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Biomedical subjects

K Moore

Publications and source records attributed to K Moore.

At least 55 records · Page 3Linked to original sources
PubMed2001

Lysostaphin expression in mammary glands confers protection against staphylococcal infection in transgenic mice.

Infection of the mammary gland, in addition to causing animal distress, is a major economic burden of the dairy industry. Staphylococcus aureus is the major contagious mastitis pathogen, accounting for approximately 15-30% of infections, and has proved difficult to control using standard management practices. As a first step toward enhancing mastitis resistance of dairy animals, we report the generation of transgenic mice that secrete a potent anti-staphylococcal protein into milk. The protein, lysostaphin, is a peptidoglycan hydrolase normally produced by Staphylococcus simulans. When the native form is secreted by transfected eukaryotic cells it becomes glycosylated and inactive. However, removal of two glycosylation motifs through engineering asparagine to glutamine codon substitutions enables secretion of Gln(125,232)-lysostaphin, a bioactive variant. Three lines of transgenic mice, in which the 5'-flanking region of the ovine beta-lactoglobulin gene directed the secretion of Gln(125,232)-lysostaphin into milk, exhibit substantial resistance to an intramammary challenge of 104 colony-forming units (c.f.u.) of S. aureus, with the highest expressing line being completely resistant. Milk protein content and profiles of transgenic and nontransgenic mice are similar. These results clearly demonstrate the potential of genetic engineering to combat the most prevalent disease of dairy cattle.

Amino Acid Substitution↗
PubMed2001

Extreme altitude mountaineering and Type 1 diabetes; the Diabetes Federation of Ireland Kilimanjaro Expedition.

AIMS: To examine the effects of extreme altitude mountaineering on glycaemic control in Type 1 diabetes, and to establish whether diabetes predisposes to acute mountain sickness (AMS). METHODS: Fifteen people with Type 1 diabetes and 22 nondiabetic controls were studied during the Diabetes Federation of Ireland Expedition to Kilimanjaro. Daily insulin requirements, blood glucose estimations and hypoglycaemic attacks were recorded in diaries by the people with diabetes. The performance of blood glucose meters at altitude was assessed using standard glucose solutions. Symptoms of acute mountain sickness were recorded daily by people with diabetes and by the nondiabetic controls using the Lake Louise Scoring Charts. The expedition medical team recorded the incidence of complications of altitude and of diabetes. The final height attained for each individual was recorded by the expedition medical team and verified by the expedition guides. RESULTS: The final altitude ascended was lower in the diabetic than the nondiabetic group (5187 +/- 514 vs. 5654 +/- 307 m, P = 0.001). The mean daily insulin dose was reduced from 67.1 +/- 28.3-32.9 +/- 11.8 units (P < 0.001), but only 50% of recorded blood glucose readings were within the target range of 6-14 mmol/L. There were few hypoglycaemic attacks after the first two days of climbing. Both blood glucose meters tested showed readings as low as 60% of standard glucose concentrations at high altitude and low temperatures. The Lake Louise questionnaires showed that symptoms of AMS occurred equally in the diabetic and nondiabetic groups. There were two episodes of mild diabetic ketoacidosis; two of the diabetic group and three of the nondiabetic group developed retinal haemorrhages. CONCLUSIONS: People with Type 1 diabetes can participate in extreme altitude mountaineering. However, there are significant risks associated with this activity, including hypoglycaemia, ketoacidosis and retinal haemorrhage, with the additional difficulties in assessing glycaemic control due to meter inaccuracy at high altitude. People with Type 1 diabetes must be carefully counselled before attempting extreme altitude mountaineering.

Altitude↗
PubMed2001

Brain natriuretic peptide increases urinary albumin and alpha-1 microglobulin excretion in Type 1 diabetes mellitus.

UNLABELLED: Atrial natriuretic peptide (ANP) increases urinary albumin excretion in Type 1 diabetes mellitus (DM). Brain natriuretic peptide (BNP) is structurally and functionally related to ANP, but its effect on urine albumin excretion rate (UAER) is unknown. AIMS: To compare the albuminuric effects of intravenous infusion of ANP and BNP, and to assess the effect of both peptides on tubular protein excretion. METHODS: Eight subjects with Type 1 DM were randomised to a three leg, double blind, and placebo controlled study. On each study day, subjects were euglycaemic clamped and subsequently water loaded (20 mL/kg orally, plus urine losses) to steady state diuresis. When in steady state, creatinine clearance was estimated in three separate 1 hour periods. At the end of the first period, a 1 hour intravenous infusion of either placebo, ANP 0.025 microg/kg/min, or BNP 0.025 microg/kg/min was administered. There followed a 1 hour recovery period. Urine was collected at 15 min intervals for estimation of urine albumin (ACR) and alpha1 microglobulin creatinine ratio (MCR). Results were analysed by anova. RESULTS: Creatinine clearance was similar on the three study days, and was unaltered by any infusion. ACR was unaltered by placebo (1.3 +/- 0.5-1.2 +/- 0.4 mg/mmol, mean +/- SD, p = 0.81), but increased compared to placebo with infusion of both ANP (1.2 +/- 0.4-9.8 +/- 8.4 mg/mmol, P = 0.0004), and BNP (1.1 +/- 0.4-13.4 +/- 8.6 mg/mmol, P = 0.0001). The MCR was unaltered by placebo infusion (P = 0.89), but increased compared with placebo after infusion of ANP (5.4 +/- 0.9-12.3 +/- 4.2 mg/mmol, P < 0.0001), and BNP (5.4 +/- 0.8-12.1 +/- 2.5 mg/mmol, P < 0.0001). CONCLUSIONS: Intravenous infusion of BNP and ANP both increase the urine excretion of albumin and the tubular protein alpha1 microglobulin, independent of creatinine clearance.

Adult↗
PubMed2001

Clinician opinion on the management of patients with hepatic colorectal metastases.

BACKGROUND AND AIMS: Clinical practice is determined by many different factors, but with the advent of evidence-based medicine, there may be a tendency to concentrate upon the scientific facts when decision-making rather than focusing on the patient. Furthermore, individual clinician opinion or bias may potentially influence patient management. This study outlines clinician opinion with regard to management of patients with hepatic colorectal metastases, and compares it to present practice in the Sydney metropolitan area. METHODS: Clinician opinion was assessed by using a questionnaire and compared to results from a prospective multicenter study looking at patterns of care of patients with hepatic colorectal metastases. RESULTS: Clinicians participating in the present study had a good knowledge of the current evidence concerning hepatic colorectal metastases and its treatment. However, there was a discrepancy between clinician knowledge that matched scientific evidence and actual clinical practice. CONCLUSIONS: This study suggests that clinician bias/opinion does influence patterns of care for patients with hepatic colorectal metastases.

Chi-Square Distribution↗
PubMed2001

The "new normal".

Explore the source record for details and available documents.

Diffusion of Innovation↗
PubMed2001

Results of salvage cryoablation of the prostate after radiation: identifying predictors of treatment failure and complications.

PURPOSE: We conduct a critical evaluation of cryoablation of prostate cancer after failure of full dose radiotherapy to identify predictors of treatment failure and complications. MATERIALS AND METHODS: A total of 125 cryoablation procedures were performed in 118 patients with proved local recurrence after full dose radiotherapy. Followup includes serial prostate specific antigen (PSA) and biopsy at 6,12 and 24 months. Kaplan-Meier plots were constructed for different PSA cutoffs. We separately analyzed different cohorts based on T stage, Gleason score, PSA before cryoablation and endocrine therapy status. RESULTS: Of the 118 patients 114 had serum PSA nadir less than 0.5 ng./ml. Median followup was 18.6 months (range 3 to 54). Of the biopsy cores 3.1% (23 of 745) from 7 patients contained persistent viable cancer. Kaplan-Meier plots showed patients free of histological failure leveling at 87% and free from biochemical failure at 68%, 55% and 34%, respectively, with PSA greater than 4, 2 and 0.5 ng./ml. PSA greater than 10 ng./ml. before cryoablation, Gleason score 8 or greater before radiation and stage T3/T4 disease appeared to predict an unfavorable biochemical outcome. Serious complications included 4 rectourethral fistulas (3.3%) and severe incontinence (6.7%). Strong predictors of complications included bulky disease for fistulas and prior transurethral surgery. CONCLUSIONS: Salvage cryoablation after radiation can achieve reasonable biochemical and histological results with acceptable morbidity. Cryoablation appears to be a reasonable treatment option for this patient population with few viable therapeutic options, provided vigorous patient selection criteria are adhered to.

Aged↗
PubMed2001

Applying the diabetes quality improvement project indicators in the Indian Health Service primary care setting.

OBJECTIVE: With publication of the Diabetes Quality Improvement Project (DQIP) measures, the Indian Health Service National Diabetes Program applied the DQIP format to its IHS Diabetes Care and Outcomes Audit for comparison and benchmarks. RESEARCH DESIGN AND METHODS: Since 1986 the IHS Diabetes Care and Outcomes Audit has been conducted by medical record review in >75% of IHS and tribal facilities. Each year systematic random sample of charts is drawn from local diabetes registries. Chart reviews are conducted by, trained professionals according to standard definitions and instructions. Abstracted data are entered into a microcomputer-based epidemiologic software package. Local, regional, and national rates are constructed for each item. During the period 1995-1997, 150 facilities submitted data for compilation, representing participation from all 12 IHS administrative regions. The IHS Diabetes Care and Outcomes Audit collected virtually all of the DQIP measures, with the exception of LDL cholesterol (which was added to the record review in 1998). RESULTS: In 1995, 1996, and 1997, a total of 9,557, 9,985, and 9,626 individuals, respectively, were included in the total IHS audit sample. The reviews for 1995, 1996, and 1997 revealed that of all subjects: 55, 65, and 80%, respectively, had more than one HbA1c test during the year (P < 0.001); 42, 38, and 34%, respectively; had a high-risk HbA1c (>9.5%) (P < 0.001); 83, 81, and 84%, respectively, were tested for macroproteinuria (P < 0.11) and 16, 17, and 23%, respectively were tested for microproteinuria (P < 0.001); total cholesterol was assessed in 80, 81, and 85%, respectively (P < 0.001), and corresponding proportions of those with values <5.17 mmol/l were 48, 50, and 52%, respectively; triglyceride values were measured for 75,75, and 80%, respectively (P < 0.001), and the corresponding median triglyceride levels were 199, 198, and 193 mg/dl, respectively (P < 0.001); the proportion of clients with a blood pressure <140/90 mmHg was 64, 64, and 66%, respectively (P < 0.05); 55, 56, and 55%, respectively, had a dilated eye exam (P < 0.053); and the proportion of clients who had a comprehensive foot exam were 59, 59, and 61%, respectively (P < 0.05). CONCLUSIONS: The DQIP accountability and quality improvement measures could be easily applied to the IHS Diabetes Care and Outcomes Audit, and the process can prove to be practical. However, data alone are not sufficient to effect change. Use of the measures to ensure that the quality of care improves must also be stressed, because measuring alone will not guarantee such improvement.

Albuminuria↗
PubMed2001

Establishing surveillance for diabetes in American Indian youth.

OBJECTIVE: To determine prevalence estimates in order to monitor diabetes, particularly type 2 diabetes, in American Indian youth. RESEARCH DESIGN AND METHODS: To explore the feasibility of developing a case definition using information from primary care records, all youth aged <20 years with an outpatient visit or hospitalization for diabetes were identified from the Billings Area Indian Health Service database in Montana and Wyoming from 1997 to 1999, and the medical records were reviewed. Classification for probable type 1 diabetes was based on age < or =5 years, weight per age < or =15th percentile at diagnosis, or positive results of islet cell antibody test. Classification for probable type 2 diabetes was based on weight per age > or =85th percentile or presence of acanthosis nigricans at diagnosis, elevated C-peptide or insulin, family history for type 2 diabetes, or use of oral hypoglycemic agents with or without insulin or absence of current treatment 1 year after diagnosis. RESULTS: A total of 52 case subjects with diabetes were identified, 3 of whom had diabetes secondary to other conditions. Of the remaining 49 case subjects, 25 (51%) were categorized as having probable type 2 diabetes, 14 (29%) as having probable type 1 diabetes, and 10 (20%) could not be categorized because of missing or negative information. Prevalence estimates for diabetes of all types, type 1 diabetes, and type 2 diabetes were 2.3, 0.6, and 1.1, respectively, per 1,000 youth aged <20 years. CONCLUSIONS: Our definitions may be useful for surveillance in primary care settings until further studies develop feasible case definitions for monitoring trends in diabetes among youth.

Acanthosis Nigricans↗
PubMed2001

Origins and complexes: the initiation of DNA replication.

Eukaryotic DNA is organized for replication as multiple replicons. DNA synthesis in each replicon is initiated at an origin of replication. In both budding yeast, Saccharomyces cerevisiae and fission yeast, Schizosaccharomyces pombe, origins contain specific sequences that are essential for initiation, although these differ significantly between the two yeasts with those of S. pombe being more complex then those of S. cerevisiae. However, it is not yet clear whether the replication origins of plants contain specific essential sequences or whether origin sites are determined by features of chromatin structure. In all eukaryotes there are several biochemical events that must take place before initiation can occur. These are the marking of the origins by the origin recognition complex (ORC), the loading onto the origins, in a series of steps, of origin activation factors including the MCM proteins, and the initial denaturation of the double helix to form a replication "bubble". Only then can the enzymes that actually initiate replication, primase and DNA polymerase-alpha, gain access to the template. In many cells this complex series of events occurs only once per cell cycle, ensuring that DNA is not re-replicated within one cycle. However, regulated re-replication of DNA within one cell cycle (DNA endoreduplication) is relatively common in plants, indicating that the "once-per-cycle" controls can be overridden.

Cell Cycle↗
PubMed2001

Mercury induced modifications in the stereochemistry of the active site through Cys-73 in a serine protease--crystal structure of the complex of a partially modified proteinase K with mercury at 1.8 A resolution.

Proteinese K (PK) isolated from Tritirachium album Limber was crystallized with HgCl2 in excess, under microgravity conditions. The intensity data were collected at 4 degrees C to 1.8 A resolution and the final R-factor after refinement for all the reflections was 0.164. Mercury has been found at two sites with partial occupancies (0.4 and 0.6) which are at distances of 2.48 A and 2.58 A respectively from Cys-73 Sgamma. The Cys-73 in the enzyme structure is located close to the active site residue, His-69. This region is completely buried and is not accessible to the solvent. It is rather tightly packed. Therefore, the binding of mercury distorts the stereochemistry of the neighbouring residues including those belonging to the catalytic triad. As a result of this, the Ogamma of Ser-224 is displaced by 0.6 A which causes the inactivation of proteinase K by increasing the H-bond distance to 3.7 A between Ser-224 Ogamma and His-69 Nepsilon2.

Amino Acids↗
PubMed2000

Analysis of 114 kb of DNA sequence from fission yeast chromosome 2 immediately centromere-distal to his5.

One hundred and fourteen kilobase pairs (kb) of contiguous genomic sequence have been determined immediately distal to the his5 genetic marker located about 0.9 Mb from the centromere on the long arm of Schizosaccharomyces pombe chromosome 2. The sequence is contained in overlapping cosmid clones c16H5, c12D12, c24C6 and c19G7, of which 20 kb are identical to previously reported sequence from clone c21H7. The remaining 93 781 bp of sequence contains 10 known genes (cdc14, cdm1, cps1, gpa1, msh2, pck2, rip1, rps30-2, sad1 and ubl1), 32 open reading frames (ORFs) capable of coding for proteins of at least 100 amino acid residues in length, one 5S rRNA gene, one tRNA(Pro) gene, one lone Tf1-type long terminal repeat (LTR) and one lone Tf2-type LTR. There is a density of one protein-coding gene per 2.2 kb and 22 of the 42 ORFs (52%) incorporate one or more introns. Twenty-one of the novel ORFs show sequence similarities which suggest functions of their products, including a cyclin C, a MADS box transcription factor, mad2-like protein, telomere binding protein, topoisomerase II-associated protein, ATP-dependent DEAH box RNA helicase, G10 protein, ubiquitin-activating e1-like enzyme, nucleoporin, prolyl-tRNA synthetase, peptidylprolyl isomerase, delta-1-pyrroline-5-carboxylate dehydrogenase, protein transport protein, coatomer epsilon, TCP-1 chaperonin, beta-subunit of 6-phosphofructokinase, aminodeoxychorismate lyase, a phosphate transport protein and a thioredoxin.

Base Sequence↗
PubMed2000

Comparison of telomerase levels before and after differentiation of two cell lines of human neuroblastoma.

BACKGROUND: Telomerase is the enzyme that is responsible for maintaining telomere length in human germ cells, tumor cells, and immortalized cells. Its specific role in the immortilization process is unknown. This study was performed to determined whether the level of telomerase activity in human neuroblastoma cell lines correlated with their level of differentiation. We proposed that as neuroblastoma cells differentiated into more mature or benign cells, the levels of telomerase expression would decrease. MATERIALS AND METHODS: Two human neuroblastoma cells lines, SK-N-AS and SK-N-DZ, were differentiated using retinoic acid. These cells were assayed for telomerase activity by the telomere repeat amplification protocol (TRAP) before, during, and after treatment with retinoic acid for 8 days. Untreated cells were used for control and were compared to the retinoic acid-treated cells. Differentiation of the cell lines was confirmed by assaying expression of ret mRNA using the reverse-transcriptase polymerase chain reaction (RT-PCR) and gel electrophoresis of the radiolabeled products. RESULTS: No statistical difference in telomerase activity was noted between control and treated groups. CONCLUSIONS: While telomerase activity has been shown by others to correlate with tumor aggressiveness in human neuroblastoma cells, the mechanism that is involved appears to be separate from cellular differentiation.

Cell Differentiation↗