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Biomedical subjects

R Davis

Publications and source records attributed to R Davis.

At least 37 records · Page 2Linked to original sources

Quantitation of the RNA polymerase II transcription machinery in yeast.

TAP tags and dot blot analysis have been used to measure the amounts of RNA polymerase II transcription proteins in crude yeast extracts. The measurements showed comparable amounts of RNA polymerase II, TFIIE, and TFIIF, lower levels of TBP and TFIIB, and still lower levels of Mediator and TFIIH. These findings are consistent with the presumed roles of the transcription proteins, but do not support the idea of their recruitment in a single large complex to RNA polymerase II promoters. The approach employed here can be readily extended to quantitative analysis of the entire yeast proteome.

Cell Division↗

6-Substituted-4-(3-bromophenylamino)quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases with enhanced antitumor activity.

A series of new 6-substituted-4-(3-bromophenylamino)quinazoline derivatives that may function as irreversible inhibitors of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases have been prepared. These inhibitors have, at the C-6 position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(3-bromophenylamino)quinazoline with unsaturated acid chlorides or mixed anhydrides. We show that attaching a basic functional group onto the Michael acceptor results in greater reactivity, due to intramolecular catalysis of the Michael addition and/or an inductive effect of the protonated basic group. This, along with improved water solubility, results in compounds with enhanced biological properties. We present molecular modeling and experimental evidence that these inhibitors interact covalently with the target enzymes. One compound, 16a, was shown to have excellent oral activity in a human epidermoid carcinoma (A431) xenograft model in nude mice.

Administration, Oral↗

Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study.

BACKGROUND: Accurate data for prevalence rates for heart failure due to various causes, and for left-ventricular systolic dysfunction in all adults are unavailable. Our aim was to assess prevalence of left-ventricular systolic dysfunction and heart failure in a large representative adult population in England. METHODS: Of 6286 randomly selected patients aged 45 years and older, 3960 (63%) participated in the study. They came from 16 randomly selected general practices. We assessed patients by history and examination, electrocardiography, and echocardiography. Prevalence of left-ventricular systolic dysfunction (defined as ejection fraction <40%) and heart failure was calculated for the overall population on the basis of strict criteria and, when necessary, adjudication by a panel. FINDINGS: Left-ventricular systolic dysfunction was diagnosed in 72 (1.8% [95% CI 1.4-2.3]) participants, half of whom had no symptoms. Borderline left-ventricular function (ejection fraction 40-50%) was seen in 139 patients (3.5% [3.0-4.1]). Definite heart failure was seen in 92 (2.3%, [1.9-2.8]) and was associated with an ejection fraction of less than 40% in 38 (41%) patients, atrial fibrillation in 30 (33%), and valve disease in 24 (26%). Probable heart failure was seen in a further 32 (0.8% [0.6-1.1]) patients. In total, 124 (3.1% [2.6-3.7]) patients aged 45 years or older had definite or probable heart failure. INTERPRETATION: Heart failure is often misdiagnosed or underdiagnosed in primary care. Our results suggest that assessment of left-ventricular function in patients with suspected heart failure could lead to more effective diagnosis and treatment of this disorder.

Aged↗

Intranasal immunisation with influenza-ISCOM induces strong mucosal as well as systemic antibody and cytotoxic T-lymphocyte responses.

Intranasal administration of vaccines is preferred for induction of mucosal immune responses. In this study, mice were immunised intranasally and subcutaneously with influenza-immuno stimulating complexes (influenza-ISCOM). The intranasal dose was 15-times the subcutaneous dose. All mice dosed with influenza-ISCOMs survived challenge with live virus and comparable serum antibody and splenic cytotoxic T-lymphocyte responses were detected in both groups. Induction of mucosal IgA was significantly higher with intranasal immunisation and was comparable to responses induced with the heat labile enterotoxin of Escherichia coli as adjuvant. These findings demonstrate that intranasal administration of high dose influenza-ISCOM results in potent systemic and mucosal immune responses.

Adjuvants, Immunologic↗

Interleukin-10 targets p38 MAPK to modulate ARE-dependent TNF mRNA translation and limit intestinal pathology.

Interleukin-10 (IL-10) is a key inhibitory signal of inflammatory responses that regulates the production of potentially pathogenic cytokines like tumor necrosis factor (TNF). We show here that the development of chronic intestinal inflammation in IL-10-deficient mice requires the function of TNF, indicating that the IL-10/TNF axis regulates mucosal immunity. We further show that IL-10 targets the 3' AU-rich elements (ARE) of TNF mRNA to inhibit its translation. Moreover, IL-10 does not alter TNF mRNA stability, and its action does not require the presence of the stability-regulating ARE binding factor tristetraprolin, indicating a differential assembly of stability and translation determinants on the TNF ARE. Inhibition of TNF translation by IL-10 is exerted mainly by inhibition of the activating p38/MAPK-activated protein kinase-2 pathway. These results demonstrate a physiologically significant cross-talk between the IL-10 receptor and the stress-activated protein kinase modules targeting TNF mRNA translation. This cross-talk is necessary for optimal TNF production and for the maintenance of immune homeostasis in the gut.

Animals↗

Calcitonin is a prostate epithelium-derived growth stimulatory peptide.

Locally secreted growth factors and neuropeptides may play an important role in sustaining the growth of hormone-independent prostate cancer. Our previous studies have shown that calcitonin-like immunoreactive peptide (CTI) is secreted by primary prostate cells in culture, and its secretion from malignant prostate cells is significantly higher than benign cells. Exogenously added calcitonin (CT) induces DNA synthesis in serum-starved prostate cancer LNCaP and PC-3M cells. Present studies extended these findings by cloning cDNAs for CT and CT receptor (CT-R) from prostate cancer cells and studying the expression of CT and CT-R mRNA in prostate cancer cell lines and primary prostate tumor specimens. The results have shown that PC-3 cells expressed CT, and not CT-R, mRNA, whereas CT-R, but not CT, mRNA was expressed by LNCaP cells. Conditioned media from PC-3 cells induced DNA synthesis of LNCaP cells, and this mitogenic response was abolished by anti-CT serum. Highly aggressive PC-3M cells co-expressed CT and CT-R mRNAs. CT also induced a twofold increase in DNA synthesis of primary prostate cells and anti-CT serum caused a 56% decline. In-situ hybridization histochemistry of archival prostate specimens has selectively localized CT and CT-R mRNA in basal epithelium of benign and low grade PC specimens, and these mRNAs were not detected in either luminal epithelium or stroma. In contrast, CT and CT-R mRNA were detected throughout the luminal epithelium of moderate and high-grade PC specimens. Most epithelial cells of low and moderately differentiated tumors expressed either CT or CT-R mRNA, suggesting that CT may serve as a paracrine factor. In contrast, CT and CT-R mRNAs were co-expressed by most tumor cells in advanced PC specimens. The cells expressing CT-R mRNA in primary tumors also co-expressed PCNA. These results, when combined with mitogenic actions of CT on primary prostate cells as well as PC cell lines, strongly support the role for CT in sustaining the growth of cancer cells.

Calcitonin↗

Search for B --> tau(nu) and B --> K(nu)nu.

We report results of a search for B-->tau(nu) in a sample of 9.7 x 10(6) charged B meson decays. We exclusively reconstruct the companion B decay to suppress background. We set an upper limit on the branching fraction B(B-->tau(nu))<8.4 x 10(-4) at 90% confidence level. We also establish B(B+/--->K+/-nu(nu))<2.4 x 10(-4) at 90% confidence level.

Journal Article↗

Measurement of the relative branching fraction of upsilon(4S) to charged and neutral B-meson pairs.

We analyze 9.7x10(6) B_B pairs recorded with the CLEO detector to determine the production ratio of charged to neutral B-meson pairs produced at the Upsilon(4S) resonance. We measure the rates for B0-->J/psiK((*)0) and B+-->J/psiK((*)+) decays and use the world-average B-meson lifetime ratio to extract the relative widths f(+-) / f(00) = gamma(Upsilon(4S)-->B+B-) / gamma(Upsilon(4S)-->B0 B-0)) = 1.04+/-0.07(stat)+/-0.04(syst). With the assumption that f(+-)+f(00) = 1, we obtain f(00) = 0.49+/-0.02(stat)+/-0.01(syst) and f(+-) = 0.51+/-0.02(stat)+/-0.01(syst). This production ratio and its uncertainty apply to all exclusive B-meson branching fractions measured at the Upsilon(4S) resonance.

Journal Article↗

First observation of the sigma(*+)(c) baryon and a new measurement of the sigma(*+)(c) mass.

Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.

Journal Article↗

Study of B Decays to Charmonium States: B-->eta(c)K and B --> chi(c0)K.

In a sample of 9.66x10(6)B&Bmacr; pairs collected with the CLEO detector we make the first observation of B decays to an eta(c) and a kaon. We measure branching fractions B(B+-->eta(c)K+) = (0.69(+0.26)(-0.21)+/-0.08+/-0.20)x10(-3) and B(B degrees -->eta(c)K degrees ) = (1.09(+0.55)(-0.42)+/-0.12+/-0.31)x10(-3), where the first error is statistical, the second is systematic, and the third is from the eta(c) branching fraction uncertainty. From these we extract the eta(c) decay constant in the factorization approximation, f(eta(c)) = 335+/-75 MeV. We also search for B decays to a chi(c0) and a kaon. No evidence for a signal is found and we set 90% C.L. upper limits: B(B+-->chi(c0)K+)<4.8x10(-4) and B(B degrees -->chi(c0)K degrees )<5.0x10(-4).

Journal Article↗

Evidence for the neural crest origin of turtle plastron bones.

The migrating cranial neural crest cells of birds, fish, and mammals have been shown to form the membranous bones of the cranium and face. These findings have been extrapolated to suggest that all the dermal bones of the vertebrate exoskeleton are derived from the neural crest ectomesenchyme. However, only one group of extant animals, the Chelonians, has an extensive bony exoskeleton in the trunk. We have previously shown that the autapomorphic carapacial and plastron bones of the turtle shell arise from dermal intramembranous ossification. Here, we show that the bones of the plastron stain positively for HNK-1 and PDGFRalpha and are therefore most likely of neural crest origin. This extends the hypothesis of the neural crest origin of the exoskeleton to include the turtle plastron.

Animals↗

Cell cultures and retroviral particles from a tumor of a moray eel.

Until recently, fish cell culture primarily has been useful only in the propagation and study of epidemic viruses significant to the fishing industry. Such fish cell lines derived were developed by appropriating classical techniques of mammalian cell culture, with serum as the major growth supplement. Using an approach in which culture medium is formulated in a cell-type-specific manner with minimal serum and a variety of synergistic supplements, several fish cell lines have been derived that may serve multiple uses. We established cell lines from a potentially tumorous skin lesion of a green moray eel (Gymnothorax funebris) and control tissues, and identified putative retroviral particles in the medium from the tumor cells that are not present in medium from cultures of normal cells from the same eel. The relationship between the virus and the cause of the tumor is not clear, but the genomic structure of this virus should provide useful information in understanding the evolution of retroviruses in general.

Journal Article↗

Temperature during coronary artery bypass surgery affects quality of life.

BACKGROUND: The objective of this study was to examine the effects of temperature on a variety of indices of psychologic adjustment and quality of life. METHODS: A total of 209 patients randomly received normothermic (warm) or hypothermic (cold) conditions during coronary artery bypass surgery (CABS), and a number of physical, social, and psychologic measures were assessed before as well as 6 weeks and 6 months after CABS. RESULTS: Repeated measures analyses of covariance revealed significant temperature group main effects for anxiety (p = 0.008) and depression (p = 0.039), with the normothermic group obtaining lower anxiety and depression levels than the hypothermic group at both 6 weeks and 6 months after surgery. Additionally, among patients who entered the study with higher depression levels, those in the hypothermic group tended to have higher depression scores at follow-up compared with patients in the normothermic condition (p = 0.012). No temperature group differences were observed on other quality of life indices. CONCLUSIONS: The results of the present study indicate that hypothermic conditions during CABS are associated with higher levels of emotional distress after CABS than normothermic conditions, particularly for patients with greater stress to begin with.

Aged↗

Outpatient radical prostatectomy: impact of standard perineal approach on patient outcome.

PURPOSE: As managed care becomes more prevalent, urologists must critically evaluate the economic aspect of and patient satisfaction with urological practice patterns. We have previously reported the advantages of radical perineal prostatectomy, which decreases hospitalization and morbidity, and provides a more rapid return to normal activity, translating into cost savings. We have since evaluated the satisfaction of patients who underwent outpatient radical prostatectomy with and without laparoscopic pelvic lymph node dissection. MATERIALS AND METHODS: We evaluated the charts of 250 consecutive patients who underwent outpatient radical perineal prostatectomy with less than 24 hours of hospitalization from 1992 to 1997. Complications, pain management, blood transfusion, and bowel and urinary dysfunction were assessed. Validated quality of life questionnaires were mailed to 200 patients several months postoperatively and a 62% response rate was achieved. RESULTS: Mean followup in the series was 30 months. In the perioperative period there were rectal perforation in less than 2% of patients, anastomotic stricture in 3%, perineal fistula in 0.4% and blood transfusion in 11%. Some problems with bowel movements immediately after the procedure, such as diarrhea, constipation or soiled underwear, developed in 17% of patients, of whom up to 20% had had some bowel dysfunction before surgery. In the majority bowel problems resolved in an average of 7.3 weeks. Persistent new onset bowel trouble developed in 9 of the 124 patients (7%). The questionnaire demonstrated persistent significant urinary incontinence in 8 cases (7%). Nerve sparing was attempted in 54 patients, including 22 (41%) who achieve erection sufficient for vaginal penetration and are satisfied with sexual function. Of the patients 17% reported problems after hospital discharge that were mostly related to Foley catheter management. Overall 94.8% of patients were satisfied with treatment. Physical and social/family well-being appeared to be excellent according to the questionnaire. Only 12% of patients would have preferred longer hospitalization. The preferred method of pain control was nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Radical perineal prostatectomy is a low morbidity alternative for localized prostate cancer. Outpatient radical perineal prostatectomy may be performed with good patient satisfaction and safety. There appear to be few bowel problems after long-term followup.

Aged↗

Development of functional electrical stimulators utilizing cochlear implant technology.

In 1983, R. Davis proposed the development of a functional electrical stimulator, based on multi-channel cochlear implant technology, for the restoration of function in spinal cord injured paraplegic subjects. In 1984, the US Veteran Administration funded the initial investigations including animal experiments and purchase of a FES stimulator based on the Nucleus 22 cochlear implant. In 1987, the US Food and Drug Administration approved an Investigational Device Exemption (IDE# G870142) for this FES project. In 1991, the first stimulator was implanted in a 21-year old male paraplegic subject (complete thoracic spinal cord lesion at level #10), who was subsequently able to stand and to perform one-handed tasks for up to 1h. In 1996-1997 development started on a new multi-function FES system. In 1998, a stimulator was implanted in a 35-year-old male paraplegic subject (complete thoracic spinal cord lesion at level #10). After 8 months of use providing multiple functions including bladder voiding, the implant's internal antenna wire broke. A modified implant (FES 24-B) is due to be implanted in July 2001.

Adult↗

Making hand-assisted laparoscopy easier: preventing CO2 leak.

Hand assistance has been a significant advance in making laparoscopy an easier and safer method for certain procedures such as nephrectomy. The value of this technique is realized when comparing patient outcomes (e.g., less postoperative pain, shorter hospital stay, quicker recovery time) with those of the standard open approaches. One reported disadvantage of the Pneumo Sleeve device for hand-assisted laparoscopy is leakage of CO2 gas from around the ring base. We describe in detail our technique to secure the Pneumo Sleeve to the abdomen in such a way as to prevent leakage of intraperitoneal gas and fluid.

Body Fluids↗