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Biomedical subjects

L Hopkins

Publications and source records attributed to L Hopkins.

At least 19 recordsLinked to original sources

Genomic and functional characterization of the oas gene family encoding O-acetylserine (thiol) lyases, enzymes catalyzing the final step in cysteine biosynthesis in Arabidopsis thaliana.

The final step of cysteine biosynthesis in plants is catalyzed by O-acetylserine (thiol) lyase (OAS-TL), which occurs as several isoforms found in the cytosol, the plastids and the mitochondria. Genomic DNA blot hybridization and isolation of genomic clones indicate single copy genes (oasA1, oasA2, oasB and oasC) that encode the activities of OAS-TL A, B and C found in separate subcellular compartments in the model plant Arabidopsis thaliana. Sequence analysis reveals that the newly discovered oasA2 gene represents a pseudogene that is still transcribed, but is not functionally translated. The comparison of gene structures suggests that oasA1/oasA2 and oasB/oasC are closely related and may be derived from a common ancestor by subsequent duplications. OAS-TL A, B and C were overexpressed in an Escherichia coli mutant lacking cysteine synthesis and exhibited bifunctional OAS-TL and beta-cyanoalanine synthase (CAS) activities. However, all three proteins represent true OAS-TLs according to kinetic analysis and are unlikely to function in cyanide detoxification or secondary metabolism. In addition, it was demonstrated that the mitochondrial OAS-TL C exhibits in vivo protein-protein interaction capabilities with respect to cysteine synthase complex formation similar to cytosolic OAS-TL A and plastid OAS-TL B. Multiple database accessions for each of the A. thaliana OAS-TL isoforms can thus be attributed to a specified number of oas genes to which functionally defined gene products are assigned, and which are responsible for compartment-specific cysteine synthesis.

Arabidopsis↗

Antibiotic prophylaxis regimens and drugs for cesarean section.

BACKGROUND: Prophylactic antibiotics for cesarean section have been shown to reduce the incidence of maternal postoperative infectious morbidity. Many different antibiotic regimens have been reported to be effective. OBJECTIVES: The objective of this review was to determine which antibiotic regimen is most effective in reducing the incidence of infectious morbidity in women undergoing cesarean section. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. The date of the most recent search was October 1998. SELECTION CRITERIA: Randomized trials that included women undergoing cesarean section were included. Trials were required to compare at least two different antibiotic regimens. Trials that compared placebo with a single antibiotic regimen were not included as these are studies which have been analyzed in another Cochrane review. DATA COLLECTION AND ANALYSIS: Data were extracted from each publication independently by the reviewers. Reviewers were not blinded to the authors or sources of the articles. The primary outcome variable was endometritis but data on other infectious complications were collected where provided. MAIN RESULTS: Fifty-one trials published between 1979 and 1994 were included in the review and four were excluded from the review. The following results refer to reductions in the incidence of endometritis. Both ampicillin and first generation cephalosporins have similar efficacy with an odds ratio (OR) of 1.27 (95% confidence interval (CI): 0.84-1.93). In comparing ampicillin with second or third generation cephalosporins the odds ratio was 0.83 (95% CI 0.54-1.26) and in comparing a first generation cephalosporin with a second or third generation agent the odds ratio was 1.21 (95% CI 0.97-1.51). A multiple dose regimen for prophylaxis appears to offer no added benefit over a single dose regimen; OR 0.92 (95% CI 0.70-1.23). Systemic and lavage routes of administration appear to have no difference in effect; OR 1.19 (95% CI 0.81-1.73). There was no significant heterogeneity between the trials contained in the various sub-group analyses, although confidence intervals were sometimes wide. REVIEWER'S CONCLUSIONS: Both ampicillin and first generation cephalosporins have similar efficacy in reducing postoperative endometritis. There does not appear to be added benefit in utilizing a more broad spectrum agent or a multiple dose regimen. There is a need for an appropriately designed randomized trial to test the optimal timing of administration (immediately after the cord is clamped versus pre-operative).

Antibiotic Prophylaxis↗

Quantitative intercellular localization of NADH-dependent glutamate synthase protein in different types of root cells in rice plants

The quantitative analysis with immunogold-electron microscopy using a single-affinity-purified anti-NADH-glutamate synthase (GOGAT) immunoglobulin G (IgG) as the primary antibody showed that the NADH-GOGAT protein was present in various forms of plastids in the cells of the epidermis and exodermis, in the cortex parenchyma, and in the vascular parenchyma of root tips (<10 mm) of rice (Oryza sativa) seedlings supplied with 1 mM NH4+ for 24 h. The values of the mean immunolabeling density of plastids were almost equal among these different cell types in the roots. However, the number of plastids per individual cell type was not identical, and some parts of the cells in the epidermis and exodermis contained large numbers of plastids that were heavily immunolabeled. Although there was an indication of labeling in the mitochondria using the single-affinity-purified anti-NADH-GOGAT IgG, this was not confirmed when a twice-affinity-purified IgG was used, indicating an exclusively plastidial location of the NADH-GOGAT protein in rice roots. These results, together with previous work from our laboratory (K. Ishiyama, T. Hayakawa, and T. Yamaya [1998] Planta 204: 288-294), suggest that the assimilation of exogeneously supplied NH4+ ions is primarily via the cytosolic glutamine synthetase/plastidial NADH-GOGAT cycle in specific regions of the epidermis and exodermis in rice roots. We also discuss the role of the NADH-GOGAT protein in vascular parenchyma cells.

Journal Article↗

The Saccharomyces cerevisiae TSC10/YBR265w gene encoding 3-ketosphinganine reductase is identified in a screen for temperature-sensitive suppressors of the Ca2+-sensitive csg2Delta mutant.

Saccharomyces cerevisiae csg2Delta mutants accumulate the sphingolipid inositolphosphorylceramide, which renders the cells Ca2+-sensitive. Temperature-sensitive mutations that suppress the Ca2+ sensitivity of csg2Delta mutants were isolated and characterized to identify genes that encode sphingolipid synthesis enzymes. These temperature-sensitive csg2Delta suppressors (tsc) fall into 15 complementation groups. The TSC10/YBR265w gene was found to encode 3-ketosphinganine reductase, the enzyme that catalyzes the second step in the synthesis of phytosphingosine, the long chain base found in yeast sphingolipids. 3-Ketosphinganine reductase (Tsc10p) is essential for growth in the absence of exogenous dihydrosphingosine or phytosphingosine. Tsc10p is a member of the short chain dehydrogenase/reductase protein family. The tsc10 mutants accumulate 3-ketosphinganine and microsomal membranes isolated from tsc10 mutants have low 3-ketosphinganine reductase activity. His6-tagged Tsc10p was expressed in Escherichia coli and isolated by nickel-nitrilotriacetic acid column chromatography. The recombinant protein catalyzes the NADPH-dependent reduction of 3-ketosphinganine. These data indicate that Tsc10p is necessary and sufficient for catalyzing the NADPH-dependent reduction of 3-ketosphinganine to dihydrosphingosine.

Acetyl Coenzyme A↗

Complement-binding anti-Jka not detectable by DiaMed gels.

BACKGROUND: An anti-Jka was not detectable by the DiaMed-ID Micro Typing System but was strongly reactive when tested using other indirect antiglobulin test (IAT) methods. However, it was detectable in the DiaMed-ID system when the recommended diluent ID-Diluent 2, was replaced by other low ionic Strength saline (LISS) solutions. This led us to believe that the problem lay with the ID-Diluent 2. METHODS: The anti-Jka was investigated using various low ionic strength diluents in the IAT against both polyspecific and monospecific antiglobulin reagents. We tested the ID-Diluent 2 for its ability to inhibit complement activation, and bind calcium. RESULTS: The anti-Jka was shown to be a 'complement-only' binding antibody that reacted in all IATs performed except when tested with ID-Diluent 2. The ID-Diluent was shown to prevent haemolysis of ABO lytic antibodies, and further testing shows that it binds calcium. CONCLUSION: The use of a diluent which prevents haemolysis and binds calcium in an IAT system that contains anti-complement as well as anti-IgG must be questioned.

Aged↗

When control measures fail.

This article describes the author's long ordeal after contracting multi-drug resistant tuberculosis (MDR-TB) from a patient in the hospital where she works. The struggle to win the battle with MDR-TB took her to a hospital far from home where she underwent surgery. In addition to physical pain, the author had to also endure frustration, depression, and loneliness.

Adaptation, Psychological↗

Implementation of a comprehensive skin care program across care settings using the AHCPR pressure ulcer prevention and treatment guidelines.

Healthcare professionals in the Central Midwest identified the need for a comprehensive skin care program for pressure ulcer prevention and treatment across care settings. A multidisciplinary team, representing acute, extended and home care, was formed to create a program for all three settings based upon the AHCPR pressure ulcer guidelines. The team performed literature reviews on which to base the development and use of tools, conducted prevalence studies, and developed educational approaches. Implementation of the program was tailored for each setting. Some of the approaches used were a skin care fair, quality studies, continuous quality improvement concepts, a "Product Book" and educational presentations. Outcomes include improvement of continuity of care across settings and the use of the Braden Scale and the NPUAP pressure ulcer staging system. The focus has turned toward patient outcomes. Professionals have a better understanding of the care that is provided by other disciplines. Referrals are made based upon decision trees. Appropriate resources are used. Other outcomes anticipated include a decrease in nosocomial pressure ulcers, shortened wound healing time, appropriate referral of unresponsive chronic wounds, decreased discrepancies in wound documentation, decreased length of stay, improved financial outcomes, and improved client knowledge and participation.

Aged↗

Interactions between model triacylglycerol-rich lipoproteins and high-density lipoproteins in rat, rabbit and man.

There are inverse relationships between HDL cholesterol and plasma triacylglycerol concentrations in normal and in hypertriglyceridemic individuals. To investigate the interactions between triacylglycerol-rich lipid particles and HDL, a lipid emulsion model of the triacylglycerol-rich lipoproteins was prepared. When emulsion particles were incubated with rat high-density lipoproteins (HDL) in the presence of lipid transfer activity (d greater than 1.21 g/ml fractions) from rabbit or human plasma there was a rapid bi-directional exchange of cholesteryl oleate (CO) and phospholipid (PL) labels between lighter and heavier fractions of HDL and emulsion particles. The transfers of CO and PL labels between both light and heavy fractions of HDL and the emulsion particles were increased with increasing amounts of emulsion added to the incubations. Incubation with the d greater than 1.21 g/ml fraction from rat plasma resulted in only a small exchange of CO whereas PL exchange was similar to rabbit and human plasma. Retinyl palmitate label was not transferred from emulsion particles to the HDL fractions even in the presence of lipid transfer activity from rabbit or human plasma. The present study shows that the transfer protein-mediated exchanges of surface and core lipids between HDL and the triacylglycerol-rich lipoproteins are affected by the quantity of triacylglycerol-rich particles in the system. This mechanism may contribute to the inverse relationships between plasma triacylglycerol concentrations and HDL concentrations in normal and hypertriglyceridemic individuals.

Animals↗

An evaluation of the potential cost reductions resulting from the use of clodronate in the treatment of metastatic carcinoma of the breast to bone.

The reported studies of clodronate in the management of osteolytic bone metastases suggest a significant palliative role for this drug. In this paper we report on analysis of the hospital costs associated with the management of osteolytic metastatic disease, and an estimate of the potential cost/benefit impact of clodronate therapy. Two separate patient populations were assessed retrospectively. The first, a sample of 120 patients with symptomatic bone metastases who had died from metastatic breast cancer over the period 1980-1990, was used to define the natural history of the disease. A second non-concurrent patient group of 337 patients was evaluated to determine the mean cost of all hospital admissions for patients with bone metastases from breast carcinoma. The length of stay and costs for hospital admissions related to the bone metastases were also assessed, in addition to the cost of out-patient radiation therapy. Our cost/benefit value analysis suggests that there are significant savings to be gained from the use of clodronate if a 20% or greater reduction occurs in the incidence of fractures, hypercalcaemia, and hospital-based treatment for pain control (via radiotherapy). We also speculate that the quality of life of patients with osteolytic bone metastases may be improved with this agent.

Ambulatory Care↗

Moxalactam myoclonus, seizures, and encephalopathy.

Severe myoclonus, generalized seizures, and marked stupor occurred in a 39-year-old woman with chronic renal insufficiency after one week of moxalactam 2 g iv q8h. Moxalactam serum levels far exceeded the recommended therapeutic range. The drug half-life was 17 hours (normal 1.9). Excessively high levels of moxalactam, which penetrates the blood-brain-barrier relatively easily, may provoke seizures and encephalopathy.

Adult↗

Immunologic function in patients with carcinoma of the pancreas.

The immune fuction of 41 patients with duct cell adenocarcinoma of the pancreas or carcinoma of the periampullary region was studied by skin testing with 2,4-dinitrocholorobenzene and common microbial antigens, in vitro lymphocyte reactivity to mitogens, T-lymphocyte and B-lymphocyte cell counts and measurements of complement levels. Results show that a great proportion of patients had depressed immune function. Depression is particularly severe in lymphocyte reactivity. Positive response to skin tests with a microbial antigen carries a slightly better prognosis. The complement level is usually normal or elevated. Correlation between immune function, prognosis and tumor resectability in individual patients is generally poor.

Adenocarcinoma↗

Type A botulism from commercially canned beef stew.

Two of three persons who ate lunch together became ill with symptoms characteristic of botulism. One died before botulism was suspected and before specimens could be collected for laboratory testing, but a serum specimen from the other patient, who survived, yielded botulinal toxin, type A. The third person remained asymptomatic, but Clostridium botulinum type A was cultured from his stool. The three persons had shared two canned foods: home-canned green beans and commercially canned beef stew. The green beans were initially assumed to be the cause of the outbreak. However, the empty stew can was recovered from the garbage, and washings from the can yielded C botulinum, type A, and its toxin.

Aged↗