an indeterminate appearance, but with the functional characteristics and cell markers typical of a macrophage. The unusual cells were esterase, F4/80 and Mac-1 positive, peroxidase, and Alcian blue negative, and were shown on sedimentation velocity separation to be phagocytic for EA and C3 (serum-treated) zymosan; 47-48% of peritoneal cells were Ia positive.

Age Factors↗
PubMed1985

Analysis of death rates in the population aged 60 years and over of Greater Glasgow by postcode sector of residence.

Using computer tapes of death registrations for the period 1980-2, and paper copy of population data for the 1981 census, death rates were calculated for the population resident in each of the 112 postcode sectors that make up the area served by the Greater Glasgow Health Board. Rates were calculated for both sexes in combination for each of the age groups 60-64, 65-69, 70-74, 75-79, 80-84, and 85 years and over. The difference in the mean death rate for the 22 postcodes in the quintile with the highest rates and the 22 postcodes in the quintile with the lowest rates was just over twofold in the 60-64 age group, just under twofold in the 65-84 age groups, but only 1.2-fold in the age group 85 years and over. There was marked consistency between the various age groups in the mortality rating for the postcode sectors, the postcode sectors with the highest death rates being located entirely in the more disadvantaged areas of the city and suburbs. The geographical mortality pattern for the older population was very similar to that (standardised for age and sex) in the 15-59 year age group.

Aged↗
PubMed1985

Linear regression: a method to accurately analyze accounts receivable.

Present methods of analysis of accounts receivable can result in information that is accurate. What is needed, therefore, is an improvement in those methods. Linear regression analysis is one improvement that can help the patient accounts manager. Its use of a standard coefficient and elimination of annualization of revenue and division of total annual revenue by accounts receivable can create more accurate and reliable information.

Accounting↗