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Biomedical subjects

J L Jones

Publications and source records attributed to J L Jones.

At least 73 records · Page 4Linked to original sources
PubMed1999

Integrins: a role as cell signalling molecules.

Integrins form the major family of proteins that mediates cell-matrix interactions. As well as an adhesive function, it is increasingly apparent that integrins can transduce messages via classic signalling pathways and impact upon such fundamental cellular processes as proliferation, apoptosis, differentiation, and motility. Dysregulation of these processes are a feature of many malignancies. Altered integrin expression has been observed in many human tumours, and perturbation of integrin function or expression in experimental systems has demonstrated that altered integrin signalling may directly contribute to the development of the malignant phenotype.

Cell Physiological Phenomena↗
PubMed1998

Relative efficacy of monophasic and biphasic waveforms for transthoracic defibrillation after short and long durations of ventricular fibrillation.

BACKGROUND: Recently, interest has arisen in using biphasic waveforms for external defibrillation. Little work has been done, however, in measuring transthoracic defibrillation efficacy after long periods of ventricular fibrillation. In protocol 1, we compared the efficacy of a quasi-sinusoidal biphasic waveform (QSBW), a truncated exponential biphasic waveform (TEBW), and a critically damped sinusoidal monophasic waveform (CDSMW) after 15 seconds of fibrillation. In protocol 2, we compared the efficacy of the more efficacious biphasic waveform from protocol 1, QSBW, with CDSMW after 15 seconds and 5 minutes of fibrillation. METHODS AND RESULTS: In protocol 1, 50% success levels, ED50, were measured after 15 seconds of fibrillation for the 3 waveforms in 6 dogs. In protocol 2, defibrillation thresholds were measured for QSBW and CDSMW after 15 seconds of fibrillation and after 3 minutes of unsupported fibrillation followed by 2 minutes of fibrillation with femoral-femoral cross-circulation. In protocol 1, QSBW had a lower ED50, 16.0+/-4.9 J, than TEBW, 20.3+/-4.4 J, or CDSMW, 27.4+/-6.0 J. In protocol 2, QSBW had a lower defibrillation threshold after 15 seconds, 38+/-10 J, and after 5 minutes, 41.5+/-5 J, than CDSMW after 15 seconds, 54+/-19 J, and 5 minutes, 80+/-30 J, of fibrillation. The defibrillation threshold remained statistically the same for QSBW for the 2 fibrillation durations but rose significantly for CDSMW. CONCLUSIONS: In this animal model of sudden death and resuscitation, these 2 biphasic waveforms are more efficacious than the CDSMW at short durations of fibrillation. Furthermore, the QSBW is even more efficacious than the CDSMW at longer durations of fibrillation.

Animals↗
PubMed1998

Synthesis and antitumor activity of 4-aminomethylthioxanthenone and 5-aminomethylbenzothiopyranoindazole derivatives.

Two new series of antitumor agents, 4-aminomethylthioxanthenones (6-50) and 5-aminomethylbenzothiopyranoindazoles (51-61), are described and compared. Nearly all members of both series display excellent in vivo activity versus murine pancreatic adenocarcinoma 03 (Panc03) although there is little to distinguish the two series from each other. In both series there is no discernible relationship between structure and in vivo efficacy. Selected analogues were evaluated in vitro; all were observed to have moderate to strong DNA binding via intercalation. However, varying degrees of in vitro P388 cytotoxicity and topoisomerase II inhibition were seen. In general, those molecules which exhibited strong topoisomerase II inhibition were significantly more cytotoxic than those which did not. In both series, those derivatives (48-50, 60, and 61) having a phenolic hydroxy substitution exhibited the most potent P388 cytotoxicity and topoisomerase II inhibition.

Adenocarcinoma↗
PubMed1998

Improved internal defibrillation success with shocks timed to the morphology electrogram.

BACKGROUND: A previous retrospective study by our group suggested that shocks timed to the upslope of the shocking lead electrogram improved defibrillation efficacy. The goal of this study was to prospectively determine whether defibrillation threshold could be reduced by use of an algorithm that timed shocks to the upslope of coarse ventricular fibrillation (test treatment) compared with shocks delivered asynchronously after 10 seconds of fibrillation (control treatment). METHODS AND RESULTS: Ten pigs were instrumented with a 3-lead system for internal defibrillation. Initial estimates of the energy required to achieve defibrillation E50 for both treatments were made by an up/down method. Subsequently, additional shocks at V50+/-10% and V50-20% were given for each treatment to obtain data points at higher and lower intensities. Probability-of-success curves were estimated for both treatments by the best-fit method. Energies required were significantly lower for the timed shocks than for the asynchronous shocks (P<0.00 1). E80 was reduced 15.5%, from 27.1+/-2.5 to 22.9+/-1.8 J (P<0.002). The width of the probability-of-success curve (E80-E20) for the test treatment was also significantly narrower than that for the control treatment (7.1+/-0.9 versus 10.8+/-1.7, P<0.01). Normalized curve width (E80-E20)/E50 was decreased from 51+/-5% of E50 for control shocks to 37+/-4% of E50 for synchronous shocks (P<0.02). CONCLUSIONS: In this model, defibrillation threshold is lower and more deterministic when shocks are timed to the upslope of the shocking lead electrogram. If a similar reduction is observed in humans, shock timing may lower defibrillation threshold and simplify programming of shock intensity.

Algorithms↗
PubMed1998

Trends in zidovudine prescription for pregnant women infected with HIV.

OBJECTIVE: The purpose of this analysis was to describe trends in zidovudine prescription during pregnancy among women infected with HIV. METHODS: We used data from the Adult and Adolescent Spectrum of Disease Surveillance Project, which collects information on HIV-related conditions through medical record review. Women who were reported pregnant from 1990 through 1996 were included in the analysis. RESULTS: From 1990 through 1996, of 7047 women in the project, 714 (10%) were pregnant for a total of 782 pregnancies. We found a high proportion (82%) of pregnancies during which zidovudine was prescribed for women with CD4+ T-lymphocyte count of 0 to 199 cells/microl (n = 125), but no trend over time. In contrast, from 1990 through 1996 zidovudine was prescribed for an increasing proportion of pregnancies in which the woman's CD4+ count was 200 to 499 cells/microl (62%-78%; p = .01; n = 337) and > or = 500 cells/microl (22%-55%; p = .001; n = 250). CONCLUSIONS: Our study demonstrated differences in zidovudine prescription over time by CD4+ count; these differences may be based on the woman's health and guidelines for perinatal prevention.

Adolescent↗
PubMed1998

Epidemiology of anemia in human immunodeficiency virus (HIV)-infected persons: results from the multistate adult and adolescent spectrum of HIV disease surveillance project.

To study the incidence of, the factors associated with, and the effect on survival of anemia in human immunodeficiency virus (HIV)-infected persons, we analyzed data from the longitudinal medical record reviews of 32,867 HIV-infected persons who received medical care from January 1990 through August 1996 in clinics, hospitals, and private medical practices in nine United States cities. We calculated the 1-year incidence of anemia (a hemoglobin level of <10 g/dL or a physician diagnosis of anemia); the adjusted odds ratios showing excess risk of anemia associated with demographic factors, prescribed therapies, and concurrent diseases; the risk of death for patients who developed anemia compared with risk for patients who did not develop anemia; and, of patients who did develop anemia, the risk of death for those who did not recover from anemia compared with the risk for those who did recover. The 1-year incidence of anemia was 36.9% for persons with one or more acquired immunodeficiency syndrome (AIDS)-defining opportunistic illnesses (clinical AIDS), 12.1% for patients with a CD4 count of less than 200 cells/micron or CD4 percentage of <14 but not clinical AIDS (immunologic AIDS), and 3.2% for persons without clinical or immunologic AIDS. Of anemia diagnoses, 22% were identified by physicians as drug related. Incidence of anemia was associated with clinical AIDS, immunologic AIDS, neutropenia, thrombocytopenia, bacterial septicemia, black race, female sex, prescription of zidovudine, fluconazole, and ganciclovir, and lack of prescription of trimethoprim-sulfamethoxazole. The increased risk of death associated with anemia differed by first CD4 count: for patients with a CD4 count of >/=200 cells/microL at the beginning of the survival analysis, the risk of death was 148% (99% confidence interval [CI], 114 to 188) greater for those who developed anemia; for patients whose first CD4 count was <200 cells/microL, the risk of death was 56% (99% CI, 43 to 71) greater for those in whom anemia developed. For persons in whom anemia developed, the risk of death was 170% (99% CI, 132 to 203) greater for persons who did not recover from anemia compared with those who did recover. Anemia is a frequent complication of HIV infection, and its incidence is associated with progression of HIV disease, prescription of certain chemotherapeutics, black race, and female sex. Anemia, particularly anemia that does not resolve, is associated with shorter survival of HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1998

Probability of induction and stabilization of ventricular fibrillation with epinephrine.

Clinical studies suggest that epinephrine facilitates ventricular fibrillation (VF) although mechanisms remain unclear. We tested the hypothesis that epinephrine increases the probability of inducing VF and stabilizes VF in association with shortening of fibrillation action potential duration. VF was induced in isolated, New Zealand White rabbit hearts (n=16) under control conditions and in the presence of 0.9 micro M/l epinephrine. Monophasic action potentials were recorded during sinus rhythm, pacing, and fibrillation. Epinephrine reduced fibrillation p80 by 80%, from 23+/-4 to 4.6+/-1 V (P<0.05); and reduced fibrillation p90 by 82%, from 29.3+/-5.4 to 5.4+/-1.9 V (P<0.05). Epinephrine also reduced the probability of spontaneous termination of VF during the first 5 s of VF from 29 to 8% (P<0.05). Epinephrine significantly decreased mean fibrillation cycle length from 104.5+/-2 to 75.7+/-2.3 ms (P<0.001). Mean action potential duration (60% repolarization) decreased from 76+/-3 to 40+/-3 ms (P<0.0003). Frequency analysis showed a mean dominant frequency during VF of 10.0+/-0.2 Hz under control conditions and 13. 3+/-0.3 Hz with epinephrine (P<0.0001). These results suggest that epinephrine increases the probability of VF induction and decreases the probability of spontaneous defibrillation. Stabilization of fibrillation is associated with shortening of action potential duration and fibrillation cycle length, which may allow a greater number of fibrillation waves in the ventricle.

Action Potentials↗
PubMed1998

Shock timing lowers transvenous defibrillation energy requirement.

Previous studies suggested that time periods exist during ventricular fibrillation when defibrillation shocks are more effective. However, there is no agreement on the amount of energy that can be saved or whether an implantable defibrillator can time shocks to these time periods. We conducted a study having two parts to investigate if there was any advantage to synchronizing internal defibrillation shocks to morphological patterns in ventricular fibrillation (VF). VF electrograms were recorded from the same three-electrode lead system used for internal defibrillation. In Part 1, we found no difference in the probability of successful defibrillation between shocks that were delivered into coarse and fine VF (48% vs 46%). However, shocks that were delivered to the upslope of coarse VF electrograms were more efficacious than those to the downslope of the waveform (67% vs 39%, P < .001). In the second study, we developed a real time computer system to prospectively deliver shocks on the upslope feature we identified in the first study. We found that the energy requirements at E50 and E80 were significantly lower for shocks delivered on the upslope of coarse VF than those delivered randomly at the end of 10 sec. We estimated a probability of success (POS) defibrillation curve using a maximum likelihood method for the timed and random shocks. The POS curve width was significantly narrower for shocks that were delivered to the upslope feature than the control treatment (7.1 +/- 0.9 vs. 10.8 +/- 1.7 J, P < 0.01). If these findings extend to clinical defibrillation, they may allow programming of internal defibrillators at lower energies. This could reduce potential postshock cardiac dysfunction, allow production of smaller devices, and improve battery life.

Animals↗
PubMed1998

Patients treated by cardiologists have a lower in-hospital mortality for acute myocardial infarction.

OBJECTIVES: We sought to determine the effect of specialty care on in-hospital mortality in patients with acute myocardial infarction. BACKGROUND: There has been increasing pressure to limit access to specialists as a method to reduce the cost of health care. There is little known about the effect on outcome of this shift in the care of acutely ill patients. METHODS: We analyzed the data from 30,715 direct hospital admissions for the treatment of acute myocardial infarction in Pennsylvania in 1993. A risk-adjusted in-hospital mortality model was developed in which 12 of 20 clinical variables were significant independent predictors of in-hospital mortality. To determine whether there were factors other than patient risk that significantly influenced in-hospital mortality, multiple logistic regression analysis was performed on physician, hospital and payer variables. RESULTS: After adjustment for patient characteristics, a multiple logistic regression analysis identified treatment by a cardiologist (odds ratio=0.83 [confidence interval ¿CI¿=0.74 to 0.94] p < 0.003) and physicians treating a high volume of acute myocardial infarction patients (odds ratio=0.89 [CI=0.80 to 0.99] p < 0.03) as independent predictors of lower in-hospital mortality. Treatment by a cardiologist as compared to primary care physicians was also associated with a significantly lower length of stay for both medically treated patients (p < 0.01) and those undergoing revascularization (p < 0.01). CONCLUSIONS: Treatment by a cardiologist is associated with approximately a 17% reduction in hospital mortality in acute myocardial infarction patients. In addition, patients of physicians treating a high volume of patients have approximately an 11% reduction in mortality. This has important implications for the optimal treatment of acute myocardial infarction in the current transformation of the health care delivery system.

Aged↗
PubMed1998

Drugs for AIDS/HIV: assessing the evidence.

This article highlights factors that may cause bias in individual controlled trials or meta-analysis of zidovudine (AZT) in HIV disease. The overall benefit of AZT and antiretroviral drug combinations in the progression of HIV disease is probably greater than has been or can ever be shown in an ethical controlled trial.

AIDS-Related Opportunistic Infections↗
PubMed1998

Trends in AIDS-related opportunistic infections among men who have sex with men and among injecting drug users, 1991-1996.

Incidence trends for the 13 most frequent AIDS-defining opportunistic infections (OIs) among men who have sex with men (MSM, n = 15,588) and injecting drug users (IDUs, n = 4475) were examined using data abstracted from medical records in >90 hospitals and clinics in nine US cities during 1991-1996. Among MSM, the most frequent OIs were Mycobacterium avium complex (MAC) disease, Pneumocystis carinii pneumonia (PCP), and cytomegalovirus (CMV) retinitis; decreasing (P < or = .05) trends occurred for 11 OIs (MAC disease, PCP, CMV retinitis, Kaposi's sarcoma, esophageal candidiasis, CMV disease, extrapulmonary cryptococcosis, toxoplasmic encephalitis, tuberculosis, chronic herpes simplex, and disseminated histoplasmosis). Among IDUs, the most frequent OIs were PCP, MAC disease, and esophageal candidiasis; decreasing trends occurred for 5 OIs (PCP, esophageal candidiasis, tuberculosis, chronic herpes simplex, and chronic cryptosporidiosis) and an increase occurred in recurrent pneumonia. The differences in trends for MSM and IDUs may be due to differences in medical care and adherence to preventive medications.

AIDS-Related Opportunistic Infections↗
PubMed1998

Risk factors for primary Pneumocystis carinii pneumonia in human immunodeficiency virus-infected adolescents and adults in the United States: reassessment of indications for chemoprophylaxis.

Risk factors for the development of a first episode of Pneumocystis carinii pneumonia (PCP) were investigated in the Adult and Adolescent Spectrum of Disease Project, a medical record review study involving longitudinal follow-up of human immunodeficiency virus-infected adults in 9 US cities. Risk factors included decreasing CD4 lymphocyte count and history of AIDS-defining illness, non-P. carinii pneumonia, oral thrush, or unexplained fever for > or = 2 days; PCP prophylaxis was protective. PCP incidence/100 person-years of observation among persons not prescribed PCP prophylaxis was higher in those with CD4 lymphocyte counts < 250 cells/microL or CD4 cell percent < 14% (8.3; 95% confidence interval [CI], 7.7-9.0) than in persons with CD4 cell counts < 200 or history of thrush or fever, which constitute current criteria for prophylaxis against PCP (5.9; 95% CI, 5.5-6.4). Because of increased efficiency in capturing persons at highest risk, CD4 cell count < 250 or CD4 cell percent < 14% should be considered as criteria for prophylaxis against first episodes of PCP.

Adolescent↗
PubMed1998

Estimation of the temporal probability of human immunodeficiency virus (HIV) dementia after risk stratification for HIV-infected persons.

We developed a scheme using routinely available data to estimate the risk of human immunodeficiency virus (HIV) dementia in HIV-infected persons over time. We performed a longitudinal review of medical records from more than 100 medical facilities in 11 U.S. cities. A total of 19,462 HIV-infected persons without history of dementia enrolled in a multi-institution survey. The main outcome measure was the development of HIV dementia (1987 case definition) during the median follow-up period of 17 months (range, 1 to 72 months). Of 19,462 HIV-infected persons, HIV dementia developed in 880 persons (4.5%; 2.6% per person-year). The strongest predictors of HIV dementia were CD4+ T-lymphocyte count, anemia, and AIDS-defining infections or cancer. The 2-year probability of HIV dementia was highest for persons who had a CD4+ T-lymphocyte count of fewer than 100 cells/microL and an AIDS-defining illness or anemia or both (18.6 to 24.9%). Intermediate risk was observed in persons with CD4+ T-lymphocyte count of 100 to 199 cells/microL and an AIDS-defining illness or anemia or both or in persons with a CD4+ T-lymphocyte count of fewer than 100 cells/microL but without another risk factor (2-year probability, 10.4 to 15.2%). The 2-year probability that HIV dementia would develop was lowest (1.0%) for persons with CD4+ T-lymphocyte count of more than 200 cells/microL and no other risk factors. Risk stratification using routine clinical information provides information that may prove useful in patient care decisions.

AIDS Dementia Complex↗
PubMed1998

The fall after the rise: Tuberculosis in the United States, 1991 through 1994.

OBJECTIVES: Factors associated with decreases in tuberculosis cases observed in the United States in 1993 and 1994 were analyzed. METHODS: Changes in case counts reported to the national surveillance system were evaluated by dividing the number of incident cases of TB reported in 1993 and 1994 by the number of cases reported in 1991 and 1992 and stratifying these ratios by demographic factors, AIDS incidence, and changes in program performance. RESULTS: Case counts decreased from 52,956 in 1991 and 1992 to 49,605 in 1993 and 1994 (case count ratio = 0.94, 95% confidence interval [CI] = 0.93, 0.95). The decrease, confined to US-born patients, was generally associated with AIDS incidence and improvements in completion of therapy, conversion of sputum, and increases in the number of contacts identified per case. CONCLUSIONS: Recent TB epidemiology patterns suggest that improvements in treatment and control activities have contributed to the reversal in the resurgence of this disease in US-born persons. Continued success in preventing the occurrence of active TB will require sustained efforts to ensure appropriate treatment of cases.

Adolescent↗
PubMed1997

Recent trends in the HIV epidemic in adolescent and young adult gay and bisexual men.

To explore recent patterns in the HIV epidemic in young gay and bisexual men, we analyzed national AIDS surveillance data for men who have sex with men (MSM) 13 to 25 years of age. Estimates of annual AIDS incidence were calculated by adjusting the surveillance data for reporting delays, unreported HIV risks, and the 1993 change in the AIDS case definition. Between 1990 and 1995, estimated AIDS incidence in young MSM declined 29%, from 1400 to 1000 cases; however, trends in incidence varied greatly by race/ethnicity. Annual AIDS incidence decreased 50% in whites during this period (from 720 to 360), but fell just 2% in blacks (from 430 to 420) and rose 5% in Hispanics (from 220 to 230). Trends in incidence also differed by metropolitan statistical area (MSA) size. Between 1990 and 1995, AIDS incidence declined 37% in MSAs with populations of 2,500,000 people or more and 28% in MSAs with 1,000,000 to 2,499,999 people, but incidence decreased only 15% in MSAs with 500,000 to 999,999 people, and 13% in MSAs with 50,000 to 499,999. Incidence in nonmetropolitan (i.e., rural) areas was unchanged. Young black and Hispanic MSM now account for most young MSM with AIDS, and incidence in young MSM in small MSAs and rural areas has been relatively constant. Trends in AIDS incidence indicate that levels of HIV infection have remained persistently high in certain populations of young MSM, underscoring the immense need for HIV prevention programs targeted specifically toward these young men.

Adolescent↗
PubMed1997

Modulation of myoepithelial-associated alpha6beta4 integrin in a breast cancer cell line alters invasive potential.

In normal breast, cell-stromal contact is mediated by myoepithelial cells which strongly express alpha2beta1, alpha3beta1, and alpha6beta4 integrins, while epithelial cells exhibit alpha2beta1 and alpha3beta1 integrins at cell-cell borders, but do not express alpha6beta4 integrin. Breast carcinomas consistently show down-regulation of all integrins. We have investigated the modulatory effect of stromal proteins, hormones, and transforming growth factor beta (TGF-beta) on integrin expression in breast cancer cell lines MCF-7, T47-D, and MDA-MB 231 using indirect immunofluorescence and confocal laser scanning microscopy. MCF-7 and T47-D cells displayed low levels of both alpha2beta1 and alpha3beta1 integrins, and no alpha6beta4 integrin, and this profile remained unchanged by modulatory agents. The MDA-MB 231 cells exhibited stronger staining for alpha2beta1 and alpha3beta1 integrins and focal staining for alpha6beta4 integrin under control conditions, but markedly enhanced reactivity for the alpha6beta4 complex in the presence of TGF-beta. This was associated with acquisition of a spread cellular morphology and localization of alpha6beta4 at the cell periphery in a discrete punctate distribution. There was associated enhanced expression of epiligrin, the ligand for alpha6beta4, with similar localization to the cell periphery. Cell invasion assays through a Matrigel barrier revealed significantly reduced invasive potential of TGF-beta-treated cells, an effect largely reversed following preincubation of the treated cells with anti-beta4 integrin antibody. We conclude that alpha6beta4 integrin can be up-regulated by TGF-beta and has an anti-invasive effect on MDA-MB 231 cells. In addition to alpha6beta4, MDA-MB 231 cells exhibit other myoepithelial markers including cytokeratin 14, vimentin, and weak expression of CALLA. These findings support the concept of a subgroup of breast carcinomas displaying features of myoepithelial differentiation.

Antigens, Surface↗