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Biomedical subjects

B J Taylor

Publications and source records attributed to B J Taylor.

At least 19 recordsLinked to original sources
PubMed2003

Respiratory responses to hypoxia/hypercapnia in small for gestational age infants influenced by maternal smoking.

AIM: To determine any variation in the respiratory responses to hypoxia/hypercapnia of infants born small for gestational age (SGA) to smoking and to non-smoking mothers. METHODS: A total of 70 average for gestational age (AGA) infants (>36 weeks gestation, >2500 g, >25th centile for gestational age, and no maternal smoking), and 47 SGA infants (<10th centile for gestational age) were studied at 1 and 3 months of age, in quiet and active sleep. Respiratory test gases were delivered through a Perspex hood to simulate face down rebreathing by slowly allowing the inspired air to be altered to a CO(2) maximum of 5% and O(2) minimum of 13.5%. The change in ventilation with inspired CO(2) was measured over 5-6 minutes of the test. The slope of a linear curve fit relating inspired CO(2) to the logarithm of ventilation was taken as a quantitative measure of ventilatory asphyxial sensitivity (VAS). RESULTS: There was no significant difference in VAS between the AGA and SGA infants (0.25 v 0.24). However within the SGA group, VAS was significantly higher (p = 0.048) in the infants whose mothers smoked during pregnancy (0.26 (0.01); n = 24) than in those that did not (0.23 (0.01); n = 23). The change in minute ventilation was significantly higher in the smokers than the non-smokers group (141% v 119%; p = 0.03) as the result of a significantly larger change in respiratory rate (8 v 4 breaths/min; p = 0.047) but not tidal volume. CONCLUSIONS: Maternal smoking appears to be the key factor in enhancing infants' respiratory responses to hypoxia/hypercapnia, irrespective of gestational age.

Female↗
PubMed2002

Prone versus supine sleep position: a review of the physiological studies in SIDS research.

A number of physiological studies, published over the last 10 years, have investigated the links between prone sleeping and sudden infant death syndrome (SIDS). This review evaluates those studies and derives an overview of the different affects of sleeping prone or supine in infancy. Generally, compared with the supine, the prone position raises arousal and wakening thresholds, promotes sleep and reduces autonomic activity through decreased parasympathetic activity, decreased sympathetic activity or an imbalance between the two systems. In addition, resting ventilation and ventilatory drive is improved in preterm infants, but in older infants (>1 month), there is no improvement in ventilation, and in 3-month-old infants, the position is adverse in terms of poorer ventilatory drive (in active sleep only). The majority of findings suggest a reduction in physiological control related to respiratory, cardiovascular and autonomic control mechanisms, including arousal during sleep in the prone position. Since the majority of these findings are from studies of healthy infants, continued reinforcement of the supine sleep recommendations for all infants is emphasized.

Arousal↗
PubMed2002

Are risk factors for sudden infant death syndrome different at night?

AIMS: To determine whether the risk factors for SIDS occurring at night were different from those occurring during the day. METHODS: Large, nationwide case-control study, with data for 369 cases and 1558 controls in New Zealand. RESULTS: Two thirds of SIDS deaths occurred at night (between 10 pm and 7 30 am). The odds ratio (95% CI) for prone sleep position was 3.86 (2.67 to 5.59) for deaths occurring at night and 7.25 (4.52 to 11.63) for deaths occurring during the day; the difference was significant. The odds ratio for maternal smoking for deaths occurring at night was 2.28 (1.52 to 3.42) and that for the day 1.27 (0.79 to 2.03); that for the mother being single was 2.69 (1.29 to 3.99) for a night time death and 1.25 (0.76 to 2.04) for a daytime death. Both interactions were significant. The interactions between time of death and bed sharing, not sleeping in a cot or bassinet, Maori ethnicity, late timing of antenatal care, binge drinking, cannabis use, and illness in the baby were also significant, or almost so. All were more strongly associated with SIDS occurring at night. CONCLUSIONS: Prone sleep position was more strongly associated with SIDS occurring during the day, whereas night time deaths were more strongly associated with maternal smoking and measures of social deprivation.

Age Distribution↗
PubMed2001

Persistent preswitch clonotypic myeloma cells correlate with decreased survival: evidence for isotype switching within the myeloma clone.

Multiple myeloma (MM) is identified by unique immunoglobulin heavy chain (IgH) variable diversity joining region gene rearrangements, termed clonotypic, and an M protein termed the "clinical" isotype. Transcripts encoding clonotypic pre and postswitch IgH isotypes were identified in MM peripheral blood mononuclear cells (PBMCs), bone marrow (BM), and mobilized blood. For 29 patients, 38 BM, 17 mobilized blood, and 334 sequential PBMC samples were analyzed at diagnosis, before and after transplantation for 2 to 107 months. The clinical clonotypic isotype was readily detectable and persisted throughout treatment. Eighty-two percent of BM and 38% of PBMC samples also expressed nonclinical clonotypic isotypes. Clonotypic immunoglobulin M (IgM) was detectable in 68% of BM and 25% of PBMC samples. Nonclinical clonotypic isotypes were detected in 41% of mobilized blood samples, but clonotypic IgM was detected in only 12%. Patients with persistent clonotypic IgM expression had adverse prognostic features at diagnosis (lower hemoglobin, higher beta(2)-microglobulin) and higher numbers of BM plasma cells compared with patients with infrequent/absent clonotypic IgM. Patients with persistent clonotypic IgM expression had significantly poorer survival than patients with infrequent IgM expression (P <.0001). In a multivariate analysis, persistent clonotypic IgM expression in the blood correlated independently with poor survival (P =.01). In nonobese diabetic severe combined immunodeficiency mice, xenografted MM cells expressed clinical and nonclinical postswitch clonotypic isotypes. MM expressing clonotypic IgM engrafted both primary and secondary mice, indicating their persistence within the murine BM. This study demonstrates that MM clonotypic cells expressing preswitch transcripts are tied to disease burden and outcomes. Because MM pathology involves postswitch plasma cells, this raises the possibility that IgH isotype switching in MM may accompany worsening disease.

Adult↗
PubMed2001

Detection of MRP functional activity: calcein AM but not BCECF AM as a Multidrug Resistance-related Protein (MRP1) substrate.

Resistance to anticancer drugs has been attributed to an array of cellular changes. The multidrug resistance-related protein (MRP1) is an efflux pump whose overexpression confers resistance to several classes of drugs, such as the anthracyclines, epipodophyllotoxins, and vinca alkaloids. These drugs are mainstays in cancer therapy. MRP1 overexpression is hypothesized to be a causative agent of clinical treatment failure. Consistently accurate methods for detecting this protein are necessary to further understand its biology and delineate its possible clinical relevance. Flow cytometric analysis of multidrug resistance (MDR) is a valuable method to evaluate both antigen expression and function. Using flow cytometry, we assayed MRP1 functional activity in pediatric leukemic blasts and an array of MDR+ and WT cell lines. We conclude that calcein AM, when used in a retention assay with MRP1-specific modulators, is able to reliably detect MRP functional activity. 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF AM) transport is not indicative of MRP1 overexpression. .

Child↗
PubMed2001

New reproductive anomalies in fruitless-mutant Drosophila males: extreme lengthening of mating durations and infertility correlated with defective serotonergic innervation of reproductive organs.

Several features of male reproductive behavior are under the neural control of fruitless (fru) in Drosophila melanogaster. This gene is known to influence courtship steps prior to mating, due to the absence of attempted copulation in the behavioral repertoire of most types of fru-mutant males. However, certain combinations of fru mutations allow for fertility. By analyzing such matings and their consequences, we uncovered two striking defects: mating times up to four times the normal average duration of copulation; and frequent infertility, regardless of the time of mating by a given transheterozygous fru-mutant male. The lengthened copulation times may be connected with fru-induced defects in the formation of a male-specific abdominal muscle. Production of sperm and certain seminal fluid proteins are normal in these fru mutants. However, analysis of postmating qualities of females that copulated with transheterozygous mutants strongly implied defects in the ability of these males to transfer sperm and seminal fluids. Such abnormalities may be associated with certain serotonergic neurons in the abdominal ganglion in which production of 5HT is regulated by fru. These cells send processes to contractile muscles of the male's internal sex organs; such projection patterns are aberrant in the semifertile fru mutants. Therefore, the reproductive functions regulated by fruitless are expanded in their scope, encompassing not only the earliest stages of courtship behavior along with almost all subsequent steps in the behavioral sequence, but also more than one component of the culminating events.

Animals↗
PubMed2001

Nosocomial infections during extracorporeal membrane oxygenation.

OBJECTIVE: To examine trends in nosocomial infection associated with Extracorporeal Membrane Oxygenation (ECMO). DESIGN: Retrospective review of all patients who underwent ECMO over a 4-year period at our institution; specifically, examining reasons for placement and duration of time on ECMO, as well as nosocomial infections incurred while on or shortly after discontinuation of support. Infections were considered ECMO-related if the organism was recovered on support or within 7 days from decannulation. Analyses were performed utilizing Pearson's chi-square for dichotomous factors and t-tests for continuous factors. RESULTS: Of 141 patients requiring ECMO support, 90 (64%) survived to hospital discharge. Indication for support included circulatory failure (53%) and non-cardiac (47%). Twenty-six percent of patients developed infections on ECMO. Organisms isolated included: bacterial 20 (54%), fungal 10 (27%), mixed five (14%) and viral two (5%). Infection sites included: blood 13 (35%), urine nine (24%), mixed eight (22%), wound five (14%) and lung two (5%). Seventy-eight percent of infections noted occurred in cardiac patients. Patients with nosocomial infections were supported for a median of 169 h (range, 84-936 h), versus those without nosocomial infection [146 h (range, 50-886 h); P<0.001]. Procedures on ECMO were associated with an increased risk of infection (P<0.001) as was the presence of an open chest (P<0.025). CONCLUSIONS: The incidence of infection in ECMO patients at our institution has not increased significantly since our previous study. Cardiac patients have increased risk for nosocomial infection while on ECMO, which may be in part due to longer cannulation times, as well as increased likelihood of undergoing major procedures or having an open chest.

Adolescent↗
PubMed2001

Detection of P-glycoprotein in cell lines and leukemic blasts: failure of select monoclonal antibodies to detect clinically significant Pgp levels in primary cells.

Multidrug resistance (MDR) is a salient feature of chemotherapy failure in pediatric patients. One of the most common and well-studied mechanisms implicated in causing MDR is P-glycoprotein (Pgp), an ATP-dependent, transmembrane drug efflux pump. Accurate and reproducible detection of this MDR protein is necessary as it may have important clinical implications. In this study comparing the directly conjugated anti-Pgp monoclonal antibodies UIC2-PE and 15D3-PE to the unconjugated anti-Pgp mAb MRK16, we analyzed cell lines, normal peripheral blood cells, and bone marrow cells from pediatric patients diagnosed with acute myeloid leukemia and acute lymphoblastic leukemia; all samples were also analyzed for Pgp function using rhodamine 123 in order to correlate results from antibody staining with functional activity. For all patient samples evaluated, only MRK16 correlated well with the rhodamine 123 assay. Both the directly conjugated antibodies UIC2-PE and 15D3-PE failed to detect Pgp in almost all cases. Pre-treatment of cells with neuraminidase did not provide a consistent enhancement of antigen detection. Based on these results, we suggest that while UIC2-PE and 15D3-PE may be able to detect the very high levels of Pgp expressing laboratory-cultured cell lines, they are not suitable for clinical application in their currently available conjugated form. When assaying patient samples for Pgp expression and function using flow cytometry, the rhodamine 123 functional assay should be performed in concert with staining with MRK16.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

International Child Care Practices Study: infant sleeping environment.

BACKGROUND: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.

Beds↗
PubMed2001

International Child Care Practices Study: infant sleep position and parental smoking.

UNLABELLED: The International Child Care Practices Study (ICCPS) collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the key sudden infant death syndrome (SIDS) risk factors of infant sleep position and parental smoking. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview, and at 3 months of age mainly by postal questionnaire. Data entry and descriptive analysis were undertaken with Epi Info. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families, and 4656 (85%) returned questionnaires at 3 months. Overall, 52.5% (95% CI, 43.5-61.3) of infants were placed in the supine or back sleep position, 37.8% (95% CI, 30.6-45.7) in the side position and 13% (95% CI, 9.3-17.9) in the prone or front position. The prevalence of supine sleeping ranged from 14% (Santiago, Chile) to 89% (Tokyo/Yokohama, Japan). The prevalence of reported smoking was between 0% and 34% for mothers and 10% and 64% for fathers. In samples from Western countries, there was a trend for rates of maternal smoking to be similar to paternal smoking, whereas in other samples, low rates of maternal smoking contrasted with high rates of paternal smoking. CONCLUSIONS: These data highlight considerable variations and interesting patterns in the prevalence of these two important SIDS risk factors in these diverse samples. Impressive differences in rates of smoking within and between these communities may reflect different stages of the inevitable progression of the smoking epidemic, but may also provide some encouragement that reduction in smoking rates, in both mothers and fathers, is possible.

Global Health↗
PubMed2001

Participation in research: informed consent, motivation and influence.

OBJECTIVE: To investigate the process and quality of informed consent, motivation and influence in parents who were invited to enroll their baby in a research project. METHODOLOGY: A mixed quantitative/qualitative questionnaire was sent to a cohort invited to participate in a physiological research project on sudden infant death syndrome (SIDS) at the Dunedin Public Hospital, Dunedin, New Zealand. Separate questionnaires were used for parents who participated (94) and those who declined to participate (103). Response rates were 69% and 47%, respectively. RESULTS: All consenting parents felt they understood the purpose and procedure of the study. The majority (90%) thought the information about the study was very good; 6.5% felt more detail was required. Eighty-five per cent found the verbal explanation the most useful source of information. All participated for altruistic reasons such as to aid SIDS research. Although 27% had concerns about safety of the tests, after the tests all responders felt happy with the safety of the tests. Inconvenience was the main reason (53%) for declining to participate. Twenty-eight per cent of declining parents were concerned about the safety of the tests. CONCLUSION: Of those who responded to the questionnaire, the process for obtaining informed consent in the SIDS studies was satisfactory. Parents' motives for participating were mostly altruistic. The role of recall bias and selection bias may make the implications of this study unclear.

Adult↗
PubMed2001

Maternal cannabis use in the sudden death syndrome.

The smoking of cannabis and tobacco is common in many countries. In contrast to tobacco, which is an established risk factor for the sudden infant death syndrome (SIDS), nothing is known about cannabis and its effects on SIDS risk. We analysed data collected in a nation-wide case control study in New Zealand (393 cases, 1592 controls) to determine if there is any association between maternal cannabis use and SIDS risk. Adjusting for ethnicity and maternal tobacco use, the SIDS odds ratio for >weekly maternal cannabis use since the infant's birth was 2.23 (95% CI = 1.39, 3.57) compared to non-users; and the multivariate odds ratio was 1.55 (95% CI = 0.87, 2.75). We conclude that frequent maternal cannabis use may be a weak risk factor for SIDS, but this finding requires further research.

Adult↗
PubMed2001

Molecular genetic dissection of the sex-specific and vital functions of the Drosophila melanogaster sex determination gene fruitless.

A multibranched hierarchy of regulatory genes controls all aspects of somatic sexual development in Drosophila melanogaster. One branch of this hierarchy is headed by the fruitless (fru) gene and functions in the central nervous system, where it is necessary for male courtship behavior as well as the differentiation of a male-specific abdominal structure, the muscle of Lawrence (MOL). A preliminary investigation of several of the mutations described here showed that the fru gene also has a sex-nonspecific vital function. The fru gene produces a complex set of transcripts through the use of four promoters and alternative splicing. Only the primary transcripts produced from the most distal (P1) promoter are sex-specifically spliced under direction of the sex-determination hierarchy. We have analyzed eight new fru mutations, created by X-ray mutagenesis and P-element excision, to try to gain insight into the relationship of specific transcript classes to specific fru functions. Males that lack the P1-derived fru transcripts show a complete absence of sexual behavior, but no other defects besides the loss of the MOL. Both males and females that have reduced levels of transcripts from the P3 promoter develop into adults but frequently die after failing to eclose. Analysis of the morphology and behavior of adult escapers showed that P3-encoded functions are required for the proper differentiation and eversion of imaginal discs. Furthermore, the reduction in the size of the neuromuscular junctions on abdominal muscles in these animals suggests that one of fru's sex-nonspecific functions involves general aspects of neuronal differentiation. In mutants that lack all fru transcripts as well as a small number of adjacent genes, animals die at an early pupal stage, indicating that fru's function is required only during late development. Thus, fru functions both in the sex-determination regulatory hierarchy to control male sexual behavior through sex-specific transcripts and sex-nonspecifically to control the development of imaginal discs and motorneuronal synapses during adult development through sex-nonspecific transcript classes.

Alleles↗
PubMed2001

Ventilatory responses to rebreathing in infants exposed to maternal smoking.

UNLABELLED: This study assessed the effect of maternal smoking during pregnancy on ventilatory and waking responses of infants to a respiratory challenge. This challenge mimicked the time-course and concentration of gases that an infant would experience rebreathing face-down into soft bedding. Control (C; n = 97) and smokers' infants (SM; n = 96) were studied at ages I and 3 mo. Asphyxial gas (hypercapnia/hypoxia) was delivered to the supine sleeping baby via a hood by slowly altering the inspired air: CO2 maximum 5% and O2 minimum 13.5%. Respiratory pattern was recorded by inductive plethysmography as the sum of ribcage and abdominal movements. The change in ventilation with inspired CO2 was measured over 5-6 min of the test. The slope of a linear curve fit relating inspired CO2 to the logarithm of ventilation was taken as a quantitative measure of ventilatory asphyxial sensitivity (VAS). Protective responses were graded from 1: no waking and an estimated arterial carbon dioxide tension (PaCO2) > or = 60 mmHg (least protective), to 4: fully awake (most protective). The results showed VAS was higher in SM infants than controls: +0.03 (p = 0.04). The oxygen saturation (SaO2) of SM infants fell -0.4% (p = 0.02) more than SaO2 of controls despite a greater tidal volume increase: +13.0% (p = 0.04). Overall protective responses were the same between groups, but grade 1, although rare, was found in 7 SM infants and only 4 control infants; this difference was not significant. CONCLUSION: The study did not confirm the postulate that infants of mothers who smoked during pregnancy have a reduced ventilatory response or raised waking thresholds.

Female↗
PubMed2000

Enrichment and localization of ganglioside G(D3) and caveolin-1 in shed tumor cell membrane vesicles.

Tumor cell ganglioside shedding has been implicated in the process of tumor formation. Previously, we identified three forms of tumor ganglioside shedding: micelles, monomers and membrane vesicles. Here, we have explored the membrane vesicle form of ganglioside shedding, using a newly identified human ovarian carcinoma cell line, CABA I. These cells synthesize and express a spectrum of gangliosides, including the disialoganglioside, G(D3). Immunostaining using the monoclonal antibody R24 confirmed G(D3) expression and its presence in the plasma membrane of these cells. Cellular gangliosides were detected in the culture supernatant by HPTLC autoradiography, confirming an active shedding rate of 3% of cellular gangliosides/24 h. CABA I cell membranes also express caveolin-1, a characteristic protein marker for caveolae, which was detected by flow cytometric analysis and by Western blotting in both the cell membranes and the isolated membrane vesicles. To further define the expression of G(D3) and caveolin-1, we used immunogold electron microscopy. This revealed localization of G(D3) in small clusters in the plasma membrane as well as enrichment and localization of ganglioside G(D3) and caveolin-1 in shed membrane vesicles, with 58-78% of vesicles carrying both G(D3) and caveolin-1. Together, these results suggest that membrane vesicle shedding originates in plasma membrane domains enriched in gangliosides and caveolin-1.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2000

Spatial, temporal, and sexually dimorphic expression patterns of the fruitless gene in the Drosophila central nervous system.

The fruitless (fru) gene of Drosophila produces both sex-specifically and non-sex-specifically spliced transcripts. Male-specific fru products are believed to regulate male courtship. To further an understanding of this gene's behavioral role, we examined the central nervous system (CNS) for temporal, spatial, and sexually dimorphic expression patterns of sex-specific fru products by in situ hybridization and immunohistochemistry. For the latter, antibodies were designed to detect only male-specific forms of the protein (FRU(M)) or amino acid sequences that are in common among all translated products (FRU(COM)). Sex-specific mRNAs and male-specific proteins were first observed in mature larvae and peaked in their apparent abundances during the first half of the pupal period. At later stages and in adults, faint mRNA signals were seen in only a few neural clusters; in contrast, relatively strong FRU(M) signals persisted into adulthood. Twenty neuronal groups composed of 1700 fru-expressing neurons were identified in the midpupal CNS. These groups overlap most of the neural sites known to be involved in male courtship. Anti-FRU(COM) led to widespread labeling of neural and nonneural tissues in both sexes, but in the female CNS, only in developing ganglia in a pattern different from that of the male's FRU(M) cells. Expression of sex-specific fru mRNAs in the CNS of males analyzed from the earliest pupal stages indicated that sex-specific alternative splicing is not the exclusive mechanism regulating expression of fruitless transcripts.

Animals↗
PubMed2000

Vasoconstriction following spontaneous sighs and head-up tilts in infants sleeping prone and supine.

The cutaneous vasoconstrictor responses following a 60 degrees head-up tilt and a spontaneous sigh were measured in 36 infants at 1 and 3 months age to investigate the effects of age, sleep state and sleep position on these responses. The vasoconstrictor response was determined by a measure of cutaneous blood flow using a laser Doppler flowmeter. The mean reduction in blood flow (vasoconstriction) was 52% following the tilt, and 33% following the sigh. Prone positioning 1-month-old infants as compared to supine, reduced the degree of vasoconstriction following the tilt (P=0.027) and sigh (P=0.026). The supine to prone reduction was: tilt, -11% in quiet sleep (QS) (from 55.1 to 49.1% vasoconstriction) and -18% in active sleep (AS) (from 52.0 to 42.9%) and; sigh, -26% in QS (35-26%), and -15% in AS (31-26%). The degree of vasoconstriction following the sigh was significantly greater in 3- compared to 1-month-old infants (+26%, P=0.040). The mean response to the tilt in the older age group was 12% greater but this did not reach significance (P=0.069). Sleep state did not affect the degree of vasoconstriction but influenced transmission of the response so that latency to minimal vasoconstriction was 1 s shorter in AS than QS. This study provides data on two simple measures of sympathetic activity during sleep that have not previously been described in any detail in infant studies, and add more evidence that autonomic activity is reduced in the prone position compared to supine during sleep.

Female↗