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Of 2157 patients with the acquired immunodeficiency syndrome (AIDS) whose cases were reported to the Centers for Disease Control by August 22, 1983, 64 (3 per cent) with AIDS and Pneumocystis carinii pneumonia had no recognized risk factors for AIDS. Eighteen of these (28 per cent) had received blood components within five years before the onset of illness. These patients with transfusion-associated AIDS were more likely to be white (P = 0.00008) and older (P = 0.0013) than other patients with no known risk factors. They had received blood 15 to 57 months (median, 27.5) before the diagnosis of AIDS, from 2 to 48 donors (median, 14). At least one high-risk donor was identified by interview or T-cell-subset analysis in each of the seven cases in which investigation of the donors was complete; five of the six high-risk donors identified during interview also had low T-cell helper/suppressor ratios, and four had generalized lymphadenopathy according to history or examination. These findings strengthen the evidence that AIDS may be transmitted in blood.

The Centers for Disease Control conducted a case-control study to investigate an outbreak of Kaposi's sarcoma and Pneumocystis carinii pneumonia in homosexual men. The occurrence of these diseases was found to be associated with certain aspects of lifestyle, including a greater number of male sex partners per year, exposure to feces during sex, history of syphilis and non-B hepatitis, treatment for enteric parasites, and use of various illicit substances. Laboratory studies reflected both this lifestyle and the probable underlying cause of the Kaposi's sarcoma and P. carinii pneumonia--cellular immune deficiency. Patients were found to have lymphopenia, specifically a deficiency of the T-helper subpopulation, resulting in a reversal of the T-helper to T-suppressor ratio. Levels of IgG and IgA were increased. When compared with controls, patients were also found to have significantly higher titers of antibody to Epstein-Barr virus and cytomegalovirus, a higher prevalence of antibody to hepatitis A virus and Treponema pallidum, a lower prevalence of antibody to varicella zoster virus, and a higher frequency of isolation of cytomegalovirus.

Twenty Haitian patients, hospitalized from 1 April 1980 to 20 June 1982, had Pneumocystis carinii pneumonia, central nervous system toxoplasmosis, esophageal candidiasis, cryptococcosis, disseminated cytomegalovirus, progressive herpes simplex virus, chronic enteric coccidiosis, or invasive Kaposi's sarcoma. Ten patients died. Opportunistic infections were frequently multiple and were recurrent in three patients. In seven patients disseminated tuberculosis preceded the other infections by 2 to 15 months. There was no evidence of an underlying immunosuppressive disease, and no history of homosexuality or intravenous drug abuse. At least three patients probably acquired the syndrome in Haiti. Lymphadenopathy was common. Seventeen patients tested had anergy, and 18 had lymphopenia. Monoclonal antibody analysis of peripheral-blood T-cell subsets done on 11 patients showed a marked decrease in T-helper cells and an inversion of the normal ratio of T-helper cells to T-suppressor cells. This syndrome among heterosexual Haitians is strikingly similar to the syndrome of immunodeficiency described recently among American homosexuals.

Sera from unrelated individuals with recurrent Neisserial infections lacked C8 hemolytic activity, but contained a protein that is antigenically related to C8. Immunochemical analysis revealed complete identity of the C8-related protein of all three sera and a marked antigenic deficiency compared with normal C8. The C8-related protein was isolated from serum by adsorption to immobilized anti-C8 IgG, elution with 3 M guanidine, and subsequent gel filtration. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, the abnormal protein resembled the alpha-gamma subunit of normal C8 with respect to mobility and its ability to be cleaved upon reduction into the alpha and gamma chains. The beta chain present in normal C8 was absent. Sedimentation equilibrium analysis indicated a molecular weight of 86,000 for the abnormal C8 protein, which is identical to that of the alpha-gamma subunit of normal C8. Amino acid analysis revealed no significant difference between the abnormal C8 and normal alpha-gamma. Unlike normal C8, the abnormal protein did not bind to EAC1-7 or to SC5b-7; however, upon addition to the deficient serum of beta chain isolated from normal C8, hemolytic activity was restored and formation of SC5b-9 occurred. We concluded that the dysfunctional C8 protein in the three individuals' serum is identical to the alpha-gamma subunit of normal C8 and that this form of C8 deficiency is distinct from the C8 deficiencies previously reported in which the entire three-chain protein is lacking.

An assay for antibodies to membrane antigens of cells infected by human T-cell leukemia virus was used to examine serum from persons who donated blood to 12 patients with acquired immunodeficiency syndrome (AIDS) associated with blood transfusions. The occurrence of positive results in the assay was significantly greater among donors to the AIDS patients (9 of 117; 7.7 percent) than among random donors (1 of 298; 0.3 percent). Of 12 sets of donors examined, 9 sets included a donor whose serum gave positive results for the presence of the antibodies. In six of these nine sets, the seropositive donor was an individual who was also identified as a possible source of AIDS transmission when epidemiologic and immunologic criteria were used.

From 1 June 1981 through 31 January 1984, 201 cases of the acquired immunodeficiency syndrome were reported involving persons who could not be classified into a group identified to be at increased risk for this syndrome. Thirty-five had received transfusions of single-donor blood components in the 5 years preceding diagnosis of the syndrome and 30 were sexual partners of persons belonging to a high-risk group. Information was incomplete for most remaining patients, but because many of these patients were demographically similar to populations recognized to be at increased risk for the syndrome, previously identified risk factors may have been present but not reported for some of them. Additionally, a few persons who met the case definition for the syndrome probably had other reasons for their opportunistic disease and did not have the acquired immunodeficiency syndrome. The slow emergence of the acquired immunodeficiency syndrome in new populations is consistent with transmission mediated through sexual contact or parenteral exposure to blood.

Genetic polymorphism in the beta-subunit of the eighth component of human complement, C8, was defined by isoelectric focusing of serum in polyacrylamide gel in the presence of urea and development of specific patterns of hemolysis in an overlay gel containing antibody-sensitized erythrocytes and C8 beta-chain-deficient serum. Bands of hemolysis induced by serum from unrelated Caucasians suggested autosomal codominant inheritance of three structural alleles at a single locus, C82: C82 degrees A (acidic), C82 degrees B (basic), and C82 degrees A1 (very acidic) with frequencies of 0.952, 0.044, and 0.004, as well as the probable null allele C82 degrees Q0. The distribution of phenotypes agreed with the Hardy-Weinberg equilibrium. The previously described genetic polymorphism in human C8 defined with the use of "complete" C8 (C8 alpha-gamma-chain)-deficient serum was distinct from and independent of the inherited structural variation at C82. Therefore, the locus for C8 alpha-gamma-chains has been redesignated C81, and has the alleles C81 degrees A, C81 degrees A1, and C81 Q0. Linkage studies failed to show close linkage between the two loci for C8, C81, and C82, and between C82 and the major histocompatibility complex or C6.

A patient had adult T-cell leukemia-lymphoma in the unusual setting of coinfection with human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type I (HTLV-I). The leukemic cells were CD4 positive and showed clonal genetic rearrangement of the T-cell receptor complex. Cytogenetic analysis showed three clonal karyotypic abnormalities: trisomy 3 and two translocations [t(1;15), (X;1)]. The patient was seropositive for HIV and HTLV-I; HTLV-I and HIV-1 DNA sequences were detected in peripheral blood leukocytes by the polymerase chain reaction. The HTLV-I sequences were detected in a relatively high proportion of mononuclear cells (at least 1 in 30 cells), whereas HIV-1 sequences were detected in a smaller proportion of cells (at least 1 in 3000 cells). Clinical remission was achieved after chemotherapy. There was a decrease in the proportion of HTLV-I positive mononuclear cells (at least 1 in 1000 cells), whereas the proportion of HIV-1 positive cells was relatively unchanged (at least 1 in 1000 cells). Adult T-cell leukemia-lymphoma in the setting of HIV coinfection may become increasingly common because asymptomatic retroviral coinfections are frequent.

A 71-year-old previously healthy woman developed unexplained thrush, onychomycosis, Pneumocystis carinii pneumonia, and a T-cell defect consistent with the acquired immunodeficiency syndrome. Her only apparent risk factor was infrequent, monogamous sexual contact with her husband, a 74-year-old hemophiliac who had received factor VIII concentrate and subsequently died due to P. carinii pneumonia. She first developed probable signs of the syndrome (recurrent thrush and onychomycosis) 1 year before her husband became ill. These findings suggest that the syndrome can be transmitted heterosexually by an asymptomatic person, and that the female sexual partners of hemophiliacs treated with factor VIII concentrate may be at risk of acquiring the syndrome; frequent sexual contact or several sexual partners are not necessary for transmission to occur; and the syndrome can occur in elderly people if exposed to risk factors. This case further supports the theory that the syndrome in hemophiliacs is due to an infectious agent that can be transmitted heterosexually as well as parenterally.

From Oct 1, 1982, to Oct 1, 1983, the Centers for Disease Control (CDC) received reports of 35 children whose illness met the CDC definition of acquired immune deficiency syndrome (AIDS). All of the children had serious opportunistic infections without a known underlying illness to explain susceptibility to the infections. The 35 children were residents of ten different states; cases clustered in five major metropolitan areas. Three of the children had a parent with AIDS, and one child who had been previously reported had received a blood transfusion from a person in whom AIDS later developed. Most of the children had at least one parent in a population group in which adult AIDS cases have occurred. Many of the children had histories of prodromal symptoms, including pneumonitis, lymphadenopathy, hepatomegaly, and oral thrush. The mean age at onset of illness was 5 months, and the mean age at diagnosis was 12 months. To determine whether opportunistic infection in children without underlying immunodeficiency was truly a new phenomenon, a review of requests to the CDC for the drug pentamidine isethionate was undertaken. This revealed an apparent increase from 1979 to 1983 in Pneumocystis carinii pneumonia in children without known underlying immunodeficiency.

A cohort of 334 intravenous (IV) drug users from New York City drug treatment programs were followed over a mean 9-month period. Among the 165 who were seropositive at enlistment, four developed clinical AIDS, for an annual rate of 3%. Elevated IgA was a significant predictor of developing AIDS. Among 72 subjects who were initially seronegative and who were re-interviewed, four were seropositive at follow-up, for a seroconversion rate of 7% per year among seronegatives. Among seropositive subjects who did not develop AIDS or fatal AIDS related complex (ARC), continued drug injection was associated with rate of T4 cell loss, and there was a non-significant trend for males to lose T4 cells more rapidly than females. While it was not possible to distinguish the mechanism underlying the relationship between continued drug injection and T4 cell loss, seropositive IV drug users should be warned that continued injection may lead to increased HIV-related immunosuppression as well as, if injection equipment is shared, risking viral transmission to others.

A patient with common variable hypogammaglobulinemia (CVH) who presented with recurrent sinopulmonary infections, nodular lymphoid hyperplasia of the small bowel, and intestinal giardiasis was studied. A diffuse lymphocytic lymphoma with small bowel, skin, and hepatic involvement subsequently developed in the patient. Light microscopy of the tumor revealed tissue infiltration with mononuclear cells having the morphologic features of T-lymphocytes. The malignant lymphocytes had characteristics of T-suppressor/cytotoxic cells as established by the absence of surface immunoglobulin and Leu 3 surface markers, and the presence of OKT3 and OKT8 surface markers. Peripheral blood lymphocyte studies revealed an increased number of T-suppressor cells, a reversal of the helper-suppressor ratio, and a generalized state of hyporesponsiveness to mitogen and antigen stimulation. No evidence of retroviral reverse transcriptase activity was detected in cultures of peripheral blood lymphocytes. The association between CVH and a lymphoma composed of cells with T-suppressor/cytotoxic surface markers has not been previously reported. The postulated role of T-suppressor cells in the failure of immunoglobulin synthesis in some forms of CVH suggests that the finding of a T-suppressor/cytotoxic cell lymphoma complicating CVH may be more than fortuitous.

Frozen sections of lymph nodes from 20 homosexual men with chronic generalized lymphadenopathy and of lymph nodes showing follicular hyperplasia from 14 patients without known risk factors of the acquired immunodeficiency syndrome were studied with monoclonal antibodies to T-cell subsets and to the HLA-DR antigen. In T-cell areas of the lymph nodes, excluding tertiary paracortical nodules, the mean T-helper-to-T-suppressor ratio (Th/Ts) +/- 1 SEM was significantly lower in the homosexual group (1.07 +/- 0.06) when compared with the control group (2.49 +/- 0.23), P less than .0001. In seven homosexual men, cell suspensions from the same lymph nodes were analyzed using a fluorescence-activated cell sorter. Results obtained by this method and by immunohistochemistry were comparable except in a homosexual man whose lymph node contained large tertiary paracortical nodules. Although the Th/Ts ratios of the blood and lymph nodes of the same patients were both low, there was not good correlation between the two sets of values (r = .2). Furthermore, there was not good correlation between blood lymphocyte count and lymph node Th/Ts ratios (r = .45). The lymph node Th/Ts ratios of the homosexual patients show less variations compared with the control group. The patient who subsequently developed multiple opportunistic infections had the lowest value. Whether the lymph node Th/Ts ratio has prognostic significance in patients with the lymphadenopathy syndrome warrants further investigation.

The acquired immune deficiency syndrome (AIDS) manifested by opportunistic infections or Kaposi's sarcoma is a newly recognized and often fatal disease. Three patients seen in Syracuse, New York, were noted to have lymphopenia and persistent serum lymphocytotoxic antibodies (LCTAs). In a double blinded study, 25 serum samples were coded and sent to us by the Centers for Disease Control Task Force on Kaposi's Sarcoma and Opportunistic Infections. Samples from 5 patients with Pneumocystis carinii pneumonia, 5 patients with Kaposi's sarcoma, 5 presumably healthy homosexual males, 5 presumably healthy heterosexual males, and 5 presumably healthy heterosexual females were included. Of the ten AIDS patients, nine had "positive" or "suspicious" results on testing for lymphocytotoxic antibodies. The five heterosexual male and five heterosexual female controls had "negative" results. Of the five homosexual male "controls," three had "positive" or "suspicious" LCTA results. Two of these three "controls" were available for follow-up. Both showed deficiencies in studies of their cell-mediated immunity. Lymphocytotoxic antibodies may participate in the ongoing immunodeficiency seen in AIDS.

Between September 1981 and June 1982, the acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia were diagnosed in seven previously healthy young men incarcerated for 5 to 38 months in New York State correctional facilities. All seven patients were anergic, six were lymphopenic, and all developed oral candidiasis. Immunologic evaluation in vitro showed profound defects in cellular immune function in patients tested, with inversion of the normal ratio of helper to suppressor T-cell populations in four of five patients studied. No underlying immunosuppressive disorder was found in any patient, including three patients who had postmortem examinations. Based on these cases, the incidence of this syndrome among inmates of New York State correctional facilities is estimated to be at least 20 out of 100 000 per year. None of the inmates was homosexual but all had used intravenous drugs extensively before incarceration. If intravenous drug use is a cause of the syndrome, then the epidemiologic findings of this study suggest a prolonged incubation period (mean, 14.6 months) before development of serious opportunistic infection. Recognition that certain prisoners are at high risk for the acquired immunodeficiency syndrome has important implications for the prison health-care system.

We describe acquired immune deficiency manifested by opportunistic infections in 10 previously healthy heterosexual Haitian men. The opportunistic pathogens included Toxoplasma gondii (in four patients), Cryptococcus neoformans (in one), Pneumocystis carinii (in four patients), and Candida albicans (in three). Six of the patients also had Mycobacterium tuberculosis. Immunologic studies of three patients showed a decrease in the numbers and activity of helper T cells, with normal or increased populations of suppressor T cells. Serologic markers for previous infections from hepatitis A, cytomegalovirus, and herpes simplex virus were detected in several patients. Six of the patients died despite specific antimicrobial therapy. The clinical and immunologic findings in these 10 Haitians are similar to those reported in drug addicts and homosexuals with the acquired immune-deficiency syndrome.

In a previous study of asymptomatic homosexual men, we found that CD8+ T-cell levels were higher in homosexual men infected with the human immunodeficiency virus (HIV) than in uninfected homosexual men because of higher numbers of CD8+ T cells that do not express the Leu15 marker, a phenotype associated with cytotoxic function. Among infected men, there was a positive correlation between the number of CD8+Leu15- T cells and the number of CD4+ T cells. If CD4+ T-cell levels are taken as a measure of severity of HIV infection and immunodeficiency, these results suggested that higher CD8+Leu15- cells may represent a phenotypic profile associated with less severe infection or better control of infection. In the present study, we extend the analysis to include a group of men who progressed to AIDS but were studied well before the onset of AIDS, and we compare results of CD8 subset analyses with results of infected men who have not progressed to AIDS. Phenotypic subsets associated with helper, suppressor, cytotoxic, and natural killer cell function were determined by two-color immunofluorescence. The only phenotypic subset that distinguished men who progressed to AIDS from those who have not was lower numbers of CD4+ T cells in the former group. If CD8+Leu15- cell numbers (or other phenotypic subsets examined) reflect effective control of HIV infection, the relationship is not strong enough to be of prognostic or predictive value with respect to outcome of infection.

Lymphocyte subset enumerations, antibody titers to specific proteins of human immunodeficiency virus (HIV), and measurement of infectious HIV titers in peripheral blood mononuclear cells were performed on serial blood specimens from 15 HIV-infected homosexual men with chronic lymphadenopathy syndrome (LAS); 6 of these men have subsequently progressed to AIDS (progressors), and 9 have remained clinically stable (nonprogressors). For the earliest samples studied, no test distinguished those who would progress to AIDS from those who have not. The two groups diverged significantly about 1 year before AIDS diagnosis in the progressor group. Virus titers rose in progressors but remained relatively stable in nonprogressors. CD4 T cells and the CD4 T cell subset, 4B4, declined more rapidly in progressors than in nonprogressors. HIV antibody titers tended to decline in progressors, but the differences were significant only for antibody and to the pol-encoded proteins, p51/65, and the gag-encoded polyprotein, p55. Before the onset of clinical AIDS, progressors are distinguished from nonprogressors by markedly different rates of CD4 cell depletion and virus replication, but the elements that control these dynamics remain to be defined.

Parenteral drug abusers are at risk for acquired immunodeficiency syndrome (AIDS), which is caused by human immunodeficiency virus (HIV). We tested stored sera for antibody to HIV (anti-HIV) using two enzyme-linked immunosorbent assay (ELISA) methods and Western blot. The patients were parenteral drug abusers who had undergone percutaneous liver biopsy for chronic liver disease. Current or former alcohol abuse was noted in 88 (80%) of the 110 patients. The sensitivities of the two ELISA tests in comparison with Western blot, the more specific test for HIV, were 100 and 94%, respectively; the specificities were 94 and 99%. Western blot was positive in 36 (33%) of 110 patients. False-positive ELISA reactions for anti-HIV were seen in five (7%) of 70 patients with negative Western blot analyses. Compared to true-negatives, false-positives had significantly more years of alcohol abuse, younger ages of onset of alcohol abuse, greater frequencies of jaundice and edema, higher levels of alkaline phosphatase, total billirubin, total protein, and globulins, and lower levels of serum albumin. In a stepwise logistic regression, only hyperglobulinemia was significantly associated with a false-positive anti-HIV. We conclude that: (a) ELISA tests for anti-HIV are useful for screening abusers of alcohol and parenteral drugs with chronic liver disease for HIV infection, but positive results must be confirmed with more specific tests such as Western blot; (b) false-positive ELISA reactions in this population are associated with hyperglobulinemia; and (c) studies of HIV testing are needed in other populations of patients with alcoholism or liver disease.

To study the association between mycobacterial disease and the acquired immunodeficiency syndrome, we reviewed the records of all cases of tuberculosis and all cases of the syndrome reported in Dade County, Florida, from January 1980 through June 1983. Tuberculosis was diagnosed in 27 of 45 Haitians with the syndrome, but in only 1 of 37 non-Haitians with the syndrome (p less than 0.001). Among the 27 Haitians with the syndrome and tuberculosis, 19 had extrapulmonary tuberculosis, whereas among 286 Haitian patients with tuberculosis without the syndrome, only 56 had extrapulmonary tuberculosis (p less than 0.001). Tuberculosis preceded the syndrome by 1 to 17 months (mean, 6) in 22 patients. In 10 patients with the syndrome and positive sputum cultures who were treated with conventional antituberculosis drugs, the cultures became negative within 1 to 4 months and tuberculosis did not recur. The frequency of disseminated atypical mycobacteriosis or positive sputum cultures for atypical mycobacteria was not significantly different between Haitian (11.3%) and non-Haitian (8.3%) patients with the syndrome.

We assessed the value of urinary neopterin concentrations for prognosis of disease progression in HIV-1-infected patients. Sixty-eight anti-HIV-1 seropositive homosexuals with lymphadenopathy syndrome were tested for urinary neopterin and T-cell subset counts in 1982-83, and the incidence rate at which they developed acquired immunodeficiency syndrome (AIDS) between then and May 1988 was evaluated. Overall, 21 of 68 (30.9%) cases progressed to AIDS, with a yearly progression rate of 4-9%. The predictive value of urinary neopterin concentrations was higher (P = 0.0042) than that of CD4+ T-cell counts (P = 0.015) or the CD4+/CD8+ T-cell ratio (P = 0.022). Counts of CD8+ T-cells failed to show predictive significance (P = 0.29). Similarly, multivariate-regression analysis indicated that neopterin concentrations and CD4+ T-cell numbers were significant copredictors. Produced by human macrophages activated by interferon gamma, neopterin is thus a marker of macrophage activation via T cells. We conclude that these data demonstrate a correlation between the amount of T-cell-macrophage activation, as measured by urinary neopterin concentrations, and the progression of the disease.

Differential centrifugation of a homogenate from a mechanically disrupted, acapsular isolate of Cryptococcus neoformans resulted in a 105,000 x g supernatant (105 K) and a microsomal fraction (MS), both of which were capable of eliciting specific delayed cutaneous hypersensitivity and in vitro blastogenesis in infected guinea pigs. Polyacrylamide gel electrophoresis revealed two major proteins in the MS and seven proteins in the 105 K fractions. Electron microscopy of the MS showed both membranes and ribosomes. In vitro lymphocyte blastogenesis elicited by 1 to 10 micrograms/ml of antigens was maximal after 4 days of incubation; the reacting populations were peripheral blood leukocytes (PBL) and peritoneal exudate cells (PEC). Spleen cells of infected animals were unresponsive to in vitro antigenic stimulation. A simplified schedule of priming animals was infection with a single dose of virulent cryptococci. Under these conditions 3 of 6 animals' PBL responded with stimulation ratios of 6.55, 21.1, 35.42 to the MS and 1.41, 9.33, 17.39 to the 105 K antigens at 1 microgram/ml. Four of six animals' PEC response were positive with stimulation ratios of 2.62, 2.72, 4.02 and 7.20 towards MS, and 2.62, 5.13, 5.71, 10.01 to the 105 K antigens at 1 microgram/ml. When small capsule and large capsule isolates were used for infection, the small capsule form was not isolated from the brain, in contrast to its isolation from 2 of 3 animals receiving large capsule forms. Two of three animals in each group responded with blastogenic indices more vigorous in the PBL, and the most potent antigen was MS. There was no obvious difference in lymphocyte reactivity between the two groups.

To identify risk factors for the occurrence of Kaposi's sarcoma and Pneumocystis carinii pneumonia in homosexual men, we conducted a case-control study in New York City, San Francisco, Los Angeles, and Atlanta. Fifty patients (cases) (39 with Kaposi's sarcoma, 8 with pneumocystis pneumonia, and 3 with both) and 120 matched homosexual male controls (from sexually transmitted disease clinics and private medical practices) participated in the study. The variable most strongly associated with illness was a larger number of male sex partners per year (median, 61 for patients; 27 and 25 for clinic and private practice controls, respectively). Compared with controls, cases were also more likely to have been exposed to feces during sex, have had syphilis and non-B hepatitis, have been treated for enteric parasites, and have used various illicit substances. Certain aspects of a lifestyle shared by a subgroup of the male homosexual population are associated with an increased risk of Kaposi's sarcoma and pneumocystis pneumonia.

A micromethod for assaying the reverse transcriptase enzyme of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus in cocultures of clinical specimens for viral isolation was developed and compared with the macromethod in use. Ultracentrifuged, pelleted, and solubilized viral culture supernatants were transferred into either tubes (macromethod) or microtiter plates (micromethod) and incubated with tritiated enzyme substrate. Trichloroacetic acid-precipitated DNA was collected on individual filter papers with a Millipore filtration manifold (macromethod) or on filter sheets using a semiautomated cell harvester (micromethod). Filters were then placed in scintillation fluid and counted on a beta scintillation counter. Results of the micromethod significantly correlated to those of the macromethod, with a linear relationship between the two. The cutoffs for positivity based on the mean + 2 standard deviations for a set of known negative specimens (n = 19) was 4,973 cpm for the micromethod compared with 5,336 for the macromethod. The intrarun and interrun variations were comparable for both methods. There was a 67% increase in the maximal daily number of specimens which could be run (100 versus 60) as well as a reduction in reagent use. In summary, the micromethod utilizing a semiautomated cell harvester is comparable to the existing macromethod in accuracy and is an improvement due to savings in time and reagents.

Seventeen patients with multiple myeloma were given intravenous immunoglobulin at doses ranging from 150 mg/kg to 500 mg/kg in a phase I study. The intravenous immunoglobulin was well tolerated with only three transient episodes of mild clinical toxicity during 27 infusions. In no instance was hepatic or renal toxicity seen. Marked biologic variability over the one month study period in total IgG levels in patients with non-IgG myeloma and IgG subclasses in many of the patients was observed, making intravenous immunoglobulin half-life determinations based on IgG or IgG subclass levels problematical. The decay of functional antibody to hepatitis B surface antigen was determined. Analysis of the hepatitis antibody data suggested that intravenous immunoglobulin half-life was in the range of seven to 20 days for the entire study group and was not related to the isotype of the myeloma paraprotein or to the baseline levels of IgG. No infections were observed in the study group during the study period, but the potential for infection prophylaxis by intravenous immunoglobulin in myeloma patients must be evaluated in a randomized, prospective, controlled phase III study.

Seventy-five homosexual men with generalized lymphadenopathy for at least three months (lymphadenopathy syndrome [LAS]), subsequently shown to be seropositive for antibody against human immunodeficiency virus, were enrolled in a prospective study in Atlanta in 1982 and 1983. As of Nov 30, 1987, twenty-two (29%) of the 75 were known to have developed acquired immunodeficiency syndrome (AIDS) three to 60 months after enrollment and five to 69 months after onset of LAS. The six-year cumulative incidence of AIDS, by Kaplan-Meier survival analysis, was 38%. The cumulative incidence in years 4, 5, and 6 (30%) was significantly higher than in years 1, 2, and 3 (11%), suggesting that the risk for AIDS increases after the third year of LAS and that many more study participants will eventually develop AIDS. A precipitous decline in the T-helper cell count frequently heralds the diagnosis of AIDS; this decrease appears to occur at different times after the onset of LAS in different persons. The four-year cumulative incidence of AIDS following observations of T-helper cell counts less than 200/mm3, 200 to 299/mm3, 300 to 399/mm3, and 400/mm3 or greater was 84%, 41%, 25%, and 18%, respectively; these data are important for determining prognosis in the individual patient as well as for determining the suitability of candidates and baseline data for drug trials.

Lymph nodes of patients symptomatically infected with the acquired immunodeficiency syndrome (AIDS) virus show a spectrum of morphologic changes ranging from marked lymphoid hyperplasia to marked lymphocytic depletion. These changes can be grouped into three distinct patterns. The type I pattern features follicular and paracortical hyperplasia, and is associated with chronic lymphadenopathy. The type II pattern, which shows diffuse lymphoid hyperplasia but loss of germinal centers, signifies evolution of chronic lymphadenopathy to AIDS. The type III pattern shows marked lymphocytic depletion and represents the end-stage lymph node seen in fatal AIDS. These histologic patterns are closely correlated with the clinical and immunologic status of patients infected with the AIDS virus.

Surface markers, terminal transferase, cytochemical staining, and function of peripheral blood lymphocytes were examined in nine patients with T-cell lymphoproliferative disease. Anti-T-cell antiserum proved useful in characterizing the phenotypes of the abnormal cells when only a minority of the abnormal cells formed E-rosettes. Anti-B-cell antiserum was consistently unreactive with the abnormal cells. Terminal transferase was elevated in T-cell ALL but low in T-cell CLL, lymphoma-leukemia, or Sézary syndrome. Lymphocyte proliferative response to nonspecific mitogens was generally depressed as was the response to allogeneic cells. The cells also failed to stimulate in mixed lymphocyte culture, implying a lack of Ia antigens on their surface. Acid phosphatase stain was positive in three patients tested. Peroxidase and esterase stains were negative, whereas PAS was positive in five of eight patients tested. Prognosis in general, regardless of the clinical picture, (ie, acute, chronic, or lymphoma-leukemia), was poor with seven of the nine patients dying within 14 months of diagnosis. Therefore, the use of anti-T-cell antisera and the E-rosette surface marker should be used to characterize the phenotype of the malignant cells in lymphoproliferative disease to enable more vigorous treatment of those that are of T-cell origin and that therefore carry a poor prognosis.

We report a case of Yersinia enterocolitica septicemia with septic arthritis. Gentamicin administration controlled the septicemia but failed to eradicate the organisms in the joint, in spite of a synovial fluid level four times its minimal inhibitory concentration after four days of therapy. Development of azotemia necessitated change of antibiotic therapy to chloramphenicol, which eradicated the infection. While Y enterocolitica infection in the United States is uncommon, it must be added to the list of organisms causing suppurative arthritis and septicemia in susceptible hosts. Septic arthritis must be distinguished from the much more common reactive theumatic polyarthritis associated with Y enterocolimica infection, for which antibiotic therapy is neither needed nor helpful.

Changes in immunologic parameters were followed in members of a cohort of human immunodeficiency virus (HIV)-positive homosexual or bisexual men with lymphadenopathy and were analyzed for differences between those who have and those who have not progressed to the acquired immunodeficiency syndrome (AIDS) (progressors, nonprogressors). T helpers and the Th/Ts ratio were lower in progressors than in nonprogressors both at entry into the study and at the latest visit. T suppressors were not different in the two groups at entry but were higher in nonprogressors at the latest visit. Evaluation of the patterns of change over time showed that T helpers and Th/Ts ratios tended to decrease over time in both nonprogressors and progressors, while T suppressors increased in nonprogressors and decreased in progressors. Although progressors had a greater deterioration in immunologic parameters over time, nonprogressors also had significant deterioration when compared with controls. Based on the respective percentages of men with abnormal or normal T helpers or Th/Ts ratio at entry who have already progressed to AIDS, we would conservatively estimate, considering their latest T helpers and Th/Ts ratio, that at least an additional 16 (32%) of our nonprogressors will develop AIDS in the next 5 years.

Antilymphocyte antibodies were studied using the Terasaki microcytotoxicity technique in 21 gay patients including 7 with Kaposi's sarcoma, 5 with opportunistic infection, and 9 with lymphadenopathy syndrome. A significant increase in lymphocyte-reactive antibody was noted in 61% of this group. Similar studies using serum from 25 apparently healthy gay males showed lymphocytotoxic antibody in only one instance. When isolated T-cell subsets (OKT4+ or OKT8+) were utilized, a few sera from acquired immune deficiency syndrome (AIDS) patients apparently showed preferential killing for helper-inducer or suppressor-cytotoxic T-cell subsets, however, this showed no correlation with T-cell phenotypic profiles of OKT4 or OKT8+ cells in concurrent peripheral blood studies. When isolated normal OKT4 or OKT8 T-cell subsets were treated with complement and AIDS serum showing apparent T-cell subset specificity and treated T cells added to B cells, macrophages, and OKT4 or OKT8 cells cultured with pokeweed mitogen, no discernible effect on either help or suppression of IgG or IgM synthesis was recorded.

The titers and isotypes of antibodies to specific proteins of the human immunodeficiency virus were determined by Western blot analysis of sera from 107 homosexual men. Antibody titers were generally lower in sera from patients with the acquired immunodeficiency syndrome (AIDS) and in sera from men whose condition subsequently progressed to AIDS than in sera from men who had not progressed to AIDS. We found no evidence of isotypic prominence or restriction of the antibody response. In multivariate analysis, lower levels of CD4 helper cells were most highly associated with progression to AIDS. Lower antibody titers to the envelope protein gp110, the core protein p24, and the reverse transcriptase enzyme p51/65 were also predictive of progression to AIDS independent of their association with CD4 cell levels. These data suggest that differences in antibody levels are not simply a consequence of severe immunodeficiency but may be markers for control of infection.

Lymphadenopathy-associated virus ( LAV ), a human T- lymphotrophic retrovirus isolated from a homosexual man with lymphadenopathy, has been causally associated with acquired immunodeficiency syndrome (AIDS). A sensitive and specific radioimmunoprecipitation test was developed for the detection of antibodies to the major core protein of LAV , p25 (molecular weight 25,000). Antibody to LAV p25 was found in the serum of 51 of 125 AIDS patients, 81 of 113 patients with lymphadenopathy syndrome, 0 of 70 workers at the Centers for Disease Control (some of whom had handled specimens from AIDS patients), and 0 of 189 random blood donors. Of a group of 100 homosexual men from San Francisco whose serum was obtained in 1978, only one had antibody to LAV p25; in contrast, of a group of 50 homosexual men in the same community whose serum was obtained in 1984, 12 had antibodies to LAV p25.