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Biomedical subjects

D J Moore

Publications and source records attributed to D J Moore.

At least 73 records · Page 4Linked to original sources

Cyclical etidronate increases lumbar spine bone density in patients on long-term glucocorticosteroid therapy.

To determine whether cyclical etidronate modifies bone density in patients on chronic glucocorticosteroid therapy, annual bone density measurements were performed on 55 patients receiving glucocorticosteroids who were randomised to either continuous calcium supplementation or cyclical etidronate plus calcium supplementation in this secondary prevention study. Median L1-L4 lumbar spine bone density decreased by 0.7% in the calcium treated group after one year but increased by 3.1% in the group treated by calcium and etidronate (p = 0.00116). Median L1-L4 bone density decreased by 2.8% from baseline after two years in the calcium treated group but increased by 4.7% from baseline in the group treated by calcium and etidronate (p = 0.04). There were no significant effects of treatment on femoral neck density. Cyclical etidronate and calcium increased lumbar spine bone density in patients established on prednisolone treatment over a two-year period but had no effect on femoral density.

Adult↗

Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum.

Malaria parasites, and other parasitic protists of the Phylum Apicomplexa, carry a plastid-like genome with greatly reduced sequence complexity. This 35 kb DNA circle resembles the plastid DNA of non-photosynthetic plants, encoding almost exclusively components involved in gene expression. The complete gene map described here includes genes for duplicated large and small subunit rRNAs, 25 species of tRNA, three subunits of a eubacterial RNA polymerase, 17 ribosomal proteins, and a translation elongation factor. In addition, it codes for an unusual member of the Clp family of chaperones, as well as an open reading frame of unknown function found in red algal plastids. Transcription is polycistronic. This plastid-like DNA molecule is conserved in several genera of apicomplexans and is conjectured to have been acquired by an early progenitor of the Phylum by secondary endosymbiosis. The function of the organelle (plastid) carrying this DNA remains obscure, but appears to be specified by genes transferred to the nucleus.

Amino Acid Sequence↗

Three of four cysteines, including that responsible for substrate activation, are ionized at pH 6.0 in yeast pyruvate decarboxylase: evidence from Fourier transform infrared and isoelectric focusing studies.

Oligonucleotide-directed site-specific mutagenesis was carried out on pyruvate decarboxylase (EC 4.1.1.1) from Saccharomyces cerevisiae at three of the four cysteines (152, 221, and 222), the fourth (69) being buried according to X-ray crystallographic results [Arjunan et al. (1996) J. Mol. Biol. 256, 590-600]. All of the variants still retained significant activity, and all could be purified to homogeneity. FT-IR experiments were run on the C221S, C222S, C221S/C222S and C152A variants, as well as on the wild-type enzyme. There is a band present at 2557 cm-1 in the spectra of all variants and the wild-type enzyme, except in the spectrum of the C152A variant. This frequency is appropriate to a cysteine S-H stretching mode. It was therefore concluded that C152 is the only undissociated cysteine on the enzyme at pH 6.0, the pH optimum of this enzyme, whereas C221, C222, and C69 are all ionized. Isoelectric focusing experiments were carried out on all of these variants, as well as on the H92A variant (H92 is across the domain divide on the alpha domain, from C221 located on the beta domain). The variation in isoelectric points deduced from the data was consistent with removal of negative charges concomitant with the C221S, C222S, and C221S/C222S substitutions and removal of a positive charge with the H92A substitution when compared to that of the wild-type enzyme. The results of these two types of experiments are in good accord and suggest that the site of substrate activation at C221 [Baburina et al. (1994) Biochemistry 33, 5630-5635] is comprised of a Cys221S- +HHis92 ion pair, not unlike that found in papain and glyceraldehyde-3-phosphate dehydrogenase. This finding suggests that the regulatory site of this enzyme has been optimized for nucleophilic reactivity between the thiolate of C221 and the keto carbon of the 2-oxoacid.

Cysteine↗

Fluctuations in IR spectral parameters detected in mixed acyl chain membranes of Acholeplasma laidlawii B.

Acholeplasma laidlawii B cells were grown at 37 degrees C on three binary C16:0-d(31)/C18:1 fatty acid mixtures at initial mol ratios of 3:2, 1:1, and 2:3. These mol ratios produced final C16:0-d(31)/C18:1 lipid acyl chain mol ratios of 1.66 +/- 0.23 (n=6), 1.3 +/- 0.20 (n=6) and 0.58 +/- 0.09 (n=10), respectively, in the membrane of the microorganism. Membrane conformational order for the deuterated and proteated acyl chains in intact cells was monitored by FT-IR spectroscopy through the thermotropic response of the acyl chain CD2 and CH2 stretching frequencies. Intact cells and isolated membranes revealed broad phase transitions centered well below the growth temperature. This result differs from previous studies (Moore, D.J. and Mendelsohn, R. (1994) Biochemistry 33, 4080-4085) of cells grown on a single saturated fatty acid source, where Tm was close to the growth temperature. Fluctuations in IR spectral parameters from the liquid crystalline phases were detected in ten separate samples of cells grown on a 2:3 mixture (final mol ratio 0.58:1) of C16:0-d(31)/C18:1, and in no other cell preparation. These were manifest by reduced precision in the measurement of CH2 and CD2 stretching frequencies and are attributed to fluctuations in the membrane conformational order. In addition to conformational order fluctuations in intact cells, similar behavior was noted for the simple binary phosphatidylcholine (PC) mixture, DOPC/1-C16:0-d(31),2-C18:1 PC (2:1 molar ratio). In this instance, the fluctuations were also detected through the temporal and thermotropic response of the relative intensity of the 1341 cm(-1) band assigned to end-gauche conformers about the penultimate C-C bond in the oleoyl chains. The relationship of these observations to the Raman spectroscopic detection of packing fluctuations in highly unsaturated PC's (Litman, B.J., Lewis, N., and Levin, I.W. (1991) Biochemistry 30, 313-319) is considered.

Acholeplasma laidlawii↗

Conformational order of phospholipids incorporated into human erythrocytes: an FTIR spectroscopy study.

Acyl chain perdeuterated dimyristoylphosphatidylcholine (DMPC-d54) and dimyristoylphosphatidylserine (DMPS-d54) were incorporated by incubation into human erythrocytes. Light microscopic analysis demonstrated that erythrocytes incubated with DMPC-d54 became echinocytic while those incubated with DMPS-d54 became stomatocytic. This indicates that DMPC-d54 was incorporated preferentially into the outer monolayer whereas DMPS-d54 was selectively incorporated into the inner monolayer. Fourier transform infrared (FTIR) spectroscopy was used to monitor the conformational order of the incorporated phospholipids. The asymmetric CD2 stretching frequency of the inserted perdeuterated acyl chains was measured in both isolated membranes and intact erythrocytes as a function of temperature. DMPC-d54 incorporated into erythrocytes exhibited a cooperative phase transition at approximately 19 degrees C, i.e., at the same temperature as pure vesicles. In contrast, DMPS-d54 incorporated into red cells exhibited no phase transition, but possessed conformational order similar to that of the liquid-crystalline state. These results suggest that DMPC-d54 persists in domains in the outer monolayer while DMPS-d54 is dispersed in the inner monolayer. These experiments are the first to demonstrate that FTIR spectroscopy can be utilized to monitor directly a specific species of lipid molecule from the entire phospholipid population.

Adult↗

Bowel habits of healthy Australian children aged 0-2 years.

OBJECTIVE: To define the bowel habits of healthy Australian children aged up to 2 years. METHODOLOGY: One hundred and forty children were recruited in six age categories with a minimum of 20 children per category. Data on bowel habit was recorded by parents daily for 1 week. RESULTS: Stool frequency decreased with age. Ninety-five per cent of infants 0-14 days passed more than two stools per day compared with 21% at age 13-24 months. Breastfed infants passed more frequent and looser stools than children fed infant formula and solids and also showed a wider variation in frequency. CONCLUSIONS: Mean stool frequency decreased with age as did the variation. This is a combined effect of age and feed type. These data can be used as a guide to the bowel habit of healthy Australian children.

Australia↗

Occlusal vertical dimension in prosthodontics.

Occlusal vertical dimension is important in all aspects of prosthodontics. Unfortunately, there is no scientific method of determining the correct occlusal vertical dimension. The amount of interocclusal rest space (IRS) is a rough guide since muscle tone, which determines the space, is variable. IRS varies greatly from one patient to the next. It will automatically be correct when the occlusal vertical dimension is correct. IRS should not be interfered with regardless of its size. Many techniques have been used for determining occlusal vertical dimension in dentulous and edentulous patients. Regardless of the technique, the occlusal vertical dimension must be determined carefully by the dentist for a successful prosthesis.

Biometry↗

Skin closure and the incidence of groin wound infection: a prospective study.

Groin wound infection is a dreaded complication of vascular surgery and may jeopardize an underlying graft. A variety of skin closures have been used and the object of this study was to prospectively determine the relationship between skin closure and wound infection. One hundred fourteen consecutive patients (70 men and 44 women) undergoing bypass surgery with a groin incision (n = 173) were randomly assigned to skin closure with subcuticular Maxon, interrupted nylon, continuous nylon, or clips following a standard two-layer closure of subcutaneous tissue. Fourteen (12%) patients had diabetes and 50 (44%) had digital ulceration and gangrene. Aortofemoral bypass was performed in 25% of the patients and infrainguinal bypass in the remaining 75%. Perioperative wound cultures were obtained before closure. Wounds were inspected and cultures repeated on postoperative days 3, 5, 7, 10, and 14. Infection was defined as a positive culture. Groin wound infection occurred in 3% of the population and graft infection in 0.6%. The type of suture did not influence the incidence of infection. This study failed to demonstrate a significant difference in the incidence of wound infection with the use of different suture materials. We conclude that suture material should be selected on the basis of surgeon preference and costs.

Aged↗

Longitudinal evaluation of serum trypsinogen measurement in pancreatic-insufficient and pancreatic-sufficient patients with cystic fibrosis.

We studied serial measurements of serum cationic trypsinogen in patients with cystic fibrosis to assess the predictability of changes in individuals and the value of longitudinal measurement in defining pancreatic status. Three hundred twenty-nine patients with cystic fibrosis, aged 3 days to 40 years, had serum levels of trypsinogen measured on 2 to 12 occasions for periods ranging from 1 week to 7 years. Patients were classified into three groups on the basis of 72-hour fecal fat studies performed at the time of diagnosis. Two hundred thirty-three patients had pancreatic insufficiency (PI), 78 had pancreatic sufficiency (PS), and 18 had PS at diagnosis but acquired PI during follow-up (PS-->PI). Infants with PI had greatly elevated serum trypsinogen levels that fell sharply in the first years of life, so that by age 7 years more than 95% had subnormal values; individual patient values followed a predictable course similar to previously reported cross-sectional age-related values. In patients with PS, serum trypsinogen levels generally remained within or above the normal range and, after age 10 years, were well above the upper limit for PI patients. Within-patient variance was significantly greater (p < 0.0001) in patients with PS than in those with PI who were older than 7 years of age. Changes in patients within PS-->PI generally followed the pattern seen in patients with PI, but values in older patients tended to be in the higher range. We concluded that serial measurement of serum trypsinogen is a valuable tool for monitoring the pancreatic status of patients with cystic fibrosis and PS.

Adolescent↗

Pentoxifylline and critical leg ischemia.

The annual incidence of critical leg ischemia has been estimated at 500-1,000 patients per million population/year. In critical ischemia there is a breakdown in the microvascular flow-regulating system and inappropriate activation of the microvascular defense system, with resultant endothelial damage and activation of platelets and leukocytes, which leads to further damage of the capillary network. The mainstay of treatment until recently has consisted of interventional procedures. However, these are not always feasible and are not without significant mortality and morbidity. Therefore, attention has been directed towards pharmacologic management. Pentoxifylline inhibits leukocyte aggregation and activation, and improves red cell deformability and oxygen release to tissue. On the basis of these properties, several pilot studies were undertaken, and most have confirmed the benefits of pentoxifylline in the management of critical ischemia. These positive results led to the initiation of a multicenter, double-blind, placebo-controlled study of intravenous pentoxifylline in the acute management of critical ischemia. Results showed a significant reduction in rest pain with pentoxifylline, and outcome was not influenced by various prognostic factors. Research to date suggests that pentoxifylline could have a definite role in the management of patients with critical ischemia.

Humans↗

An in vivo evaluation of adhesives used in extraoral maxillofacial prostheses.

PURPOSE: This investigation introduces percent adherent area and 10-minute and 8-hour peel-strength values as an in vivo evaluation of three popular maxillofacial prosthetic adhesives when used with three extraoral prosthetic polymers. MATERIALS AND METHODS: Specimens of Silastic MDX 4-4210, Silastic Medical Adhesive A (Dow Corning Corporation, Midland, MI), and Silicone A-2186 (Factor II, Inc, Lakeside, AZ) were adhered to 25 subjects' arms using Secure Medical Adhesive (Factor II, Inc), Pros-Aide Adhesive (ADM Tronics Inc, Northvale, NJ), and Hollister Colostomy Adhesive (Hollister Inc, Libertyville, IL). After 10 minutes, the peel strength required to remove the specimens was measured. Additional specimens were then adhered to the subjects and worn for 8 hours. The nonadherent areas of the specimens were then marked, the peel strength was measured again, and then the percent adherent area was calculated. RESULTS: Hollister Colostomy Adhesive showed greater 10-minute peel-strength values when used with Silastic Medical Adhesive A. The peel-strength values of the Hollister Colostomy Adhesive when used with Silastic MDX 4-4210 increased with time. The greatest percent adherent area was obtained with Silastic MDX 4-4210 using Pros-Aide Adhesive, and the lowest was obtained with Pros-Aide Adhesive using Silicone A-2186 and Silastic Medical Adhesive A. CONCLUSIONS: There was no clearly superior adhesive/prosthetic material combination based on the tests used in this study; however, individual skin variations between patients affect the adhesive properties.

Adhesiveness↗

Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis.

OBJECTIVES: To determine the prevalence of vertebral fracture in postmenopausal women with steroid treated rheumatoid arthritis (RA), and whether the risk of vertebral fracture could be predicted from measurements of bone mineral density (BMD). METHODS: Vertebral deformities were defined from spine radiographs in 76 postmenopausal women with steroid treated RA (aged 50-79 years) and 347 age matched women from a population based group, using a morphometric technique. Lumbar spine (LS) BMD was measured by dual energy x ray absorptiometry. RESULTS: The odds ratio for vertebral fracture in the women with RA was 6.2 (95% confidence interval 3.2 to 12.3). The decrease in LS-BMD was less than expected for the observed prevalence of vertebral fracture and, among the women with RA, LS-BMD was not lower in those with vertebral fractures. CONCLUSIONS: We conclude that patients with steroid treated RA may have abnormal bone quality, and that LS-BMD cannot be used to predict the risk of vertebral fracture in these patients.

Aged↗

Age-related variation in the hydraulic conductivity of Bruch's membrane.

PURPOSE: To determine whether alterations in local fluid dynamics are associated with aging of the Bruch's membrane-choroid complex. In the macula, such changes have been postulated as causative factors underlying some pathologic manifestations of age-related macular degeneration (AMD). METHODS: The pressure-induced flow of physiological buffer through isolated human Bruch's membrane-choroid complex was measured using a modified Ussing chamber. Values of flow facilitated the calculation of hydraulic conductivity (flow per unit pressure), for individual complexes, which subsequently allowed for the development of an age-related profile. RESULTS: In all specimens, flow across the Bruch's membrane-choroid complex was found to be directly proportional to the applied pressure, whereas hydraulic conductivity was independent of pressure over the range studied. The hydraulic conductivity of the complex exhibited an exponential decrease with increasing age of donor, the most rapid decline occurring during the first four decades of life. The age-related change was most pronounced in the macula, where hydraulic conductivity halved every 9.5 years, compared to a t1/2 for the periphery of 19 years. CONCLUSIONS: The decline in the hydraulic conductivity of the Bruch's membrane-choroid complex with age implies a decreased capacity for the exchange of fluid between the choroidal and retinal pigment epithelial compartments. The relevance of these findings to the development of AMD is discussed.

Adolescent↗

Adaptation to altered growth temperatures in Acholeplasma laidlawii B: Fourier transform infrared studies of acyl chain conformational order in live cells.

Acholeplasma laidlawii B cells, highly enriched in saturated C14 and C15 fatty acids, have been grown at several temperatures. Conformational order in the acyl chains of live cell membranes has been monitored with Fourier-transform infrared (FT-IR) spectroscopy. Coupled CH2 wagging progressions, characteristic of the all-trans conformation, have been used to quantitatively monitor the extent of trans-gauche isomerization. A simple model relating the changes in the progression intensity to the introduction of gauche rotamers into the acyl chains suggest that at the growth temperature (25 or 37 degrees C for the C14-enriched cells, 30 or 37 degrees C for the C15-enriched cells) the cell membrane contains about 1.5 gauche bonds per acyl chain. The thermotropic response of the CH2 stretching frequencies near 2850 cm-1 reveals that the gel-liquid-crystal phase transition is shifted toward lower temperatures when the growth temperature is reduced. In addition, at any given temperature, the cells grown at lower temperature are more conformationally disordered than their counterparts grown at higher temperature. This behavior is consistent with the quantitative results from the CH2 wagging measurements. The data reveal that A. laidlawii B cells can control the overall conformational state of their membranes and that the observed degree of disorder (1.5 +/- 0.3 gauche bonds/acyl chain), when achievable, provides optimum cell viability. The ability of this microorganism to control the degree of membrane disorder delineates one possible pathway for homeoviscous adaptation.

Acholeplasma laidlawii↗

Erythrocyte peroxidation: quantitation by Fourier transform infrared spectroscopy.

We used Fourier transform infrared spectroscopy (FT-IR) to quantitatively monitor peroxidative damage in model phospholipids and in human erythrocyte membranes. The 3012-cm-1 band arising from olefinic C-H stretching modes diminished in intensity during membrane peroxidation as a result of loss of unsaturation in the phospholipid acyl chains. A precise (correlation coefficient = 0.99) linear relationship between the number of C = C bonds in the chains and the fraction of the total C-H stretching contour occupied by the olefinic C-H stretch was established for model phospholipids. Intact human erythrocytes and isolated ("ghost") membranes were also peroxidized and the loss of C = C bonds was demonstrated by FT-IR. GC studies of erythrocyte membranes confirmed that the primary site of peroxidation occurred at phospholipids containing arachidonate acyl chains. Finally, the formation of a new feature at 1260 cm-1 in the FT-IR spectrum was observed in both model compounds and erythrocyte membranes undergoing peroxidative damage. The feature corresponds to a C-O stretching and/or O-H in-plane bending vibration and is suggestive of the formation of these functional groups during peroxidation. FT-IR provides an accurate means for monitoring the effects of peroxidative damage in human erythrocytes.

Erythrocyte Membrane↗