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Biomedical subjects

J F Jones

Publications and source records attributed to J F Jones.

At least 55 records · Page 3Linked to original sources
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

Mosaic variegated trisomy (42,XY/43,XY, + variable) in a male pigtail macaque monkey.

We identified an infant male pigtail macaque monkey with a bizarre karyotype which, to the best of our knowledge, has never before been reported in any species. Examination of 107 nuclei from cultured lymphocytes revealed 81 (75.7%) to be trisomic, but with the supernumerary chromosome varying from cell to cell, trisomy 16 being the most common. A small percentage (11.2%) of the nuclei had a normal 42,XY karyotype, and the balance, with the exception of one apparent monosomic (possibly a technical artifact), had multiple chromosome abnormalities. Examination of cultured skin fibroblasts revealed a similar karyotype. We called this karyotype a mosaic variegated trisomy. At birth, the animal had a cleft lip and palate and situs inversus of the heart. He subsequently showed significant developmental delay and apparent mental retardation. There were no clinical symptoms of hematological malignancy, which often have associated acquired chromosome abnormalities such as those described here. The animal survived for 2 yr and 8 mo under intensive care.

Animals↗
PubMed1985

Immune function in chronic active Epstein-Barr virus infection.

The spectrum of illness attributed to Epstein-Barr virus (EBV) includes patients with symptoms persisting for more than 1 year without any other obvious underlying disease. High titers of antibodies to EBV, either IgG antiviral capsid antigen or anti-early antigen, can be demonstrated. In this study, 13 patients diagnosed as having chronic active EBV infection were examined to determine aspects of their immunologic status. Morphological examination and fluorescent antibody analysis revealed no abnormalities in the phenotypes of peripheral blood white cells present in these patients. Compared to those from healthy control individuals, mononuclear cells from the patients showed a markedly depressed ability to produce both interleukin-2 and interferon after stimulation with mitogen and a phorbol ester. Studies of natural killer (NK) cell activity revealed that unfractionated mononuclear cells from patients with chronic active EBV infection were significantly lower in killing activity compared to the control group. Fractionation procedures to enrich for large granular lymphocytes resulted in an increase in NK activity for all individuals, but killing activity still remained slightly lower in the patients than in the control group. The dysfunctions which were found in patients with chronic active EBV infection may reflect a primary defect in natural immune functions of the patients predisposing them to a chronic or intermittent clinical disease rather than a self-limiting illness. Alternatively, the abnormalities detected in these experiments may be a result of the viral infection itself.

Adolescent↗
PubMed1985

Deficiency of UV-induced excision repair in human thymocytes.

The capacity of human thymocytes and of differentiated lymphocytes circulating in peripheral blood to perform unscheduled DNA synthesis (a measure of nucleotide excision repair) after UV irradiation was measured by radioautographic analysis. Only 4% of immature T lymphocytes, but 68% of circulating lymphocytes exhibited unscheduled DNA synthesis. When UV sensitivity of peripheral blood lymphocytes and thymocytes from the same donor were compared, the thymocytes, in each case, were significantly more UV sensitive than were the circulating lymphocytes. Peripheral blood lymphocytes from subjects undergoing halothane and morphine anesthesia during surgery showed 56% less excision repair capacity than those from unanesthetized donors. The difference occurred in the number of cells capable of repair rather than in the extent of repair synthesis per cell. Ultraviolet-induced unscheduled DNA synthesis occurred in only 3% of the thymocytes removed from rats killed by cervical dislocation. Therefore, the deficiency of excision repair was observed in rat thymocytes which had not been affected by anesthesia or surgical trauma. Since the thymus contains more than 90% immature T-cells, our results indicate that immature T-cells are deficient in nucleotide excision repair whereas the majority of mature peripheral blood lymphocytes exhibit such repair.

Animals↗
PubMed1985

Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies.

Forty-four patients, including 26 adults and 18 children under 15 years of age, were referred for evaluation of recurrent or persistent illnesses, with symptoms including pharyngitis, lymphadenopathy, fever, headaches, arthralgia, fatigue, depression, dyslogia, and myalgia. Thirty-nine patients were positive for Epstein-Barr virus antibody with antibody levels compatible with active infection for at least 1 year. Antiviral capsid antigen and anti-early antigen titers of patients were significantly greater (p less than 0.001) than age-group-matched controls. The frequency, number, duration, and patterns of symptoms, as well as patient sex, were compared by age in study patients seropositive and seronegative for Epstein-Barr virus. Illness patterns were not associated with changes in specific antibody titers or clinical findings. Lymphocyte phenotype and function analyses were done in 11 of the 39 patients positive for Epstein-Barr virus antibody; no consistent differences from normal were found. Only 1 of 32 patients had circulating interferon, in contrast to 7 of 7 patients with acute infectious mononucleosis. There were many adverse consequences of the illness. Epstein-Barr virus infection may not be self-limiting, and the virus may be associated with clinically recognizable illness other than infectious mononucleosis in children as well as in adults.

Adolescent↗