Clinical observations during virtual reality therapy for specific phobias.

Virtual environments offer a new method of providing exposure therapy to patients with specific phobias. Although the stimuli (three-dimensional computer simulations) is new, the method of systematically desensitizing the patient to phobic stimuli until habituation occurs is a concept that was formally introduced by Joseph Wolpe over 40 years ago. Our article discusses some of the clinical observations that have been made during nearly 500 virtual reality exposure therapy sessions with patients and research participants who have come to our center in the past 15 months with a fear of flying or driving.

The effects of immersiveness on physiology.

The effects of varying levels of immersion in virtual reality environments on participant's heart rate, respiration rate, peripheral skin temperature, and skin resistance levels were examined. Subjective reports of presence were also noted. Participants were presented with a virtual environment of an airplane flight both as seen from a two-dimensional computer screen and as seen from within a head-mounted display. Subjects were randomly assigned to different order of conditions presented, but all subjects received both conditions. Differences between the non-phobics' physiological responses and the phobic's response when placed in a virtual environment related to the phobia were noted. Also noted were changes in physiology based on degree of immersion.

Adenosine deaminase isoenzyme levels in patients with human T-cell lymphotropic virus type 1 and human immunodeficiency virus type 1 infections.

In serum, the enzyme adenosine deaminase (ADA) is known to be divided into two isoenzymes, ADA1 and ADA2, which have different molecular weights and kinetic properties. The present study investigated ADA isoenzyme levels in the sera of patients infected with retroviruses associated with adult T-cell leukemia (ATL), human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM), and AIDS, ADA isoenzyme activities were found to be significantly (P < 0.001) higher in the sera of patients with ATL, HAM, and AIDS than in the sera of healthy controls. In the case of the ADA subtypes in the sera of patients with ATL, ADA1 activity was significantly (P < 0.001) elevated in patients with the acute and lymphoma types of ATL compared with that in patients with the chronic and smoldering types of ATL. ADA2 activity was significantly elevated in the sera of patients with the acute, lymphoma, and chronic types of ATL (P < 0.001) compared with that in patients with smoldering ATL and HTLV-1 carriers. In the case of patients with human immunodeficiency virus type 1 (HIV-1) infection, ADA1 and ADA2 activities in the sera of patients with AIDS and HIV-1 antibody-positive individuals were significantly (P < 0.001) higher than those in the sera of HIV-1 antibody-negative individuals. A significant elevation in ADA2 activity was also seen in the sera of AIDS patients (P < 0.01) compared with that in the sera of HIV-1 antibody-positive individuals. These results suggest that the magnitude of elevation of ADA isoenzyme levels in serum correlates well with the clinical conditions of the patients with these diseases. Measurement of the activities of ADA isoenzymes may therefore provide an additional parameter for distinguishing the subtypes of ATL and may prove to be useful as prognostic and therapeutic monitors in diseases associated with HTLV-1 and HIV-1 infections.

Suppression of macrophage reactive intermediates by cocaine.

The in vivo or in vitro effects of cocaine on the production of hydrogen peroxide (H2O2), superoxide (O2-), and nitrite (NO2-) by sodium periodate-elicited macrophages were studied. Hydrogen peroxide and superoxide productions were suppressed by both in vitro treatments and in vivo administrations of cocaine. The H2O2 and O2- production partially recovered after 150 min in vitro. However, cocaine inhibited NO2- production only in vitro, failing to suppress it through in vivo administration.

The suppression of macrophage secretion by calcium blockers and adenosine.

In an effort to examine the effects of calcium blockers and adenosine on superoxide, hydrogen peroxide, and nitrite secretions by mouse peritoneal macrophages, we have utilized the phenol red method, the superoxide dismutase-inhibitable reduction of ferricytochrome c method, and the Griess reagent method to test products after treating periodate-elicited mouse peritoneal macrophages with verapamil, nifedipine, and adenosine. The results show that after treating the macrophages with chemicals 10 minutes before adding PMA (100 ng/ml), all three chemicals inhibited superoxide (O2-) and hydrogen peroxide (H2O2) secretions dose-dependently, yet they failed to suppress macrophage reactive oxygen intermediates (ROI) after a 24 hour treatment. On the other hand, calcium blockers, verapamil and nifedipine, could reduce nitrite secretion (NO2-), while adenosine did not show the ability to inhibit NO2-. This indicates that calcium, as a secondary messenger, is important for the production of ROI and RNI. The reason behind the loss of the ability to suppress macrophage ROI production in a 24 hour treatment remains unexplored.

P300 assessment of chronic fatigue syndrome.

The P3(00) event-related brain potential (ERP) was elicited with an auditory tone-discrimination paradigm in 25 patients diagnosed with chronic fatigue syndrome (CFS) and 25 matched normal control subjects. Target stimulus probability was varied systematically (0.20, 0.50, 0.80) in different task conditions. No differences between the CFS and control subjects were found for either P3 amplitude or latency. No group effects were observed for the N1, P2, and N2 components. Despite the attentional and immediate memory deficits reported in CFS, the P3 ERP from auditory stimuli does not reliably discriminate CFS from matched control subjects.

Effects of cannabinoids and cocaine on the mitogen-induced transformations of lymphocytes of human and mouse origins.

The effects of delta 9-tetrahydrocannabinol (d9THC), delta 6-tetrahydrocannabinol (d6THC), and cocaine on the mitogen-induced transformations of lymphocytes of human and mouse origins were examined in an in vitro system. None of the three compounds is mitogenic in nature. The effects of the two components of marijuana on the mitogen-induced transformation are biphasic. Both compounds stimulated the lymphocyte transformation at low concentrations and inhibited mitogenesis at high concentrations. Cocaine, on the other hand, neither affected mitogen-induced lymphocyte transformations nor altered d9THC's transformation effects when both compounds were added together. Human lymphocytes and mouse splenocytes appeared to respond in similar patterns.

Labelling of lipids and phospholipids with [3H]arachidonic acid and the biosynthesis of eicosanoids in U937 cells differentiated by phorbol ester.

Phorbol esters induce morphologic and biochemical differentiation in U937 cells, a monocyte/macrophage-like line derived from a human histiocytic lymphoma. We are interested in the phorbol ester-stimulated release of arachidonic acid from cellular membranes and the subsequent synthesis of eicosanoids, as it may prove to correlate with the induced cellular differentiation. Undifferentiated log-phase U937 cells released little recently incorporated [3H]arachidonic acid, but phorbol 12-myristate 13-acetate increased its apparent rate of release to that of cells differentiated by exposure to phorbol myristate acetate for 3 days. Exposure of washed differentiated cells immediately prelabelled with [3H]arachidonic acid to additional phorbol myristate acetate did not augment the release of [3H]arachidonic acid. The basal release of nonradioactive fatty acids from differentiated cells was 5-10 times that of undifferentiated cells, and phorbol myristate acetate increased their release from both types of cell 2- to 3-fold. Differentiated cells immediately prelabelled with [3H]arachidonic acid exhibited greater incorporation into phosphatidylinositol and phosphatidylcholine, and contained more radioactive free arachidonic acid, compared with undifferentiated cells. Undifferentiated cells contained more radioactivity in phosphatidylserine, phosphatidylethanolamine and neutral lipids. Phorbol myristate acetate caused differentiated cells to release [3H]arachidonic acid from phosphatidylinositol, phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine, but release from neutral lipids was reduced, and the content of [3H]arachidonic acid increased. In undifferentiated cells incubated with phorbol myristate acetate, radioactivity associated with phosphatidylserine, phosphatidylethanolamine and neutral lipid was reduced and [3H]arachidonic acid was unchanged. Synthesis of cyclooxygenase products exceeded that of lipoxygenase products in both differentiated and undifferentiated cells. Phorbol myristate acetate increased the synthesis of both types of product, cyclooxygenase-dependent more than lipoxygenase-dependent, especially in differentiated cells. The biological significance of these changes in lipid metabolism that accompany phorbol myristate acetate-induced differentiation are yet to be established.

Synthesis of eicosanoids by gamma-interferon-differentiated U937 cells.

Interferons induce morphological, biochemical and functional alterations in monocyte macrophage and myeloid cell lines. We studied the effect of 3 days incubation with gamma-interferon from human buffy coats on the global synthesis of arachidonic acid metabolites by U937 cells. Interferon-induced morphologic changes including cytoplasmic and nuclear changes and the appearance of multiple lysosomal-like granules consistent with cellular differentiation were observed by electron microscopy. The labeling of phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine was increased and that of phosphatidylinositol, free fatty acids as 3H-arachidonic acid and neutral lipids reduced, when interferon-treated cells were incubated with 3H-arachidonic acid. Interferon caused qualitative and quantitative changes in the synthesis of cyclooxygenase and lipoxygenase products. A23187, a calcium ionophore, and the tumor promotor, phorbol myristate acetate, greatly increased the synthesis by interferon-differentiated cells of 2 cyclooxygenase products; synthesis of lipoxygenase products was reduced. In the presence of indomethacin, 'shunting' into putative lipoxygenase products occurred. The relationship between interferon-induced morphologic and functional changes, the development of altered phospholipid and eicosanoid metabolism and the identity of these metabolites are yet to be established.

Transient autoantibodies with elevated complement levels in common viral diseases.

Autoantibodies including rheumatoid factor (RF), anti-DNA antibody (ADA), and anti-nuclear factor (ANF) in addition to cold agglutinin and heterophil antibody titers were tested for in a total of 219 patients with common viral diseases. The diseases included varicella, influenza, measles, mumps, herpes zoster, hand-foot-mouth syndrome, and exanthem subitum . A high incidence of RF (23%) was demonstrated in varicella patients, and ADA and ANF (16% and 12%, respectively) were most frequently detected in the influenza cases. Those autoantibodies were most frequently found in patients with influenza. Each serum complement component and total hemolytic complement (CH50) were also assayed. Elevated levels of the fourth (C4) and ninth (C9) components of complement, along with elevated CH50, were observed in most patients. Follow-up studies indicated that those autoantibodies as well as other antibodies disappeared 3 to 8 weeks after the onset of infection. The present study indicates that substantial but transient alterations in the immune system accompanied by autoimmune phenomena and elevated levels in the complement components can occur in viral infections.

Prostaglandins in histiocytosis-X. PG synthesis by histiocytosis-X cells.

Histiocytosis-X cells were obtained at autopsy from the lungs and lymph nodes of a patient who died of the disseminated infantile form of this disease (Letterer-Siwe disease). The ability of these cells to synthesize and release prostaglandins was investigated in culture, by prelabeling the cell lipids with [14C] arachidonic acid and measuring the subsequent release of radioactive metabolites. The cells were seen to release primarily PGD2 and thromboxane. Correlative morphologic studies ensured the purity of the cell preparations, ruling out extraneous origin of the prostaglandins from sources other than the lesional histiocytes. Electron-microscopic study confirmed that the same cells that release prostaglandins and are capable of engulfing particles also bear the Langerhans' inclusions considered to be cell markers of histiocytosis-X. The prostaglandin production profile of alveolar macrophages from an infant who died as a result of congestive heart failure, but without histiocytosis, was studied for comparison. These cells produced PGE2 and thromboxane, but not PGD2. The theoretical implications of these findings are discussed.

Congenital fibrosarcoma: presence of a histiocytic component.

We describe the histologic and ultrastructural appearance of a massive soft-tissue tumor in the left lower extremity of a newborn girl. In its clinical presentation and morphologic features, this tumor corresponded to the entity currently known as congenital fibrosarcoma. The variability of histologic conformation of these lesions is emphasized. Ultrastructural study disclosed many cells with the subcellular morphology of elements of the histiocytic-macrophagic series. Whether these cells are viewed as an integral part of the tumor or as a secondary feature, their presence in a congenital fibrosarcoma is of interest for understanding of biologic behaviour of these uncommon tumors.