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John Hines

Publications and source records attributed to John Hines.

17 recordsLinked to original sources
PubMed2006

Microfabrication of screen-printed nanoliter vials with embedded surface-modified electrodes.

A self-contained ion-selective sensing system within a nanoliter-volume vial has been developed by integrating screen printing, laser ablation, and molecular imprinting techniques. Screen printing and laser ablation are used in tandem to fabricate nanoliter-volume vials with carbon and Ag/AgCl ring electrodes embedded in the sidewalls. Using multisweep cyclic voltammetry, the surface of the carbon electrode can be modified with a polypyrrole film. By polymerizing pyrrole in the presence of nitrate, pores complementary to the nitrate anion in size, shape, and charge distribution are formed in the resulting film. Electrochemical cells modified with this nitrate-imprinted polypyrrole film show a near-Nernstian response to nitrate, and excellent reproducibility. The integration of molecular recognition and electrochemical response in the nanoliter vials is demonstrated by the detection of as little as 0.36 ng nitrate in nanoliter-volume samples. The integration of tailored molecular recognition within nanoliter vials via established fabrication and imprinting protocols should result in a number of nanosensor devices with applications in BioMEMS and micro total analysis systems.

Electrochemistry↗
PubMed2006

Myriaporone 3/4 structure--activity relationship studies define a pharmacophore targeting eukaryotic protein synthesis.

Myriaporones are naturally occurring compounds which structurally resemble the southern hemisphere of the tedanolide family of macrolide antitumor agents. Despite the fact that myriaporone 3/4 represents only a portion of tedanolide, it nonetheless retains much of its biological activity. We show here that like tedanolide, myriaporone 3/4 inhibits protein synthesis and proliferation of mammalian cells with low nanomolar potencies but displays no prokaryotic growth inhibitory effect. Moreover, myriaporone 3/4 displays a very rapid, reversible and p21-independent activity to block S phase progression in mammalian cells. Structure-activity relationship studies revealed that the C18-C19 epoxide and the C14 hydroxymethyl group (tedanolide numbering) of myriaporone 3/4 are required for cell cycle inhibition. These constitute previously unidentified and/or novel pharmacophores for myriaporone 3/4. Our results show that the important biological activities associated with the structurally complex tedanolides are present and can be harnessed in the chemically much simpler myriaporones. This greatly increases the value of the latter as investigative tools for biochemical research as well as for development of potential therapeutics.

Animals↗
PubMed2006

Neurotrophic peptide aldehydes: solid phase synthesis of fellutamide B and a simplified analog.

A combination of solid phase and solution phase synthetic methods have been used to complete the total synthesis of the neurotrophic lipopeptide aldehyde fellutamide B (2). The beta-hydroxy aliphatic tail was prepared by regioselective reductive opening of a cyclic sulfate, and later coupled to a solid phase resin. The synthetic compound was then examined in cytotoxicity and nerve growth factor (NGF) induction assays. A simplified analog of fellutamide B also showed activity.

Aldehydes↗
PubMed2005

Developing microcolin A analogs as biological probes.

Three microcolin A and B analogs have been synthesized. Their biological activity profiles were evaluated against several cell lines, revealing the existence of a structural determinant whose role in mediating the antiproliferative effect of the microcolins has heretofore gone unrecognized. While previously described as potent immunosuppressive natural products, we found that these microcolin analogs possessed no selective cytotoxicity when comparing immune cell versus nonimmune cell proliferation. In addition, the amino-terminus of microcolin A has been modified to incorporate a biotinylated polyethylene glycol linker. The biological activity of this biotinylated microcolin A analog was determined. This affinity reagent was shown to retain limited biological activity and thus can serve as a useful probe for elucidating the mechanism of action of microcolin A.

Animals↗
PubMed2005

Identification of a molecular recognition role for the activation loop phosphotyrosine of the SRC tyrosine kinase.

A human cDNA phage display library screen, using a phosphopeptide designed to mimic the activation loop phosphotyrosine of the Src tyrosine kinase, has identified the N-terminal SH2 domain of the p85 regulatory subunit of phosphatidyl inositol-3 kinase (PI3K) as an interacting recognition domain. Activation loop phosphorylation is known to play a conformational role in kinase activation, but is largely not thought to play a role in protein/protein recognition. Affinity chromatography and biochemical evaluation in mouse fibroblast cells has confirmed the dependence of this interaction on both the Src activation loop phosphotyrosine and the N-terminal SH2 domain of PI3K.

Animals↗
PubMed2005

Small molecules driving myotube fission.

In this issue of Chemistry & Biology, Duckmanton et al. have rigorously studied myotube fragmentation, or "cellularization," triggered by microtubule-disrupting agents. They convincingly demonstrate that cellularization remains integral to myogenic dedifferentiation, but is insufficient for reentry of the mononucleate progeny into the cell cycle.

Animals↗
PubMed2003

Structural determinants for the activation mechanism of the angiotensin II type 1 receptor differ for phosphoinositide hydrolysis and mitogen-activated protein kinase pathways.

While the mechanism whereby the angiotensin II type 1 receptor (AT(1) receptor) activates its classical effector phospholipase C-beta (PLC-beta) has largely been elucidated, there is little consensus on how this receptor activates a more recently identified effector, the p42/44 mitogen-activated protein kinases (p42/44(MAPK)). Using transfected COS-1 cells, we investigated the activation of this signaling pathway at the receptor level itself. Previous mutational studies that relied on phosphoinositide turnover as an index of receptor activation have indicated that key residues in the second and seventh transmembrane domains participate in AT(1) receptor activation mechanisms. Thus, we introduced a variety of mutations-AT(1)[D74N], AT(1)[Y292F], AT(1)[N295S], and AT(1)[AT(2) TM7], which is composed of a chimeric substitution of the AT(1) seventh transmembrane domain with its AT(2) counterpart. These mutations that strongly diminished the receptor's ability to activate PLC-beta had little to no effect on its ability to activate p42/44(MAPK), which not only suggests that p42/44(MAPK) does not exclusively lie downstream of the G-protein G(q)/PLC-beta pathway but also indicates that more than one activation state may exist for the AT(1) receptor. The failure of a protein kinase C inhibitor to block AT(1) receptor activation of p42/44(MAPK) further corroborated evidence that the receptor's activation of p42/44(MAPK) is largely independent of the G(q)/PLC-beta/PKC pathway. Taken together, the experimental evidence strongly suggests that the mechanism whereby the AT(1) receptor activates p42/44(MAPK) is fundamentally different from that for PLC-beta, even at the level of the receptor itself.

Animals↗
PubMed2003

5-year outcome of a prospective randomized trial to compare transurethral electrovaporization of the prostate and standard transurethral resection.

OBJECTIVES: To update our prospective randomized trial comparing the safety, efficacy, and durability of transurethral electrovaporization of the prostate (TUVP) using the VaporTrode with standard transurethral resection of the prostate (TURP). METHODS: A total of 104 patients, taken from the waiting list for surgery for benign prostatic hyperplasia were randomized to TUVP (52 patients, mean age 67.5 years) or TURP (52 patients, mean age 70.2 years). In each group, 51, 47, and 40 patients completed 1, 2, and 3 years of follow-up, respectively. Of the 104 patients, 27 TURP and 26 TUVP patients completed 5 years of follow-up. RESULTS: Both groups were comparable in terms of the mean preoperative International Prostate Symptom Score, quality-of-life score, maximal urinary flow rate, and postvoid residual volume. The follow-up data at 5 years showed a significant and maintained improvement in the mean International Prostate Symptom Score (TUVP: 5.9 +/- 6.3 versus TURP: 8.6 +/- 7.1, P = 0.16), quality-of-life score (TUVP: 1.1 +/- 1.2 versus TURP: 1.7 +/- 1.4, P = 0.09), and mean maximal urinary flow rate (TUVP: 21 +/- 9 mL/s versus TURP: 17.9 +/- 13.1 mL/s, P = 0.17), with decreases in the mean postvoid residual volume (TUVP: 27.3 +/- 44.3 mL versus TURP: 10.7 +/- 13.1 mL, P = 0.08). Two patients in each group (4%) developed urethral strictures. Two TURP patients (4%) developed bladder neck strictures compared with one TUVP patient (2%). In each arm, 7 patients (13%) underwent reoperation during a 5-year period (approximate reoperation rate: 3% in each arm per year). Postoperatively and during 3 years of follow-up, impotence was reported in 17% of the TUVP group and 11% of the TURP group (P = 0.49); retrograde ejaculation was reported in 72% of the TUVP group and 89% of the TURP group (P = 0.47). CONCLUSIONS: Our 5-year follow-up results confirm that TUVP is as effective as standard TURP in the treatment of moderate-size benign prostatic hyperplasia. The reoperation rate and long-term complication rate are comparable and the initial improvement has been maintained during a 5-year period for most patients in both groups.

Adenocarcinoma↗
PubMed2003

Modified external needle drainage procedure for rhegmatogenous retinal detachment.

PURPOSE: To describe the results of a modified external needle subretinal fluid drainage technique to treat eyes with a rhegmatogenous retinal detachment. METHODS: One hundred eighty-seven consecutive patients with a rhegmatogenous retinal detachment who underwent scleral buckle and modified external needle drainage at Duke Eye Center or Vistar Eye Associates were included in this study. Subretinal fluid was drained by a technique whereby the intraocular pressure was raised to a supranormal level by tightening an encircling scleral buckle and then the subretinal space was entered by a needle introduced externally while the retina was directly viewed with an indirect ophthalmoscope. Subretinal fluid drainage success rate, one-operation reattachment rate, final retinal reattachment rate, intraoperative and postoperative complication rates, and final visual acuity were the main outcome measures. RESULTS: Subretinal fluid was successfully drained in all eyes. The one-operation reattachment rate was 91%, and the final reattachment rate was 98%. Intraoperatively, 15% of eyes required corneal debridement to obtain an adequate view for safe subretinal fluid drainage. Subretinal hemorrhage of no more than one clock hour occurred in 4.2% of eyes. A total of 2.6% of eyes developed an epiretinal membrane postoperatively that required a vitrectomy to improve the visual acuity. The postoperative visual acuity, 0.54 by logMAR (20/69 by Snellen), was significantly better than the preoperative visual acuity, 1.1 logMAR (20/250 by Snellen) (P < 0.0001). CONCLUSIONS: The modified external needle drainage technique is a flexible, effective method to drain subretinal fluid in eyes with a rhegmatogenous retinal detachment. The retinal reattachment rate and complication rate compare favorably to alternative subretinal fluid drainage techniques.

Body Fluids↗
PubMed2002

Total synthesis of luminacin D.

[reaction: see text] A highly convergent synthesis of the angiogenesis inhibitor luminacin D has been achieved in 13 linear steps (19 steps total, 5.3% overall yield) utilizing a samarium(II) iodide-mediated mixed tandem aldol/Evans-Tishchenko reaction to construct the carbohydrate precursor. The modular synthetic design will allow derivatization at key positions necessary for biochemical mode of action studies.

Angiogenesis Inhibitors↗
PubMed2002

Analysis of age, estimated creatinine clearance and pretreatment hematologic parameters as predictors of fludarabine toxicity in patients treated for chronic lymphocytic leukemia: a CALGB (9011) coordinated intergroup study.

PURPOSE: Fludarabine is a renally excreted agent that is an effective treatment for chronic lymphocytic leukemia (CLL), a disease predominantly of the elderly. We sought to determine whether age, renal function or pretreatment hematologic status predicted toxicity of fludarabine treatment for CLL. METHODS: We evaluated 192 patients with previously untreated B-cell CLL who were entered onto the fludarabine treatment arm (25 mg/m(2) daily for 5 days every 28 days) of CALGB study 9011, an intergroup study with participation from SWOG, CTG/NCI-C and ECOG. Patients were required to have serum creatinine within 1.5 times normal. Hematologic indices and infections were recorded during the first 28-day cycle of treatment. A time-to-toxicity endpoint was evaluated over the entire course of fludarabine treatment. Creatinine clearance (CrCl(est)) was estimated using serum creatinine, age and body mass index. RESULTS: The median age was 64 years (range 37-87 years) and median CrCl(est) was 62 ml/min (range 27-162 ml/min, interquartile range 52-79 ml/min). We found no association between age and incidence of hematologic toxicity or infection during the first cycle of treatment. There was a strong association between CrCl(est) and the time-to-toxicity endpoint. Patients with CrCl(est) below 80 ml/min had increased incidence of toxicity during their treatment course ( P<0.0001). Pretreatment anemia, thrombocytopenia and Rai stage were highly associated with the incidence of neutrophil toxicity and grade III/IV hematologic toxicities during the first cycle of treatment ( P<0.0001). CONCLUSIONS: Patient age was not an independent risk factor for fludarabine-related toxicity, but CrCl(est) was associated with time to toxicity.

Adult↗
PubMed2002

Mesenteric adenitis: CT diagnosis of primary versus secondary causes, incidence, and clinical significance in pediatric and adult patients.

OBJECTIVE: Our objective was to determine the clinical significance of mesenteric adentitis when detected on CT. MATERIALS AND METHODS: Mesenteric adenitis was considered present if a cluster of three or more lymph nodes measuring 5 mm or greater each was present in the right lower quadrant mesentery. If no other abnormality was detected on CT, then mesenteric adenitis was considered primary. If a specific inflammatory process was detected in addition to the lymphadenopathy, then mesenteric adenitis was considered secondary. Patients with a known neoplasm or HIV infection were excluded. Three separate groups of patients were examined for the presence and cause of mesenteric adenitis. Group 1 consisted of 60 consecutive patients prospectively identified with mesenteric adenitis on CT examinations. Group 2 consisted of 60 consecutive patients undergoing abdominal and pelvic CT for evaluation of blunt or penetrating abdominal trauma. Group 3 consisted of 60 consecutive patients undergoing abdominal and pelvic CT with acute abdominal symptoms. In all patients, the indication for imaging was documented, and the size of the largest lymph node, when present, was measured. In patients with mesenteric adenitis, the CT findings, clinical history, and clinical or surgical follow-up were subsequently evaluated to determine the cause of mesenteric adenitis. RESULTS: In the 60 patients prospectively identified with CT findings of mesenteric adenitis (group 1), 18 (30%) of 60 had primary mesenteric adenitis. The remaining 42 patients (70%) had an associated inflammatory condition that was established on CT as the likely cause of mesenteric adenitis. Mesenteric adenitis was present in none (0%) of the 60 patients in group 2 and in five (8.3%) of 60 patients in group 3. CONCLUSION: The incidence of mesenteric adenitis in patients with and those without abdominal pain is low. When evidence of mesenteric adenitis is present on CT examinations, usually a specific diagnosis can be established as its cause.

Abdomen, Acute↗