Biological and molecular characteristics of human herpesvirus 7: in vitro growth optimization and development of a syncytia inhibition test

Abstract:

Two isolates of human herpesvirus 7 (HHV-7) were recovered from phytohemagglutinin-activated peripheral blood mononuclear cells of a patient with chronic fatigue syndrome and of a healthy blood donor. A genetic polymorphism between the two isolates was detected by Southern blot analysis using a novel HHV-7 genomic clone (pVL8) as a probe. We developed optimized conditions for the in vitro propagation of HHV-7 by using enriched populations of activated CD4+ T lymphocytes derived from normal peripheral blood, resulting in the production of high-titered extracellular virus (> 10(6) cell culture infectious doses/ml). Bona fide syncytia formation was documented both in normal CD4+ T lymphocytes and in the Sup-T1 CD4+ T-cell line following infection with high-titered HHV-7. To identify neutralizing antibodies to HHV-7, a syncytia-inhibition test was developed. Variable titers of syncytia-neutralizing antibodies were detected in all the human sera tested, thus confirming the high prevalence of HHV-7 in the human population.

 

Source: Secchiero P, Berneman ZN, Gallo RC, Lusso P. Biological and molecular characteristics of human herpesvirus 7: in vitro growth optimization and development of a syncytia inhibition test. Virology. 1994 Jul;202(1):506-12. http://www.ncbi.nlm.nih.gov/pubmed/8009865

 

The etiology and possible treatment of chronic fatigue syndrome/fibromyalgia

Abstract:

It is suggested that chronic fatigue syndrome/fibromyalgia is caused by virus injury to the calcium channels leading to larger quantities than usual of calcium ions entering the striated muscle cells. Should this be true, then treatment with a calcium antagonist (CA) may possibly be of value.

 

Source: Lund-Olesen LH, Lund-Olesen K. The etiology and possible treatment of chronic fatigue syndrome/fibromyalgia. Med Hypotheses. 1994 Jul;43(1):55-8. http://www.ncbi.nlm.nih.gov/pubmed/7968720

 

Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome

Erratum in: Med Hypotheses 1995 Aug;45(2):219.

 

Abstract:

Abnormalities of Essential Fatty Acid (EFA) incorporation into phospholipid are found in chronic diseases. More recently changes in circulating EFA metabolites (EFAM) together with EFAM hypo-responsiveness of immune cells and EFAM production from cells have been found associated with disease.

We hypothesize that changes in ratio of EFAMs are the normal physiological responses to stressors, but when stressors are excessive or prolonged, EFAM systems may become unpredictably hypo-responsive owing to factors such as receptor down regulation and substrate depletion. In time, many homeostatic system become deranged and held in that state by minor stressors.

Literature review of chronic fatigue syndrome (CFS) shows hyper and hypo-responsiveness in immune function, several Hypothalamo-Pituitary (HP) axes and sympathetic nervous system, all relatable to dysfunctional changes in EFA metabolism.

For the first time, we explain chronic immune system activation and hypo-responsive immune function in CFS; through EFAMs. Dietary EFA modulation (DEFA) can alter ratios of both membrane EFAs and produced EFAMs, and if maintained can restore hypo-responsive function.

We discuss dietary strategies and relevance in CFS, and a case series of CFS patients applying DEFA with other titrated published managements which saw 90% gaining improvement within 3 months and more than 2/3 fit for full time duties. This hypothesis and DEFA may have relevance in other chronic conditions.

 

Source: Gray JB, Martinovic AM. Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome. Med Hypotheses. 1994 Jul;43(1):31-42. http://www.ncbi.nlm.nih.gov/pubmed/7968718

 

Dimensional assessment of chronic fatigue syndrome

Abstract:

The absence of laboratory tests and clear criteria to identify homogeneous (sub)groups in patients presenting with unexplained fatigue, and to assess clinical status and disability in these patients, calls for further assessment methods. In the present study, a multi-dimensional approach to the assessment of chronic fatigue syndrome (CFS) is evaluated.

Two-hundred and ninety-eight patients with CFS completed a set of postal questionnaires that assessed the behavioural, emotional, social, and cognitive aspects of CFS. By means of statistical analyses nine relatively independent dimensions of CFS were identified along which CFS-assessment and CFS-research can be directed.

These dimensions were named: psychological well-being, functional impairment in daily life, sleep disturbances, avoidance of physical activity, neuropsychological impairment, causal attributions related to the complaints, social functioning, self-efficacy expectations, and subjective experience of the personal situation. A description of the study sample on these dimensions is presented.

 

Source: Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. Dimensional assessment of chronic fatigue syndrome. J Psychosom Res. 1994 Jul;38(5):383-92. http://www.ncbi.nlm.nih.gov/pubmed/7965927

 

Gender differences in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine whether there are differences between men and women patients who have chronic fatigue syndrome (CFS) and, if so, to ascertain whether a gender-related pattern exists.

DESIGN: A descriptive study of demographic, clinical, and psychosocial measures, the results of which were prospectively collected for patients who had CFS.

SETTING: A university-based referral clinic devoted to the evaluation and management of chronic fatigue.

PATIENTS: 348 CFS patients who had undergone complete medical evaluations.

MEASURES: Clinical variables included symptoms, physical examination findings, and laboratory results. Psychosocial assessment consisted of a structured psychiatric interview, the Medical Outcomes Study Short-form General Health Survey to assess functional status, the General Health Questionnaire to ascertain psychological distress, the Multidimensional Health Locus of Control, and measures of attribution, social support, and coping.

MAIN RESULTS: Overall, few gender-related differences were identified. Women had a higher frequency of tender or enlarged lymph nodes (60% versus 33%, p < or = 0.01) and fibromyalgia (36% versus 12%, p < or = 0.001) and lower scores on the physical functioning subscale of the Medical Outcomes Study Short-form General Health Survey (37.6 versus 52.2, p < 0.01); men more often had pharyngeal inflammation (42% versus 22%, p < or = 0.001) and reported a higher lifetime prevalence of alcoholism (20% versus 9%, p < or = 0.01).

CONCLUSIONS: In general, demographic, clinical, and psychosocial factors do not distinguish men from women CFS patients.

 

Source: Buchwald D, Pearlman T, Kith P, Schmaling K. Gender differences in patients with chronic fatigue syndrome. J Gen Intern Med. 1994 Jul;9(7):397-401. http://www.ncbi.nlm.nih.gov/pubmed/7931750

 

Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(I)-poly(C12U) in chronic fatigue syndrome

Abstract:

Latent 2′, 5′-oligoadenylate (2-5A) synthetase activity, bioactive 2-5A and RNase L activity were measured in extracts of peripheral blood mononuclear cells (PMBC) before and during a randomized, multicenter, placebo-controlled, double-blind study of poly(I)-poly(C12U) in individuals with chronic fatigue syndrome (CFS) as defined by the Centers for Disease Control and Prevention. The mean values for bioactive 2-5A and RNase L activity were significantly elevated at baseline compared to controls (p < .0001 and p = .001, respectively). In individuals that presented with elevated RNase L activity at baseline, therapy with poly(I)-poly(C12U) resulted in a significant decrease in both bioactive 2-5A and RNase L activity (p = .09 and p = .005, respectively). Decrease in RNase L activity in individuals treated with poly(I)-poly(C12U) correlated with cognitive improvement (p = .007). Poly(I)-poly(C12U) therapy resulted in a significant decrease in bioactive 2-5A and RNase L activity in agreement with clinical and neuropsychological improvements (Strayer DR, et al., Clin. Infectious Dis. 18:588-595, 1994). The results described show that poly(I)-poly(C12U) is a biologically active drug in CFS.

 

Source: Suhadolnik RJ, Reichenbach NL, Hitzges P, Adelson ME, Peterson DL, Cheney P, Salvato P, Thompson C, Loveless M, Müller WE, et al. Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(I)-poly(C12U) in chronic fatigue syndrome. In Vivo. 1994 Jul-Aug;8(4):599-604. http://www.ncbi.nlm.nih.gov/pubmed/7893988

 

Human herpesvirus-7 (HHV-7)

Abstract:

HHV-7 first isolated in 1990 from a healthy individual, is a ubiquitous agent. The second independent isolation of HHV-7 from a chronic fatigue syndrome patient was reported in 1992. The seroepidemiology of HHV-7 suggested that its prevalence rate in the U.S.A. population is > 85%; however, in Japan a low prevalence rate has been reported. HHV-7 can be more readily isolated from the saliva than HHV-6. The primary infection of HHV-7 appears later in life than HHV-6. No disease has been reported that is etiologically linked to HHV-7. HHV-7 is more closely related to HHV-6 and the human cytomegalovirus than other members of the human herpesvirus family.

 

Source: Ablashi DV, Berneman ZN, Kramarsky B, Asano Y, Choudhury S, Pearson GR. Human herpesvirus-7 (HHV-7). In Vivo. 1994 Jul-Aug;8(4):549-54. http://www.ncbi.nlm.nih.gov/pubmed/7893982

 

Clinical correlates of infection with human herpesvirus-6

Abstract:

Human herpesvirus-6 is a lymphotropic virus which infects susceptible individuals during the first year of life and usually causes life-long latency. In a variable percentage primary infections are followed by a short acute disease, exanthema subitum. Older individuals may suffer from infectious mononucleosis-like illnesses or from Kikuchi-Fujimoto’s disease. In addition, there is a fairly wide spectrum of lymphoid and hematopoietic diseases or autoimmune disorders, which are associated with elevated titers of HHV-6 antibody, and from which replicating virus may be isolated. Such diseases include atypical polyclonal lymphoproliferation, Hodgkin’s disease, chronic fatigue syndrome and systemic lupus erythematosus. The present article reviews the current knowledge of such associations.

 

Source: Krueger GR, Klueppelberg U, Hoffmann A, Ablashi DV. Clinical correlates of infection with human herpesvirus-6. In Vivo. 1994 Jul-Aug;8(4):457-85. http://www.ncbi.nlm.nih.gov/pubmed/7893974

 

Neuropsychology and psychology of MCS

Abstract:

Neurological symptoms are frequently reported by patients with multiple chemical sensitivities (MCS). Methods to compare the psychiatric, personality, and neuropsychological function of patients with MCS, chronic fatigue syndrome (CFS), and normal controls are described. Increased rates of Axis I psychiatric diagnoses are observed in the literature for MCS and CFS subjects relative to controls.

Findings on the MMPI-2 and the Toronto Alexithymia Scale reveal profiles consistent with the tendency to report somatic rather than emotional symptoms in response to stress. However, many of the reported somatic symptoms also coincide with those found in neurologic disorders. The overall neuropsychological profile for MCS subjects does not reflect cognitive impairment.

Relative to normal controls, the only difference in neuropsychological performance observed is reduced recognition of nontarget designs on a visual memory task. More fruitful areas for future psychological research will include measurement of the interaction between behavioral response styles and attentional processes in cognition, as well as observations under controlled challenge conditions.

 

Source: Fiedler N, Kipen H, Deluca J, Kelly-McNeil K, Natelson B. Neuropsychology and psychology of MCS. Toxicol Ind Health. 1994 Jul-Oct;10(4-5):545-54. http://www.ncbi.nlm.nih.gov/pubmed/7778113

 

Neuropsychiatric status of patients with chronic fatigue syndrome: an overview

Abstract:

Chronic fatigue syndrome (CFS) is an illness that results in debilitating fatigue as well as rheumatological, infectious, and neuropsychiatric symptoms. The present paper is a brief overview of the neuropsychological and psychiatric research on CFS. Studies from our laboratory contrasting CFS with patients with multiple sclerosis, depression, and healthy controls are detailed. Our hypothesis of neuropsychological impairments in CFS is discussed.

 

Source: Deluca J, Johnson SK, Natelson BH. Neuropsychiatric status of patients with chronic fatigue syndrome: an overview. Toxicol Ind Health. 1994 Jul-Oct;10(4-5):513-22. http://www.ncbi.nlm.nih.gov/pubmed/7778111