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Biomedical subjects

J Washington

Publications and source records attributed to J Washington.

At least 19 recordsLinked to original sources

Progression of head and neck cancer in an in vitro model.

OBJECTIVE: To identify alterations in angiogenesis and cell cycle regulation as preneoplastic cells progress to cancer in an in vitro model of head and neck tumor progression. METHODS: Immortal human gingival keratinocyte (IHGK) cells (preneoplastic) were derived from normal oral keratinocytes and were immortalized with human papillomavirus 16. Transformation of IHGK cells with a carcinogen (NNK, 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone) gave rise to IHGKN cells. We determined the growth rates, cell cycle phase, expression of cell cycle regulators, and expression of vascular endothelial growth factor along with the organotypic features of these cells and compared them with characteristics of head and neck cancer cells. RESULTS: IHGK and IHGKN cells grown in raft culture were morphologically similar to severe dysplasia and carcinoma, respectively. The proportion of cells in G(0)/G(1) was similar between IHGK and IHGKN. However, the proportion of IHGK cells was 35% greater in S phase as compared with the IHGKN cells, while a greater percentage (40%) of IHGKN cells were in G(2)/M. The expression of the other cell cycle regulators tested was unchanged. IHGK cells secreted less vascular endothelial growth factor on day 1 when compared with IHGKN (50.6 vs 245.6 pg/mL), along with a lower overall production rate (79% vs 133%). CONCLUSIONS: Transformation of IHGK cells resulted in the activation of vascular endothelial growth factor associated with angiogenesis. Inactivation of the G(1) cell cycle regulation occurred during immortalization and before transformation, and was sustained after carcinogen exposure. These alterations correspond to changes observed in patients with head and neck squamous cell carcinoma. This model can be useful in testing novel therapeutic and preventive strategies.

Blotting, Western↗

The possible role of volcanic aquifers in prebiologic genesis of organic compounds and RNA.

In a volcanic aquifer, a wide range of physical and chemical conditions are not merely possible, but to be expected: relatively oxidizing and reducing environments both are present; hot and moderate temperatures can be expected; distillation and reflux conditions are probable to allow concentration of reactants, stimulation of reaction and fractionation of isotopes; apatite, hydroxides, clays and sulfide minerals are present to act as chromatographic media for separating compounds, to serve as catalytic surfaces and to provide potential energy sources; supersaturated precipitation of optically active crystals is reasonable, allowing for chromatographic separation of racemic mixtures by the resulting fixed chiral phase; and saturated and unsaturated conditions both are present for promotion of constructive reactions and inhibiting destructive hydrolysis reactions. Because the multitude of physical-chemical environments makes the setting robust with respect to circumventing commonly identified problems in origin-of-life theories, even if objections to details proposed herein are identified, the setting is favorable for devising alternatives. This paper describes a theory for the genesis of organic compounds, including RNA, in the mixing zone of juvenile and meteoric waters above a leaky semi-confined aquifer. Starting with basic reactants for best-guess conditions on Archean Earth, parallel sequences of specific reactions are proposed that culminate with RNA oligonucleotides, key molecules in contemporary life. All proposed reactions, or close analogues, are experimentally confirmed and all are set in plausible Archean conditions. Calculations indicate that the proposed reactions would yield C isotopic compositions that are consistent with observed biologic C.

Archaea↗

Trends in the antimicrobial susceptibility of bacterial respiratory tract pathogens--findings of the Alexander Project 1992-1996.

The Alexander Project is an ongoing, multicenter surveillance study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens with testing undertaken in a central laboratory. During the period 1992-1995, isolates were collected from geographically separate centers in countries of the EU and various states in the USA. In 1996, the project was extended to centers in Mexico, Brazil, Saudi Arabia, South Africa, Hong Kong and other European countries not previously included. Within Europe, France and Spain are established as centers with a high prevalence of both penicillin-intermediate (MIC 0.12-1 mg/l) and resistant (MIC > or = 2 mg/l) strains of Streptococcus pneumoniae, with combined resistance rates in excess of 40% in Toulouse and Barcelona in 1996. Combined rates of intermediate and resistant strains in excess of 10% were found in 1996, the first year of sampling, in Belgium, Switzerland, the Slovak Republic and Hungary. Penicillin resistance has evolved in the USA during the period of study, with rates for combined pneumococcal isolates increasing from 5.6% in 1992 to 16.4% in 1996. Of the new, non-European centers joining the project in 1996, Mexico (intermediate 31.4%, resistant 15.7%) and, in particular, Hong Kong (intermediate 9.1%, resistant 50%) are centers with a high prevalence of penicillin resistance. Macrolide resistance has increased generally among pneumococcal isolates examined during the study period, both in penicillin-susceptible and resistant isolates, and was evident in 16.5% of the 2160 isolates collected during 1996. In four centers (London, UK; Genoa, Italy; Pokfulum, Hong Kong; Leuven, Belgium), macrolide resistance rates exceeded those of combined penicillin-intermediate and resistant strains; in 12/19 centers (63.2%) macrolide resistance was more prevalent than penicillin resistance. In 1996, macrolide resistance was found in excess of 10% of isolates in Poland, Hungary, London, UK, combined USA isolates, the Slovak Republic, Barcelona, Spain, Genoa, Italy, Mexico, Toulouse, France and Pokfulum, Hong Kong. beta-lactamase production was the principal mechanism of resistance found among isolates of Haemophilus influenzae, with rates in 1996 of around 20% or more in France, Belgium and Spain, and in excess of 10% in the UK and the Czech Republic. In the same year in non-European centers, Mexico (25%), Saudi Arabia (27.9%), Hong Kong (37.1%) and the USA (30.4% of combined isolates) had a high prevalence of beta-lactamase production. Isolates of beta-lactamase-negative, ampicillin-resistant H. influenzae were generally very uncommon, with only Barcelona, Spain consistently associated with rates in excess of 1%. beta-lactamase production in Moraxella catarrhalis was observed in over 90% of isolates tested in 1996.

Anti-Bacterial Agents↗

Prediction of preschool behavioral problems in healthy and pediatric samples.

In a prospective study of 137 children (47 with cystic fibrosis, 48 with congenital heart disease, 42 with no chronic illness), four domains were examined as predictors of parent-reported behavioral problems, particularly internalizing problems, at 4 years of age: child health, child temperament, parent-child relationships, and family environment. Family environment, as measured by the Parenting Stress Index at 1,2, and 3 years, was the most powerful predictor. This suggests that this index is useful as an early screen for children at risk for behavioral problems and that a reduction of parenting stress is an appropriate target of preventive interventions.

Adult↗

Comparison of spiral gradient endpoint and agar dilution methods for susceptibility testing of anaerobic bacteria: a multilaboratory collaborative evaluation.

A multilaboratory collaborative study was carried out to assess the utility of the spiral gradient endpoint (SGE) method for the determination of the antimicrobial susceptibilities of anaerobes and to evaluate the equivalence of the MICs obtained by the SGE method with those obtained by the reference agar dilution method of the National Committee for Clinical Laboratory Standards. The standard deviation of the MIC obtained by the SGE method for the five participating laboratories was +/- 0.26 of a twofold dilution, whereas it was +/- 1 twofold dilution by the reference method. The interlaboratory reproducibility of the results for two control strains tested with imipenem, chloramphenicol, and metronidazole indicated that 96% of the measurements fell within +/- 1 twofold dilution of the mode. The equivalence of the SGE method with the agar dilution method was assessed with a wide variety of anaerobic organisms. The MICs by both methods were within 1 doubling dilution in 93% of the measurements (n = 1,074). Discrepancies generally occurred with those organism-drug combinations that resulted in tailing endpoints (Fusobacterium nucleatum, 86% agreement) or in cases of light growth (Peptostreptococcus spp., 86% agreement).

Agar↗

Infant-mother attachment and nutrition in children with cystic fibrosis.

The association between nutritional status (percentage of weight for height) and infant-mother relationship was studied over 4 years in 38 children diagnosed with cystic fibrosis in the first year of life. Infant-mother relationship was assessed in a standardized laboratory observation. Although they could not be distinguished medically from the others at the time of diagnosis, infants showing a specific form of insecure relationship with their mothers (insecure-avoidant) differed from the others in: (1) failure to improve in nutritional status in the first year; (2) continuing decline in weight for height in the first 3 years; and (3) significantly lower weight for height at 1, 2, and 3 years of age. These data suggest that attention to mother-infant relationships, particularly feeding interactions, may improve nutritional status in children with cystic fibrosis.

Activities of Daily Living↗

Mesolimbic dopamine mediates gastric mucosal protection by central neurotensin.

Bilateral microinjection (1.0 microliter/side) of neurotensin (NT; 0.3, 1.5, and 3.0 micrograms/side) into the nucleus accumbens (NACB) and ventral tegmental area (VTA) but not in substantia nigra and striatum reduced gastric mucosal injury produced by 2 h of cold-water restraint (CWR). The minimal effective dose for NT-induced protection was 10-100 times lower when administered directly into NACB than into the lateral ventricle. These effects were blocked by pretreatment with the dopamine (DA) receptor antagonist, haloperidol (Hal; 0.5 microgram/side) given directly into NACB. Injection of 6-hydroxydopamine into VTA depleted endogenous DA and inhibited gastric mucosal protection against CWR-induced injury afforded by NT pretreatment. NT, given into either VTA and NACB, inhibited pentagastrin-stimulated gastric acid secretion. These results suggest that VTA and NACB, which represent the mesolimbic DA system, are important locations for interaction between NT and DA receptors to produce gastric mucosal protection against CWR-induced injury.

Animals↗

Monoamine oxidase B inhibition reduces gastric mucosal blood flow, basal acid secretion, and cold water restraint-induced gastric mucosal injury in rats.

Inhibition of monoamine oxidase B (MAO B) by selective inhibitors pargyline and L-deprenyl increases dopamine (DA) and norepinephrine (NE) concentrations in nucleus accumbens (NACB) and is associated with reduction in cold water restraint-induced gastric mucosal injury, inhibition of basal gastric acid output, and regional gastric mucosal blood flow. Similar effects were not observed with administration of MAO A inhibitors. These observations suggest that activation of central dopamine and norepinephrine receptors, particularly in NACB, are involved in the control of gastric mucosal function.

Animals↗

Early diagnosed chronic illness and mother-child relationships in the first two years.

As part of a longitudinal study, children in three groups (healthy, n = 33; cystic fibrosis (CF) n = 28; congenital heart disease (CHD) n = 23) were seen between the ages of 12 and 18 months to assess infant-mother attachment and at two years to observe parent-child negotiation of autonomy/dependence in a puzzle task. Although the healthy group included the highest proportion of securely attached infants and the CHD group the lowest, the distribution of attachment patterns did not differ significantly between groups, or between any of the groups and established norms. At two years the healthy children had the most positive experience in the puzzle task while the children in the CF group had the least positive experience. When diagnostic groups were divided according to prior attachment status, the data for the healthy group were consistent with the prediction that securely attached children would have the most positive mother-child interaction at age two. This was not the case in either of the medically diagnosed groups. These data suggest that the influence of the early parent-child relationship may be altered by a child's health status. We may need different models to account for development in healthy and medically compromised children.

Adult↗

Central neurotensin inhibits gastric acid secretion: an adrenergic mechanism in rats.

Although parenteral neurotensin (NT) inhibits stimulated gastric acid secretion, published reports on the effect of centrally administered NT on gastric acid secretion are conflicting. This study provides evidence suggesting that, in chronic gastric fistula rats, intracerebroventricularly administered NT (15-60 micrograms) significantly reduces both basal and pentagastrin-, 2-deoxy-D-glucose-, and carbachol-but not histamine-stimulated gastric acid secretion. Using radioimmunoassay, the concentration of plasma immunoreactive NT increased from 30 to 200 pg/ml at 30 and 60 min, respectively after a single intracerebroventricular (i.c.v.) administration of NT at a dose of 60 micrograms. These serum NT concentrations can be reproduced by a constant NT i.v. infusion at 2 micrograms/kg.h. This parenteral infusion dose does not inhibit acid secretion as does i.c.v. NT. Pretreatment with the i.c.v. dopamine-2 receptor antagonists haloperidol or domperidone totally abolishes the inhibitory effect of i.c.v. NT on pentagastrin-stimulated gastric acid secretion. In contrast, pretreatment with the specific dopamine-1 receptor antagonist SCH 23900 or the specific dopamine-2 receptor antagonist sulpiride does not affect i.c.v. NT-induced inhibition of pentagastrin-stimulated gastric acid secretion. Pretreatment (intracerebroventricularly) with the alpha-adrenergic antagonist phentolamine blocks the antisecretory effect of i.c.v. NT. Administration of 3.0 micrograms NT per side directly into nucleus accumbens (NACB), using a stereotaxic technique, significantly reduces basal gastric acid secretion. This effect of central NT is blocked by pretreatment with intra-NACB haloperidol (0.5 microgram per side). These findings suggest that NT acts centrally to inhibit gastric acid secretion, an effect that may occur within NACB and be mediated by central nervous system alpha-adrenergic receptor activation.

Animals↗

Limited usefulness of quantitative culture of blood drawn through the device for diagnosis of intravascular-device-related bacteremia.

The use of a differential quantitative blood culture technique (Isolator) to diagnose intravascular-device-related bacteremia (IDRB) was studied prospectively. During septic episodes in 44 patients, blood was obtained simultaneously through the suspected infected device and from a peripheral venipuncture. The blood samples were processed by the Isolator technique, which enables easy quantification of microorganisms. The cannula was removed, and its tip was cultured semiquantitatively. Of the 52 cannulas studied, 15 were the cause of IDRB, but only 7 of these showed a significantly higher bacterial count in blood obtained through the device compared with peripheral blood. The bacterial count was higher in blood drawn through the device than in peripheral blood in four of six cases that did not fulfill the definition of IDRB. Some blood cultures obtained through the device were positive despite negative cultures of peripheral blood and cannula tips (six cannulas). Quantitative blood cultures were not useful in diagnosing IDRB in this study.

Adult↗

Continuities and discontinuities in the development of 64 very small premature infants to 4 years of age.

The psychiatric, psychological, school and overall family functioning of 64 very small premature infants was assessed from birth up to 48 mnths of age. Results indicated that 43% of infants scored in the abnormal range on a behaviour rating scale filled in by the mothers and 24% on a teacher rating scale at age 4. However, only 11% of the children received a psychiatric diagnosis. Traditional attachment ratings at 1 yr were not related to psychiatric status at age 4, but family functioning was. Disturbed children had also suffered more perinatal difficulties.

Brain Damage, Chronic↗

Endoscopic measurement of gastric corpus mucosal blood flow in conscious dogs.

This study reports the feasibility of applying the hydrogen gas clearance technique with 3% hydrogen in air and platinum contact electrode to measure corpus mucosal blood flow in conscious dogs. Three percent hydrogen in air is safe and does not produce hypoxia during inhalation. A specially prepared, six-inch polyvinyl chloride pipe was used as a bite-block. The platinum contact electrode, attached to (but not within) a soft rubber suction cup, was passed into the stomach with the aid of a gastroscope. Because of gastric contractions, low, continuous suction was required to maintain the electrode in contact with the corpus mucosa. Stable baseline corpus mucosal blood flow measurements were obtained on control and experimental days in five of 10 dogs. In these five dogs during 2 micrograms/kg/hr pentagastrin infusion, which induced submaximal acid secretion, corpus mucosal blood flow and gastric acid output were increased significantly (P less than 0.05) by 26 +/- 4% and 238 +/- 79%, respectively. These increases were similar to those previously observed in anesthetized rats, cats, rabbits, and dogs. In an anesthetized rat study, the measurement of corpus mucosal blood flow was found to be unaffected by the low continuous suction. Since the use of 3% hydrogen in air is safe, the technique deserves to be further evaluated in human studies.

Animals↗