Elena Buimovici-Klein

Elevated β2-microglobulin and lysozyme levels in patients with acquired immune deficiency syndrome

beta 2-Microglobulin (beta 2-M) levels in sera and urines, and lysozyme levels in sera, were quantitated in healthy heterosexual men and several groups of homosexual males. The mean beta 2-M levels in sera and urines and lysozyme levels in sera of healthy heterosexual and homosexual men were not significantly different. However, beta 2-M levels in patients with lymphadenopathy syndrome and AIDS were elevated. The mean beta 2-M level in sera of 11 patients with the lymphadenopathy syndrome was 4016 +/- 473 micrograms/l (SEM) (P less than 0.001) and 5409 +/- 462 micrograms/l (P less than 0.001) in 27 patients with AIDS. Similarly, beta 2-M levels in the urines of patients with chronic diarrheal syndrome, lymphadenopathy syndrome, and those meeting the CDC surveillance definition of AIDS were also significantly elevated (P less than 0.025). The mean lysozyme levels in the sera of 11 patients with the lymphadenopathy syndrome was 16.58 +/- 0.04 microgram/ml, and in 27 patients with AIDS 15.40 +/- 1.16 microgram/ml, compared to the mean level obtained in normal heterosexual men of 6.67 +/- 0.42 microgram/ml (P less than 0.001). The results of this study suggest that measuring beta 2-M in serum and urine and lysozyme levels in serum might provide additional useful parameters for the evaluation of patients with AIDS and prodromal syndromes.

Efficacy of a virion envelope herpes simplex virus vaccine against experimental skin infections in hairless mice.

SummaryHairless mice were immunized with herpes simplex virus type 1 (HSV-1) envelope antigen (EAG), EAG in association with polyriboinosinic · polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose (PICLC), and inactivated purified HSV-1 (VAG). After 2 weeks the mice were challenged by a percutaneous HSV-1 infection in the orofacial (OF) or lumbosacral (LS) skin area. Following immunization a consistent cell-mediated immune response was observed in all immunized mice, although the humoral immune response was very low, or not detectable. After challenge, a marked secondary humoral and cell-mediated immune response developed in all immunized mice, and the animals were protected against the development of skin lesions and the fatal outcome of infection. However, the establishment of latent infections in the sensory ganglia was not prevented by the immunization procedure.

Low level rubella immunity detected by ELISA and specific lymphocyte transformation.

SummaryThe level of humoral and cell mediated immunity in persons with low or undetectable hemagglutination-inhibition (HAI) rubella titers was investigated by ELISA, IgG presence in sucrose gradient separated serum fractions and lymphocyte transformation. The study population consisted of persons with stated history of natural rubella infection and rubella vaccinees. Persons with natural rubella infection and HAI titers of 1:8 or ±1:8 (i.e., incomplete HAI at serum dilution of 1:8) were all ELISA positive and the stimulation index (SI) of specific lymphocyte transformation was higher than 2.5. Among the 20 persons with HAI titers of <1:8, 8 were found to be ELISA positive and their SI was also >2 and IgG was detected in their serum. Rubella vaccinees with HAI titers of 1:8 or ±1:8 were likewise ELISA positive. Their SI was lower: none higher than 3, but none lower than 1.5. Among 23 HAI negative vaccinees, 14 were found ELISA positive. This serum fraction contained IgG and the SI was >1.5. It appears that ELISA test is able to detect antibodies where the HAI test fails. The positive outcome of ELISA test in this case was confirmed by the presence of IgG in serum fractions and by the lymphocyte response to rubella specific stimulation.

Inhibition of HIV replication in lymphocyte cultures of virus-positive subjects in the presence of sho-saiko-to, an oriental plant extract.

An oriental remedy, Sho-saiko-to (SST) consisting of a mixture of aqueous extracts from seven different plants and whose most active component is the chemically defined compound baicalein was tested for its ability to inhibit the production of the human immunodeficiency virus (HIV). The testing was done with cultures of human lymphocytes obtained from HIV-positive asymptomatic subjects and patients with ARC or AIDS. The replication of the virus was monitored by quantitative assay of the reverse transcriptase (RT) activity and of the synthesis of antigen p24. The lymphocyte cultures (LC) were maintained in the absence and in the presence of 25, 50 or 100 micrograms/ml of SST, and monitored for up to 5 weeks. The results showed that in LC from asymptomatic subjects RT activity and synthesis of p24 was completely inhibited by low concentrations of SST. High concentrations of SST inhibited virus replication in 80% of LC from ARC patients, but were completely ineffective in LC from AIDS patients. It was observed that the RT activity was more sensitive to inhibition by SST than the synthesis of p24, and that the antiviral effect was dependent on the virus load of the LC.

Study of the lymphocyte in vitro response to rubella antigen and phytohemagglutinin by a whole blood method.

SummaryA whole blood culture method was used to study lymphocytein vitro responses to rubella antigen and to phytohcmagglutinin (PHA) in rubella infection. The acute phase of infection in four cases was characterized by high spontaneous incorporation of14C-thymidine in the cultures, unresponsiveness of lymphocytes to rubella antigen, and absence of response, or relatively low response, to PHA. Cells showing vigorousin vitro response to rubella antigen appeared at about two weeks after the onset of rash. Lymphocyte PHA response returned to normal by day 31. Three rubella vaccinees exhibited a similar response. The use of whole blood lymphocyte cultures stimulated with multiple doses of mitogen and with antigen appears to be a promising technique for studies of “general” and “specific” cell-mediated immunity in viral infections.

Subclinical congenital rubella infection associated with maternal rubella vaccination in early pregnancy.

the etiology of this syndrome, since the amenorrhea often precedes the weight loss? ~ Further observation and inves= tigation and long-term follow:ups may clarify the true significance of the findings. Our data indicate that in a group of patients with the syndrome of anorexia nervosa, one is more likely to find an abnormal CT scan in a male patient, and in a patient who loses considerable weight over a brief period of time.

Open study of AL-721 treatment of HIV-infected subjects with generalized lymphadenopathy syndrome: An eight week open trial and follow-up

AL-721 is a lipid compound composed of neutral lipids, phosphatidylcholine and phosphatidylethanolamine in a 7:2:1 ratio. The objective of this open study was to evaluate the effects of AL-721 in vivo in an 8-week open trial in which 10 g twice daily was administered on a low fat diet to eight HIV-infected subjects with lymphadenopathy syndrome (LAS). Serial lymphocyte cocultivation studies in 7 patients with initial culture positivity appeared to demonstrate reduction of reverse transcriptase peak counts in 5 with the trough noted in 4 at 8 weeks and in one at 4 weeks following termination of therapy. The mean values for all 7 patients revealed a baseline value of 73,419 with decrease to a low of 27418 at 8 weeks. Mean levels of total lymphocytes, T-4, T-8 and T-11 cells were not altered but lymphoproliferative responses to concanavalin A and pokeweed mitogens appeared to be augmented in 4 of the 8 subjects in association with AL-721 treatment. No side effects were noted. In a subsequent follow-up study using a normal diet in the same subjects lymphocyte cocultivation and mitogen-induced responses were less consistently affected when 15 g twice daily AL-721 was readministered. In addition, serum HIV p24 antigen and CD4 levels were not altered during both the 8-week open and subsequent AL-721 readministration. Four of the 8 patients have progressed to AIDS over the subsequent 14 months.

Prospective observations of viral and immunologic abnormalities in homosexual males.

This article presents preliminary observations on the immunologic and viral status of 103 homosexual men from New York who were enrolled in a prospective study begun in late 1981. At the time of enrollment, none of the study participants had acquired immunodeficiency syndrome (AIDS) as defined by the Centers for Disease Control (CDC). The initial laboratory investigation indicated that 82.7% of the 1st 81 volunteers had a OKT4:OKT8 ratio lower than the control range of 1.4-2.8. 31 (38.3%) of these 81 volunteers had 1 or more of the following signs and symptoms: history of fever, weight loss, diarrhea, lymphadenopathy, recurrent amebiasis, or persistent amebiasis. As part of the initial study, intensive laboratory investigations were performed on 30 of these subjects, including 20 who were symptomatic. Findings included abnormal T-cell markers, elevated immunoglobulins, circulating immune complexes, and cryoglobulins, as well as B-cell dysfunction. Follow-up of these patients 1 year later indicated that there was no significant improvement in T4:T8 ratio, and those volunteers originally identified as symptomatic continued to contribute the most abnormal ratios. A decrease in the absolute number of T4 lymphocytes contributed most to the ratio reversal. In addition, 26 of the 30 volunteers underwent viral isolation studies from 5 body sites or secretions. 23 of 26 were positive for virus from 1 or more sites compared with 3 of 33 heterosexual controls. Isolation of cytomegalovirus, especially from semen, was most frequent. It remains unclear whether the abnormal immunologic findings in healthy homosexual volunteers represent a transient response to viral infection, an epiphenonomenon due to multifactorial causes that make subjects susceptible to an unidentified AIDS agent, or AIDS itself. The cohort study will continue.

CELL-MEDIATED IMMUNITY IN RUBELLA ASSAYED BY A CYTOTOXICITY TEST AND BY LYMPHOCYTE STIMULATION

Preferential cytotoxic activity against rubella-infected target cells was discovered in the supernatants of rubella virus-stimulated human lymphocytes from rubella-seropositive but not seronegative donors. Supernatants from unstimulated lymphocyte cultures failed to show such activity. Assay of cytotoxic activity of lymphocyte culture supernatants against rubella-infected and uninfected human fibroblast cells, using cell counting in microplates, provided a method for studies of cell-bound immunity in rubella. This assay was more sensitive in detecting remote past immunity to rubella than was lymphocyte stimulation with rubella virus as measured by uptake of C-14-thymidine. Good correlation between the two methods was found when development of immunity was followed during the course of rubella infection and vaccination. By both tests, lymphocytes from rubella vaccinees became responsive to rubella antigen 4 weeks after vaccination. This late detection of specific cell-mediated immunity may be due to rubella virus-induced immunosuppression after vaccination, an early and transient phenomenon demonstrable by phytohemagglutinin-unresponsiveness of the lymphocytes.