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Biomedical subjects

J F Jones

Publications and source records attributed to J F Jones.

At least 19 recordsLinked to original sources

Chronic fatigue syndrome: I. Epstein-Barr virus immune response and molecular epidemiology.

Patients with chronic fatigue syndrome were compared to healthy seropositive control subjects in an open study and a case-control study analyzing spontaneous transformation rates of peripheral blood lymphocytes, EBV viral genome characteristics as determined by DNA restriction fragment polymorphisms, and antibody production by Western blot analysis. Thirty percent of patients versus 8% of control subjects underwent spontaneous transformation in the two studies. Viral genome patterns were overall similar to one another, with polymorphisms frequently present in BamHI B', K, H, and Y fragments. Only one line was found with the EBNA-2B genotype. Nineteen lines were found to contain viral DNA in the linear form suggesting active lytic replication. Western blot studies suggested that ill subjects made antibodies to lytic proteins more frequently than did healthy control subjects. Lack of control of EBV outgrowth in vitro is correlated with antibody evidence of active infection in vivo in some patients with chronic fatigue syndrome.

Antibodies, Viral

Stress-related activation of Epstein-Barr virus.

Herpesviruses characteristically persist in a latent state in the body over the lifetime of an individual. Under certain conditions, any one of the herpesviruses can be reactivated. The mechanisms underlying the establishment of latent virus infection or viral reactivation are not well understood; however, it is known that the cellular immune response plays a very important role in the maintenance of latency and in virus reactivation. One of the factors thought to be associated with the reactivation of latent herpes-viruses is psychological stress. Using an examination stress model with medical student subjects, we previously demonstrated the reactivation of latent Epstein-Barr virus (EBV), as measured by increases in antibody titers. In this follow-up study using the same group of medical students, we found evidence for incomplete reactivation of latent EBV, with only selective expression of the latent virus genome.

Adult

Severe combined immunodeficiency among the Navajo. I. Characterization of phenotypes, epidemiology, and population genetics.

Previous studies have identified a high incidence of severe combined immunodeficiency (SCID) among the Navajo Native American population. To determine the incidence and population genetics of this condition, we reviewed the death certificates of all children who died between 1969 and 1982, established the cases that met criteria identified in previously investigated cases, and interviewed the selected children's families. SCID cases were distributed spatially and temporally. Segregation parameter estimates of 0.27-0.38 were obtained from data from 24 interviewed families, suggesting an estimated gene frequency of 2.1% (arguing against a multifactorial inheritance). SCID cases referred to specialty centers lacked T and B cells in their blood, and their serum immunoglobulins ranged from absent to near normal.

Arizona

The elderly on dialysis: some considerations in compliance.

Compliance with scheduled treatments, dietary and fluid restrictions, and multiple medications is an important component in the care and well-being of end-stage renal disease (ESRD) patients. Given the rigorus and complex demands of dialysis, it is important to examine the issue of compliance, focusing on a large and ever-increasing segment of our patient population, the elderly. The ESRD literature reflects efforts to define and measure levels of compliance, identify factors that influence and predict compliance, and develop intervention strategies to improve adherence to treatment regimens. While limited attention has been focused specifically on the elderly, there are studies suggesting that age may be a factor associated with improved adherence and that social support may be a significant contributor to compliance in this patient group. In an effort to examine the current status and needs of the dialysis elderly, research is in progress at Chromalloy American Kidney Center, Washington University, which replicates a study of 5 years ago. Eighty-four patients age 60 and over, on dialysis for a minimum of 6 months, were identified. Sociodemographic, treatment, compliance, and functional capacity data were collected; additional mental and psychological testing was completed on patients willing and able to participate. Preliminary data suggest the current elderly population is larger and significantly older than that of 5 years ago. Other sociodemographic data indicate the population is increasingly female, black, and more socioeconomically disadvantaged. In regard to compliance, the vast majority of elderly demonstrate good compliance as measured by serum potassium, fair to good compliance with phosphorus, and fair to poor compliance with fluid restrictions.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living

T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections.

Fatal T-cell lymphomas developed in three patients with a chronic illness manifested by fever, pneumonia, dysgammaglobulinemia, hematologic abnormalities, and extraordinarily high titers of antibody to the Epstein-Barr virus (EBV) capsid antigen (greater than 10,000) and early antigen (greater than 640) but low titers to the EBV nuclear antigen (less than or equal to 40). To understand the pathogenesis of these tumors better, we determined the immunophenotype of the tumor cells and analyzed tumor-cell DNA for EBV genomes and for lymphoid-cell gene rearrangements. More than 80 percent of the cells in tumors had an activated helper T-cell phenotype (T4, T11, la positive). The EBV genome was found by in situ hybridization in tumor tissue from each patient. Southern blot assay of DNA digests from one patient showed the same pattern as that of the EBV-infected marmoset line, B95-8. DNA digests from two patients showed a monoclonal proliferation of T cells determined on the basis of uniform T-cell-receptor gene rearrangements and a single band for the joined termini of the EBV genome. We conclude that EBV may infect T cells and contribute to lymphomas in selected patients with severe EBV infections.

Adult

Chronic fatigue syndrome: a working case definition.

The chronic Epstein-Barr virus syndrome is a poorly defined symptom complex characterized primarily by chronic or recurrent debilitating fatigue and various combinations of other symptoms, including sore throat, lymph node pain and tenderness, headache, myalgia, and arthralgias. Although the syndrome has received recent attention, and has been diagnosed in many patients, the chronic Epstein-Barr virus syndrome has not been defined consistently. Despite the name of the syndrome, both the diagnostic value of Epstein-Barr virus serologic tests and the proposed causal relationship between Epstein-Barr virus infection and patients who have been diagnosed with the chronic Epstein-Barr virus syndrome remain doubtful. We propose a new name for the chronic Epstein-Barr virus syndrome--the chronic fatigue syndrome--that more accurately describes this symptom complex as a syndrome of unknown cause characterized primarily by chronic fatigue. We also present a working definition for the chronic fatigue syndrome designed to improve the comparability and reproducibility of clinical research and epidemiologic studies, and to provide a rational basis for evaluating patients who have chronic fatigue of undetermined cause.

Chronic Disease

Antibodies to Epstein-Barr virus-specific DNase and DNA polymerase in the chronic fatigue syndrome.

In an attempt to examine further the association between active Epstein-Barr virus (EBV) infection and the chronic fatigue syndrome (chronic EBV syndrome, or chronic or atypical mononucleosis), antibodies acting against EBV-specific DNase and DNA polymerase, which are expressed only during virus replication, were assayed. Serum samples from 25 healthy EBV-seropositive individuals neutralized 3.5 +/- 5.1 U (mean +/- SD) of DNase activity and 14.7 +/- 8.5 U of DNA polymerase activity. From these values were selected upper limits of anti-EBV enzyme activity of 17.9 and 31.3 U neutralized in normal individuals, respectively (representing the 95% confidence limit). Serum samples from six groups of subjects representing a variety of EBV-related illnesses were then studied. Only patients with notably elevated anti-EBV antibody titers to viral capsid antigen (VCA) (greater than 10,000) had elevated levels of anti-EBV DNase (38 to 56 U neutralized) and anti-EBV DNA polymerase (72 to 106 U neutralized). Three additional patients and two geriatric controls with average anti-EBV early antigen/VCA titers had slightly elevated levels of antibody to EBV DNA polymerase. IgA anti-VCA, anti-early antigen antibodies, or both, were also detected in the same patients who had high EBV DNase and polymerase antibody levels. These antibody profiles are similar to those in patients with nasopharyngeal carcinoma. Since three of the six patients with elevated anti-EBV enzyme antibody levels developed fatal lymphomas, patients with chronic EBV and this antibody profile might be in another illness category at risk for malignant disease.

Aged

Epstein-Barr virus and the chronic fatigue syndrome: a short review.

Chronic Fatigue Syndrome (CFS), previously known as neuroasthenia is often considered to be due to psychiatric causes. Evidence for a possible role for the Epstein-Barr virus in CFS is summarized. A plea is made for physicians to accept CFS as a non-psychiatric chronic illness to encourage further research into a clear definition of the syndrome.

Fatigue Syndrome, Chronic

Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle.

Purified dihydropyridine-sensitive calcium channels from rabbit transverse-tubule membranes consist of three noncovalently associated classes of subunits: alpha (167 kDa), beta (54 kDa), and gamma (30 kDa). Cleavage of disulfide bonds reveals two distinct alpha polypeptides and an additional component, delta. The alpha 1 subunit, a 175-kDa polypeptide that is not N-glycosylated, contains the dihydropyridine binding site, cAMP-dependent protein kinase phosphorylation site(s), and substantial hydrophobic domain(s). alpha 2, a 143-kDa glycoprotein, has none of the properties characteristic of alpha 1 but binds lectins and contains about 25% N-linked carbohydrate. alpha 2 is disulfide-linked to delta, a 24- to 27-kDa glycopeptide. beta (54 kDa) contains a cAMP-dependent phosphorylation site but is not N-glycosylated and does not have a hydrophobic domain. gamma (30 kDa) has a carbohydrate content of about 30% and extensive hydrophobic domain(s). Precipitation with affinity-purified anti-alpha 1 antibodies or alpha 2-specific lentil lectin-agarose demonstrated that alpha 1 alpha 2 beta gamma delta behaves as a complex in the presence of digitonin or 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, whereas the alpha 2 delta complex dissociates from alpha 1 beta gamma in the presence of Triton X-100. A model for subunit interaction and membrane insertion is proposed on the basis of these observations.

Animals

Chronic Epstein-Barr virus infection.

The Epstein-Barr virus (EBV) has been associated with classic infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, and B-cell lymphomas in primary and secondary immunodeficiency disease. The availability of specific serologic diagnosis of EBV, rather than dependence on heterophile antibody positivity, has broadened the scope of EBV-associated diseases. A chronic neuroasthenia syndrome accompanied by antibody titers to the viral capsid antigen and early antigen of EBV, which are higher than found in asymptomatic individuals, is one such additional EBV-associated syndrome. This paper describes the clinical and laboratory responses to EBV that are present in this chronic syndrome. It then discusses management of these patients and the difficulties in establishing a cause-and-effect relationship between EBV and chronic neuroasthenia along with recommendations for future studies.

Adult

Trypanosoma rhodesiense: variable effects of cyclophosphamide on antibody production, survival, and parasitemia in infected mice.

Mice of the CBA/CaJ strain, infected with Trypanosoma rhodesiense, were injected with a single high dose (approximately 200 mg/kg) of the immunosuppressive drug cyclophosphamide to determine if an induced, transient inability to make antibody affected survival or parasitemia. When given on the day of infection, the drug had no significant effect on survival. It delayed, but did not prevent, the appearance of specific antibodies and the clearance of the infecting trypanosome variants. When cyclophosphamide was injected 1 week after infection, survival mass significantly decreased. Antibody production to specific variant antigens and to common trypanosome antigens were terminated, but the mice were able to eliminate the infecting trypanosomes. These findings suggest that a temporary inability to make antibody to trypanosomes does not result in more rapid death when only the infecting trypanosome variant is present. However, immunosuppression may accelerate death if it occurs when there are many different types of trypanosomes present.

Animals

Noma in children with severe combined immunodeficiency.

Three Native American children with severe combined immunodeficiency developed noma, a necrotizing gingivostomatitis not previously reported in this country. The similarity between the clinical findings and those observed in monkeys with simian AIDS prompted us to evaluate our patients and their families for human retroviral infection. Antibodies to HTLV-I or HTLV-III/LAV proteins were not identified in patients nor in their family members. Standard bacterial and viral cultures similarly failed to identify a suspect pathogen.

Antibodies, Viral

Correlation between allergy and persistent Epstein-Barr virus infections in chronic-active Epstein-Barr virus-infected patients.

Forty-six anti-Epstein Barr nuclear antigen-positive allergic patients, 11 of whom having clinical and laboratory evidence of chronic-active Epstein-Barr virus (CA-EBV) infections, were characterized by EBV serology, percentages of T cells, B cells, and IgE+ cells, serum levels of IgE, and allergen-induced responsiveness of lymphocytes. Results demonstrated patients with CA-EBV have significantly increased responsiveness toward specific allergens, responses toward greater numbers of allergens, numbers of IgE+ T and B cells, and levels of background DNA activity in nonstimulated lymphocytes than do subjects who suffer from allergies in the absence of the CA-EBV syndrome. Further comparison between subjects with laboratory-determined mild and moderate allergy and those with CA-EBV demonstrated a progressive increase in the serum levels of IgE as the degree of allergy increased, no difference in concentrations of T and B cells, and titers of anti-viral capsid antigen and anti-early antigen to be significantly greater in patients with CA-EBV. Statistical analysis demonstrated that patients with CA-EBV could be separated from subjects with allergies by metabolic and immunologic variables. The data suggested that allergen-induced responses may contribute to the CA-EBV syndrome.

Adult

Specific allergen-induced Epstein-Barr nuclear antigen-positive B cells from patients with chronic-active Epstein-Barr virus infections.

Enriched B cells and peripheral blood lymphocytes from patients with chronic-active Epstein-Barr virus (CA-EBV) infections and subjects with mild and moderate allergies were cultured in vitro with specific allergens known to cause allergic reactions. A significant increase in Epstein-Barr nuclear antigen+ cells occurred only in the B cells obtained from patients with CA-EBV when cells were stimulated with the specific antigen. Results indicate an association between EBV-transformed cells and B cells with idiotypic expressions and may help to explain the association between CA-EBV and allergy in these patients.

Allergens