Roberto Patarca

Massage therapy is associated with enhancement of the immune system's cytotoxic capacity.

Twenty-nine gay men (20 HIV+, 9 HIV-) received daily massages for one month. A subset of 11 of the HIV+ subjects served as a within subject control group (one month with and without massages). Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number, Natural Killer Cell Cytotoxicity, soluble CD8, and the cytotoxic subset of CD8 cells. There were no changes in HIV disease progression markers (CD4, CD4/CD8 ratio, Beta-2 microglobulin, neopterin). Major neuroendocrine findings, measured via 24 hour urines included a significant decrease in cortisol, and nonsignificant trends toward decrease of catecholamines. There were also significant decreases in anxiety and increases in relaxation which were significantly correlated with increases in NK cell number. Thus, there appears to be an increase in cytotoxic capacity associated with massage. Implications for HIV+ men as those with other illnesses, particularly cancer, are discussed.

Cytokines and Chronic Fatigue Syndrome

Abstract: Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent immunoglobulin deficiencies, most often IgG1 and IgG3. Immune dysfunction in CFS, with predominance of so‐called T‐helper type 2 and proinflammatory cytokines, can be episodic and associated with either cause or effect of the physiological and psychological function derangement and/or activation of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of disease with remission/exacerbation cycles. A T‐helper type 2 predominance has been seen among Gulf War syndrome patients and this feature may also be present in other related disorders, such as multiple chemical sensitivity. Therapeutic intervention aimed at induction of a more favorable cytokine expression pattern and immune status appears promising.

Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion.

Objectives:(1) To determine the safety and feasibility of repetitive reinfusions of activated autologous CD8 cells followed by low-dose continuous interleukin (IL)-2 infusion in patients with AIDS. (2) To study the relationships between clinical responses, surface marker phenotypic distributions and cytokine expression patterns of both cultured CD8 cells and lymphocytes in the peripheral blood compartment. Design:Six adult patients with Centers for Disease Control and Prevention group IV HIV-1 disease ranging from mild to severe, were studied. All patients were receiving zidovudine prior to and during the study period, and had initial CD4 and CD8 cell counts >50 and 200×106/l, respectively. Methods:Autologous CD8 T cells (108-1010) were reinfused five times after ex vivo culture and stimulation with phytohemagglutinin and recombinant (r) IL-2. The fifth such infusion was followed by 5 days of rlL-2 infusion. Phenotypes and cytokine expression patterns of the expanded cells were determined as well as serum levels of immune mediators throughout the study. Results:Patients showed stable CD4 and CD8 cell counts, p24 antigenemia, and minimal toxicity over the 24-week protocol study. Clinical improvement was observed in lymphadenopathy (six out of six), oral hairy leukoplakia (three out of four), and Kaposis sarcoma (KS; two out of two) in the patients studied. In vivo induction of detectable levels of bioactive acid-stable interferon (IFN)-a, but not of other cytokines studied, upon activated CD8 cell reinfusion was associated consistently with improvement of oral hairy leukoplakia. However, partial regression of KS was observed after the CD8 cell infusion cycles and without IFN-α induction. In one of the two patients studied, KS regression was associated with decreased IL-1 α serum levels. In the other patient, who had failed previous IFN-α therapy, KS regression was observed after a decline in reinfused CD8 cell-associated gene expression of tumor necrosis factor (TNF)-β. Both IL-1 α and TNF-β are growth factors for KS cells. Conclusions:These observations demonstrate the feasibility and safety of ex vivo CD8 cell activation, expansion, and reinfusion, and rlL-2 infusion in AIDS patients. The findings in this Phase I trial suggest potential clinical efficacy and encourage Phase II trials. The correlations obtained between clinical and immunological states could contribute to an understanding of the relationship between CD8 T-cell function and HIV-1-associated disease progression.

Differential induction of interferon gamma gene expression after activation of CD4+ T cells by conventional antigen and Mls superantigen.

We have analyzed cytokine gene expression by a murine CD4+ T-cell clone that expresses three forms of T-cell recognition. The clone employs a V beta 6-containing T-cell receptor to recognize (i) a self class II major histocompatibility complex and an ovalbumin-derived peptide (OVA), (ii) an I-Ab alloantigen, and (iii) Mls-1a. All three responses are accompanied by similar levels of cell proliferation. However, although interferon gamma gene expression is strongly induced during both physiological recognition of the OVA peptide and allogeneic major histocompatibility complex recognition, expression of this gene was not detected during the Mls response. These studies indicate that Mls recognition is functionally distinct from T-cell recognition of peptides and alloantigens and leads to an alternative pattern of cytokine gene expression. They also suggest the possibility that encounter with these two classes of T-cell antigen in vivo may generate subsets of T helper cells that display different patterns of cytokine gene expression.

Serum Neopterin and Somatization in Women with Chemical Intolerance, Depressives, and Normals

The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation. Serum neopterin, which has an inverse relationship with l-tryptophan availability, may offer a marker of inflammation and macrophage/monocyte activation. This study compared middle-aged women with CI (who had high levels of affective distress; n = 14), depressives without CI (n = 10), and normals (n = 11). Groups did not differ in 4 p.m. resting levels of serum neopterin. However, the CI alone had strong positive correlations between neopterin and all of the scales measuring somatization. These preliminary findings suggest the need for additional research on biological correlates of ‘unexplained’ multiple somatic symptoms in subtypes of apparent somatizing disorders.

Ring finger in the peroxisome assembly factor-1

The peroxisome assembly factor‐1 (PAF‐1) is reported here to contain the signature subsequence for a ring finger motif in its carboxyl‐terminus. This conserved subsequence in PAF‐1 may be the key to a gene expression regulatory pathway important in peroxisome biogenesis.

Hydrochlorothiazide-Induced Pulmonary Edema and Associated Immunologic Changes

OBJECTIVE: To describe a patient with noncardiogenic acute pulmonary edema induced by hydrochlorothiazide and to investigate the possible involvement of an immunologic mechanism in this adverse reaction. CASE SUMMARY: A 66-year-old Hispanic woman developed acute pulmonary edema 30 minutes after the ingestion of one tablet of triamterene 75 mg/hydrochlorothiazide 50 mg. The reaction was associated with hemoconcentration; a decreased white blood cell count with a shift to a predominance of polymorphonuclear cells; decreased serum immunoglobulin (Ig) G, IgG1, and IgG4; and increased serum IgM and complement 3 concentrations. DISCUSSION: Although there have been 35 reports of cases of hydrochlorothiazide-induced pulmonary edema, the etiology of this adverse reaction remains unknown. The observations presented in this case report, along with commonalities with previously reported cases, suggest that granulocytic infiltration into the lungs and IgG deposition in alveolar membranes may play a role in hydrochlorothiazide-induced pulmonary edema. CONCLUSIONS: Noncardiogenic pulmonary edema may be an immunologically mediated rare idiosyncratic reaction to hydrochlorothiazide.

Effects of retroviral infections on immune function in African-American intravenous drug users.

ObjectivesTo determine the effect of retrovirus infection and co-infection, and intravenous substance use, on immune function in African-Americans. DesignA cohort of South Florida street-recruited African-American intravenous drug users formed the study population. The cohort consisted of 90 HIV-negative & human T-lymphotropic virus (HTLV)-negative, one HIV-negative & HTLV-I-positive, 11 HIV-negative & HTLV-II-positive, 79 HIV-positive & HTLV-negative, one HIV-positive & HTLV-I-positive and 21 HIV-positive & HTLV-II-positive individuals. The results reported are for the cross-sectional, baseline assessment of immune parameters. MethodsLymphocyte phenotypic distributions and functional markers, including proliferative response to mitogens and natural killer cell cytotoxicity, were determined. Serum immunoglobulin (lg) levels were determined as a measure of B-cell activity. ResultsHTLV-II infection was associated with increases in CD8 lymphocyte count and serum lg, but with no other significant immunologic changes. The distribution of CD4 and CD8 percentages, CD4: CD8 ratio, phytohemagglutinin (PHA) and pokeweed mitogen (PWM) reactivity, lgA and lgG for the four retrovirus serostatus groups suggested the possibility of interactive effects in the co-infected group, as demonstrated by a trend toward lower medians for CD4 and for PHA and PWM response and higher medians for lgC, lgA and CD8. Retrovirus-seronegative intravenous drug users had significantly impaired immune status compared with non-drug-using control individuals. ConclusionsImmunologic dysfunction attributable to HTLV-II infection was minor compared with HIV infection in this population. Study subjects who were co-infected with HIV and HTLV demonstrated more impairment of immune function than individuals with single retrovirus infections.

Structure and Function of the Genome of HTLV

We are still in the early stages of discovery of the full range of biological activity of a newly discovered and most interesting family of human pathogens, the human T-cell leukemia viruses (HTLVs). This chapter is intended as a rough roadmap of the salient features of the viral genome. This overview is based in large measure on the sequence of one strain of HTLV that was obtained from lymphocytes of a patient with adult T-cell leukemia in Japan. Information is also drawn from protein sequence analysis and DNA sequence analysis of several other strains of HTLV isolated from patients with adult T-cell leukemia (ATLL) or acquired immune deficiency syndrome (AIDS) in our own laboratory. Similarities to other retroviruses are noted. The limits of our present knowledge will be outlined.

Differential enhancement of rapid eye movement sleep signs in the cat: a comparison of microinjection of the cholinergic agonist carbachol and the β-adrenergic antagonist propranolol on pontogeniculo-occipital wave clusters

The cholinergic agonist carbachol and the beta-adrenergic antagonist propranolol were microinjected at the same pontine sites and their effects on polygraphic rapid eye movement (REM) sleep, especially pontogeniculo-occipital (PGO) waves, were measured. While both propranolol and carbachol enhanced PGO wave activity and polygraphic REM sleep, the carbachol-correlated enhancement was more impressive. The increases in REM sleep signs elicited by carbachol were 5-fold over baseline and lasted throughout the 4-h recording period. Propranolol elicited 2.5-fold increases that were significant in the first 2 h only. Yet, the increase in PGO wave activity evoked by propranolol was equal to that of carbachol during non-REM sleep and wakefulness. The results indicate that while propranolol is less potent in activating the distributed neuronal network responsible for REM sleep generation, it selectively facilities that part of the network responsible for PGO waves.