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G Wilcox

Publications and source records attributed to G Wilcox.

At least 19 recordsLinked to original sources

Patterns of high-grade prostatic intraepithelial neoplasia associated with clinically aggressive prostate cancer.

High-grade prostatic intraepithelial neoplasia (PIN) is the only widely accepted precursor lesion for prostatic adenocarcinoma (PCa). However, the spread of established PCa within prostatic ducts may be indistinguishable morphologically from high-grade PIN. By convention, all cytologically malignant cellular proliferations within prostatic ducts have been lumped into a PIN category, although there have been recent attempts by McNeal to develop reproducible criteria to separate high-grade PIN from the spread of established PCa within prostatic ducts--intraductal carcinoma (IDCa). Using McNeal's criteria for IDCa, we studied whole-mount sections from 252 patients with pT3NO PCa for the presence of IDCa and correlated the presence or absence of IDCa with Gleason score, total tumor volume, surgical margin status, seminal vesicle involvement, and disease progression. Patients with IDCa had higher Gleason score and total tumor volume and were more likely to show seminal vesicle involvement and disease progression than those patients without IDCa. In addition, IDCa was of independent prognostic significance. Total tumor volume and surgical margin status had no independent prognostic significance in this data set.

Adenocarcinoma

Clinical review 92: Phytoestrogens.

We have reviewed the literature regarding the food sources, potency, population intakes, and known biological effects of phytoestrogens in humans using MEDLINE data base from the years 1975-1996. Over 600 articles pertinent to the metabolism of phytoestrogens, including female reproduction (in particular menstruation and menopause), cardiovascular disease, osteoporosis, and cancer were assessed including relevant case control or cohort studies, as well as randomized trials and review articles. Epidemiological studies regarding human data were included, as well as human cell line and animal studies when there were no relevant human data available. We conclude that phytoestrogens exhibit physiological effects in humans. Mild estrogenic changes occur in postmenopausal women. Benefits are seen regarding hypercholesterolaemia. Epidemiological, animal, and in vitro data encourage further assessment of the role of phytoestrogens in cancer prevention.

Cardiovascular Diseases

Visualization of ventricular fibroelastoma with a video-assisted thoracoscope.

Left ventricular papillary fibroelastomas are associated with a high risk of cerebral embolization. Two-dimensional echocardiography and intraoperative transesophageal echocardiography are helpful in diagnosing tumors, planning a surgical approach, and achieving adequate excision. A video-assisted thoracoscope via the left atrium was used to visualize a left ventricular papillary fibroelastoma. Thoracoscopic visualization facilitated excision of a mass within the chordae tendineae between the anterolateral papillary muscle and the left ventricular wall. Video-assisted thoracoscopy greatly facilitates exposure/excision of deeper intracavitary left ventricular masses.

Endoscopy

In vitro and in vivo evidence for a tachykinin NK1 receptor antagonist effect of vapreotide, an analgesic cyclic analog of somatostatin.

Vapreotide, a long-acting somatostatin analog, possesses an analgesic effect. The purpose of this work was to determine a tachykinergic involvement. Vapreotide reduced substance P-induced biting and scratching in mice. This inhibitory effect of substance P action was confirmed by experiments performed on the bronchial apparatus of guinea-pigs known to possess tachykinin NK1 and NK2 receptors. (i) Vapreotide reduced the substance P-induced plasmatic exudation. (ii) It inhibited selectively the tachykinin-dependent second contractile phase induced by electrical field stimulation of isolated bronchi. (iii) It shifted to the right the concentration-effect curve of substance P-induced contraction of isolated main bronchi. The peptide displaced [3H]substance P (IC50 = 3.3 +/- 1.8 x 10(-7) M) from guinea-pig bronchial tachykinin NK1 sites. The displacement of [125I]neurokinin A, a specific tachykinin NK2 receptor ligand, needed higher concentrations (IC50 = 4.5 +/- 0.6 x 10(-6) M). It is concluded that vapreotide possesses an antagonist activity on guinea-pig tachykinin NK1 receptors; the involvement in its analgesic action is discussed.

Acetylcholine

Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat.

Plants contain compounds with oestrogen-like action called phytoestrogens. Soy contains daidzin, a potent phytoestrogen, and wheat flour contains less potent enterolactones. We aimed to show in 58 postmenopausal women (age 54, range 30-70 years) with at least 14 hot flushes per week, that their daily diet supplemented with soy flour (n = 28) could reduce flushes compared with wheat flour (n = 30) over 12 weeks when randomised and double blind. Hot flushes significantly decreased in the soy and wheat flour groups (40% and 25% reduction, respectively < 0.001 for both) with a significant rapid response in the soy flour group in 6 weeks (P < 0.001) that continued. Menopausal symptom score decreased significantly in both groups (P < 0.05). Urinary daidzein excretion confirmed compliance. Vaginal cell maturation, plasma lipids and urinary calcium remained unchanged. Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group.

Adult

A method to perform direct transcutaneous intrathecal injection in rats.

This work describes a method for performing direct intrathecal (i.t.) injections in rats without introducing a spinal catheter. Its ease of use in awake animals yields rapid and reproducible results with no sign of motor impairment. The quality of each injection was ensured by the observation of an injection-induced tail-flick. A 10-microL injection of methylene blue was well localized yielding a very limited diffusion along the spinal cord. The method was validated by demonstrating that morphine (i.t.) had a marked antinociceptive effect and that naloxone (i.t.) blocked the effect of systemic (s.c.) morphine in mononeuropathic rat.

Administration, Cutaneous

Determination of lignans and isoflavonoids in human female plasma following dietary supplementation.

Plasma levels of the lignans enterodiol and enterolactone, and also the isoflavonic phyto-oestrogens daidzein, equol and genistein, are reported for postmenopausal Australian women consuming a traditional diet supplemented with linseed, soya flour or clover sprouts. Analysis was performed by gas chromatography-mass spectrometry, after enzymatic hydrolysis and ion-exchange chromatography. Following linseed supplementation, combined levels of enterolactone and enterodiol reached 500 ng/ml, whereas after soya flour or clover sprouts the respective concentrations of equol, daidzein and genistein reached 43, 312 and 148 ng/ml. Not all subjects were able to produce equol from daidzein. The possible relationship and role of these weak dietary oestrogens as restraining factors in the development of hormone-dependent cancers in Asian populations is discussed.

4-Butyrolactone

Modification of the C terminus of cecropin is essential for broad-spectrum antimicrobial activity.

Cecropin A is a naturally occurring peptide with bactericidal activity against gram-negative and gram-positive bacteria. Production of large quantities of bactericidal peptides that are similar in structure and activity to cecropin A has been achieved by combining recombinant DNA techniques and techniques and chemical modification. Expression of the bactericidal peptide in Escherichia coli was accomplished through the formation of a fusion protein. The 5' end of the L-ribulokinase gene was fused to a single copy of a synthetic gene encoding cecropin A. A methionine codon was engineered between the two genes, and a methionylglycine extension was introduced at the C terminus of cecropin A. Cyanogen bromide treatment of the fusion protein yielded cecropin A with a C-terminal homoserine. The recombinant cecropin A with a homoserine at the C terminus did not kill most gram-positive bacteria tested. However, recombinant cecropin A with a chemically modified C terminus has antimicrobial activity similar to that of cecropin produced by cecropia pupae.

Anti-Bacterial Agents

Mutations in the araC gene of Salmonella typhimurium LT2 which affect both activator and auto-regulatory functions of the AraC protein.

The araC gene encodes a regulatory protein, AraC, that acts as both an activator and a repressor of transcription of the genes involved in the transport and catabolism of L-arabinose in Salmonella typhimurium LT2. Five araC mutants which have altered regulatory properties were characterized. All are point mutations which would result in amino acid substitutions near the C terminus of AraC. Each mutation results in altered activator and auto-regulatory AraC function in vivo. In vitro DNA-binding assays showed that three mutant AraC have measurable lowered affinity for ara controlling site DNA. The data are consistent with a model in which there is a DNA-binding domain in the C terminus of AraC which functions in both activation and repression.

Alleles

Characterization of the Erwinia carotovora peh gene and its product polygalacturonase.

The peh gene, encoding polygalacturonase (Peh), was identified in Erwinia carotovora strain EC and cloned in Escherichia coli. Recombinant Peh (re-Peh) was purified from E. coli strain 706 containing peh on a recombinant plasmid. The activity of the re-Peh protein is optimal at pH 5.5. The N-terminal and internal amino acid (aa) sequences of re-Peh were determined and compared to the aa sequence deduced from the nucleotide (nt) sequence of the cloned peh. The re-Peh has no similarity, based on either the nt sequences or the deduced aa sequences, to pectate lyases from the same Er. carotovora strain or other organisms.

Amino Acid Sequence

Cloning and characterization of the L-rhamnose regulon in Salmonella typhimurium LT2.

A Salmonella typhimurium LT2 cosmid library was constructed, and a 46-kb recombinant plasmid was isolated that could complement an Escherichia coli rha mutant. Subsequent subcloning generated a 13.6-kb ClaI restriction fragment that contained a functional regulatory element. By complementation analyses using different subclones, the approximate physical locations of rhaT, rhaC1, rhaC2, rhaB, rhaA, and rhaD were determined. The nucleotide sequence spanning the rhaB and rhaC2 genes was determined.

Amino Acid Sequence

Improved patient selection for angioplasty utilizing color Doppler imaging.

The accepted approach to patients with intermittent calf claudication is nonoperative unless the symptoms are truly incapacitating, in which case arteriography and either percutaneous angioplasty or operation is indicated. Arteriography is considered a preoperative procedure. However, with improvements in percutaneous angioplasty, we have altered our approach to those patients with limiting, but not incapacitating, claudication. These patients are given the choice of conservative treatment or percutaneous angioplasty, but not operation. In an attempt to limit arteriography to only those patients who would benefit from angioplasty, we have employed color Doppler imaging as a screening technique. Over a 2-year period, 62 patients with limiting claudication were evaluated with color Doppler imaging. Thirty-six patients had long occlusions and did not undergo arteriography since they were not believed to be candidates for percutaneous angioplasty. Three short (less than 5 cm) occlusions and 23 localized stenoses were identified in the superficial femoral and popliteal arteries. Angiography confirmed the Doppler findings in all 26 cases. In 24 patients, dilatation was successful, whereas 2 patients' arteries could not be dilated. Two stenoses recurred early and were redilated. There were no complications from the angioplasties. We conclude that in the subset of patients with limiting, but not incapacitating, claudication, color Doppler imaging can accurately select those patients who will benefit from angioplasty. In this way, patients can be spared unnecessary angiograms.

Angiography

Effect of mutations in the cyclic AMP receptor protein-binding site on araBAD and araC expression.

Maximum expression of the adjacent but divergently transcribed araBAD operon and araC gene requires the presence of cyclic AMP (cAMP) and the cAMP receptor protein (CRP). DNase I protection studies have previously revealed a high-affinity CRP-binding site in the ara regulatory region. Deletion mutations introduced into this site resulted in reduced expression of araBAD and araC. However, other experiments have demonstrated that spacing changes in the ara regulatory region may have multiple effects due to disruption of a DNA loop. Thus, the deletions could have destroyed the CRP-binding site, the ability to form a loop, or both. In the present study, substitution mutations were introduced into the CRP site in order to avoid creating spacing changes. We found that a 3-base-pair substitution resulted in a 30% reduction in araBAD expression, whereas a 6-base-pair substitution resulted in an 80% reduction. Both of these substitution mutations reduced araC expression threefold. We conclude that CRP bound to this site regulates expression in both directions. We found that a spacing change in the CRP site does not alter araBAD expression any more than does a substitution mutation.

Arabinose

Soybean products.

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Chromans