Leveraging legacy archaeological collections as proxies for climate and environmental research.

Understanding the causes and consequences of previous climate changes is essential for testing present-day climate models and projections. Archaeological sites are paleoenvironmental archives containing unique ecological baselines with data on paleoclimate transformations at a human timescale. Anthropogenic and nonanthropogenic forces have destroyed many sites, and others are under immediate threat. In the face of this loss, previously excavated collections from these sites-referred to as legacy collections-offer a source of climate and other paleoenvironmental information that may no longer exist elsewhere. Here, we 1) review obstacles to systematically using data from legacy archaeological collections, such as inconsistent or unreported field methods, inadequate records, unsatisfactory curation, and insufficient public knowledge of relevant collections; 2) suggest best practices for integrating archaeological data into climate and environmental research; and 3) summarize several studies to demonstrate the benefits and challenges of using legacy collections as archives of local and regional environmental proxies. Data from archaeological legacy collections contribute regional ecological baselines as well as serve to correct shifting baselines. They also enable regional climate reconstructions at various timescales and corroborate or refine radiocarbon dates. Such uses of legacy collections raise ethical concerns regarding ownership of and responsibility for cultural resources and highlight the importance of Indigenous involvement in planning and executing fieldwork and stewardship of cultural heritage. Finally, we discuss methodologies, practices, and policies pertaining to archaeological legacy collections and support calls for discipline-wide shifts in collections management to ensure their long-term utility in multidisciplinary research and public engagement.

A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.

The progressive familial intrahepatic cholestases (PFIC) are a group of inherited disorders with severe cholestatic liver disease from early infancy. A subgroup characterized by normal serum cholesterol and gamma-glutamyltranspeptidase (gammaGT) levels is genetically heterogeneous with loci on chromosomes 2q (PFIC2) and 18q. The phenotype of the PFIC2-linked group is consistent with defective bile acid transport at the hepatocyte canalicular membrane. The PFIC2 gene has now been identified by mutations in a positional candidate, BSEP, which encodes a liver-specific ATP-binding cassette (ABC) transporter, sister of p-glycoprotein (SPGP). The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro. These data provide evidence that SPGP is the human bile salt export pump (BSEP).

Time toxicity associated with early phase clinical trial participation.

BACKGROUND: Early phase cancer clinical trials (EPCTs) involve experimental drugs being used for the first time in humans. These studies are designed for dose determination and safety, and represent the most time intensive of all clinical trials for both clinicians and patients. We sought to quantify the amount of patient time consumed through EPCT participation. PATIENTS AND METHODS: A retrospective audit of patients treated in the EPCT unit at Liverpool Hospital, Sydney was carried out from 2013 to 2023. We defined 'time toxicity' (TT) as a composite measure where time-toxic days were considered days with any health care system contact, including clinic visits, infusions, procedures or blood work. RESULTS: A total of 219 patients across 36 EPCTs were included. The median age was 65 years (range 31-81 years). Patients spent a median of 29% (range 4%-100%) of their days in direct contact with the health care system during their study. Protocol-specified visits accounted for the greatest contribution to total TT in 101 (46%) patients. In 7% (n = 16) of patients, unscheduled visits due to either adverse events or cancer-related symptoms accounted for the greatest TT. TT reduced as patients completed additional cycles of treatment. Patients who completed >10 cycles spent 14% of their days interacting with health care systems compared with 35% for those who completed ≤2 cycles. No statistically significant difference in TT was noted between dose-expansion and dose-escalation studies or trials focusing on immune-oncology versus targeted therapy. CONCLUSIONS: Our study is the first to report TT in EPCTs with an extended follow-up. Clinicians should be aware of TT when discussing risks and benefits. TT also may not be the appropriate term when describing the time patients invest during EPCTs. Toxicity implies a negative impact, but for many patients, trial participation would be seen as positive. There should be efforts to streamline health care visits to limit TT in EPCTs.

A prevalence study of errors in opioid prescribing in a large teaching hospital.

AIM: In 2007, the National Patient Safety Agency performed a study demonstrating that errors in prescribing led to nearly 12,000 adverse clinical incidents a year. The following year, they issued a rapid response report entitled 'Reducing Dosing Errors with Opioid Medicines' designed to be implemented by all NHS trusts. We performed a prevalence study to assess opioid prescribing errors in our large multi-speciality teaching hospital prior to implementation of these recommendations. METHODOLOGY: We conducted a 1 day snapshot of opioid prescriptions on inpatient drug charts. For every chart, all opioid information was entered into the study proforma. All data were reviewed by consensus group and errors categorised by quality and whether they were potentially lethal, serious, significant or minor. RESULTS: A total of 330/722 (46%) charts were found to have opioid prescriptions. On the study day, there were 74 charts with errors and on expert review another 16 erroneous charts were found giving a total of 90/330 (27.2%). The largest quality statement error group was 'unclear prescription, missing information'. There were 4 potentially lethal, 26 serious, 38 significant and 22 minor errors. DISCUSSION: Previous studies have reported opioid prescription error rates of 51.2-70%. Compared with the opioid literature, our trust fares well with an error rate of 27%- four of these errors being potentially lethal. This study has identified where there are weaknesses in our hospital opioid prescribing practice and has aided us in rewriting our acute and chronic pain guidelines with the explicit inclusion of the National Patient Safety Agency recommendations. We have also disseminated the study results at the Trust academic meeting and developed an opioid e-learning package which will be mandatory for all new staff.

Fatty acid concentration of plasma, muscle, adipose and liver from beef heifers fed an encapsulated n-3 polyunsaturated fatty acid supplement.

Increasing the content of polyunsaturated fat in the human diet is a priority for reducing cardiovascular disease and cancer risks. Beef has the potential to contribute to the polyunsaturated fat content in the human diet; however, ruminants cannot synthesise many long-chain fatty acids de novo; they require dietary supplementation. The objectives of the current study were to evaluate (i) the effect of a partially rumen protected n-3 long-chain polyunsaturated fatty acid (LC-PUFA) dietary supplement on the fatty acid composition of muscle (Longissimus dorsi), adipose and liver tissues of beef heifers and (ii) the usefulness of blood plasma as a predictor of tissue concentrations of specific fatty acids. Charolais crossbred heifers (n = 20) were assigned to one of two isolipid dietary treatments namely palmitic acid (control) or an n-3 LC-PUFA supplement for a 91-day period. Blood plasma and adipose tissue samples were taken to determine the temporal effect of these diets on fatty acid composition (days 0, 10, 35 and 91), while liver and muscle samples were taken following slaughter. Dietary lipid source did not influence animal growth rate or body condition score. At day 91, the percentage differences between control and n-3 LC-PUFA heifers in concentrations of eicosapentaenoic acid were +61, +176 and +133 % in liver, muscle and adipose, respectively. For docosahexaenoic acid, at the same time point, the percentage differences were +57, +73 and +138 % for liver, muscle and adipose, respectively. Medium-to-strong positive correlation coefficients were evident for liver and plasma fatty acids, in particular, there were positive relationships with concentrations of total saturated fatty acid (SFA), total n-6 PUFA and total n-3 PUFA. This trend also extended to both the ratio of PUFA to SFA (slope (ß1) = 0.56 ±â€¯0.167, intercept (ß0) = 0.56, R2 = 0.61, P < 0.05) and the ratio of n-6 to n-3 PUFA (ß1 = 0.15 ±â€¯0.054, ß0 = 0.24, R2 = 0.52, P < 0.05). A strong correlation was also detected in the ratio of n-6 to n-3 in plasma and muscle tissue of heifers fed the n-3 LC-PUFA diet (ß1 = 0.53 ±â€¯0.089, ß0 = -0.31, R2 = 0.83, P < 0.001). The results of this study show that the n-3 LC-PUFA can be readily increased through targeted supplementation and that plasma concentrations of n-3 LC-PUFA are useful predictors of their concentrations in a number of economically important tissues.

Embryo yield and quality following dietary supplementation of beef heifers with n-3 polyunsaturated fatty acids (PUFA).

The objective of this study was to examine the effects of dietary n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on embryo yield and quality in heifers. Animals were individually offered barley straw and concentrate diets supplemented with either palmitic acid (C16:0; CON) or a partially rumen protected n-3 PUFA-enriched supplement. Following oestrous cycle synchronisation, superovulation was induced using FSH. Blood samples were collected for the measurement of fatty acids, metabolites, insulin and IGF-1. On day 7 post-insemination the number of ovulations was estimated and embryos recovered non-surgically and quality graded. At embryo recovery 50 ml of the uterine flushing was collected from each horn for fatty acid analysis. Grade 1 embryos were isolated, snap frozen in liquid nitrogen and stored at -80 degrees C. mRNA expression for six genes, LIF, BAX, Cx43 and E-CAD associated with embryo development, and PPAR-alpha and -delta, associated with lipid metabolism was analysed. The n-3 PUFA supplementation increased plasma n-3 PUFA concentration (P<0.05) and reduced n-6:n-3 PUFA ratio (P<0.05). Uterine concentration of the n-3 PUFA, eicosapentaenoic acid was increased (P<0.05) and the concentration of arachidonic acid decreased (P<0.05) following n-3 PUFA supplementation. While CON increased triglyceride concentrations, diet did not affect the other plasma metabolites, insulin or IGF-1 (P>0.05). Similarly, there was no effect of diet on superovulation rate, embryo recovery rate, embryo quality (P>0.05) or mRNA expression of the genes examined (P>0.05).

Dietary n-3 polyunsaturated fatty acids alter the expression of genes involved in prostaglandin biosynthesis in the bovine uterus.

Nutrition plays a critical role in the regulation of cow fertility. There is emerging evidence that dietary long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may act as specific regulators of some reproductive processes. In vitro studies suggest that the n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may play pivotal roles by suppressing the synthesis of uterine prostaglandin F(2alpha) (PGF(2alpha)) which is centrally involved in the control of the bovine oestrous cycle and in early embryo survival. The objective of the current study was to determine the effect of dietary inclusion of n-3 PUFA on uterine endometrial mRNA expression of key genes regulating PGF(2alpha) biosynthesis. Beef heifers were fed either a low (CON; n=10) or high (HIGH PUFA; n=10) n-3 PUFA diet for 45 days and endometrial tissues were harvested following slaughter. Following analysis, tissues within each dietary group were ranked on the basis of their PUFA concentrations and the highest (n=7) and lowest (n=7) within each of HIGH PUFA and CON, respectively, were used in gene expression studies. Endometrial n-3 PUFA concentrations were more than two-fold higher (P<0.05) and EPA concentrations alone more than seven-fold higher (P<0.01) in the HIGH PUFA than the CON group. Endometrial concentrations of arachidonic acid, were lower (P<0.001) in the tissues from HIGH PUFA than those from the CON group. Total RNA was isolated from all endometrial tissues and real-time reverse transcription (RT) PCR conducted to compare the relative expression of 11 genes with known involvement in uterine biosynthesis of 2-series prostaglandins. Expression of mRNA for prostaglandin E synthase (PGES) and peroxisome proliferator-activated receptors, PPAR alpha and delta was increased (P<0.05) while mRNA expression of phospholipase A(2) (PLA(2)) was decreased (P=0.06) in the HIGH PUFA endometrial tissues. Expression of genes coding for the oxytocin receptor (OTR), phospholipase C (PLC), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), PGE(2) 9-ketoreductase (9-KPR), prostaglandin F synthase (PGFS), and the nuclear transcription factor, PPAR gamma was not different (P>0.05) between HIGH PUFA and CON tissues. Overall the results indicate that key genes regulating uterine PGF(2alpha) biosynthesis can be regulated by dietary inclusion of LC n-3 PUFA which may influence uterine function and embryo survival.

Effect of level of dietary n-3 polyunsaturated fatty acid supplementation on systemic and tissue fatty acid concentrations and on selected reproductive variables in cattle.

Reproductively normal crossbred beef heifers were individually offered a diet of barley straw and concentrate supplemented with one of four levels of a fish oil (FO) enriched supplement. Following oestrous cycle synchronisation, blood samples were collected at appropriate intervals for the measurement of progesterone (P(4)), oestradiol (E(2)), fatty acids, insulin-like growth factor 1 (IGF-1) and metabolites. On days 15 and 16 of the cycle, oxytocin was administered intravenously and the prostaglandin F(2alpha) (PGF(2alpha)) response was measured as venous concentrations of 13,14-dihydro-15-keto PGF(2alpha) (PGFM). The heifers were slaughtered on days 17 or 18 of the oestrous cycle and endometrial tissue, rumen fluid and follicular fluid were collected for determination of fatty acid concentrations. In general there was no effect (P>0.05) of diet on plasma P(4) or E(2) concentrations. Increasing FO supplementation increased CL diameter on day 7 post-oestrus (P<0.0001) but had no effect on diameter on day of slaughter (P>0.05). On day 15, PGFM concentration was greater on the highest level of FO supplementation compared to controls (P<0.05), however, there were no differences between other diet comparisons (P>0.05). There was no effect of diet on PGFM concentration on day 16 (P>0.05). There was a strong positive relationship between plasma and uterine endometrial concentrations of both EPA (R(2)=0.86; P<0.0001) and total n-3 PUFA (R(2)=0.77; P<0.0001). IGF-1 concentrations increased on all diets and were greatest at the highest level of n-3 PUFA supplementation (P<0.05).

Zebrafish dracula encodes ferrochelatase and its mutation provides a model for erythropoietic protoporphyria.

Exposure to light precipitates the symptoms of several genetic disorders that affect both skin and internal organs. It is presumed that damage to non-cutaneous organs is initiated indirectly by light, but this is difficult to study in mammals. Zebrafish have an essentially transparent periderm for the first days of development. In a previous large-scale genetic screen we isolated a mutation, dracula (drc), which manifested as a light-dependent lysis of red blood cells [1]. We report here that protoporphyrin IX accumulates in the mutant embryos, suggesting a deficiency in the activity of ferrochelatase, the terminal enzyme in the pathway for heme biosynthesis. We find that homozygous drc(m248) mutant embryos have a G-->T transversion at a splice donor site in the ferrochelatase gene, creating a premature stop codon. The mutant phenotype, which shows light-dependent hemolysis and liver disease, is similar to that seen in humans with erythropoietic protoporphyria, a disorder of ferrochelatase.

The Drosophila dorsal morphogen represses the tolloid gene by interacting with a silencer element.

The dorsal protein (DL) regulates the transcriptional activity of several genes that determine cell fate along the dorsoventral axis of the Drosophila melanogaster embryo. DL is present at high levels in ventral nuclei, where it activates some genes (twi and sna) and represses others (zen, dpp, and tld). DL shows homology to the Rel family of proteins and interacts with specific DNA sequences in the regulatory regions of its target genes. The distal portion of the zen gene acts as a silencer that can mediate the repression of a heterologous promoter in ventral regions of the embryo. It contains four DL binding sites which alone are sufficient for activation but not repression. Here we analyze the interaction of DL with another one of its repressed targets, the tolloid (tld) gene. Approximately 800 bp of 5'-flanking sequences upstream of the tld coding region were shown to drive an expression pattern indistinguishable from the wild-type pattern. A 423-bp fragment located within these sequences contains two DL binding sites and was shown to act as a silencer to mediate ventral repression. Point mutations in the sites abolish not only DNA binding but also ventral repression. We discuss a comparison of the DNA sequences from the zen and tld promoters and the possible mechanisms of transcriptional silencing.

Two distinct transmembrane serine/threonine kinases from Drosophila melanogaster form an activin receptor complex.

A transmembrane protein serine/threonine kinase, Atr-I, that is structurally related to receptors for members of the transforming growth factor-beta (TGF-beta) family has been cloned from Drosophila melanogaster. The spacing of extracellular cysteines and the cytoplasmic domain of Atr-I resemble most closely those of the recently described mammalian type I receptors for TGF-beta and activin. When expressed alone in test cells, Atr-I is unable to bind TGF-beta, activin, or bone morphogenetic protein 2. However, Atr-I binds activin efficiently when coexpressed with the distantly related Drosophila activin receptor Atr-II, with which it forms a heteromeric complex. Atr-I can also bind activin in concert with mammalian activin type II receptors. Two alternative forms of Atr-I have been identified that differ in an ectodomain region encompassing the cysteine box motif characteristic of receptors in this family. Comparison of Atr-I with other type I receptors reveals the presence of a characteristic 30-amino-acid domain immediately upstream of the kinase region in all these receptors. This domain, of unknown function, contains a repeated Gly-Ser sequence and is therefore referred to as the GS domain. Maternal Atr-I transcripts are abundant in the oocyte and widespread during embryo development and in the imaginal discs of the larva. The structural properties, binding specificity, and dependence on type II receptors define Atr-I as an activin type I receptor from D. melanogaster. These results indicate that the heteromeric kinase structure is a general feature of this receptor family.

Effects of interventions aimed at changing the length of primary care physicians' consultation.

BACKGROUND: Observational studies have shown differences in process and outcome between the consultations of primary care physicians whose average consultation lengths differ. These differences may be due to self selection. OBJECTIVES: To assess the effectiveness and efficiency of interventions to alter the length of primary care physicians' consultations. SEARCH STRATEGY: The following electronic databases were searched: Cochrane Effective Practice and Organisation of Care Group (EPOC) Specialised Register (October 2002); CENTRAL (The Cochrane Library June 2003); MEDLINE (1966 to October 2002);EMBASE (1981 to October 2002); NHS National Research Register (June 2003). The search strategies combined subject terms for 'general practice', 'consultation' and 'length' with methodological filters. SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) of interventions to alter the length of primary care physicians' consultations. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two authors using agreed criteria. Disagreements were resolved by discussion. Where data were missing attempts were made to contact authors. Given the heterogeneity of studies meta-analysis was not attempted, and results are presented as a narrative summary. MAIN RESULTS: Six articles describing four UK trials met the inclusion criteria. All tested short term changes in the consultation time allocated to each patient and all had methodological weaknesses, particularly due to non-random allocation of patients. Altering appointment length resulted in modest changes in average length of consultation. There were no consistent differences in problem recognition, examination, prescribing, referral or investigation rates. There was some evidence that blood pressure was checked and smoking discussed more often when more time was available. None of the interventions were associated with differences in patient satisfaction. No trials examined efficiency. AUTHORS' CONCLUSIONS: The findings of this review do not provide sufficient evidence to support or resist a policy of altering the lengths of primary care physicians' consultations. Further trials are needed that focus on health outcomes and cost effectiveness.

Identification of a sister gene to P-glycoprotein.

The P-glycoproteins (Pgps) are a small family of transport proteins associated with the multidrug resistance phenotype of cell lines selected for growth in cytotoxic drugs. Utilizing low stringency screening, we have identified a novel gene closely related to the Pgps expressed in the pig and other mammalian liver which we have called Sister of P-glycoprotein (spgp). Sequence of this gene shows it to be a member of the ATP-binding cassette family of transporters and the gene most closely related to Pgp identified to date. The function of spgp is not known, but it can be recognized by at least one Pgp mAb, C219. This cross-reactivity has implications for expression studies in tissues and tumors utilizing this and other Pgp antibodies.

Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein.

The sister gene of P-glycoprotein (Spgp) is a liver-specific ATP-binding cassette protein highly related to the P-glycoprotein (Pgp) family (S. Childs et al, Cancer Res., 55: 2029-2034, 1995). Spgp appears to be related to the Pgp family by an ancient duplication occurring before the division of fish and mammals. P-Glycoproteins have diverse functions including broad specificity multidrug resistance in cell lines and tumors, detoxification of tissues such as the intestine and blood-brain barrier, and phosphatidylcholine transport in liver. Spgp is a Mr approximately 170,000 glycosylated plasma membrane protein localized to the canalicular surface of hepatocytes in the rat liver. The full-length cDNA of Spgp was isolated from rat, and its expression was characterized in situ and in transfected cells. The expression of Spgp correlates with the differentiation of hepatocytes and is seen only in late liver development. It is not observed in hepatoma cell lines. The physiological function of Spgp in liver is unknown, but it maps to 2q31 in humans, in the vicinity of liver transport disorders for bile acids and cholesterol. Spgp may therefore be involved in some aspect of bile acid or cholesterol metabolism. Spgp transfectants have a low level resistance to Taxol but not to other drugs that form part of the multidrug resistance phenotype. This resistance is reversible by the Pgp-reversing agents cyclosporin A, PSC833, and verapamil, suggesting a conservation in some functions of Pgps across large evolutionary distance.

Duplication and evolution of the P-glycoprotein genes in pig.

The P-glycoproteins (Pgp's) are a small family of proteins frequently associated with the multidrug resistance phenotype in drug-selected cell lines. The number of Pgp isoforms in different mammalian species is variable although the reason for having a larger or smaller number of isoforms is not known. Two isoform classes from human, and three from rodents have been extensively characterised and have been shown to have independent expression patterns and substrate preferences. We have cloned 3' terminal genomic fragments for five members of the Pgp multigene family from the pig, which is the largest number of Pgp genes found in any mammalian species to date. Sequential duplications of one class of Pgp gene have given rise to this large gene family since four genes show similarity to the drug resistance-causing Class I isoform of Pgp. The fifth pig Pgp gene shows similarity to the phosphatidylcholine-translocating Class III isoform. The history of the duplications creating this large gene family can be traced by atypical features which have been inherited in common. These include a mutation in the stop codon at the 3' end of four Class I Pgp genes, increasing the coding region by six amino acids, and a SINE element of the PRE1 family inserted into the 3' untranslated region of three Class I Pgp's. We demonstrate expression of Class I pgp in pig brain cultured capillary endothelial cells, and Class III pgp in the liver, two important sites of expression of Pgp in rodents and humans. Thus there appears to be strong phylogenetic conservation in mammals of both sequence and expression of these two Pgp isoforms.

P-glycoprotein genes in the winter flounder, Pleuronectes americanus: isolation of two types of genomic clones carrying 3' terminal exons.

In mammals, P-glycoprotein (P-gp) is encoded by two or more highly conserved genes that differ in their abilities to transport drugs. One isoform class (class I) is consistently associated with the multidrug resistance phenotype, while the other (class III) is not. This study was designed to enumerate the P-gp genes in fish and determine how they are related to the two functional classes already defined in mammals. Southern blot analysis using a conserved single exon from the 3' terminal region of hamster P-gp cDNA (pEX1-172) as a probe indicated that there were two P-gp genes in right-eye flounders. Subsequently, two sets of clones were isolated from a winter flounder genomic library that correspond to the 3' ends of the two flounder P-gp genes. Sequence analysis was done on two key areas: the 3' ATP binding site and the 3' terminal exon, both of which were found to be homologous with their mammalian counterparts. Despite high levels of sequence identity in the predicted coding regions of the gene fragments it has not been possible to use these sequences to relate the homologs to particular mammalian classes of P-gp genes, perhaps because of gene conversion between mammalian P-gp genes. These cloned sequences are the first set of P-gp genes reported in lower vertebrates and will be useful for delineating the expression of P-gp genes in fish and understanding the role of P-gp in fish physiology.

An improved temporal formulation of pupal transpiration in Glossina.

The temporal aspect of a model of pupal dehydration is improved upon. The observed dependence of pupal transpiration on time is attributed to an alternation between two, essential modes, for which the deposition of a thin, pupal skin inside the puparium and its subsequent demise are thought to be responsible. For each mode of transpiration, the results of the Bursell investigation into pupal dehydration are used as a rudimentary data set. These data are generalised to all temperatures and humidities by invoking the property of multiplicative separability. The problem, then, is that as the temperature varies with time, so does the metabolism and the developmental stages to which the model data pertain, must necessarily warp. The puparial-duration formula of Phelps and Burrows and Hargrove is exploited to facilitate a mapping between the constant-temperature time domain of the data and that of some, more general case at hand. The resulting, Glossina morsitans model is extrapolated to other species using their relative surface areas, their relative protected and unprotected transpiration rates and their different fourth instar excretions (drawing, to a lesser extent, from the data of Buxton and Lewis). In this way the problem of pupal dehydration is formulated as a series of integrals and the consequent survival can be predicted. The discovery of a distinct definition for hygrophilic species, within the formulation, prompts the investigation of the hypothetical effect of a two-day heat wave on pupae. This leads to the conclusion that the classification of species as hygrophilic, mesophilic and xerophilic is largely true only in so much as their third and fourth instars are and, possibly, the hours shortly before eclosion.

M-ABC2, a new human mitochondrial ATP-binding cassette membrane protein.

We have isolated a human cDNA encoding a novel ATP-binding cassette (ABC) protein whose gene was previously localized to chromosome 1q42 [Allikmets et al. (1995) Mamm. Genome 6, 111-117]. The gene transcript is expressed in all human tissues examined, with the highest levels in bone marrow. A non-expressed pseudogene also exists at chromosome 15q13-14. The new protein, which is most similar to the mitochondrial (M)-ABC1 protein, was also localized to mitochondria and therefore designated 'M-ABC2'. The N-terminus of M-ABC2 was shown to contain a mitochondrial-targeting signal sequence.

Current concepts in the treatment of urinary tract infections and prostatitis.

Urinary tract infection is a common medical diagnosis. The decision to treat is based on presenting signs and symptoms, bacterial colony counts in urine, and the nature of the infection. Escherichia coli is the single most frequent cause of urinary tract infections, although, depending on the clinical presentation and presence of risk factors, other pathogens may also be implicated. A variety of antimicrobial agents are available for the treatment of urinary tract infections. Fluoroquinolones are useful because these agents have broad-spectrum antimicrobial activity, resistance to these agents is minimal, and they achieve high concentrations in the urinary tract, have long elimination half-lives in urine, and are well tolerated.

Aztreonam in the treatment of urinary tract infection.

The possible advantages of the monobactam antibiotic aztreonam in the treatment of hospital-acquired urinary tract infection were assessed in a study comparing aztreonam (0.5 to 1 g twice daily or three times daily) to cefamandole (1 g three times daily) in 159 patients. Initial pathogens were eradicated in 91.7 percent of the patients of the aztreonam group who were treated three times daily, in 82.7 percent of the group treated twice daily, and in 78.3 percent of the patients receiving cefamandole. Reinfection and superinfection were most commonly caused by enterococci in the aztreonam groups and by Pseudomonas aeruginosa in the cefamandole group. In a second study, 35 patients infected with organisms resistant to other antibiotics were treated with aztreonam 1 to 6 g per day for eight days. The overall cure rates were 93 percent for Pseudomonas infections, 87.5 percent for Escherichia coli infections, and 100 percent for other pathogens.