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Biomedical subjects

S Taylor

Publications and source records attributed to S Taylor.

At least 181 records · Page 10Linked to original sources
PubMed1998

Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization.

To investigate the possible consequences of uterine contractions (UC) as visualized by ultrasound (US) on in-vitro fertilization (IVF)-embryo transfer outcome, we studied prospectively 209 infertile women undergoing 220 cycles of controlled ovarian stimulation. Inclusion criteria were age < or = 38 years, a morphologically normal uterus, and at least three good quality embryos transferred. Just before embryo transfer, women underwent 5 min digital recordings of the uterus using US image analysis software for UC assessment. Plasma progesterone and oestradiol concentrations were measured. Four groups were defined according to UC frequency: < or = 3.0 (n = 53), 3.1-4.0 (n = 50), 4.1-5.0 (n = 43), and > 5.0 (n = 74) UC/min respectively. Patients, controlled ovarian hyperstimulation and embryology characteristics were comparable in all groups. A stepwise decrease in clinical and ongoing pregnancy rates as well as in implantation rates occurred from the lowest to the highest UC frequency groups (53, 36, 21; 46, 32, 20; 23, 19, 10; and 14, 11, 4%; P < 0.001). Plasma progesterone and UC frequency were negatively correlated (r = -0.34, P < 0.001). Direction of UC did not affect embryo transfer outcome. As this study was controlled strictly for confounding variables and UC were assessed objectively by a computerized system, its results indicate that high frequency UC on the day of embryo transfer hinder IVF-embryo transfer outcome, possibly by expelling embryos out of the uterine cavity. The negative correlation between UC frequency and progesterone concentrations supports the uterine relaxing properties of progesterone.

Chorionic Gonadotropin↗
PubMed1998

Combined bladder closure and epispadias repair in the reconstruction of bladder exstrophy.

PURPOSE: Children with bladder exstrophy in whom initial closure fails are less likely to achieve adequate bladder capacity for later bladder neck reconstruction and continence. Repeat bladder closure may be combined with epispadias repair as initial management, decreasing the need for repeat anesthesia as well as providing increased outlet resistance to permit bladder growth in preparation for later bladder neck reconstruction. We compared results in boys who underwent combined bladder closure and epispadias repair or staged reconstruction. MATERIALS AND METHODS: A total of 16 boys with a mean age of 22 months with bladder exstrophy were referred for bladder closure after previous closure had failed in 15 and for delayed primary closure in 1. Osteotomies were performed in all patients, with bladder closure and epispadias repair as initial treatment. Results were compared to those in 21 boys with a mean age of 26 months in whom exstrophy closure had failed, and who underwent standard staged reconstruction by repeat closure followed by epispadias repair and subsequent bladder neck reconstruction in those who achieved adequate bladder capacity. RESULTS: At a mean followup of 87 months fistula rates were similar in the 2 groups. Eventual bladder neck reconstruction was possible in 69% of the patients in each group. In addition, 2 boys in the combined repair group achieved continence before bladder neck reconstruction was performed. CONCLUSIONS: We recommend epispadias repair combined with bladder exstrophy closure for treating failed exstrophy closure or late initial closure. Operative complications and results are comparable to those in patients in whom previous exstrophy closure failed and who undergo standard staged repair.

Abnormalities, Multiple↗
PubMed1998

Cytoskeletal reorganization by G protein-coupled receptors is dependent on phosphoinositide 3-kinase gamma, a Rac guanosine exchange factor, and Rac.

Reorganization of the actin cytoskeleton is an early cellular response to a variety of extracellular signals. Dissection of pathways leading to actin rearrangement has focused largely on those initiated by growth factor receptors or integrins, although stimulation of G protein-coupled receptors also leads to cytoskeletal changes. In transfected Cos-7SH cells, activation of the chemoattractant formyl peptide receptor induces cortical actin polymerization and a decrease in the number of central actin bundles. In this report, we show that cytoskeletal reorganization can be transduced by G protein betagamma heterodimers (Gbetagamma), phosphoinositide 3-kinase gamma (PI3-Kgamma), a guanosine exchange factor (GEF) for Rac, and Rac. Expression of inactive variants of either PI3-Kgamma, the Rac GEF Vav, or Rac blocked the actin rearrangement. Neither wortmannin nor LY294002, pharmacologic inhibitors of PI3-K, could inhibit the actin rearrangement induced by a constitutively active Rac. The inhibition of cytoskeletal reorganization by the dominant negative Vav variants could be rescued by coexpression of a constitutively active form of Rac. In contrast, a Vav variant with its pleckstrin homology (PH) domain missing constitutively induced JNK activation and led to cytoskeletal reorganization, even without stimulation by PI3-Kgamma. This suggests that the PH domain of Vav controls the guanosine exchange activity of Vav, perhaps by a mechanism regulated by D3 phosphoinositides generated by PI3-K. Taken together, these findings delineate a pathway leading from activation of a G protein-coupled receptor to actin reorganization which sequentially involves Gbetagamma, PI3-Kgamma, a Rac GEF, and Rac.

Actins↗
PubMed1998

Genital ulcers associated with acute Epstein-Barr virus infection.

To date there have been only five reported cases of females with genital ulceration associated with primary Epstein-Barr virus infection. We describe two further patients and review the clinical features of all seven cases, noting the typical features, particularly purple ulcer margins and systemic symptoms, which should alert the physician to consider this diagnosis.

Acyclovir↗
PubMed1998

Fundamental concepts in statistics: elucidation and illustration.

Fundamental concepts in statistics form the cornerstone of scientific inquiry. If we fail to understand fully these fundamental concepts, then the scientific conclusions we reach are more likely to be wrong. This is more than supposition: for 60 years, statisticians have warned that the scientific literature harbors misunderstandings about basic statistical concepts. Original articles published in 1996 by the American Physiological Society's journals fared no better in their handling of basic statistical concepts. In this review, we summarize the two main scientific uses of statistics: hypothesis testing and estimation. Most scientists use statistics solely for hypothesis testing; often, however, estimation is more useful. We also illustrate the concepts of variability and uncertainty, and we demonstrate the essential distinction between statistical significance and scientific importance. An understanding of concepts such as variability, uncertainty, and significance is necessary, but it is not sufficient; we show also that the numerical results of statistical analyses have limitations.

Humans↗
PubMed1998

Effects of antipsychotic treatment on polysomnographic measures in schizophrenia: a replication and extension.

OBJECTIVE: The authors sought to replicate and extend previous observations of improvement in some EEG sleep measures during the course of antipsychotic treatment in schizophrenia patients. METHOD: Fourteen medication-free patients with schizophrenia underwent 2 nights of sleep EEG monitoring before and after 3-4 weeks of treatment with clinically determined doses of haloperidol or thiothixene. RESULTS: Measures of sleep continuity improved consistently. REM latency increased, although five of 14 patients continued to exhibit short REM latencies (less than 60 minutes). Stage 3 sleep increased during neuroleptic treatment, while stage 4 sleep did not change. CONCLUSIONS: These data demonstrate partial improvement of some but not all EEG sleep measures in schizophrenic patients through the course of neuroleptic treatment. They suggest that shortened REM latency and disturbed sleep continuity might represent reversible state abnormalities, while reduced slow-wave sleep may represent a more persistent trait abnormality in schizophrenia.

Adolescent↗
PubMed1998

Extent and appropriateness of benzodiazepine use. Results from an elderly urban community.

BACKGROUND: We sought to determine the extent and appropriateness of benzodiazepine use in an elderly community, by measuring prevalence and incidence of benzodiazepines and examining mental health status as a predictor of benzodiazepine use. METHOD: Data were collected from two longitudinal studies of people from the same community, sampled in 1982-1983 and again in 1989-1991. RESULTS: Benzodiazepine prevalence did not decrease during the period under study, but there was a significant reduction in anxiolytic use. Prevalence of benzodiazepines in women in twice that in men, and incidence of hypnotics is slightly higher in women. Prevalence and incidence of hypnotics are strongly associated with increasing age. There were high proportions of long-term users (61 and 70%), and continued use was high (52%) among new users. A large proportion of benzodiazepine use was by those who were concurrently depressed. Similarly, anxiety predicted both current and subsequent use of hypnotics. CONCLUSIONS: Many older people still use benzodiazepines, contrary to official guidelines with regard to their mental health. Our findings add to the weight of opinion that persistent and long-term use should be discouraged.

Aged↗
PubMed1998

Cyclopropyl indolequinones: mechanistic probes for bioreductive anticancer drug action.

A series of cyclopropyl indolequinones based on structures 5-7 was designed and synthesized to probe the structural features essential for bioreductive cytotoxicity. Ring opening of the cyclopropane ring under radical conditions was demonstrated to be mechanistically feasible, and related to the involvement of such one-electron processes in the cytotoxicity of cyclopropyl indolequinones under hypoxic conditions.

Animals↗
PubMed1997

Two hepatic enhancers, HCR.1 and HCR.2, coordinate the liver expression of the entire human apolipoprotein E/C-I/C-IV/C-II gene cluster.

We show that the liver-specific expression of all four genes in the human apolipoprotein (apo) E/C-I/C-IV/C-II gene cluster in transgenic mice is determined by the coordinate action of two distinct hepatic control regions (HCR). These enhancers are positioned 15 kilobases (kb) (HCR.1) and 26 kb (HCR.2) downstream of the apoE gene. To investigate the action of each HCR, transgenic mice were generated with a 70-kb human genomic fragment that contained the complete apoE gene cluster or with this fragment modified by the specific deletion of HCR.1, HCR.2, or both HCR domains. Hepatic expression of all four apolipoprotein genes was observed in transgenic mice in which either HCR.1 or HCR.2 was deleted, but no transgene expression was found in the liver in the absence of both HCR domains. The overall patterns of transgene expression suggested that HCR.2 was the dominant element for apoC-IV and apoC-II expression and that HCR.1 was dominant for the apoE/C-I expression. No liver-specific transcriptional activity was identified for the proximal promoter of any gene in the cluster; all liver-specific activity was associated with HCR.1 and HCR.2. Thus, the HCRs of the apoE gene cluster constitute unique regulatory domains for determining the requirements for apolipoprotein gene expression in the liver.

Animals↗
PubMed1997

Transgenic mice expressing human ApoB95 and ApoB97. Evidence that sequences within the carboxyl-terminal portion of human apoB100 are important for the assembly of lipoprotein.

The structural features of apolipoprotein (apo) B that are important for its covalent linkage to apo(a) to form lipoprotein(a) (Lp(a)) are incompletely understood. Although apoB100 cysteine 4326 is required for the disulfide linkage with apo(a), other structural features, aside from a single free cysteine residue, must be important for apoB's initial interaction with apo(a) and for facilitating the formation of the disulfide bond. To determine if sequences carboxyl-terminal to cysteine 4326 affect the efficiency of Lp(a) formation, we used "pop-in, pop-out" gene targeting in a human apoB yeast artificial chromosome to introduce nonsense mutations into exon 29 of the apoB gene. The mutant yeast artificial chromosomes, which coded for the truncated versions of human apoB, apoB95, and apoB97, were then used to express these mutant forms of apoB in transgenic mice. As judged by in vitro assays of Lp(a) formation, apoB95 (4330 amino acids) formed a small amount of Lp(a) but did so slowly. In contrast, apoB97 (4397 amino acids) formed Lp(a) rapidly, although not quite as rapidly as the full-length apoB100 (4536 amino acids). These results were supported by an analysis of double-transgenic mice expressing both human apo(a) and either apoB95 or apoB97. In mice expressing both apoB95 and apo(a), there was only a trace amount of Lp(a) in the plasma, and most of the apo(a) was free, whereas in mice expressing both apoB97 and apo(a), virtually all of the apo(a) was bound to apoB97 in the form of Lp(a). These results show that sequences carboxyl-terminal to apoB95 (amino acids 4331-4536) are not absolutely required for Lp(a) formation, but this segment of the apoB molecule, particularly residues 4331-4397, is necessary for the efficient assembly of Lp(a).

Animals↗
PubMed1997

Dual role of a dileucine motif in insulin receptor endocytosis.

Two leucines (Leu986 and Leu987) have recently been shown to take part in the control of human insulin receptor (HIR) internalization (Renfrew-Haft, C., Klausner, R. D., and Taylor, S. I. (1994) J. Biol. Chem. 269, 26286-26294). The aim of the present study was to further investigate the exact mechanism of this control process. Constitutive and insulin-induced HIR internalizations were studied biochemically and morphologically in NIH 3T3 cells overexpressing either a double alanine (amino acid residues 986-987) mutant HIR (HIR AA1) or HIR truncated at either amino acid residue 981 (HIR Delta981) or 1000 (HIR Delta1000). Data collected indicate that: (a) the three mutant HIR show a reduced association with microvilli as compared with HIR wild-type; (b) the two receptors containing the dileucine motif (HIR WT and HIR Delta1000) show the highest propensity to associate with clathrin-coated pits, independently of kinase activation; (c) the two receptors lacking the dileucine motif but containing two tyrosine-based motifs, previously described as participating in clathrin-coated pit segregation, associate with these surface domains with a lower affinity than the two others, (d) in the presence of the kinase domain, an unmasking of the tyrosine-based motifs mediated by kinase activation is required. These results indicate that the dileucine motif is not sufficient by itself, but participates in anchoring HIR on microvilli and that another sequence, located downstream from position 1000 is crucial for this event. This dileucine motif also plays a role in HIR segregation in clathrin-coated pits. This latter function is additive with that of the tyrosine-based motifs but the role of the dileucine motif predominates. Eventually, the clathrin-coated pit anchoring function of the dileucine motif is independent of receptor kinase activation in contrast to the tyrosine-based motifs.

3T3 Cells↗
PubMed1997

Phase II study of induction and adjuvant chemotherapy for squamous cell carcinoma of the head and neck. A long-term analysis for the Illinois Cancer Center.

BACKGROUND: In 1982, the Illinois Cancer Center initiated a Phase II trial in which the following treatment was administered: Induction chemotherapy (cisplatin and infusional 5-fluorouracil [5-FU]) was administered before definitive local therapy. Definitive local therapy, consisting of surgery, radiation, or both, was followed by three cycles of the same chemotherapy program. METHODS: Eligible patients had Stage III or IV squamous cell carcinoma of the head and neck with no distant metastases. Three cycles of induction chemotherapy were given. Cisplatin, 100 mg/m2, was infused over 60 minutes on Day 1; thereafter, 5-FU (1000 mg/m2/day) was given continuously for 5 days. Cycles were repeated at 3-week intervals. Local therapy was individualized, according to tumor stage and site. Patients who responded were to receive an additional three cycles of chemotherapy after surgery or radiation. RESULTS: Eighty-one patients were entered into the trial, and 71 were considered both eligible and evaluable. After induction chemotherapy, 59 patients (83%) responded, 23 of whom experienced complete response. Sixty-nine patients completed definitive local treatment, but only 22 proceeded to the planned adjuvant cycles of treatment. Median follow-up of surviving patients was 12 years. At last follow-up, 13 patients were alive and free of malignancy, 9 of whom never had disease recurrence or a second primary tumor. These 13 patients had an acceptable quality of life, were ambulating, and were fully capable of caring for themselves. Overall, nine patients had second primary malignancies. Thirty-four percent of patients were alive at 5 years, and 21% were alive at 10 years. Of 58 deaths, 44 resulted from progressive disease and 8 resulted from second primary cancers. Four patients died of unrelated causes, and two suffered lethal acute toxicity from the chemotherapy program. Late toxicity was moderate. Among 23 patients surviving at least 6 years, there were 3 cases of hypothyroidism, presumed to be secondary to radiation. Xerostomia was modest, consistent with usual radiation effects. Of the 13 patients who were alive and free of malignancy at last follow-up, none had clinical manifestations of serious late end organ toxicity. CONCLUSIONS: During long term follow-up after multimodal treatment of locally advanced squamous cell carcinoma, no obvious benefit was observed from the chemotherapy component of the treatment regimens rendered. Only 21% of patients achieved 10-year survival with the following causes of failure, in descending order of frequency: disease recurrence, second malignancies, other medical problems, and treatment-related deaths. The results of this trial are consistent with the results of other induction chemotherapy trials, indicating the need for innovative treatment strategies. These data do not support the continued use of induction chemotherapy with the cisplatin and infusional 5-FU program.

Adult↗
PubMed1997

Segmentation, not rhyming, predicts early progress in learning to read.

We present a longitudinal study of children in the first two years of learning to read. A battery of tests of phonological skills administered when the children were prereaders identified two distinct and relatively independent factors, Rhyming (defined by measures of rhyme detection and rhyme production) and Segmentation (defined by measures of phoneme identification and phoneme deletion). Segmentation was strongly correlated with attainment in reading and spelling at the end of the first year at school, though Rhyming was not. In addition, letter name knowledge predicted both reading and spelling skill and showed an interactive effect with children's segmentation skills. By the end of the second year of school, however, rhyming had started to exert a predictive effect of spelling, but not on reading. The results are discussed in the context of current theories of the role of phonological skills in learning to read.

Achievement↗
PubMed1997

A normative study of the maintenance of wakefulness test (MWT).

The maintenance of wakefulness test (MWT) is a daytime polysomnographic procedure which quantifies wake tendency by measuring the ability to remain awake during soporific circumstances. We present normative data based on 64 healthy subjects (27 males and 37 females) who adhered to uniform MWT procedural conditions including polysomnographic montage, illuminance level, seating position, room temperature, meal timing, and subject instructions. When allowed a maximum trial duration of 40 min, subjects' mean sleep latency to the first epoch of sustained sleep was 35.2 +/- 7.9 min. The lower normal limit, defined as two standard deviations below the mean, was 19.4 min. Calculation of data on the basis of a maximum trial duration of 20 min and sleep latency to the first appearance of brief sleep (a microsleep episode or one epoch of any stage of sleep) yielded a mean sleep latency of 18.1 +/- 3.6 min and a lower normal limit of 10.9 min. Sleep latency scores were significantly higher than those previously reported in patients with disorders of excessive somnolence. Therefore, the MWT appears to be a useful procedure in differentiating groups with normal daytime wake tendency from those with impaired wake tendency and in identifying individuals with pathologic inability to remain awake under soporific circumstances.

Adult↗
PubMed1997

A longitudinal study of early intellectual development in hemiplegic children.

Thirty-eight 3- to 5-year-old children with unilateral lesions sustained pre- or peri-natally were studied longitudinally over a 2-year period, and their IQ scores compared with those of 20 "medical' controls. The failure to discover laterality effects following early unilateral injury supports the hypothesis of at least broad functional equipotentiality. There were few decrements in intellectual functioning provided the injury was not accompanied by seizures. The presence of seizures in contrast had a deleterious effect on both verbal and nonverbal aspects of cognitive functioning. While the IQs of the hemiplegic groups showed considerable stability over the 2-year span of the study, there was evidence that performance IQ, even in seizure-free patients, might be selectively impaired because of competition within the intact neural space for the sparing of verbal IQ.

Analysis of Variance↗
PubMed1997

Liver hemostasis using high-intensity focused ultrasound.

Liver hemorrhage, the major cause of death in hepatic trauma, is notoriously difficult to control. We report on the use of high-intensity focused ultrasound (HIFU) to arrest the bleeding from incisions made in rabbit livers. A HIFU transducer, with a spherically curved aperture of 6.34 cm2 area, a focal length of 4 cm and a frequency of 3.3 MHz was used. In approximately 94% of the incisions, the hemorrhage was reduced to a slow oozing of blood in less than 2 min. The maximum temperature of liver tissue around the incision area, during HIFU application, was measured to be 86 degrees C. The mechanism of hemostasis, confirmed by histological examination, appears to be coagulative necrosis of a volume of liver tissue around the incision. We believe that acoustic hemostasis, with the unique characteristic of "volume cauterization," offers a novel method for the management of liver hemorrhage and, thus, has major clinical implications.

Animals↗