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Biomedical subjects

J A Jones

Publications and source records attributed to J A Jones.

At least 73 records · Page 4Linked to original sources
PubMed1998

Oral/pharyngeal, laryngeal, and lung cancer discharge trends in Department of Veterans Affairs hospitals.

OBJECTIVE: This paper describes trends in oral and pharyngeal (O/P) cancer diagnoses in Department of Veterans Affairs (VA) hospitals from 1983 to 1993 and compares these trends to those of laryngeal and lung cancers. METHODS: The VA patient treatment file was used to identify unique hospital discharges from 1983 to 1993 having ICD-9-CM codes for O/P, laryngeal, and lung cancers. Descriptive statistics were tabulated to determine prevalence and distribution. Trends of change over time were analyzed using regression analyses of the percent rate on year. RESULTS: Between 1983 and 1993 the annual number of O/P cases among users of VA hospitals decreased from 4,983 to 3,298. Despite overall declines in O/P cancer discharges in VA, cancer of the pharynx, tongue, and salivary gland continues to increase. O/P cancer in younger persons also continues to increase in VA. Overall, laryngeal cancers significantly increased, while no significant change was associated with lung cancer. CONCLUSIONS: VA needs to evaluate the changes in the patterns of O/P cancer to ascertain whether this represents a shift in care from inpatient to outpatient care. VA should seek further information regarding these trends to better plan, implement, and evaluate programs to provide early diagnosis and treatment targeted to veterans.

Age Factors↗
PubMed1998

Using oral quality of life measures in geriatric dentistry.

OBJECTIVE: The purpose of this paper is to present potential uses of existing oral-specific quality of life (OQOL) instruments in geriatric dentistry. METHOD: Selected existing OQOL instruments were reviewed. Three examples of how such instruments have or could be used in geriatric dentistry are presented. CONTENT OF REVIEW: Nine OQOL instruments are briefly reviewed. The potential uses in geriatric dentistry include population applications and uses with individuals for political, theoretical and practical reasons. Practical uses include identification of persons needing treatment, assessing oral health needs in populations and estimating resources required to meet those needs, as endpoints in clinical trials and as measures of the impact of care provided. CONCLUSIONS: The ultimate value of OQOL measures will be measured by their usefulness in improving care of patients. The development of streamlined instruments and a core instrument which can be used in multiple populations and serve as a baseline to which other measures are added is recommended.

Activities of Daily Living↗
PubMed1997

Structural and dynamical properties of a denatured protein. Heteronuclear 3D NMR experiments and theoretical simulations of lysozyme in 8 M urea.

Oxidized and reduced hen lysozyme denatured in 8 M urea at low pH have been studied in detail by NMR methods. 15N correlated NOESY and TOCSY experiments have provided near complete sequential assignment for both 1H and 15N resonances. Over 900 NOEs, including 130 (i, i + 2) and 23 (i, i + 3) NOEs, could be identified by analysis of the NOESY spectra of the denatured states, and 3J(HN, Halpha) coupling constants and 15N relaxation rates have been measured. The coupling constant and NOE data were analyzed by comparisons with theoretical predictions from a random coil polypeptide model based on amino acid specific phi,psi distributions extracted from the protein data bank. There is significant agreement between predicted and experimental NMR parameters suggesting that local conformations of the denatured states are largely determined by short-range interactions within the polypeptide chain. This result is supported by the observation that the chemical shift, coupling constant, and NOE data are little affected by whether or not the four disulfide bridge cross-links are formed in the denatured protein. The relaxation data, however, show significant differences between the oxidized and reduced protein. Analysis of the relaxation data in terms of simple dynamics models provides evidence for weak clustering of hydrophobic groups near tryptophan residues and increased barriers to motion in the more compact conformers formed when the polypeptide chain is cross-linked by the disulfide bridges. Using this information, a structural description of these denatured states is given in terms of an ensemble of conformers, which have a complex relationship between their local and global characteristics.

Amino Acid Sequence↗
PubMed1997

Detection of residue contacts in a protein folding intermediate.

Protein folding can be described in terms of the development of specific contacts between residues as a highly disordered polypeptide chain converts into the native state. Here we describe an NMR based strategy designed to detect such contacts by observation of nuclear Overhauser effects (NOEs). Experiments with alpha-lactalbumin reveal the existence of extensive NOEs between aromatic and aliphatic protons in the archetypal molten globule formed by this protein at low pH. Analysis of their time development provides direct evidence for near-native compactness of this state. Through a rapid refolding procedure the NOE intensity can be transferred efficiently into the resolved and assigned spectrum of the native state. This demonstrates the viability of using this approach to map out time-averaged interactions between residues in a partially folded protein.

Animals↗
PubMed1997

Synergy between tamoxifen and cisplatin in human melanoma cells is dependent on the presence of antiestrogen-binding sites.

We have demonstrated previously that cisplatin (DDP) and tamoxifen (TAM) act synergistically to kill human melanoma T-289 cells, and that the observed synergy is lost in the 3-fold TAM-resistant subline, 289/TAM6. We have identified the intracellular antiestrogen-binding sites (AEBSs), defined by their ability to bind antiestrogens while having no affinity for estrogen, as a possible mediator of this synergy. We report here that [3H]TAM binds to AEBSs, as defined by the ability of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl, an AEBS-specific ligand, to compete with [3H]TAM binding. Furthermore, we have characterized the number of binding sites and their affinity for [3H]TAM by Scatchard analysis in whole-cell lysates, microsomal fractions, and nuclear fractions of both cell lines by competing [3H]TAM binding with increasing concentrations of unlabeled TAM. These data demonstrate that the loss of a high-affinity AEBS from the nuclear fraction of the 289/TAM6 cell line correlates with the loss of synergy between DDP and TAM in these cells. This implicates AEBSs as a critical component of the mechanism that mediates the synergistic interaction of DDP and TAM in human melanoma cells.

Binding, Competitive↗
PubMed1997

A phase I and pharmacokinetic study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma.

BACKGROUND: The authors have previously demonstrated that tamoxifen (TAM) is synergistic with cisplatin (DDP) in patients with metastatic melanoma. In vitro studies have demonstrated that TAM/DDP synergy is dependent on a TAM effect that is currently under investigation. In an attempt to improve the complete response rate of this regimen, the authors initiated a Phase I trial to determine the maximum tolerated dose (MTD) of TAM that could be safely administered with weekly DDP. METHODS: TAM was started on Day 1 at a dose of 80 mg/day and was increased by 40 mg to the MTD in groups of 3 patients. DDP (80 mg/m2) was begun on Day 2 and repeated weekly for a total of 3 weeks. During Week 4, the patients were not treated with DDP but instead evaluated for response. If disease stabilization or regression was documented, the patients received a second 3-week cycle of DDP and were then reevaluated for response. Patients with progressive disease were removed from the study. RESULTS: In 25 consecutive patients, the overall response rate was 20%. No responses were observed in patients treated with TAM at a dose of <240 mg/day. Among 13 patients treated at or above this dose, there were 2 complete responses, 3 partial responses, 2 mixed responses, and 6 patients with progressive disease. The overall response rate for patients treated with 240 mg of TAM or higher was 38.5%. Dose-limiting toxicity, which occurred at a TAM dose of 280 mg/day, was primarily hematologic and gastrointestinal in nature. There was one toxic death (due to septic neutropenia) at this dose. There were no episodes of thrombosis. CONCLUSIONS: A TAM dose of 240 mg/day is the recommended Phase II dose. Based on the 38.5% overall response rate at this dose, the authors have initiated a Phase II study.

Adult↗
PubMed1997

Use of DHEA in a patient with advanced prostate cancer: a case report and review.

Dehydroepiandrosterone (DHEA) is being evaluated in the basic science laboratories as a potential treatment for adenocarcinomas, with some initial promise for success. However DHEA can be metabolically converted to androgenic compounds, possessing unwanted side effects. A patient with advanced prostate cancer with progressive symptomatology was treated with DHEA after other treatment regimens failed. Many of his symptoms improved on DHEA therapy, but his cancer also flared dramatically during treatment. His previous hormonally unresponsive cancer subsequently responded transiently to third-line hormonal therapy with diethylstilbestrol (DES). Adrenal precursor molecules such as DHEA may have significant therapeutic benefits in a number of diseases of the elderly, however their utility may be limited by potential androgenic side effects including endocrine epithelial cell growth. The development of analogue compounds with less conversion to androgenic metabolites should be considered, as molecules such as DHEA are more widely tested and utilized clinically.

Aged↗
PubMed1997

Tracking and follow-up of 16,915 adolescents: minimizing attrition bias.

This paper reports a multi-dimensional approach to minimize drop-outs from a two-year follow-up of a clinical trial designed to reduce initiation of tobacco use in 16,915 adolescent orthodontic patients. A hierarchical approach to data collection and tracking was employed. Seventy percent of participants were reached and interviewed at home by telephone. Strategies used to survey remaining participants included calling parents' work numbers and directory assistance, reviewing orthodontists' charts, sending surveys by mail, offering incentives, and using reverse telephone directories. More than 92% of the participants completed follow-up surveys. Multivariate analyses showed that baseline tobacco and alcohol use predicted loss to follow-up. Similarly, the number of procedures used to track each participant predicted presence of risk behaviors at post-test, demonstrating that an organized tracking hierarchy curtailed even greater compromises to internal and external validity. Evaluation and costs of individual strategies are discussed.

Adolescent↗
PubMed1997

Access to psychiatric care; the results of the Pathways to Care study in Preston.

BACKGROUND: The aim of the present research was to study factors that might determine speed of access to psychiatric care, including the effect of the introduction of a community psychiatric service. METHODS: A Pathways to Care analysis was used to detail new referrals to mental health professionals (MHPs) during two one-month intervals one year apart, before and after the introduction of a community service (n = 279). Univariate analysis of possible factors that might affect access was undertaken, including socio-demographic factors, clinical factors and style of service. Significant associations were then investigated using stepwise logistic regression. RESULTS: The inception rate for treatment was similar to that reported for other services (0.10 per cent). After the establishment of community teams, there was an overall 22 per cent increase in the number of patients seen, with the greatest increase being for neurotic disorders and patients seen by non-medical staff. Of patient-based factors, younger age and suicidal ideation were associated with shorter pathways. Older age, married status, somatic symptoms, anxiety and depression were associated with slower pathways. Patients with suicidal ideation were seen within three days. The introduction of a community pathways team was associated with a lengthening of time to specialist care. CONCLUSIONS: Following a non-experimental change in service delivery, an increase in referrals for less severe mental illness was demonstrated. Continued comprehensive data collection of this type can be used by purchasers to monitor referral patterns and can provide a basis for determining priorities in service delivery.

Adolescent↗
PubMed1997

Predictors of tobacco use initiation in adolescents: a two-year prospective study and theoretical discussion.

OBJECTIVE: To test whether baseline data from a randomised clinical trial are predictive of initiation of tobacco use over a two-year follow-up interval, and to discuss results in the context of a theoretical model. DESIGN: Secondary, non-experimental analyses of data collected from a prospective cluster-randomised clinical trial comparing an intervention with a control condition for reduction of tobacco incidence rates. Orthodontic offices in southern California were recruited and randomised to an experimental or control group. Patient participants were sampled within each office, and completed a short survey, repeated two years later. SUBJECTS: 13,923 patients, 11-18 years of age, randomly sampled from each office. MAIN OUTCOME MEASURES: The ability of baseline data to predict initiation of tobacco use over the two-year follow-up interval was tested through a series of logistic regression models. Significant predictors and their interactions were identified in fixed-effects models, and verified in a mixed-effects logistic regression model to account for cluster randomisation. RESULTS: Clinician advice against tobacco use was associated with a lower rate of tobacco use initiation among young people whose peer group considered smoking socially desirable. Rates of initiation increased with age, but this association differed by gender and by whether the adolescent had been offered tobacco within 30 days prior to the baseline assessment. People from minority groups were less likely to initiate tobacco use than whites, and young people engaging in other risk practices were more likely to initiate tobacco use. CONCLUSIONS: Findings support predictions based on learning theory that social processes are critical in the development of health-risk behaviours. Future preventive efforts should target changing the density with which young people encounter pro- and anti-tobacco prompts and consequences in the community.

Adolescent↗
PubMed1996

delta 12-Prostaglandin-J2 is cytotoxic in human malignancies and synergizes with both cisplatin and radiation.

We have been investigating the synergistic cytotoxic interactions between tamoxifen (TAM) and cisplatin (DDP) in human malignant cell lines. Recent data have demonstrated that TAM activates phospholipase D, which can increase the production of prostaglandin D2. Prostaglandin D2 has been shown to have growth inhibitory properties in several malignant cell lines. delta 12-Prostaglandin-J2 (delta 12-PG J2) is a derivative of prostaglandin D2 that has been shown to have similar inhibitory properties. We hypothesized that TAM may increase the production of delta 12-PG J2, which in turn may synergize with DDP. To begin our investigation of this interaction, we sought to determine if delta 12-PG J2 was cytotoxic and synergistic in our melanoma system and then expanded our observations to include a wide range of malignant cells. We have demonstrated that delta 12-PG J2 is cytotoxic to multiple malignant cell lines including melanoma, ovarian, prostate, colon, pancreas, small cell lung cancer, and breast cancer lines. The IC50s ranged from 0.70 microM (small cell lung cancer) to 3.30 microM (DDP-resistant melanoma). Additionally, delta 12-PG J2 exhibited synergistic cytotoxicity with both DDP and ionizing radiation. These data suggest that delta 12-PG J2 should be further evaluated in an in vivo model to confirm activity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Determinants of tamoxifen sensitivity control the nature of the synergistic interaction between tamoxifen and cisplatin.

The cytotoxic effect of tamoxifen (TAM) was investigated in the T-289 melanoma cell line, as well as the 289 DDP3 cisplatin (DDP)-resistant and the 289 TAM6 TAM-resistant variant melanoma cell lines to determine the effect of drug resistance on synergy. T-289 melanoma cells were made DDP or TAM resistant through chronic exposure to increasing concentrations of the respective drugs. Whereas DDP resistance could be overcome by increasing the concentration of TAM, the development of TAM resistance completely abolished synergy. TAM resistance was not related to the development of estrogen receptors, decreased TAM uptake, or the increased expression of the mdr-1 gene. TAM did not inhibit the action of Topoisomerase 1; however, TAM did induce apoptosis in the 289 melanoma cells. In contrast, TAM did not induce apoptosis in the TAM-resistant variant 289 TAM6 cells. To our knowledge, these are the first data associating TAM resistance with the inhibition of apoptosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Enhanced antiopiate activity and enzyme resistance in a peptidomimetic of FMRFamide containing E-2,3-methanomethionine and E-2,3-methanophenylalanine.

FMRFamide is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. Peptidomimetics of FMRFamide substituted with conformationally constrained stereoisomers of Z-2,3-methanomethionine or E-2,3-methanomethionine precipitated abstinence syndrome far more potently than FMRFamide itself. The current study determined the effect on antiopiate potency of an additional rigid substitution. A peptidomimetic containing a stereoisomer of E-2,3-methanomethionine was compared with a peptidomimetic additionally substituted at the C-terminal with E-2,3-methanophenylalanine. Morphine abstinence signs were observed after varying doses (0.125-25.0 micrograms) of these two peptidomimetics were injected into the third ventricle of morphine-dependent rats. The peptidomimetic containing both rigid substitutions was far more potent than the peptidomimetic of FMRFamide containing methanomethionine alone. The increased potency appears to be related to enzyme resistance rather than receptor affinity.

Amino Acid Sequence↗
PubMed1996

Nitric oxide synthesis inhibition attenuates behavioral actions of neuropeptide FF.

Neuropeptide FF (NPFF) has certain antiopiate actions and may play a role in opiate tolerance and dependence. Third ventricle injection of 10 micrograms NPFF induces a quasimorphine abstinence syndrome in opiate-naive rats. Nitric oxide synthesis may also contribute to opiate tolerance and dependence. The present study tests the hypothesis that NPFF acts through stimulation of nitric oxide synthase (NOS). Third ventricular injection of 10 micrograms NPFF precipitated an average of 46 abstinence-like signs during a 20-min observation. Pretreatment (30 min earlier) with 7.5 or 15 mg/kg s.c. of the NOS inhibitor nitro-L-arginine (L-NNA) resulted in a significant and dose-dependent alleviation of NPFF-induced abstinence-like signs. The anti-NPFF activity of 15 mg/kg L-NNA was blocked by 750 mg/kg L-arginine, but not by the same amount of D-arginine, indicating that L-NNA attenuates NPFF activity through a stereospecific inhibition of NOS.

Animals↗
PubMed1996

Complete edentulism and denture use for elders in New England.

The purpose of this study was to collect information about the oral health of a representative group of elders in the New England states. This study provides the most current descriptive analysis of completely edentulous noninstitutionalized elders to date. In-home examinations and interviews were conducted for a representative sample of elders over 70 years of age. The oral examinations and interviews were conducted by calibrated dentists and trained interviewers, respectively. Of 1156 study participants, 424 (36.7%) were edentulous. Edentulous rates were similar for men and women and were negatively related to levels of education and income. Of the completely edentulous individuals, 89.9% had maxillary and mandibular complete dentures. Most of these dentures (83.2%) were worn during the day. More than one third of the respondents reported wearing one or both of their dentures while sleeping at night. For 77 of the completely edentulous individuals, examination revealed denture irritations, most of which were on the hard palate.

Aged↗
PubMed1996

Geriatric oral health and its impact on eating.

OBJECTIVE: Adequate food and fluid intake and nutritional health are requisites for sustaining life. The oral-pharyngeal region has evolved multiple, highly regulated processes to ensure that the intake, chewing, and swallowing of foods and beverages is maintained. The objective of this paper is to identify the independent and collective roles of oral health on eating in older people. DESIGN: Research reports from peer-reviewed scientific journals. Hypothesis-driven research that objectively examined taste, smell, dental and oral mucosal health, dental prostheses, chewing, and swallowing in the context of aging. DATA EXTRACTION AND SYNTHESIS: Data results were extracted independently by multiple observers. A qualitative synthesis of data results from independent studies was made in order to form conclusions regarding the role of oral health on eating in older people. CONCLUSIONS: Many oral functions remain intact in healthy older adults. However, significant alterations arise from oral and systemic diseases and their treatments, and these may have a profound effect on eating, drinking, and the nutritional status of older individuals. The care of older persons with smell, taste, dental/alveolar, oral mucosal, chewing, and swallowing problems requires a multidisciplinary team of health care providers. Recognition of the interrelationship between oral, pharyngeal, and systemic physiological processes will help practitioners identify the etiology of these disorders and implement appropriate therapy.

Aged↗
PubMed1996

Tobacco use prevalence and correlates among adolescents in a clinician initiated tobacco prevention trial in California, USA.

OBJECTIVES: Baseline data for the clinician initiated, tobacco prevention trial, the first non-school based clinician mediated tobacco prevention study, were used to explore the degree to which young people receiving orthodontic treatment use tobacco and the differences in use rates between national, California, and patient samples. Correlates of tobacco use were identified and these correlates were contrasted with findings from the published reports. DESIGN AND SETTING: A 26 item telephone survey assessed demographic information, tobacco use, selected health related behaviours, and variables based on social learning theory. The study was conducted among 11 to 18 year old orthodontic patients from San Diego, Orange, Riverside, San Bernardino, and Los Angeles Counties, California, USA. PARTICIPANTS: Of the 17925 patients who were eligible, 16915 (> 94%) completed the survey. MEASUREMENTS AND MAIN RESULTS: Multivariate analyses were conducted using a logistic mixed effects model. Although the 30 day prevalence rate of tobacco use (6%, n = 1010) proved lower than California and national samples, the rates for the age, gender, and race ethnicity subgroups showed trends similar to those seen in California and national samples. Ten variables were significantly associated with tobacco use (p < 0.05), including 30 day alcohol use (OR = 7.88), age (OR = 1.32), and living with a tobacco user (OR = 1.72). CONCLUSIONS: Because 6% of orthodontic patients use tobacco, interventions are warranted to reach the health "Objectives for the Nation". Patterns of correlates of tobacco use were essentially the same for orthodontic patients, California, and national samples, suggesting that these associations are generalisable.

Adolescent↗