Utility of sonographic transcerebellar diameter in the assessment of gestational age in normal and intrauterine growth-retarded fetuses.

BACKGROUND: The fetal cerebellum has been shown to be least affected by external pressures and molding during pregnancy and therefore might provide more accurate estimation of GA. AIMS: To study the utility of transcerebellar diameter (TCD) measured by ultrasound for the detection of GA in normal and intrauterine growth-retarded (IUGR) fetuses. SUBJECTS AND METHODS: This cross-sectional study comprised 500 antenatal patients with a GA between 14 and 39 weeks and who were certain of their last menstrual periods. The TCD was measured ultrasonographically and the corresponding GA was determined. The GA was also determined with other customarily used sonographic parameters such as biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) and compared with TCD. Data of normal pregnancy patients was used to formulate nomograms by taking the 5th, 50th, and 95th percentile measurements. TCD to AC ratio was also calculated in both normal (n = 424) and IUGR pregnancies (n = 76). RESULTS: TCD showed significant correlation with gestational age (GA) measured by last menstrual period (LMP) as well as with GA calculated with other biometric fetal parameters. TCD also showed significant correlation with GA in normal (R2 = 0.979) as well as with IUGR pregnancies (R2 = 0.942). TCD to AC ratio remained fairly constant in normal pregnancies while it was increased in IUGR pregnancies. CONCLUSIONS: TCD and TCD/AC ratio can be employed as an objective parameter to establish the GA in normal as well as IUGR pregnancy cases.

In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6).

We investigated the cellular tropism of human B-lymphotropic virus (HBLV) (also designated Human Herpesvirus-6) in vitro by infecting fresh MN cells from normal human adult peripheral blood, umbilical cord blood, bone marrow, tonsil, and thymus. Cultures from all the sources examined contained infectable cells, as shown by the appearance of characteristic enlarged, round-shaped, short-lived cells expressing HBLV-specific markers. Detailed immunological analysis demonstrated that the vast majority of these cells expressed T cell-associated antigens (i.e., CD7, CD5, CD2, CD4, and to a lesser extent, CD8). The CD3 antigen and the TCR-alpha/beta heterodimer were not detectable on the surface membrane, but were identified within the cytoplasm of HBLV-infected cells, by both immunofluorescence and radioimmunoprecipitation assay. A proportion of the HBLV-infected cell population also expressed the CD15 and class II MHC DR antigens. By means of immunoselection procedures it was possible to show that a consistent proportion of HBLV-infectable cells were contained within the CD3-depleted immature T cell population, while the depletion of CD2+ cells completely abrogated the infectability of the cultures. Northern blot analysis confirmed the T cell origin of HBLV-infected cells, demonstrating the expression of full size TCR-alpha and -beta chain mRNA. In addition to fresh T cells, HBLV was able to infect normal T lymphocytes expanded in vitro with IL-2 for greater than 30 d. These results indicate that HBLV is selectively T cell tropic in the course of the in vitro infection of normal mononuclear cells and may therefore be directly involved in the pathogenesis of T cell related hematological disorders. In particular, in light of the cytopathic effect exerted in vitro on CD4+ T lymphocytes, a possible role of HBLV in immune deficiency conditions should be considered.

Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway.

Human immunodeficiency virus-type 1 (HIV-1) infection is characterized by a chronic state of immune hyperactivation in patients. Infection of human peripheral blood lymphocytes with HIV-1 in vitro resulted in increased interleukin-2 (IL-2) secretion in response to T cell activation via the CD3 and CD28 receptors. Expression of the HIV-1 transactivator Tat recapitulated this phenotype and was associated with increased IL-2 secretion in response to costimulation with CD3 plus CD28. IL-2 superinduction by Tat occurred at the transcriptional level, was mediated by the CD28-responsive element in the IL-2 promoter, and was exclusively dependent on the 29 amino acids encoded by the second exon of Tat.

Genetic evaluation of suspected cases of transient HIV-1 infection of infants.

Detection of human immunodeficiency virus-type 1 (HIV-1) on only one or a few occasions in infants born to infected mothers has been interpreted to indicate that infection may be transient rather than persistent. Forty-two cases of suspected transient HIV-1 viremia among 1562 perinatally exposed seroreverting infants and one mother were reanalyzed. HIV-1 env sequences were not found in specimens from 20; in specimens from 6, somatic genetic analysis revealed that specimens were mistakenly attributed to an infant; and in specimens from 17, phylogenetic analysis failed to demonstrate the expected linkage between the infant's and the mother's virus. These findings argue that transient HIV-1 infection, if it exists, will only rarely be satisfactorily documented.

Role of CD4 molecule in the induction of interleukin 2 and interleukin 2 receptor in class II major histocompatibility complex-restricted antigen-specific T helper clones. T cell receptor/CD3 complex transmits CD4-dependent and CD4-independent signals.

The CD4 molecule plays an essential role in antigen-induced activation of T helper (Th) cells, but its contribution to signal transduction events resulting in physiologic T cell function is ill defined. By utilizing anti-CD4 monoclonal antibodies (MAbs) that recognize distinct epitopes of CD4, we have investigated the role of CD4 molecule in antigen-induced interleukin 2 (IL-2) and IL-2 receptor (IL-2R) alpha chain expression in class II major histocompatibility complex-restricted antigen-specific human Th clones. Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression. IL-2R mRNA accumulation, however, was unaffected even at highest Leu3a concentrations. Leu3a treatment did not affect bypass activation of T cells with PMA plus ionomycin or activation via CD2 molecule. The MAb OKT4, which binds another domain of CD4, was not inhibitory. These results suggest that after T cell antigen receptor-CD3 activation, IL-2 gene induction, IL-2 secretion, and membrane IL-2R expression are absolutely dependent upon participation of CD4 molecules, phosphatidylinositol (PI) hydrolysis, and increase in [Ca2+]i. The requirement for IL-2R gene induction, however, occurs independently of CD4 molecule participation and PI hydrolysis.

Heterogeneity of b lymphocyte differentiation in severe combined immunodeficiency disease.

Pokeweed mitogen-induced B lymphocyte differentiation in vitro into antibody secreting plaque-forming cells (PFC) was investigated in nine patients with severe combined immunodeficiency having variable proportions of circulating B lymphocytes. When cultured by themselves, the peripheral blood mononuclear cells did not respond to stimulation with pokeweed mitogen in any patient. In the presence of irradiated allogeneic T cells as helpers, however, PFC responses were elicited in lymphocyte cultures from peripheral blood and/or bone marrow in some patients. In one of these patients, results of allogeneic co-culture experiments were suggestive of genetically restricted suppressor cells. In a single patient with deficiency of the enzyme adenosine deaminase, PFC were generated in bone marrow lymphocyte cultures only when they were supplemented with exogenous adenosine deaminase and allogeneic helper cells. A parallel study of T lymphocyte differentiation in vitro performed in fractionated bone marrow cells was suggestive of arrested differentiation at different steps along the differentiation pathway. In two patients with evidence of functional B cell precursors, deficiencies of helper T cell function could be attributed to differentiation defects at the level of the stem cells in one and the thymus in the other. The findings reported here further substantiate the heterogeneity of the severe combined immunodeficiency disease syndromes.

T-lymphocyte differentiation in vitro in severe combined immunodeficiency. Defects of stem cells.

A study of T-lymphocyte differentiation was made on fractionated bone marrow cells from normal volunteers and from 11 patients with severe combined immunodeficiency (SCID) using normal thymic epithelial monolayers and their culture supernates as inducing agents. Normal marrow cells could regularly be induced to bear the human T-lymphocyte antigen (HTLA), to form rosettes with sheep erythrocytes (E rosettes), and to respond to the mitogen concanavalin A (Con A) after coculture with the thymic epithelial monolayers or their culture supernates. In contrast, studies of T-cell differentiation on the marrow cells of patients with SCID revealed varying defects, ranging from a complete "absence" of definable T-cell precursors to partial differentiation resulting in acquisition of one (HTLA) or two (HTLA and E rosettes) markers for T lymphocytes. Only in one patient was there induction of all three T-cell markers, namely, HTLA, E rosettes, and responsiveness to Con A. These observations indicate that SCID is a heterogeneous disorder in which defects of differentiation can occur at one or more multiple sites of differentiation leading the the clinical expression of T- and B-cell dysfunction. Further, our studies indicate that in T-cell differentiation, HTLA probably appears before the capacity to form E-rosettes, and development of the latter capacity is followed by a state of responsiveness to mitogens. A scheme of normal differentiation along with the defects of precursor T cells seen in SCID is presented.

Decreased in vitro humoral immune responses in aged humans.

Induction of antigen-specific and non-specific (polyclonal) humoral immune responses in vitro was investigated in peripheral blood mononuclear cells of aged (65-85 yr) and young (20-30 yr) volunteers. In vitro immunization of lymphocytes with antigen (sheep erythrocytes) was performed in a recently described microculture system, and anti-sheep erythrocyte plaque forming cells were quantitated in a direct hemolytic plaque assay. Immunoglobulin secreting cells, induced polyclonally with pokeweed mitogen, were quantitated in a reverse hemolytic plaque assay. Significant depressions of antigen-specific as well as polyclonal responses were noted in relation to advancing age. Antigen-specific responses were more frequently depressed than polyclonal responses. T cell mitogen concanavalin A (Con A) was used to amplify functions of autologous immunoregulatory T cells. Addition of 10 microgram/ml Con A to lymphocytes of young donors at culture initiation resulted in activation of suppressor cells and abrogated antigen-specific responses. Delayed addition of Con A, on the other hand, enhanced responses, presumably because of activation of helper T cells. Similar manipulations of lymphocyte cultures from aged donors showed failure of Con A to suppress antigen-specific responses in approximately half of the responders. In many nonresponders, responses within normal range were elicited by the delayed addition of Con A to their lymphocyte cultures. Deviations beyond the range of expected responses were noted in 32.5% of the co-cultures between pokeweed mitogen stimulated young and aged cells. Our findings suggest that age-related deficiencies of B cell function are frequently associated with dysfunction of immunoregulatory T cells and are only occasionally due to intrinsic defects of B cells.

X-linked severe combined immunodeficiency. Diagnosis in males with sporadic severe combined immunodeficiency and clarification of clinical findings.

Over 80% of infants with severe combined immunodeficiency (SCID) of unknown genetic etiology are males, yet less than a third of these affected males have a family history of X-linked disease. To help identify new mutations of the X-linked SCID gene and to provide genetic counseling, X chromosome inactivation patterns in T cells from 16 women who had sons with sporadic SCID were examined. Between 9 and 35 human/hamster hybrids that selectively retained the active human X chromosome were produced from the T cells of each woman and analyzed with an X-linked restriction fragment length polymorphism for which the woman in question was heterozygous. Exclusive use of a single X as the active X was seen in the T cell hybrids from 7 of the 16 women, identifying these women as carriers of X-linked SCID. Studies on additional family members confirmed the mutant nature of the inactive X and revealed the source of the new mutation in three families. To determine whether there were any laboratory characteristics that might differentiate the boys whose mothers were identified as carriers of X-linked SCID from those whose mothers were not, the clinical records of both groups were compared to each other and to a group of 14 boys with a family history of X-linked SCID. The most consistent finding in the 21 patients with X-linked SCID was an elevated proportion of B cells. These data demonstrate the high incidence of spontaneous mutation for the X-linked SCID gene and help clarify the characteristic presenting features of this disorder.

MR Fingerprinting of Adult Brain Tumors: Initial Experience.

BACKGROUND AND PURPOSE: MR fingerprinting allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assessed the utility of MR fingerprinting in differentiating common types of adult intra-axial brain tumors. MATERIALS AND METHODS: MR fingerprinting acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 World Health Organization grade II lower grade gliomas, and 8 metastases. T1, T2 of the solid tumor, immediate peritumoral white matter, and contralateral white matter were summarized within each ROI. Statistical comparisons on mean, SD, skewness, and kurtosis were performed by using the univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple-comparison testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases, and area under the receiver operator curve was calculated. RESULTS: Mean T2 values could differentiate solid tumor regions of lower grade gliomas from metastases (mean, 172 ± 53 ms, and 105 ± 27 ms, respectively; P = .004, significant after Bonferroni correction). The mean T1 of peritumoral white matter surrounding lower grade gliomas differed from peritumoral white matter around glioblastomas (mean, 1066 ± 218 ms, and 1578 ± 331 ms, respectively; P = .004, significant after Bonferroni correction). Logistic regression analysis revealed that the mean T2 of solid tumor offered the best separation between glioblastomas and metastases with an area under the curve of 0.86 (95% CI, 0.69-1.00; P < .0001). CONCLUSIONS: MR fingerprinting allows rapid simultaneous T1 and T2 measurement in brain tumors and surrounding tissues. MR fingerprinting-based relaxometry can identify quantitative differences between solid tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas.

A classification of HTLV-III infection based on 75 cases seen in a suburban community.

Since 1981, 75 patients have been seen at our hospital with human T-cell lymphotropic virus type III (HTLV-III) infection. We have classified their clinical presentation into Groups 0 to 6. Groups 0 to 3 all have antibody to the Mr 41,000 protein of HTLV-III. Group 0 has no evident disease (9 patients), Group 1 has lymphadenopathy with or without exaggerated infection (16 patients), Group 2 has persistent lymphadenopathy with chronic hepatitis B surface antigenemia or profound hypergammaglobulinemia (7 patients), Group 3 has oral candidiasis with or without lymphadenopathy (7 patients). In Group 4 are acquired immunodeficiency syndrome (AIDS) adults or children (32 patients). Group 5 is a special classification for immunocompromised patients. Group 6 patients have lymphomas and Mr 41,000 protein antibody. Four children were classified separately. Three patients in Group 3 developed Group 4 disorders (AIDS). Four patients in Group 4 developed Group 6 disorders. HTLV-III infection spread in families (8 of 36), all from infected mothers to children. In 17 sexual partners, 6 were found to be infected. Five of 6 infected partners were homosexuals. We saw an inordinate number of transfusional AIDS (4 of 29) and 1 of 46 other disorders. Two infants also presented with severe intracranial defects, one with microcephaly and one with cranial calcifications and lucency. HTLV-III is spreading with alarming speed.

Specific inhibitory activity against granulocyte-progenitor cells produced by non-T lymphocytes from patients with neutropenia.

Bone marrow and peripheral blood cells of patients with non-leukemic neutropenia contain and elaborate a granulocyte-progenitor cell inhibitory activity. The inhibitory activity is common to the neutropenias of the various etiologies studied, which included congenital, idiopathic, autoimmune, cyclical, common variable immuno-deficiency with hypogammaglobulinemia and drug induced states. It derives from non-adherent, low density, slowly sedimenting and non-E-rosetting cells and appears to require RNA and protein synthesis, but not cell division, for its production. The material is not species specific, inhibits autologous and allogeneic normal CFUgm and leukemic CFUgm, is not cell-cycle specific in action and is most effective against granulocyte colony forming cells (CFUg), less effective against mixed granulocyte-macrophage colony forming cells (CFUgm) and least or non-effective against macrophage colony forming cells (CFUm). This inhibitory activity has no influence on cells which generate CFUc in suspension culture or on the erythroid colony forming (CFUe) and burst forming (BFUe) units. It is different from other known inhibitory activities such as lactoferrin, leukemia inhibitory activity, E type prostaglandins, interferon and immunoglobulins. This inhibitory activity, while at present an in vitro phenomenon, may be produced as a secondary response within a compromised host.

Magnetic resonance imaging for prostate cancer: what the urologist needs to know.

The use of magnetic resonance imaging (MRI) for prostate cancer imaging has been an area of burgeoning research activity with a goal of finding imaging characteristics that will allow for improved diagnosis and surveillance of prostate cancer. This article will review the MRI sequences currently used for imaging the prostate and describe the scoring and reporting system used by radiologists for prostate MRI known as the Prostate Imaging Reporting and Data System (PI-RADS). Current research regarding the role of prostate MRI for patients without prior biopsy, with prior negative biopsy and elevated PSA, and on active surveillance protocols will also be reviewed.

The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children.

The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies) project arises from the firm belief that perinatally infected children treated with suppressive antiretroviral therapy (ART) from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART-free remission. This is because HIV-infected infants treated within 2-3 months of life have a much reduced viral reservoir size, and rarely show HIV-specific immunity but preserve normal immune development. The goal of EPIICAL is the establishment of an international collaboration to develop a predictive platform using this model to select promising HIV therapeutic vaccine candidates, leading to prioritisation or deprioritisation of novel immunotherapeutic strategies. To establish this platform, the EPIICAL Consortium aims to: develop predictive models of virological and immunological dynamics associated with response to early ART and to treatment interruption using available data from existing cohorts/studies of early-treated perinatally HIV-infected children; optimise methodologies to better characterise immunological, virological and genomic correlates/profiles associated with viral control; test novel immunotherapeutic strategies using in vivo proof-of-concept (PoC) studies with the aim of inducing virological, immunological and transcriptomic correlates/profiles equivalent to those defined by the predictive model. This approach will strengthen the capacity for discovery, development and initial testing of new therapeutic vaccine strategies through the integrated efforts of leading international scientific groups, with the aim of improving the health of HIV-infected individuals.

Nef protein of HIV-1 has B-cell stimulatory activity.

OBJECTIVE: To examine the B-cell stimulatory properties of the regulatory Nef protein of HIV-1. METHODS: The effect of the HIV-1 regulatory proteins Nef, Tat and Vif, were analyzed for their ability to induce differentiation of normal B lymphocytes into immunoglobulin secreting cells (ISC). RESULTS: A recombinant Nef protein, but neither Tat or Vif, was able to induce ISC in peripheral blood lymphocyte (PBL) cultures of HIV-1-seronegative donors. Another recombinant Nef protein, d-Nef, with a truncated amino terminal (deletion of 34 amino acids) failed to induce B-cell differentiation. Pretreatment of the Nef protein with a polyclonal anti-Nef-antibody abrogated its B-cell stimulatory activity. The Nef-induced B-cell differentiation was dependent on cell-to-cell contact. Cell surface molecules leukocyte function-associated molecule (LFA)-1, intracellular adhesion molecule (ICAM)-1, human lymphocyte antigen-DR and B7 were involved in the T-B-cell interaction because monoclonal antibodies to these molecules abrogated the Nef-induced B-cell differentiation response. The Nef protein was able to induce interleukin (IL)-6 messenger (m)RNA and IL-6 protein secretion in PBL, with monocytes as the primary source. CONCLUSIONS: These findings indicate that regulatory (Nef) proteins of HIV-1 contribute to the intense B-cell activation that occurs in association with HIV-1 infection. T-B-cell contact-dependent interaction and induction of IL-6 by these proteins appear to play major roles in this process.

Patterns of CD8 T cell clonal dominance in response to change in antiretroviral therapy in HIV-infected children.

OBJECTIVE: To examine the influence of change in antiretroviral therapy (ART) on patterns of CD8 T cell clonal dominance in HIV-infected children. DESIGN: Seventeen HIV-infected children with plasma virus loads between 3.1 and 5.7 log10 were investigated before and after changes in ART. METHODS: CDR3 spectratyping was performed in 22 T cell receptor (TCR) Vbeta subfamilies by multiplex polymerase chain reaction (PCR) in purified peripheral blood CD8 T cells in conjunction with CD4 cell counts, plasma HIV-RNA copies and lymphoproliferative assays (LPA). RESULTS: CD8 T cell clonal dominance in two or more Vbeta families was present in eight out of 17 children. After a change in therapy, 13 patients (76%) acquired new clones whereas three patients (17.6%) showed a loss in CD8 cell clones. An increase in the numbers of dominant clones correlated with an increase in percentage CD4 cell counts (P < 0.001) and with improved LPA responses to tetanus (P < 0.05) and alloantigens (P < 0.01). CD4 cell increase was associated with an initial mean gain of 3.1+/-2.1 CD8 cell clones, independent of a virological response. A loss of CD8 cell clones or failure to achieve CD4 T cell increase was associated with failure to achieve virological suppression. CONCLUSION: Children with chronic HIV infection manifest CD8 T cell clonal dominance, which appears to be dependent upon the adequacy of the CD4 cells. With optimization of therapy, a gain in clonal dominance is the predominant response, except in situations of failure to contain viral replication.

Central brain atrophy in childhood AIDS encephalopathy.

OBJECTIVE: To determine differential patterns of brain atrophy in pediatric AIDS encephalopathy. DESIGN: We measured the bicaudate, bifrontal, and ventricle-brain ratio in brain magnetic resonance imaging scans of 42 control children, nine children with progressive AIDS encephalopathy, 25 AIDS children without progressive encephalopathy, and 23 children with cerebral atrophy of other causes. RESULTS: When compared with controls, encephalopathy patients showed significantly increased bicaudate and ventricle-brain ratios, but no significant increase in bifrontal ratio, whereas children with brain atrophy from causes other than AIDS showed increases in all three ratios. CONCLUSION: Children with AIDS encephalopathy demonstrate a specific pattern of brain atrophy distinct from other etiologies: a central atrophy, primarily affecting the subcortical white matter or the basal ganglia regions.

Serum HIV-1 p24 antibody, HIV-1 RNA copy number and CD4 lymphocyte percentage are independently associated with risk of mortality in HIV-1-infected children. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

OBJECTIVE: The role of HIV-1 antibody in modulating disease progression must be assessed in the context of other immune and viral load markers. We evaluated the association between HIV-1 p24 antibody, HIV-1 RNA, immune complex-dissociated (ICD) p24 antigen, CD4 cell percentage, and mortality in a cohort of 218 HIV-infected children enrolled in a trial of intravenous immunoglobulin prophylaxis of bacterial infections. METHODS: CD4 cell percentage was measured and sera collected and stored at baseline and every 3 months on study (1988-1991). Stored sera were assayed for HIV-1 p24 antibody, HIV-1 RNA, and ICD p24 antigen. Mortality was recorded during the trial and updated through 1996 (mean total follow-up, 6.3 years). RESULTS: Eighty-one (37%) children died; probability of mortality for children with baseline HIV-1 p24 antibody concentrations of undetectable (< 1), 1-4, 5-124, and > or = 125 reciprocal titer units (RTU) was 61, 50, 24, and 10%, respectively. A 3.5-fold increase in the relative risk (RR) of death [95% confidence interval (CI), 2.2-5.5] was observed among children with baseline HIV-1 p24 antibody concentration < 5 RTU compared with > or = 5 RTU. In multivariate analyses, p24 antibody, HIV-1 RNA, and CD4 cell percentage but not ICD p24 antigen were independently associated with mortality; the RR of death increased by 1.7 (95% CI, 1.3-2.1) for each log10 decrement in baseline HIV-1 p24 antibody. CONCLUSIONS: HIV-1 p24 antibody, HIV-1 RNA and CD4 cell percentage independently predict mortality amongst infected children. Whereas CD4 cell percentage provides an estimate of the general degree of immune suppression, HIV-1 p24 antibody could provide an easily obtained, inexpensive assessment of CD4 cell function and could augment prognostic information provided by CD4 cell count and viral load for clinical management of infected children.

Inhibitory influences of envelope glycoproteins of HIV-1 on normal immune responses.

Infection with the human immunodeficiency virus (HIV-1) leads to a wide range of immunological abnormalities. We have shown that native envelope glycoproteins (gp120) of HIV-1 inhibit antigen-specific and anti-CD3 induced lymphoproliferation of normal lymphocytes. We have demonstrated that gp120 binds to CD4 positive T lymphocytes and is internalized. These studies suggest that interaction of gp120 with the CD4 receptor may be sufficient to inhibit antigen-specific T cell responses that are mediated via the CD3-Ti receptor complex. Such an event could represent another mechanism by which the overall immune function of the CD4 positive T lymphocyte is depressed and may be relevant in planning investigations on the ongoing vaccine trial involving envelope glycoproteins.

Neoplastic complications of HTLV-III infection. Lymphomas and solid tumors.

Neoplastic disease arose in 29 of 200 patients infected with human T lymphotropic virus type III (HTLV-III) seen at a suburban hospital. Seventeen patients had Kaposi's sarcoma, one of whom also had colon carcinoma. Nine patients had lymphoproliferative disorders (seven lymphomas, one T suppressor cell chronic lymphocytic leukemia, and one multiple myeloma), including three with concomitant Kaposi's sarcoma and one with colon cancer. One other patient had colon cancer, one had a seminoma, and one had pancreatic cancer. Kaposi's sarcoma as a complication of AIDS occurred mainly in homosexuals (17 of 42 homosexuals, one of 17 drug abusers, one of five heterosexually promiscuous patients, and one of six patients who had previously received transfusions). The high-grade lymphomas did not show a predilection for any particular AIDS risk group. Three of four solid tumors arose in elderly AIDS patients. Twenty-five of 75 patients with CDC-defined AIDS had a neoplastic disorder (26 are still alive and may yet demonstrate malignancy). Few other diseases of man have been associated with as high an incidence of neoplastic transformation as occurs with HTLV-III infection.