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Biomedical subjects

M Piper

Publications and source records attributed to M Piper.

At least 19 recordsLinked to original sources
PubMed2001

Epoetin treatment of anemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials.

Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95% confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95% CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.

Anemia↗
PubMed2001

Race-specific results of Papanicolaou testing and the rate of cervical neoplasia in the National Breast and Cervical Cancer Early Detection Program, 1991-1998 (United States).

OBJECTIVE: To describe differences in cervical screening and biopsy results by race or ethnicity from women in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). METHODS: We examined the percentage of abnormalities detected by Papanicolaou (Pap) tests and the rate of biopsy-diagnosed high-grade precancerous or cancerous lesions by racial or ethnic group. RESULTS: Almost half the 628,085 women screened were members of racial or ethnic minority groups. American Indian or Alaska Native women were more likely than others to report never having had a prior Pap test. American Indian or Alaska Native women had the highest proportion of abnormal Pap tests for first program screens (4.4%), followed by blacks (3.2%), whites (3.0%), Hispanics (2.7%), and Asians or Pacific Islanders (1.9%). Whites had the highest biopsy detection rate of high-grade lesions for first program screens (9.9 per 1000 Pap tests), followed by Hispanics (7.6), blacks (7.1), American Indians or Alaska Natives (6.7), and Asians or Pacific Islanders (5.4). CONCLUSIONS: This program provides important data on the prevalence of cervical neoplasia among diverse populations. Our findings that black women with a high-grade Pap test were less likely to get a work-up are disconcerting and merit further study and ultimate correction.

Adolescent↗
PubMed2001

Health of elderly male prisoners: worse than the general population, worse than younger prisoners.

BACKGROUND: Assessment of the health of men aged 60 and over in English and Welsh prisons. METHODS: 203 men were interviewed from 15 prisons, comprising one-fifth of all sentenced men in this age group in England and Wales. Assessment included semi-structured interviews covering chronic and acute health problems, and recording of major illnesses from the medical notes and prison reception health screen. RESULTS: 85% of the elderly prisoners had one or more major illnesses reported in their medical records, and 83% reported at least one chronic illness on interview. The most common illnesses were psychiatric, cardiovascular, musculoskeletal and respiratory. CONCLUSION: The rates of illness in elderly prisoners are higher than those reported in other studies of younger prisoners and surveys of the general population of a similar age. The increasing number of elderly people in prison poses specific health challenges for prison health-care services.

Adult↗
PubMed2001

Dual trafficking of Slit3 to mitochondria and cell surface demonstrates novel localization for Slit protein.

Drosophila slit is a secreted protein involved in midline patterning. Three vertebrate orthologs of the fly slit gene, Slit1, 2, and 3, have been isolated. Each displays overlapping, but distinct, patterns of expression in the developing vertebrate central nervous system, implying conservation of function. However, vertebrate Slit genes are also expressed in nonneuronal tissues where their cellular locations and functions are unknown. In this study, we characterized the cellular distribution and processing of mammalian Slit3 gene product, the least evolutionarily conserved of the vertebrate Slit genes, in kidney epithelial cells, using both cellular fractionation and immunolabeling. Slit3, but not Slit2, was predominantly localized within the mitochondria. This localization was confirmed using immunoelectron microscopy in cell lines and in mouse kidney proximal tubule cells. In confluent epithelial monolayers, Slit3 was also transported to the cell surface. However, we found no evidence of Slit3 proteolytic processing similar to that seen for Slit2. We demonstrated that Slit3 contains an NH(2)-terminal mitochondrial localization signal that can direct a reporter green fluorescent protein to the mitochondria. The equivalent region from Slit1 cannot elicit mitochondrial targeting. We conclude that Slit3 protein is targeted to and localized at two distinct sites within epithelial cells: the mitochondria, and then, in more confluent cells, the cell surface. Targeting to both locations is driven by specific NH(2)-terminal sequences. This is the first examination of Slit protein localization in nonneuronal cells, and this study implies that Slit3 has potentially unique functions not shared by other Slit proteins.

Amino Acid Sequence↗
PubMed2001

Erythropoietin: a paradigm for the development of practice guidelines.

Erythropoietin (EPO) is an endogenous hormone produced in the kidney that regulates red blood cell production within the body. Since the cloning and first clinical introduction of recombinant erythropoietin (epoetin) in the late 1980s indications and usage of epoetin have expanded significantly. It is estimated that as many as one third of patients with substantial anemia (hemoglobin less than 10.0 g/dL) resulting from chemotherapy for cancer are treated with epoetin. Though use of epoetin may avoid the inconvenience and infectious risk of blood transfusions, it is expensive and its benefit in some clinical scenarios has been modest. Like many new technologies, strong evidence suggesting situations where the benefit is high has lagged behind its adoption by patients and practitioners. As well, epoetin is expensive and third party payers do not always reimburse it. Research suggests there is considerable variation in epoetin usage in practice. To provide guidance to hematology/oncology specialists regarding use of epoetin, the American Society of Hematology (ASH) and the American Society of Clinical Oncology (ASCO) proposed that the Agency for Healthcare Research and Quality (AHRQ) fund an evidence review by one of the Evidence-based Practice Centers (EPC) that would be used to develop evidence-based guidelines for members of the society. This review highlights principles of evidence-based medicine, distills and appraises the evidence in the published literature that supports the use of epoetin, and presents evidence-based recommendations for use of epoetin in situations where benefit is substantiated by high-quality studies. As well, this review addresses some of the difficulties of performing clinical research in this area, provocative research findings that will require further study, and suggestions regarding epoetin in those areas where further strong evidence has yet to be developed.

Anemia↗
PubMed2000

Expression of the vertebrate Slit gene family and their putative receptors, the Robo genes, in the developing murine kidney.

The slit (sli) gene, encoding a secreted glycoprotein, has been demonstrated to play a vital role in axonal guidance in Drosophila melanogaster by acting as a signalling ligand for the robo receptor (Rothberg, J.M., Jacobs, J.R., Goodman, C.S., Artavanis-Tsakonas, S., 1990. slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains. Genes Dev. 4, 2169-2187; Kidd, T., Bland, K.S., Goodman, C. S., 1999. Slit is the midline repellent for the robo receptor in Drosophila. Cell 96, 785-794). Multiple homologs of both sli and robo have been identified in vertebrates and are thought to play similar roles to their fly counterparts in neural development (Brose, K., Bland, K.S., Wang, K.H., Arnott, D., Henzel, W., Goodman, C.S., Tessier-Lavigne, M., Kidd, T., 1999. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96, 795-806). Slit2 has been shown to bind Robo1, mediating both neuronal and axonal guidance in the developing central nervous system (CNS), (Brose et al., 1999; Hu, H., 1999. Chemorepulsion of neuronal migration by Slit2 in the developing mammalian forebrain. Neuron 23, 703-711). Importantly, both gene families display distinct expression patterns outside the CNS (Holmes, G.P., Negus, K., Burridge, L., Raman, S., Algar, E., Yamada, T., Little, M.H., 1998. Distinct but overlapping expression patterns of two vertebrate slit homologs implies functional roles in CNS development and organogenesis. Mech. Dev. 79, 57-72; Yuan, W., Zhou, L., Chen, J.H., Wu, J.Y., Rao, Y., Ornitz, D.M., 1999. The mouse SLIT family: secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance. Dev. Biol. 212, 290-306). Using in situ hybridization on metanephric explant cultures and urogenital tract sections, the expression patterns of Slit1, 2, 3 and Robo1 and 2 were investigated during murine metanephric development. Slit1 was expressed in the metanephric mesenchyme (MM) surrounding the invading ureteric tree (UT). Slit2 was expressed at the tips of the UT and both Slit2 and Slit3 were expressed at the far proximal end of the comma shaped and S-shaped bodies. Expression of Robo1 was initially diffuse throughout the MM, then upregulated in the pretubular aggregates, and maintained at the distal end of the comma and S-shaped bodies. Robo2 was detected in the induced MM surrounding the arborizing UT tips and later in the proximal end of the S-shaped bodies. Coincident expression of Robo1 with Slit1 in the metanephric mesenchyme and Robo2, Slit2 and Slit3 in the far proximal end of the S-shaped bodies was observed during metanephric development.

Animals↗
PubMed2000

Protective effect of HOE642, a selective blocker of Na+-H+ exchange, against the development of rigor contracture in rat ventricular myocytes.

The objective of this study was to investigate the effect of Na+-H+ exchange (NHE) and HCO3--Na+ symport inhibition on the development of rigor contracture. Freshly isolated adult rat cardiomyocytes were subjected to 60 min metabolic inhibition (MI) and 5 min re-energization (Rx). The effects of perfusion of HCO3- or HCO3--free buffer with or without the NHE inhibitor HOE642 (7 microM) were investigated during MI and Rx. In HCO3--free conditions, HOE642 reduced the percentage of cells developing rigor during MI from 79 +/- 1% to 40 +/- 4% (P < 0.001) without modifying the time at which rigor appeared. This resulted in a 30% reduction of hypercontracture during Rx (P < 0.01). The presence of HCO3- abolished the protective effect of HOE642 against rigor. Cells that had developed rigor underwent hypercontracture during Rx independently of treatment allocation. Ratiofluorescence measurement demonstrated that the rise in cytosolic Ca2+ (fura-2) occurred only after the onset of rigor, and was not influenced by HOE642. NHE inhibition did not modify Na+ rise (SBFI) during MI, but exaggerated the initial fall of intracellular pH (BCEFC). In conclusion, HOE642 has a protective effect against rigor during energy deprivation, but only when HCO3--dependent transporters are inhibited. This effect is independent of changes in cytosolic Na+ or Ca2+ concentrations.

Animals↗
PubMed1998

Genomic and functional map of the chromosome 14 t(12;14) breakpoint cluster region in uterine leiomyoma.

A translocation involving chromosomes 12 and 14 [t(12;14)(q15;24.1)] is commonly seen in benign smooth muscle tumor as uterine leiomyoma (UL). A contig of P1-derived artificial chromosome and bacterial artificial chromosome clones on chromosome 14, encompassing a t(12;14) breakpoint cluster region (BCR) in UL, was generated principally using the recently developed HAPPY map of chromosome 14 as a framework (P. H. Dear et al., 1998, Genomics 48: 232-241). Three UL t(12;14) breakpoints have been localized within this contig, showing that a BCR of at least 400 kb exists on chromosome 14. Other studies of tumors with t(12;14) rearrangements similarly show breakpoints within a 475-kb multiple aberration region on chromosome 12. Thus t(12;14) is an example of a translocation in which the breakpoints are located within a BCR on both chromosome 12 and chromosome 14, justifying the identification of expressed sequences that are altered in these BCR regions. A total of four expressed sequences were identified in the BCR on chromosome 14. Two of these were novel cDNAs (D14S1460E and D14S1461E). The chromosome 14 cDNAs were expressed in multiple adult tissues. The identification of a large breakpoint cluster region on chromosome 14 suggests that translocations in this region mediate their effects at a distance and also that elements that predispose this region to recurrent chromosomal translocation may be widely distributed.

Amino Acid Sequence↗
PubMed1998

Assessment of gross motor skills of at-risk infants: predictive validity of the Alberta Infant Motor Scale.

The Alberta Infant Motor Scale (AIMS) is a norm-referenced measure of infant gross motor development. The objectives of this study were: (1) to establish the best cut-off scores on the AIMS for predictive purposes, and (2) to compare the predictive abilities of the AIMS with those of the Movement Assessment of Infants (MAI) and the Peabody Developmental Gross Motor Scale (PDGMS). One hundred and sixty-four infants were assessed at 4 and 8 months adjusted ages on the three measures. A pediatrician assessed each infant's gross motor development at 18 months as normal, suspicious, or abnormal. For the AIMS, two different cut-off points were identified: the 10th centile at 4 months and the 5th centile at 8 months. The MAI provided the best specificity rates at 4 months while the AIMS was superior in specificity at 8 months. Sensitivity rates were comparable between the two tests. The PDGMS in general demonstrated poor predictive abilities.

Child Development↗
PubMed1998

Alterations in skeletal muscle gene expression of ob/ob mice by mRNA differential display.

To identify molecules that contribute to insulin resistance, we compared the patterns of gene expression in skeletal muscle of the obese ob/ob mouse, a genetic model of obesity and severe insulin resistance, with that of its thin littermate (ob/+) using the mRNA differential display method. From about 9,000 cDNAs displayed, we found 12 differentially expressed in ob/ob mice skeletal muscle that could be recovered from the differential display gels and confirmed by Northern blot analysis and sequenced. Eight mRNAs were overexpressed in ob/ob muscle: Id2 (a negative regulator of the basic helix-loop-helix family of transcription factors), fast skeletal muscle troponin T, ribosomal protein L3, the integral protein of the peroxisomal membrane 22PMP, the mammalian homolog of geranylgeranyl pyrophosphate synthase, an mRNA related to phosphatidylinositol-glycan-specific phospholipase D, and two unknown mRNAs. The level of overexpression of these mRNAs in skeletal muscle varied from a 500% increase to as little as a 25% increase. Two mRNAs were underexpressed 20-35%, including the f-subunit of mitochondrial ATP synthase and a retrovirus-related DNA. Two proteins with multiple transcripts, skeletal muscle alpha-tropomyosin and one for a repetitive sequence, showed a change in mRNA pattern of expression in the muscle of the ob/ob mouse. Because the primary genetic defect in the ob/ob mouse is known to be in the leptin gene, these data indicate how acquired alterations in gene expression of multiple classes of proteins may play a role in the complex pathogenesis of insulin resistance in obesity and diabetes.

Alkyl and Aryl Transferases↗
PubMed1997

Differential responsiveness of somatotrophs to growth hormone-releasing hormone and thyrotropin-releasing hormone during chicken embryonic development.

This study was designed to evaluate responsiveness and sensitivity of pituitaries from chickens to growth hormone (GH) secretagogues during late embryonic development. Anterior pituitary cells from 16-, 18- and 20-day-old chicken embryos were subjected to reverse hemolytic plaque assays (RHPAs) for GH in the presence of GH-releasing hormone (GHRH) and thyrotropin-releasing hormone (TRH). The proportion of somatotrophs detected increased between embryonic days 16 and 20, from 16 to 19.5% of all pituitary cells. Sensitivity to GHRH and TRH was similar and increased between embryonic days 16 and 20. On embryonic day 16, about 50% of somatotrophs that were not detected under basal conditions released GH in the presence of GHRH at 2 and 6 h. In contrast, only 15 and 30% of day 16 somatotrophs released GH by 2 and 6 h, respectively, following exposure to TRH. Thus, at least one of five somatotrophs responded to GHRH but not to TRH. By embryonic day 20, the proportions of somatotrophs that responded to GHRH and TRH were approximately equal at about 40%. These results provide additional evidence that GHRH and TRH may be involved in hypothalamic regulation of GH secretion during chicken embryonic development. Furthermore, it appears that full differentiation of functional chicken somatotrophs does not occur abruptly but rather gradually between embryonic days 16 and 20, during which a subpopulation of GH cells undergoes changes in sensitivity and responsiveness to TRH.

Animals↗
PubMed1997

Primitive reflexes and the determination of fetal presentation at birth.

Ninety term breech-presenting singletons with birth weights greater than 2500 g and no congenital anomalies were matched with similar cephalic-presenting infants on gender and mode of delivery (n = 180). Thirteen primitive reflexes were examined at birth, 6 weeks and 3 and 5 months. No significant differences in the intensity of the asymmetrical tonic neck, symmetrical tonic neck, positive support tonic labyrinthine (prone and supine), segmental rolling (head-on-body and body-on-body), Galant, Moro, upper and lower extremity grasp, lower extremity placing and stepping reflexes were observed between these two groups of infants. Infants delivered vaginally, regardless of presentation, had weaker Moro reflexes at 5 months than infants delivered by cesarean section. The popular notion that precursors to early motor behaviors, such as the placing and stepping reflexes, are determinants of fetal presentation at the end of pregnancy is not supported by these results. Instead, spontaneously generated active whole body movements may be more significant influences of fetal orientation at the time of birth.

Adult↗
PubMed1996

A role for melanin-concentrating hormone in the central regulation of feeding behaviour.

The hypothalamus plays a central role in the integrated regulation of energy homeostasis and body weight, and a number of hypothalamic neuropeptides, such as neuropeptide Y (ref. 1), galanin, CRH (ref. 3) and GLP-1 (ref. 4), have been implicated in the mediation of these effects. To discover new hypothalmic peptides involved in the regulation of body weight, we used differential display polymerase chain reaction to identify messenger RNAs that are differentially expressed in the hypothalamus of ob/+ compared with ob/ob C57B1/6J mice. We show here that one mRNA that is overexpressed in the hypothalamus of ob/ob mice encodes the neuropeptide melanin-concentrating hormone (MCH). Fasting further increased expression of MCH mRNA in both normal and obese animals. Neurons containing MCH are located in the zona incerta and in the lateral hypothalamus. These areas are involved in regulation of ingestive behaviour, but the role of MCH in mammalian physiology is unknown. To determine whether MCH is involved in the regulation of feeding, we injected MCH into the lateral ventricles of rats and found that their food consumption increased. These findings suggest that MCH participates in the hypothalamic regulation of body weight.

Amino Acid Sequence↗
PubMed1996

Conserved structure and adjacent location of the thrombin receptor and protease-activated receptor 2 genes define a protease-activated receptor gene cluster.

BACKGROUND: Thrombin is a serine protease that elicits a variety of cellular responses. Molecular cloning of a thrombin receptor revealed a G protein-coupled receptor that is activated by a novel proteolytic mechanism. Recently, a second protease-activated receptor was discovered and dubbed PAR2. PAR2 is highly related to the thrombin receptor by sequence and, like the thrombin receptor, is activated by cleavage of its amino terminal exodomain. Also like the thrombin receptor, PAR2 can be activated by the hexapeptide corresponding to its tethered ligand sequence independent of receptor cleavage. Thus, functionally, the thrombin receptor and PAR2 constitute a fledgling receptor family that shares a novel proteolytic activation mechanism. To further explore the relatedness of the two known protease-activated receptors and to examine the possibility that a protease-activated gene cluster might exist, we have compared the structure and chromosomal locations of the thrombin receptor and PAR2 genes. MATERIALS AND METHODS: The genomic structures of the two protease-activated receptor genes were determined by analysis of lambda phage, P1 bacteriophage, and bacterial artificial chromosome (BAC) genomic clones. Chromosomal location was determined with fluorescent in situ hybridization (FISH) on metaphase chromosomes, and the relative distance separating the two genes was evaluated both by means of two-color FISH and analysis of YACs and BACs containing both genes. RESULTS: Analysis of genomic clones revealed that the two protease-activated receptor genes share a two-exon genomic structure in which the first exon encodes 5'-untranslated sequence and signal peptide, and the second exon encodes the mature receptor protein and 3'-untranslated sequence. The two receptor genes also share a common locus with the two human genes located at 5q13 and the two mouse genes at 13D2, a syntenic region of the mouse genome. These techniques also suggest that the physical distance separating these two genes is less than 100 kb. CONCLUSIONS: The fact that the thrombin receptor and PAR2 genes share an identical structure and are located within approximately 100 kb of each other in the genome demonstrates that these genes arose from a gene duplication event. These results define a new protease-activated receptor gene cluster in which new family members may be found.

Amino Acid Sequence↗