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Biomedical subjects

J L Jones

Publications and source records attributed to J L Jones.

At least 91 records · Page 5Linked to original sources
PubMed1997

Surveillance for thrombocytopenia in persons infected with HIV: results from the multistate Adult and Adolescent Spectrum of Disease Project.

Thrombocytopenia in persons infected with HIV is prevalent and has numerous causes. To study the occurrence, associations, and effect on survival of thrombocytopenia in HIV-infected persons, we used surveillance data from a longitudinal survey of the medical records of 30,214 HIV-infected patients who received medical care from January 1990 through August 1996 in more than 100 medical clinics in 10 U.S. cities. Thrombocytopenia was defined as a physician diagnosis of thrombocytopenia or a platelet count of < 50,000 platelets/ microliter. Analysis of associations of thrombocytopenia was conducted using logistic regression. In HIV+ patients, the 1-year incidence [corrected] of thrombocytopenia was 8.7% in persons with one or more AIDS-defining opportunistic illnesses (clinical AIDS), 3.1% in patients with a CD4 count < 200 cells/mm3 but not clinical AIDS (immunologic AIDS), and 1.7% in persons without clinical or immunologic AIDS. The incidence of thrombocytopenia was associated with clinical AIDS (adjusted odds ratio [AOR] 2.2; 99% confidence interval [CI] 1.7-3.0), immunologic AIDS (AOR 1.5, CI 1.0-2.1), history of injecting drug use (AOR 1.4, CI 1.0-1.9), anemia (AOR 5.0, CI 3.8-6.7), lymphoma (AOR 3.7, CI 1.3-10.6), and black race (AOR 0.7, CI 0.5-0.9). After controlling for anemia, clinical AIDS, CD4 count, neutropenia, antiretroviral therapy, and Pneumocystis carinii pneumonia prophylaxis, thrombocytopenia was significantly associated with decreased survival (risk ratio 1.7; 95% CI, 1.6-1.8). Thrombocytopenia in HIV-infected persons is an important clinical condition associated with shorter survival.

AIDS-Related Opportunistic Infections↗
PubMed1997

Control of matrix metalloproteinase activity in cancer.

Remodelling of extracellular matrix (ECM) and basement membranes is a key component of the process of tumour cell invasion and metastasis. Matrix metalloproteinases (MMPs) are one of the major classes of enzymes involved in degrading ECM, having different substrate specificities and being inhibited by naturally occurring tissue inhibitors (TIMPs). Elevated levels of MMPs have been associated with poor prognosis for a variety of malignancies. However, the expression and effective action of MMPs are influenced by multiple factors: most are synthesized by stroma rather than tumour cells, suggesting tumour cell-stromal cell co-operation; receptors (MT-MMPs) have to be present on tumour cells for binding and activation of MMP; co-ordination of tissue proteolysis and subsequent integrin binding will aid cell movement through a matrix; integrin receptors can directly moderate the production of MMP. These various components need to be considered when trying to determine the key events regulating matrix proteolysis and hence invasion.

Extracellular Matrix↗
PubMed1997

Epinephrine facilitates cardiac fibrillation by shortening action potential refractoriness.

Epinephrine released during ventricular tachycardia (VT) or early fibrillation (VF) appears to be instrumental in stabilizing fibrillation. However, mechanisms remain unclear. Effects of epinephrine on refractory period at normal sinus rates depend on basic cycle length, but effects at short cycle lengths, typical of VT/VF, are unknown. Therefore, the goal of this study was to determine whether epinephrine shortens action potential duration and refractoriness at these short cycle lengths. To simulate early VT/VF, myocardial cell aggregates (n = 35) were paced using field stimulation (5 ms rectangular waveform) at cycle lengths of 200, 180, 160 and 140 ms, which occur during in situ fibrillation: normal sinus rhythm was simulated by pacing at 600 and 400 ms intervals. Action potentials and excitation threshold were recorded with intracellular microelectrodes under control conditions, with 0.9 microM/l epinephrine, and with 0.9 microM/l epinephrine and 0.5 microM/l propranolol. At short cycle lengths, epinephrine significantly shortened action potential duration and refractoriness compared to control. At a cycle length of 160 ms, action potential duration was reduced by 14 ms at 60% repolarization (P < 0.0002) and stimulation threshold by 18% (P < 0.02). Epinephrine also allowed pacing at a cycle length of 140 ms, not achievable under control conditions. Because epinephrine decreases action potential duration at short cycle length in situ, re-entry wavefronts are less likely to encounter refractory tissue: fibrillation is more likely to occur and to remain stabilised. Reduction in action potential duration and excitation threshold were reversed by propranolol, suggesting that epinephrine effects are produced by beta-stimulation.

Action Potentials↗
PubMed1997

Calcium dynamics in cultured heart cells exposed to defibrillator-type electric shocks.

Spatial and temporal changes in intracellular calcium ion concentration and transmembrane voltage were recorded optically from single-isolated cultured chick-embryo heart cells exposed to high-voltage, defibrillator-type shocks. Fluorescence changes were measured during 5 msec electric shocks of field strengths up to 56 volts/cm in single myocytes stained with a Ca(++)-sensitive or voltage-sensitive dye. Shocks caused a reversible period of depolarization, elevated cytosolic Ca++, and refractoriness. Intracellular Ca++ elevation had two temporal phases: first, a Ca++ spike with morphology independent of shock intensity; and second, a prolonged Ca++ elevation with a shock-intensity-dependent magnitude and duration, and with greatest Ca++ elevation at the poles of the cell adjacent to the electrodes. The prolonged elevation (second phase) was initiated earlier at the anode-facing pole of the cell than at the cathode-facing pole. These results suggest that postshock Ca++ entry consists of two parts: early normal entry through excitation channels plus a prolonged elevation which may be related to cellular damage.

Animals↗
PubMed1997

Elevated levels of the complement components C3 and factor B in ventricular cerebrospinal fluid of patients with traumatic brain injury.

Immunological events occurring in the central nervous system (CNS) as a result of head trauma are largely unexplored. We report here that the levels of the alternative pathway complement proteins C3 and factor B are elevated in the cerebrospinal fluid (CSF) of head-injured patients. C3 and factor B indices suggest that changes in C3 and factor B levels in CSF are most likely due to altered blood-brain barrier integrity and not to intrathecal synthesis. These data demonstrate, for the first time, elevated levels of complement proteins in CSF of patients with severe traumatic brain injury. Elevated complement levels in brain injury may contribute to secondary damage.

Adolescent↗
PubMed1997

Molecular pathology of breast cancer and its application to clinical management.

Breast cancer is a major cause of morbidity and mortality in women in many parts of the world. Breast carcinomas are heterogenous in their biological and clinical behaviour and a greater understanding of how they develop and progress could lead to more directed forms of screening and therapy. It is important to determine the molecular mechanisms underlying the natural history of breast cancer. Developments in the techniques for molecular analysis have meant that they can now be applied to a large range of clinical material such as cytological preparations and fixed, embedded material, so increasing the potential for relating any molecular alterations to clinical behaviour and response to therapy. In this review we consider recent developments in three areas of importance to breast cancer; genetic analysis-oncogenes, tumour suppressor genes, loss of heterozygosity, microsatellite instability, familial breast cancer; steroid receptors, oestrogen regulated proteins, epidermal growth factor receptor, growth factors particularly transforming growth factor beta; and cell adhesion, invasion and metastasis-E-cadherin, integrins, proteases. These are discussed in relation to potential for screening, prognosis and treatment.

Breast Neoplasms↗
PubMed1997

Relationship between "extension of refractoriness" and probability of successful defibrillation.

The "extension of refractoriness" hypothesis, which suggests that the shock halts fibrillation by extending the refractory period, has not been directly tested. Defibrillation (5 isolated rabbit hearts; 111 episodes) was attempted by 8-ms pulses (65% tilt) delivered through epicardial patches. Monophasic action potentials were recorded in a low current density region (6.3 V/cm at 90% success). Fifty shocks failed to convert; 61 shocks successfully defibrillated. Postshock response duration (from shock to repolarization) was significantly longer for successful type A (with no postshock activations) defibrillation (102.3 +/- 7.5 ms) than for unsuccessful defibrillation (47.6 +/- 4.3 ms; P < 0.0001) for shocks occurring during the last 40% of the fibrillation action potential. Probability of success and postshock response duration both increased with current intensity. However, at each intensity, response durations for successful defibrillation were significantly longer than those for unsuccessful defibrillation. A minimum prolongation of 75 ms was associated with type A defibrillation. These results suggest that shock-induced response duration correlates with successful defibrillation and that a response of 75 ms is required to completely block fibrillation wavefronts.

Action Potentials↗
PubMed1996

The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina.

BACKGROUND: In a previous study, we did follow-up on 418 patients who were exposed to tryptophan in 1989, of whom 47 (11%) had definite and 63 (9%) possible eosinophilia-myalgia syndrome (EMS). METHODS: We assessed mortality and clinical spectrum of illness since 1989 for 242 (58%) of the 418 tryptophan-exposed patients from the original study. To assess outcomes, we used hospital and death records, interviewer-administered questionnaires, physical examinations, and laboratory tests. RESULTS: During the follow-up interval, mortality from all causes was 19% in those with definite EMS, 7% in possible EMS, and 3% in those who were not ill. The age- and sex-adjusted mortality in those with definite EMS was more than 3 times that of the general population or of tryptophan users in the practice who were not ill. Six deaths (66%) among the definite EMS case patients occurred during the 18 months immediately after symptom onset. Compared with the tryptophan users who were not ill, survivors with definite EMS continued to report excess morbidity for 6 major EMS symptoms (myalgia, arthralgia, weakness, rash, alopecia, and sclerodermiform skin changes), but they also reported that the symptom number and severity diminished with time. None of the tryptophan users who were not ill in 1989 developed a symptom complex suggesting new EMS during the follow-up interval. CONCLUSIONS: This study assessing a tryptophan-exposed population found those persons who developed EMS during the 1989 epidemic were at increased risk for death, particularly early after disease onset. Survivors reported improvement or resolution of major symptoms, suggesting that the severity of EMS diminishes with time. We found no evidence of delayed onset of EMS in tryptophan users who were not ill in 1989, regardless of the brand used.

Drug Contamination↗
PubMed1996

Chronic complement C3 gene expression in the CNS of transgenic mice with astrocyte-targeted interleukin-6 expression.

Both cytokines and complement are thought to play significant, but poorly understood roles, in the pathogenesis of a variety of neurodegenerative diseases. In this study, we examined the expression of C3, the central component of complement, in the brains of transgenic mice with constitutive astrocyte expression of the proinflammatory cytokine, interleukin-6 (IL-6). Immunohistochemistry studies demonstrated elevated deposition of C3 in the brains of transgenic animals compared with normal animals. Northern blot analysis of mRNA from brain and other tissues demonstrated an age-related increase in C3 gene expression only in the brains of transgenic animals, indicative of local synthesis. In situ hybridization studies revealed coincidence between C3 and IL-6 transgene expression, as well as areas of neuronal and white matter damage observed in cerebellum and hind brain. Furthermore, C3 mRNA expression was observed in ependymal cells, perivascular mononuclear cells, endothelial cells, and scattered cells throughout the white matter and the brain stem. The overlap in C3 mRNA expression with areas of pathology suggests that complement may contribute to the inflammation and cellular injury observed in this model. The transgenic mice used in these studies provide a novel and valuable tool for examining the role of complement in central nervous system pathobiology.

Animals↗
PubMed1996

Pregnancy rates among women infected with human immunodeficiency virus. Adult/Adolescent HIV Spectrum of Disease Project Group.

OBJECTIVE: To examine pregnancy rates among women infected with human immunodeficiency virus (HIV). METHODS: We used data from an ongoing survey of medical records of 3915 women who were 15-44 years of age, infected with HIV, and who received care between January 1990 and August 1994 in more than 90 clinics, hospitals, and private practices in 11 United States cities. RESULTS: At enrollment, 570 (14%) of these women were pregnant. Pregnancy rates at entry varied significantly (P < .05) by age in years (15-19 [47%], 20-24 [30%], 25-29 [18%]; 30-34 [11%]; 35-39 [5%]; 40-44 [2%]); clinical status (with AIDS opportunistic illness [3%], without AIDS opportunistic illness [17%]; and race-ethnicity (white [12%], black [17%], Hispanic [8%], Asian [0%], Native American [30%]) but not by mode of exposure (injecting drug use [10%], heterosexual contact [15%], and blood transfusion [12%]). After enrollment, 5.8% of women became pregnant each year. New pregnancies were significantly less likely to occur among women with an AIDS opportunistic illness (adjusted rate ratio 0.4, 95% confidence interval [CI] 0.2-0.6), and significantly more likely to occur among women who were less than 25 years of age (adjusted rate ratio 8.3, 95% CI 5.3-13.2) and who were black (adjusted rate ratio 1.6, 95% CI 1.2-2.1). Among women who were pregnant at enrollment or during observation, 12% were pregnant more than once. CONCLUSIONS: High rates of pregnancy at entry to medical care among HIV-infected women stress the importance of counseling and voluntary testing as routine obstetric-gynecologic practice. In some groups, rates of new pregnancies remain high; standard HIV care for women should include family planning services and assurance that if a woman chooses to practice contraception, contraceptives will be available and affordable.

Adolescent↗
PubMed1996

Enhanced expression of chemotactic receptors in multiple sclerosis lesions.

We have previously shown that astrocytes and microglia express the receptors for C5a, interleukin-8 (IL-8) and N-formyl-Met-Leu-Phe (FMLP) in vitro. The expression and function of chemotactic receptors in the central nervous system (CNS) is, however, largely unexplored. In this study, we examined tissue sections from normal human brain and active, chronic active and chronic silent multiple sclerosis (MS) lesions for the expression of the receptors for C5a, IL-8 and FMLP by immunohistochemistry. In normal brain tissue, the expression of all three receptors was seen at low levels on astrocytes and microglia. In contrast, expression for all three receptors was markedly elevated on foamy macrophages in the acute and chronic active MS lesions. In addition, fibrous astrocytes stained intensely for the C5a receptor in the chronic active disease. Receptor expression in the chronic silent lesion was low and similar to that seen in normal brain, with staining confined to a few hypertrophic astrocytes and foamy macrophages. These are the first studies to demonstrate expression of these receptors in the CNS and elevated receptor expression in inflammatory MS lesions. The data suggest that these chemotactic receptors may play a role in inflammatory responses in MS and possibly in other CNS diseases.

Acute Disease↗
PubMed1996

E-cadherin relates to EGFR expression and lymph node metastasis in primary breast carcinoma.

Expression of the calcium-dependent cell-cell adhesion molecule E-cadherin has been examined in 187 primary breast carcinomas using an immunohistochemical technique. The pattern and extent of reactivity has been correlated with clinicopathological data including tumour type, grade and lymph node status and with other prognostic parameters including oestrogen receptor (ER) status, expression of c-erbB-2, pS2 protein and epidermal growth factor receptor (EGFR). Two patterns of E-cadherin staining were observed in carcinomas, membrane reactivity and a diffuse cytoplasmic staining. A marked difference in expression of E-cadherin was observed between infiltrating lobular carcinomas (ILC) and infiltrating ductal carcinomas (IDC), the former showing complete loss of membrane staining, whereas 93% of IDC retained some level of expression. In IDC reactivity was not related to tumour grade but there was a significant association between reduced membrane levels of E-cadherin and the presence of lymph node metastasis, and a highly significant correlation between the presence of cytoplasmic E-cadherin and metastasis. A significant relationship was also demonstrated between reduced E-cadherin reactivity and expression of EGFR. These findings emphasise the complexity of control of E-cadherin in breast carcinomas and provide evidence of a link between membrane signalling pathways and modulation of E-cadherin expression.

Breast Neoplasms↗
PubMed1996

Protection from Mycobacterium avium complex disease in human immunodeficiency virus-infected persons with a history of tuberculosis.

Risk of Mycobacterium avium complex disease was examined in human immunodeficiency virus (HIV)-infected patients with and without a history of tuberculosis. Information was obtained by retrospective review of charts of patients in HIV clinics in 10 US cities. Among 1363 patients with <200 CD4 cells/mm3 seen at Grady Memorial Hospital (GMH), 11 (17%) of 66 with a history of a positive purified protein derivative (PPD) skin test acquired M. avium infection, while 29 (16%) of 185 who were PPD-negative (but not anergic) did not (P = .85). Only 4 (8%) of 49 GMH patients with a history of tuberculosis acquired M. avium infection compared with 252 (19%) of 1314 GMH patients without a history of tuberculosis (P = .05). Proportional hazards analysis of risk factors for M. avium infection among 441 persons with and 8702 persons without a history of tuberculosis in 9 other cities confirmed protection from M. avium infection in persons with a history of tuberculosis (relative risk, 0.52; 95% confidence interval, 0.36-0.76; P < .001). Prior tuberculosis provides protection against M. avium infection in HIV-infected persons, possibly by stimulation of antimycobacterial immunity.

Adolescent↗
PubMed1996

Toxoplasmic encephalitis in HIV-infected persons: risk factors and trends. The Adult/Adolescent Spectrum of Disease Group.

OBJECTIVE: To evaluate the incidence of and risk factors for toxoplasmic encephalitis among HIV-infected persons. DESIGN: Medical facility-based prospective medical record reviews of consecutive patients. METHODS: We analysed data collected from January 1990 through August 1995 in more than 90 inpatient and outpatient medical facilities in nine US cities. Incidence was calculated as cases per 100 person-years and risk ratios (RR) for annual incidence were calculated using proportional hazards regression while controlling for city, sex, race, age, county of birth, HIV exposure mode, and prior prescription of trimethoprim-sulfamethoxazole (TMP-SMX). RESULTS: The incidence of TE was 4.0 cases per 100 person-years among persons with a CD4+ T-lymphocyte count of < 100 x 10(6)/l. In multivariate analysis, among the nine cities the annual incidence of toxoplasmosis was significantly lower only in Denver [RR, 0.3; 95% confidence interval (CI), 0.1-0.7; referent city, Seattle]. Persons prescribed TMP-SMX were half as likely to develop toxoplasmic encephalitis as those who were not (RR, 0.5; 95% CI, 0.4-0.7). Of the 4173 persons with AIDS (1987 Centers for Disease Control and Prevention definition) who died during the study period, 267 (6.4%) had toxoplasmic encephalitis in the course of HIV disease. CONCLUSIONS: Toxoplasmic encephalitis in HIV-infected persons varies by geographic area in the United States. TMP-SMX reduces the risk for toxoplasmic encephalitis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Tuberculosis among AIDS patients in the United States, 1993.

To evaluate the demographic characteristics, risk factors, and reported mortality of adults and adolescents with AIDS and tuberculosis (TB), we analyzed surveillance reports of persons with AIDS from state, territorial, and local health departments. Of 72,306 persons with AIDS diagnosed in 1993, 3,589 (5%) were reported with TB; of these, 2,782 (78%) with pulmonary TB, 552 (15%) with extrapulmonary TB, and 255 (7%) with both pulmonary and extrapulmonary TB were reported. In multivariate analysis, black [odds ratio (OR) 3.3, 95% confidence interval (CI) 2.9-3.7] and Hispanic (OR 2.5, 95% CI 2.2-2.9) persons had a higher risk of TB than white persons; injecting drug users (IDUs: OR 2.3, 95% CI 2.0-2.5) and persons exposed to HIV by heterosexual contact (OR 1.4, 95% CI 1.2-1.7) had a higher risk than men who have sex with men, and persons who were foreign born (OR 2.1, 95% CI 1.8-2.4) had a higher risk than those born in the United States. The highest proportions of AIDS patients with TB were in New York (11%), Illinois (7%), Florida (6%), Georgia (6%), and Texas (5%). The 1-year mortality rate among AIDS patients with pulmonary TB only (26%) and among those with extrapulmonary TB only (28%) was lower than among those with other AID-defining illnesses (38%) (p<0.001 and p<0.001, respectively). The high rate of TB among persons with AIDS, particularly in specific areas of the country and HIV exposure groups, emphasizes the need for continued support of strong TB control measures among persons infected with HIV.

AIDS-Related Opportunistic Infections↗
PubMed1996

Defibrillation using a high-frequency series of monophasic rectangular pulses: observations and model predictions.

INTRODUCTION: Capacitor-discharge type waveforms are practical for defibrillation devices but may not be optimum. Discharging a capacitor as a series of high-frequency (HF) pulses may allow effective waveform shaping by modulating the pulses. This approach could lead to improved defibrillation by allowing waveforms that would otherwise be unachievable with a capacitor-discharge approach. However, little is known about defibrillation with HF. METHODS AND RESULTS: In open chest pentobarbital anesthetized dogs, we measured defibrillation thresholds for continuous rectangular waveforms with 5-, 10-, and 20-msec durations and for 10- and 20-msec long series of HF rectangular pulses. HF series had a 50% "on-time" duty cycle at 100 Hz to 20 kHz. At 1 kHz and above, defibrillation with HF required the same time-averaged current but approximately twice the peak current and energy as defibrillation with continuous waveforms having the same envelope duration. At lower frequencies, defibrillation peak current and energy approached values required for the continuous waveforms. While waveforms were not actually filtered, the heart responded as though the HF series were low-pass filtered. A filtered effective waveform model with a 3.7-msec time constant predicts these HF data and makes reasonable predictions for various continuous waveform shapes. CONCLUSION: Defibrillation is possible using HF pulses up to 20 kHz and has a frequency response similar to a low-pass filter. A filtered effective waveform model predicts these HF results and may help explain how waveforms influence defibrillation efficacy. While the unmodulated HF pulsing used in this study increased defibrillation requirements, these findings support the concept that HF pulse modulation can be used to change the effective shape of a waveform, which could permit more efficacious waveform shapes and a net reduction of thresholds.

Analysis of Variance↗
PubMed1996

An immunohistochemical study of the dermal infiltrate and epidermal staining for interleukin 1 in 12 cases of Sweet's syndrome.

Interleukin 1 (IL-1) has been proposed as a possible mediator in Sweet's syndrome. We examined all cases of Sweet's syndrome (n = 12) presenting to the department over a 10-year period, from 1982 to 1992, for the presence of IL-1 and also assessed the nature of the dermal inflammatory infiltrate in those cases. Staining for IL-1 alpha and IL-1 beta was stronger in control tissues than in Sweet's syndrome. This may possibly be explained by the release of IL-1 alpha and IL-1 beta into the dermis in Sweet's syndrome. Contrary to recent reports, we found that neutrophils predominated in all cases examined, although histiocytes were present in increased numbers indicating their possible role in the pathophysiology of Sweet's syndrome.

Epidermis↗