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Biomedical subjects

M Rose

Publications and source records attributed to M Rose.

At least 37 records · Page 2Linked to original sources
PubMed1999

Severe anorexia nervosa associated with osteoporotic-linked femural neck fracture and pulmonary tuberculosis: a case report.

We report a case study of a 38-year-old woman who had been suffering from anorexia nervosa (AN) since the age of 26. Before admittance to our clinic, she weighed 23.8 kg (at a height of 164 cm, 8.8 body mass index [BMI]) but still carried out strenuous physical activities. After good psychotherapeutic response and weight gain (34.4 kg), she accidentally fell and broke her femoral neck-favored as it was by osteoporosis. The X-ray taken before dynamic hip screw implantation coincidentally showed signs of pulmonary tuberculosis (TB), which could then be proven by computed tomography (CT) scans and cultures from a bronchoscopy. Other than lack of appetite and loss of weight, which we attributed to AN, there were no other clinical or biochemical indicators which could have pointed to an earlier TB diagnosis. As a result, the need for screening procedures is discussed. The manifestation of TB during the first weight gain after 12 years of severe malnutrition, during which there were no serious infections, seems to endorse former observations that AN patients appear to be "resistant" to some extent against infectious diseases, a "protection" which may be lost with convalescence and weight gain.

Adult↗
PubMed1999

Antibodies to endothelial cells identify myocardial damage and predict development of coronary artery disease in patients with transplanted hearts.

BACKGROUND: Transplant-induced coronary artery disease is a leading cause of graft failure in cardiac allograft recipients after the first year of transplantation, but there presently is no test to identify patients at high risk for developing the disease. Our research is focused on development of a predictive test to identify patients at high risk of developing the disease. METHODS: Sixty-eight cardiac allograft recipients transplanted and followed at Methodist Hospital between 1982 and 1996 were studied. Serial annual angiograms were used to diagnose coronary artery disease, and serial endomyocardial biopsies were used to detect cellular infiltrates and microvascular disease. Biopsy-matched serum samples were used for cardiac troponin-T determinations as measures of myocardial damage, and serum antibodies to endothelial cells were determined by using flow cytometry, enzyme-linked immunosorbent assay and immunoblotting techniques. The endothelial antibody data were evaluated statistically for associations with angiographic changes, biopsy findings and biochemical evidence of myocardial damage. FINDINGS: Antibodies to endothelial cells were identified by all three techniques, and significant associations were found for the amount of antibody identified by Western immunoblotting with histological rejection grades in biopsies, which were confirmed immunocytochemically as macrophages (p<0.01) and T lymphocytes (P = 0.03). These antibodies also associated significantly with vascular antithrombin depletion (p = 0.02), biochemical evidence of myocardial damage (p = 0.005) and subsequent development of coronary artery disease (p = 0.03). INTERPRETATION: The significant association of anti-endothelial antibodies with cellular infiltrates, depletion of vascular antithrombin and myocardial damage suggests a role for antibody in the development of transplant-induced arteriopathy. The significant association of antiendothelial antibodies with the future development of coronary artery disease further suggests that assessment of these antibodies may provide a non-invasive test to predict the development of transplant-induced coronary artery disease.

Adult↗
PubMed1999

Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats.

The current study was designed to evaluate the toxicity and activity of Spartaject Busulfan, a microcrystalline preparation of busulfan, following its intrathecal administration into a nude rat model of human neoplastic meningitis. Animals were treated through permanent indwelling subarachnoid catheters. Human glioma D-456 MG growing in the subarachnoid space was treated with 8.1 micromol of intrathecal Spartaject Busulfan. Single-dose therapy was also subsequently compared with 4 doses of 8.1 and 2.0 micromol busulfan, respectively, against D-456 MG neoplastic meningitis. Additional experiments evaluated a saline control versus 8.1 micromol x 1, 6.2 micromol x 4 and 4.1 micromol x 4, respectively, against D-456 MG. A single dose of 8.1 micromol of intrathecal Spartaject Busulfan resulted in an increase in median survival of 61.7% compared with the saline control. In experiment 2, all busulfan treatments showed increases in median survival of 142.8% (8.1 micromol x 1), 52.3% (2.0 micromol x 4), and 23% (8.1 micromol x 4) (p < 0.001 for all groups) compared with the saline control. These results suggest that a narrow therapeutic dose range for both toxicity and activity has been defined for intrathecal busulfan in the treatment of human neoplastic meningitis in athymic nude rats. Although busulfan has only limited activity against solid tumors, the high doses achievable in the CSF following intrathecal administration coupled with the steep dose-response relationships of alkylating agents, provide rationale for further evaluation of this agent.

Animals↗
PubMed1999

A phase I study of paclitaxel for mobilization of peripheral blood progenitor cells.

We conducted a phase I trial to determine the dose and schedule of paclitaxel, when given together with filgrastim, which would optimally promote mobilization of stem cells with tolerable toxicity. Dose escalation began at 275 mg/m2 3 h infusion. Dose-limiting neuropathy was observed at the 300 mg/m2 dose level. A second dose escalation was conducted utilizing 24 h infusion schedules, beginning at 225 mg/m2. Dose escalation was continued by 25 mg/m2 increments to 300 mg/m2, at which dose neuropathy was again dose-limiting. The recommended dose and schedule of paclitaxel for the purpose of mobilization of stem cells, when given together with filgrastim, are 275 mg/m2 as a 24 h infusion. The median stem cell yield after this dose of paclitaxel was 6.6 x 10(6) CD34+ cells/kg/apheresis (range 3.6 x 10(6)-7.7 x 10(6)).

Adult↗
PubMed1999

ClpE, a novel type of HSP100 ATPase, is part of the CtsR heat shock regulon of Bacillus subtilis.

Clp ATPases, which include the ubiquitous HSP100 family, are classified according to their structural features and sequence similarities. During the course of the Bacillus subtilis genome sequencing project, we identified a gene encoding a new member of the HSP100 family. We designated this protein ClpE, as it is the prototype of a novel subfamily among the Clp ATPases, and have identified homologues in several bacteria, including Listeria monocytogenes, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus pneumoniae, Lactobacillus sakei and Clostridium acetobutylicum. A unique feature of these Hsp100-type Clp ATPases is their amino-terminal zinc finger motif. Unlike the other class III genes of B. subtilis (clpC and clpP ), clpE does not appear to be required for stress tolerance. Transcriptional analysis revealed two sigmaA-type promoters, expression from which was shown to be inducible by heat shock and puromycin treatment. Investigation of the regulatory mechanism controlling clpE expression indicates that this gene is controlled by CtsR and is thus a member of the class III heat shock genes of B. subtilis. CtsR negatively regulates clpE expression by binding to the promoter region, in which five CtsR binding sites were identified through DNase I footprinting and sequence analysis.

Adenosine Triphosphatases↗
PubMed1999

Alterations in expression and in serum activity of dipeptidyl peptidase IV (DPP IV, CD26) in patients with hyporectic eating disorders.

The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leucocyte antigen CD26, is considered to participate in T-cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 34 patients [anorexia nervosa (AN): n = 11, bulimia (B): n = 23] in four consecutive weekly analyses. In addition, the expression of CD25 (interleukin-2 receptor alpha chain) was evaluated to estimate the degree of T-cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD2-CD26-positive cells were reduced in patients compared with healthy controls [mean 40.2% (AN) and 41.1% (B) versus 47.4% (HC), P < 0.01], while the DPP IV activity in serum was elevated [mean 108.4 U/l (AN) versus 91.1 U/l (B) and 80.3 U/l (HC), P < 0.01]. The potential implications of our observations on, and beyond, immune function are discussed.

Anorexia Nervosa↗
PubMed1999

A study of the variability seen in the international normalized ratio obtained using different sensitivity thromboplastin reagents on different instrument types.

We performed an extensive study to check international normalized ratio (INR) recovery using three different rabbit thromboplastin reagents of different sensitivities [international sensitivity index (ISI) circa 1.1, 1.3 and 2.0] on two different instrument types. Both instrument types used an optical end point: one nephelometric at 660 nm, one photometric at 880 nm. Each thromboplastin reagent in the study had an instrument-specific ISI value assigned to it by the reagent manufacturer. Samples obtained from stable orally anticoagulated patients were tested on four different instruments of each type with the three different sensitivity reagents. Excellent correlation between INR values was seen between all results (r values between 0.97 and 0.99). Regression analysis gave slopes between 0.92 and 1.07, and a maximum deviation of intercept from zero of 0.21. Variations in CV of less than 2% were seen within each instrument type. This study shows that if instrument-specific ISI values are used, comparable INR values can be obtained using reagents of different sensitivity on multiple instruments of the same or different types. This study demonstrates the validity of the INR/ISI system.

Adult↗
PubMed1999

Detecting and analyzing DNA sequencing errors: toward a higher quality of the Bacillus subtilis genome sequence.

During the determination of a DNA sequence, the introduction of artifactual frameshifts and/or in-frame stop codons in putative genes can lead to misprediction of gene products. Detection of such errors with a method based on protein similarity matching is only possible when related sequences are available in databases. Here, we present a method to detect frameshift errors in DNA sequences that is based on the intrinsic properties of the coding sequences. It combines the results of two analyses, the search for translational initiation/termination sites and the prediction of coding regions. This method was used to screen the complete Bacillus subtilis genome sequence and the regions flanking putative errors were resequenced for verification. This procedure allowed us to correct the sequence and to analyze in detail the nature of the errors. Interestingly, in several cases in-frame termination codons or frameshifts were not sequencing errors but confirmed to be present in the chromosome, indicating that the genes are either nonfunctional (pseudogenes) or subject to regulatory processes such as programmed translational frameshifts. The method can be used for checking the quality of the sequences produced by any prokaryotic genome sequencing project.

Bacillus subtilis↗
PubMed1999

Functional identification of the product of the Bacillus subtilis yvaL gene as a SecG homologue.

Protein export in Escherichia coli is mediated by translocase, a multisubunit membrane protein complex with SecA as the peripheral subunit and the SecY, SecE, and SecG proteins as the integral membrane domain. In the gram-positive bacterium Bacillus subtilis, SecA, SecY, and SecE have been identified through genetic analysis. Sequence comparison of the Bacillus chromosome identified a potential homologue of SecG, termed YvaL. A chromosomal disruption of the yvaL gene results in mild cold sensitivity and causes a beta-lactamase secretion defect. The cold sensitivity is exacerbated by overexpression of the secretory protein alpha-amylase, whereas growth and beta-lactamase secretion are restored by coexpression of yvaL or the E. coli secG gene. These results indicate that the yvaL gene codes for a protein that is functionally homologous to SecG.

Amino Acid Sequence↗
PubMed1999

Importance of glucose-6-phosphate dehydrogenase activity in cell death.

The intracellular redox potential plays an important role in cell survival. The principal intracellular reductant NADPH is mainly produced by the pentose phosphate pathway by glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme, and by 6-phosphogluconate dehydrogenase. Considering the importance of NADPH, we hypothesized that G6PDH plays a critical role in cell death. Our results show that 1) G6PDH inhibitors potentiated H2O2-induced cell death; 2) overexpression of G6PDH increased resistance to H2O2-induced cell death; 3) serum deprivation, a stimulator of cell death, was associated with decreased G6PDH activity and resulted in elevated reactive oxygen species (ROS); 4) additions of substrates for G6PDH to serum-deprived cells almost completely abrogated the serum deprivation-induced rise in ROS; 5) consequences of G6PDH inhibition included a significant increase in apoptosis, loss of protein thiols, and degradation of G6PDH; and 6) G6PDH inhibition caused changes in mitogen-activated protein kinase phosphorylation that were similar to the changes seen with H2O2. We conclude that G6PDH plays a critical role in cell death by affecting the redox potential.

3T3 Cells↗
PubMed1999

[Mobile computer-assisted psychometric diagnosis. Economic advantages and results on test stability].

In psychotherapy, there is a rising need to evaluate the therapeutic process and outcome quality. However, the effort for documentation binds manpower and is a burden on economic resources. Hence, we studied the usability of a new by developed, mobile, computer-assisted basis assessment (ComBas 1.3) in comparison with paper-and-pencil versions with respect to its effects on data structure and cost reduction. More than 9000 standardised psychometric tests (personality inventory: Giessentest, complaint checklist: Giessener Beschwerdebogen, mood checklist: Berliner Stimmungsfragebogen) were applied with each method to 1400 psychosomatic patients. It was found that usage of the mobile computer-assisted assessment reduced the time by 2/3 spent on documentation, because data organisation and accessibility for clinical, scientific, and educational needs were significantly improved. Moreover, no differences in stability coefficients and data distribution were seen between the two methods. In trait variables, there was also an equivalence in scale means, but in state variables, especially in complaint scales, we identified a tendency toward higher scale means in computer-assisted measurement. We cannot establish whether this is only a methodical effect or is additionally influenced by changes in samples during the evaluation period between 1989 and 1996. Hence, we concluded that comparison samples for state instruments should be adjusted to the applied test form and actualised for use in individual diagnostics.

Diagnosis, Computer-Assisted↗
PubMed1998

Proteins of newly isolated mutants and the amino-terminal proline are essential for ubiquitin-proteasome-catalyzed catabolite degradation of fructose-1,6-bisphosphatase of Saccharomyces cerevisiae.

Addition of glucose to cells of the yeast Saccharomyces cerevisiae growing on a non-fermentable carbon source leads to selective and rapid degradation of fructose-1,6-bisphosphatase. This so called catabolite inactivation of the enzyme is brought about by the ubiquitin-proteasome system. To identify additional components of the catabolite inactivation machinery, we isolated three mutant strains, gid1, gid2, and gid3, defective in glucose-induced degradation of fructose-1,6-bisphospha-tase. All mutant strains show in addition a defect in catabolite inactivation of three other gluconeogenic enzymes: cytosolic malate dehydrogenase, isocitrate lyase, and phosphoenolpyruvate carboxykinase. These findings indicate a common mechanism for the inactivation of all four enzymes. The mutants were also impaired in degradation of short-lived N-end rule substrates, which are degraded via the ubiquitin-proteasome system. Site-directed mutagenesis of the amino-terminal proline residue yielded fructose-1,6-bisphosphatase forms that were no longer degraded via the ubiquitin-proteasome pathway. All amino termini other than proline made fructose-1,6-bisphosphatase inaccessible to degradation. However, the exchange of the amino-terminal proline had no effect on the phosphorylation of the mutated enzyme. Our findings suggest an essential function of the amino-terminal proline residue for the degradation process of fructose-1,6-bisphosphatase. Phosphorylation of the enzyme was not necessary for degradation to occur.

Amino Acid Sequence↗
PubMed1998

Effects of r-metHuG-CSF on polymorphonuclear leucocyte kinetics and function in patients on continuous ambulatory peritoneal dialysis.

End-stage renal failure (ESRF) patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are immunocompromised and exhibit abnormal circulating polymorphonuclear leucocyte (PMN) function, including reduced phagocytosis and intracellular killing. Six uraemic patients on CAPD were each given 300 microg granulocyte colony stimulating factor (G-CSF) every day for 5 d and PMN function tests were performed daily. By day 5 of the study CD11b expression was significantly decreased in response to N-formylmethionylleucylphenylalanine (fMLP) and opsonized Staphylococcus epidermidis stimulation, and expression of L-selectin (CD62L) was significantly decreased in response to opsonized Staphylococcus epidermidis stimulation. Further, superoxide anion production and Fc gammaRI (CD64) expression were found to be significantly increased and Fc gammaRII (CD16) expression was lowered. Circulating white cell and PMN counts were significantly elevated in response to treatment. Administration of G-CSF did not appear to have corrected the abnormalities in phagocytosis and intracellular killing. This study suggests that G-CSF does no harm to ESRF patients and influences uraemic PMN function in a manner that is comparable to its effects on PMN in non-uraemic subjects.

Adult↗
PubMed1998

PcrA is an essential DNA helicase of Bacillus subtilis fulfilling functions both in repair and rolling-circle replication.

The only DNA helicase essential for Escherichia coli viability is DnaB, the chromosome replication for helicase. In contrast, in Bacillus subtilis, in addition to the DnaB counterpart called DnaC, we have found a second essential DNA helicase, called PcrA. It is 40% identical to the Rep and UvrD DNA helicases of E. coli and 61% identical to the PcrA helicase of Staphylococcus aureus. This gene is located at 55 degree on the chromosome and belongs to a putative operon together with a ligase gene (lig) and two unknown genes named pcrB and yerH. As PcrA was essential for cell viability, conditional mutants were constructed. In such mutants, chromosomal DNA synthesis was slightly decreased upon PcrA depletion, and rolling-circle replication of the plasmid pT181 was inhibited. Analysis of the replication intermediates showed that leading-strand synthesis of pT181 was prevented upon PcrA depletion. To compare PcrA with Rep and UvrD directly, the protein was produced in rep and uvrD mutants of E. coli. PcrA suppressed the UV sensitivity defect at a uvrD mutant but not its mutator phenotype. Furthermore, it conferred a Rep-phenotype on E. coli. Altogether, these results show that PcrA is an helicase used for plasmid rolling-circle replication and suggest that it is also involved in UV repair.

Adenosine Triphosphatases↗
PubMed1998

'Back to sleep': the position in Oxfordshire and Northampton.

We examined hospital and domestic infant care practices in Oxfordshire and Northampton Health Districts to measure changes in prevalence of sudden infant death syndrome (SIDS) risk factors, and to evaluate a specific educational intervention restricted to Oxfordshire. We sent a postal questionnaire to 2781 parents of babies newly born in January 1992, July 1992 and January 1993 and achieved an 88% response rate. Overall, in hospital a relatively constant proportion (81%) slept on their sides and few prone, whereas at home 52% (but increasing) slept supine and 8% prone part or all of the time. Significant differences existed by district, both in hospital and at home, with more sleeping supine in Oxfordshire and more side-sleeping/propping in Northampton. First-time parents were more receptive to safety guidelines about sleeping position and several other risk factors also. We detected no modifying effect of the Oxfordshire advice. Professional practice can influence parental behaviour but general media coverage may produce the biggest effects.

Bedding and Linens↗
PubMed1998

Determinants of the quality of life of patients with diabetes under intensified insulin therapy.

OBJECTIVE: The concept of quality of life (QOL) is understood as a multidimensional construct made up of physiological, psychological, and social aspects, but their particular weightings for the global QOL are rarely investigated. We examined 1) the general QOL of patients with diabetes, 2) the significance of the individual QOL aspects for the overall assessment of QOL, and 3) the modulating function of coping mechanism and particular personality traits. RESEARCH DESIGN AND METHODS: A total of 116 diabetes patients under intensified insulin therapy were studied, as were 107 patients with inflammatory bowel disease, 66 patients with chronic hepatitis C, and 229 students who served as control subjects. The examination was based on eight standardized QOL and personality questionnaires (354 items) and assessed by means of linear structural regression models (AMOS 3.6). RESULTS: The QOL of diabetes patients appears to be higher than the QOL of other chronically ill patients. Social, psychological, and physical aspects contribute to the overall QOL, although physical complaints receive a comparatively low weighting. Coping behavior and particular personality traits covary with all QOL aspects, giving these variables greater significance for the QOL than the existence of secondary illnesses. CONCLUSIONS: The hypothesis that the various factors involved in the multidimensional construct QOL receive different weightings was confirmed, making a simple summary score for the general QOL appear unjustifiable. In addition, all aspects that are commonly understood as parameters of QOL are influenced by external factors, such as coping behavior, based on individual personality characteristics.

Activities of Daily Living↗
PubMed1998

Technetium-99m dimercaptosuccinic acid scintigraphy studies of renal cortical scarring and renal length.

UNLABELLED: The aims of this study were to validate 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy appearances with histopathological features of scarring; to evaluate the sensitivity and specificity of 99mTc-DMSA and ultrasound for the detection of renal scarring; to compare planar, pinhole and SPECT techniques when using 99mTc-DMSA; and to compare 99mTc-DMSA and ultrasound renal length measurement. METHODS: Reflux nephropathy was induced in large white pigs using established methods. To ensure that the abnormalities detected were scars and not inflammatory changes, the pigs were not studied until 3 mo after the treated episode of acute pyelonephritis confirmed by 99mTc-DMSA. RESULTS: Twenty pigs were enrolled in the study. Eleven reached the end point, but only nine pigs (18 kidneys) were available for analysis. Thirty-four scars were identified pathologically; 24 were present macroscopically and a further 10 were seen only on microscopy. Technetium-99m-DMSA abnormalities correlated with scars histopathologically with an accuracy of 92% versus that of ultrasound, 75% (p < 0.001). Technetium-99m-DMSA more accurately identified scarring with a higher sensitivity (76% versus 29%) and specificity (98% versus 92%) than ultrasound. On the 99mTc-DMSA study, pinhole imaging had the highest accuracy (92%) when compared with planar (90%) and SPECT (87%) data. These differences were not statistically significant. Renal lengths as measured on 99mTc-DMSA more closely correlated with length measurement at pathological examination than ultrasound. Technetium-99m-DMSA measurement was, on average, 6% higher than pathology, and ultrasound was, on average, 22% lower. CONCLUSION: Technetium-99m-DMSA appears to be the preferred method for the detection of renal cortical scarring and accurate renal length measurement when compared with ultrasound examination.

Animals↗