19F spectroscopy and relaxation behavior of trifluorovinyldichloroborane.

The 19F NMR spectra and spin-lattice relaxation rate, R1, of trifluorovinyldichloroborane as shown in were studied as a function of temperature, T, and magnetic field, B. All logR1 vs 1/T plots show a minimum at 299K indicating the presence if dipolar relaxation at lower T and spin-rotation relaxation at higher T. The R1 values increase with increasing B due to chemical shift anisotropy relaxation. Estimates of the fluorine chemical shift values for F3 (cf. Fig. 1) suggest that there is pi character in the F-C bond. The other two C-F bonds are largely single bonded. No evidence was found for intermolecular exchange of the trifluorovinyl group. Two of the three fluorine atoms show large increases in their NMR linewidth with increasing temperature while the third shows only a small increase but the activation energy for the process is the same for all. The increase in linewidths is due to scalar coupling to the boron atoms. The boron linewidths were measured between 253 and 363K and decreased with increasing temperature. A plot of logR2, where R2 is the linewidth of the boron as a function of 1/T shows some curvature indicating a second relaxation mechanism. This is ascribed to spin-rotation but not enough data are available to be conclusive. In all cases there is a second small set of fluorine peaks that are due to 10B interactions separated from the 11B peaks by amounts varying from 1 to 4 ppm depending on the field and fluorine atom.

The structural analysis of a levan produced by Streptococcus salivarius SS2.

The structure of a water-soluble levan produced by Streptococcus salivarius SS2 has been determined by means of various chemical and instrumental methods. Methylation and periodate oxidation studies demonstrate that the levan is comprised of D-fructofuranosyl backbone residues linked beta-(2----6) (about 70%) with beta-(2----1) branches (about 30%). 13C-N.m.r. spectral analysis of the polymer is consistent with the structure determined by chemical means.

Acute HIV infection presenting with painful swallowing and esophageal ulcers.

We describe an acute human immunodeficiency virus (HIV) infection in 16 homosexual men who presented with painful swallowing (odynophagia). Eleven men had a maculopapular rash and 3 had palatal ulcers. At esophagogastroduodenoscopy (endoscopy), multiple discrete esophageal ulcers measuring 0.3 to 1.5 cm in diameter were observed. Electron microscopy of biopsy specimens taken from the ulcer margins in 8 men revealed viral particles 120 to 160 nm in diameter whose morphologic characteristics were those of retroviruses. Human immunodeficiency virus seroconversion was documented in 15 men by Western blot analysis. In 3 men, HIV-1 was isolated from peripheral blood mononuclear cells, in 2 men HIV-1 was isolated from peripheral blood monocytes, and in 1 man HIV-1 was isolated from tissue taken from the margins of the esophageal ulcers. These observations extend our knowledge of the clinical spectrum of acute HIV infection syndromes and suggest that cells in the esophagus are a target for HIV-1 infection.

Evidence that prior immune dysfunction predisposes to human immunodeficiency virus infection in homosexual men.

To investigate the role of host susceptibility to HIV-1 infection, we studied subsequent seroconversion in 161 individuals, initially seronegative to HIV-1, who underwent skin testing for cutaneous anergy at an index visit within a prospective study of homosexual men. There were 23 seroconversions in these men by 45 months following the skin testing, yielding a crude rate of seroconversion of 14.3%. While results of purified protein derivative (PPD), Candida, and Trichophyton skin tests were not associated with subsequent course, anergy to dinitrochlorobenzene (DNCB) was predictive of subsequent seroconversion. Kaplan-Meier estimates for the risk of seroconversion during 45 months of follow-up in those men initially anergic and reactive to DNCB were 28.9 and 11.1%, respectively, yielding a relative risk of 2.6 (p = 0.006). The estimated relative risk was stable with adjustment by Cox regression for annual number of male sexual partners and frequency of receptive anal intercourse, and was not sensitive to various changes in the definition of seroconversion time and of eligibility criteria. These data suggest that an impaired host immune status may be associated with an increased risk of HIV-1 infection that is independent of risk of exposure to the virus, supporting earlier speculations that HIV-1 may itself be opportunistic. The notion of varying host susceptibility to infection, at least with regard to sexual transmission in homosexual men, may help to explain the frequent observation of individuals who have been repeatedly exposed to the virus and yet have remained uninfected.

X-ray structural and n.m.r.-spectral studies of methyl alpha-L-evalopyranoside: reassignment of anomeric configuration for the methanolysis product of methyl 6-deoxy-3-C-methyl-alpha-L-mannofuranoside.

The methanolysis product of methyl 6-deoxy-3-C-methyl-alpha-L-mannofuranoside has been reassigned as methyl 6-deoxy-3-C-methyl-alpha-L-mannopyranoside by X-ray crystallographic and n.m.r.-spectral analyses. The crystals of methyl alpha-L-evalopyranoside are monoclinic, space group C2, with cell dimensions: a = 12.913(2), b = 8.052(1), c = 9.766(2) A, B = 105.13(2) degrees. The pyranoside ring exists in the 1C4 conformation, with the methoxyl and 3-C-methyl groups axial. Nuclear Overhauser effects were measured for selected proton resonances in the 1H-n.m.r. spectrum. Irradiation of the 3-C-methyl and 5-C-methyl group proton signals resulted in enhancements for H-2, H-4, H-5, and the methoxyl group hydrogen atoms, but not for H-1.

Analysis of absolute T helper cell number and cellular immune defects in HIV antibody positive and negative homosexual men.

To investigate if serial measurement of T helper (CD4) lymphocyte number in peripheral blood is of prognostic value, we determined lymphocyte function in asymptomatic and symptomatic HIV antibody positive and negative homosexual males and related the results to absolute number of CD4 lymphocytes in peripheral blood. Lymphocyte function was determined by measuring streptolysin O (SLO)-induced proliferative responses of peripheral blood lymphocytes (PBL) and of PBL depleted of CD8 lymphocytes. Phytohemagglutinin (PHA) induced interleukin-2 (IL-2) production was also measured. In all functional tests values were significantly lower in HIV antibody-positive subjects than in HIV antibody-negative subjects. Results lower than the 95% confidence limit in HIV antibody-negative individuals were therefore defined as "decreased." Decreased functional responses were most frequent (83-100%) in individuals with a number of CD4 lymphocytes of less than 400/microliters, and were least frequent (3-21%) in subjects with a CD4 lymphocyte count of greater than 600/microliters. Frequency of decreased functional responses was intermediate in the population with 600-400/microliters CD4 lymphocytes. The magnitude of functional responses differed significantly between groups with less than 400, 400-600, and greater than 600 CD4 lymphocytes per microliter, indicating that T helper cell number decreases with loss of immune function.

The Vancouver Lymphadenopathy-AIDS Study: 7. Clinical and laboratory features of 87 cases of primary HIV infection.

In an ongoing prospective study of homosexual men conducted in Vancouver since November 1982, 87 cases of human immunodeficiency virus (HIV) seroconversion have been documented to date. Comparison of laboratory results obtained a mean of 4.9 months before and 5.4 months after the estimated date of seroconversion revealed that a significant increase in the serum IgG level (from 1149 to 1335 mg/dl on average) and in C1q binding (from 8.8% to 14.2% on average) was associated with early HIV infection (p less than 0.001). A marginally significant decrease in the ratio of helper to suppressor (CD4 to CD8) cells (from 1.55 to 1.29 on average) was also noted (p = 0.025). A marked decrease in absolute number of CD4 cells was not seen with seroconversion, which suggests that profound loss of these cells may be a long-term effect of HIV infection. The occurrence of symptoms (including fatigue, fever, night sweats, unintentional weight loss, diarrhea, joint pains, cough unrelated to smoking, shortness of breath, oral thrush, herpes zoster and rash) did not increase with seroconversion. This finding suggests that most cases of HIV seroconversion may be asymptomatic or associated with relatively minor symptoms. On the other hand, generalized lymphadenopathy was found to develop after HIV seroconversion in about 50% of cases.

Effects of long-term seropositivity to human immunodeficiency virus in a cohort of homosexual men.

The long-term effects of HIV infection were evaluated by comparing data from two visits a mean of 18 months apart in groups of 148 persistently seropositive and 287 persistently seronegative homosexual men. At each visit, the seropositive men exhibited lower CD4 counts, CD4/CD8 ratios, hemoglobin concentrations and lymphocyte counts, and higher C1q binding, IgG and IgA levels. More important, the decline of the CD4/CD8 ratio and the rise of the C1q binding, IgG and IgA, progressed significantly in the seropositive group between visits. Seropositive men were at elevated risk of developing constitutional symptoms and generalized lymphadenopathy. An association was present between development of symptoms and inversion of the CD4/CD8 ratio. The 11 seropositive men who have progressed to AIDS had lower CD4 counts and CD4/CD8 ratios, and higher C1q binding, IgG and IgA, than 134 seropositive AIDS-free men a mean of 21.4 months prior to diagnosis. The AIDS group demonstrated greater decline between visits in the CD4 count, hemoglobin and white blood count (WBC) than the seropositive AIDS-free group. The present data document the long-term effects of HIV infection in a seropositive cohort and suggest the possibility of a subgroup particularly susceptible to the progressive effects of HIV that precede the development of the acquired immunodeficiency syndrome (AIDS).

Increased interleukin-2 receptor expression after mitogen stimulation on CD4- and CD8-positive lymphocytes and decreased interleukin-2 production in HTLV-III antibody-positive symptomatic individuals.

We investigated the expression of the interleukin-2 (IL-2) receptor on phytohaemagglutin-stimulated peripheral blood lymphocytes from homosexual men with persistent generalized lymphadenopathy, the prodrome of the acquired immune deficiency syndrome. The subjects were positive for antibody against human T-cell lymphotropic virus III. Using two-colour fluorescence flow cytometry, IL-2 receptor expression was determined on both the CD4- and CD8-positive lymphocyte subpopulations. After 48 hr of stimulation, expression of the IL-2 receptor on both T-cell subsets was significantly increased in lymphadenopathy patients as compared to values in heterosexual age-matched controls; this difference was less after 72 hr of stimulation. Results from two AIDS patients were within the normal range. IL-2 production was significantly reduced in both lymphadenopathy and AIDS patients as compared to values in heterosexual controls. We conclude that a defect in IL-2 production is associated with human T-cell lymphotropic virus III infection, but that the expression of the IL-2 receptor on T cells is not greatly affected.

The Vancouver Lymphadenopathy-AIDS Study: 6. HIV seroconversion in a cohort of homosexual men.

In an ongoing prospective study of homosexual men conducted since November 1982 in Vancouver, we identified 345 men who did not have antibody to human immunodeficiency virus (HIV) at the time of enrolment and for whom results of follow-up serologic testing were available. A total of 66 cases of seroconversion were documented among the 345 men between November 1982 and October 1985. Methods of survival data analysis that take into account the varying durations of follow-up were used to study the epidemiologic features of seroconversion in this group. The probability of seroconversion during the entire observation period was 23.1%. The seroconversion rates remained stable, at 10.5% and 10.0% during the last 2 years of the observation period. Cox regression analysis revealed the following variables to be independently associated with risk of seroconversion: frequent receptive anal intercourse, elevated number of male sexual partners in the year before enrolment, use of illicit drugs, a history of gonorrhea and age less than 30 years in November 1982. Multivariate analysis failed to reveal any role of oral sexual activity in the transmission of HIV. Oral ingestion of semen was not associated with seroconversion in either univariate or multivariate analysis. The observation that younger men were more likely to seroconvert suggests that young homosexual men were less likely than older men to modify their sexual behaviour.

Absolute lymphocytosis associated with nonsurgical trauma.

Absolute lymphocytosis after nonsurgical trauma was investigated in three patient groups at an acute-care tertiary referral hospital. The first group, with mild-to-moderate trauma, consisted of 64 patients who survived knife wounds to the chest and abdomen. Thirteen of the 64 patients had admission lymphocyte counts greater than 5.0 X 10(9)/L (mean +/- SD: 6.0 X 10(9) +/- 2.4 X 10(9]. Within 24 hours, all 13 showed a significant drop in lymphocyte count to 1.9 X 10(9) +/- 0.9 X 10(9)/L. The second group, with severe trauma, consisted of 11 patients admitted to the intensive care unit. Admission lymphocyte values averaged 5.9 X 10(9) +/- 0.6 X 10(9)/L and decreased to 1.54 X 10(9) +/- 0.3 X 10(9)/L within six hours. The relative importance of trauma as a cause of lymphocytosis was established by reviewing all hospitalized patients with lymphocyte counts greater than 5.0 X 10(9)/L between August 1983 and October 1985. The survey indicates that trauma and hemorrhage account for 16% of all cases of lymphocytosis, and that trauma, together with other acute stresses, constitutes the most common cause of lymphocytosis studied. The authors conclude that trauma is frequently associated with a lymphocytosis that usually changes to a lymphopenia within hours of injury.

The Vancouver Lymphadenopathy-AIDS Study: 5. Antecedent behavioural, clinical and laboratory findings in patients with AIDS and HIV-seropositive controls.

In a group of homosexual men in Vancouver studied prospectively since November 1982, 26 cases of acquired immune deficiency syndrome (AIDS) have arisen. To identify behavioural, clinical and laboratory findings that might predict the development of AIDS in people with antibody to human immunodeficiency virus (HIV), we compared data for 25 patients with AIDS with corresponding data for 80 controls serologically positive for HIV selected from the cohort. The clinical and laboratory data for the patients with AIDS preceded the diagnosis of the syndrome by a mean of 17.5 months. The controls had been both seropositive and AIDS-free for a mean of 16.7 months after acquisition of their data. We detected significant differences between the patients with AIDS and the controls in IgG and IgA levels, absolute number of helper T cells and ratio of helper to suppressor T cells but not in lifetime number of male sexual partners, frequency of receptive anal intercourse or receptive fisting, illicit drug use or history of infectious disease. We also detected an increased risk of AIDS among those who had an elevated number of sexual contacts in AIDS-endemic areas in the 5 years before enrollment. A history of increased early sexual contact in AIDS-endemic areas is likely to be associated with early infection and with an increased risk of AIDS among men with HIV infection of unknown duration. Thus, although our analysis had limited statistical power, we conclude that most lifestyle variables appear to act as exposure factors in HIV infection but not as cofactors in the development of AIDS.

Unusual esophageal ulcers containing enveloped viruslike particles in homosexual men.

Eight homosexual men presented with odynophagia. Five had a maculopapular rash and 2 had oral ulcers. Upper panendoscopy revealed the presence of multiple discrete ulcers measuring 3 mm-1.5 cm in diameter in the esophagus of each patient. The intervening mucosa appeared normal. Endoscopic brushings and biopsy specimens taken from the ulcer margins and examined by light microscopy showed no inclusion bodies or giant cells. Fungal stains were negative. Biopsy specimens examined by electron microscopy revealed enveloped virus-like particles 100-140 nm in diameter, exhibiting morphologic features consistent with retroviruses. No virus was isolated after incubation in either rhesus monkey kidney or human foreskin fibroblast culture. Serology for cytomegalovirus and herpes simplex virus was consistent with past infection. In each patient the esophageal ulcers healed completely. In summary, an illness characterized by the presence of esophageal ulcers is described in 8 homosexual men, 5 of whom also had a skin rash and 2 of whom had oral ulcers. The cause of the esophageal ulcers is likely to be the enveloped viruslike particles observed at electron microscopy.

Diagnostic utility of lymphocyte subset analysis in AIDS case finding.

Abnormalities of lymphocyte subsets, especially low absolute number of helper T cells, are characteristically present in acquired immune deficiency syndrome (AIDS). Similar abnormalities can be found in patients with persistent generalized lymphadenopathy (PGL) or AIDS-related complex (ARC) and, to a lesser degree, in asymptomatic people who have been exposed to human T-lymphotropic virus type III (HTLV-III). Nevertheless, there appears to be a widespread perception that lymphocyte subset analysis may be useful in AIDS case finding within high-risk groups. We evaluated the diagnostic utility of absolute number of helper T cells and ratio of helper to suppressor T cells in 33 patients with AIDS, 43 patients with PGL who had been referred for lymph node biopsy, 90 patients with PGL and 195 male homosexual controls. At conventional cutoff levels the tests did not appear to revise the probability of AIDS upward to any clinically significant degree when the pretest probability of AIDS was low. Lymphocyte subset analysis does not appear to be a cost-effective method of AIDS case finding in identified groups at risk in which the prevalence of AIDS is low.

Diagnostic value of bone marrow examination in isolated thrombocytopenia.

Bone marrow examination often is performed to assess isolated thrombocytopenia. A three-year retrospective study demonstrates that bone marrow aspiration in isolated thrombocytopenia predictably shows megakaryocytic thrombocytopenia. Little additional information is obtained by bone marrow examination that cannot be determined by noninvasive tests. In this series, the Jamshidi biopsy did not add significant information to that obtained from the aspirate. The authors conclude that bone marrow examination is not necessary in patients with isolated thrombocytopenia. In acute care hospital patients, the cause of the thrombocytopenia usually is apparent from the clinical history, and bone marrow examination is necessary infrequently.

Evaluation of natural killer cell activity in patients with persistent generalized lymphadenopathy and acquired immunodeficiency syndrome.

Natural killer (NK) cell activity was quantitated using 51Cr release from the human erythroleukemia cell line K562 in 39 heterosexual males, 60 asymptomatic homosexuals, 39 patients with persistent generalized lymphadenopathy (PGL), and 16 patients with acquired immunodeficiency syndrome (AIDS). PGL and AIDS patients showed a slight decrease in NK cell activity compared to control groups. Absolute numbers of Leu 11a-positive cells were decreased in PGL and AIDS patients, and this decrease correlated with a decrease in absolute number of both the T4+ and T8+ cell subsets. Autologous plasma inhibited NK cell activity in 48% of asymptomatic homosexuals, 63% of PGL patients, and 63% of AIDS patients, but in none of the heterosexual controls. NK cell responses in fetal calf serum, normal human plasma, or autologous plasma showed no correlation with absolute numbers of T4+ cells, or with T4/T8 ratio. We conclude that NK cell responses are not of prime importance in the pathogenesis of PGL and AIDS.

The Vancouver Lymphadenopathy-AIDS Study: 4. Effects of exposure factors, cofactors and HTLV-III seropositivity on number of helper T cells.

Results of testing for antibody to human T-lymphotropic virus (HTLV-III) and absolute numbers of helper T cells in 219 participants in the Vancouver Lymphadenopathy-AIDS (acquired immune deficiency syndrome) Study were analysed. The mean absolute helper T-cell counts in the 141 HTLV-III seronegative and the 78 seropositive men were 897/mL and 659/mL respectively (p less than 0.001). Established AIDS risk factors such as elevated lifetime number of male sexual partners and frequent receptive anal intercourse did not appear to have any significant effect on number of helper T cells that was independent of HTLV-III antibody status. Seropositive men with less than 100, 100 to 500 or more than 500 male sexual partners in their lifetime had mean absolute helper T-cell counts of 667/mL, 651/mL and 662/mL respectively. Most other risk factors, as well, did not appear to exert any effect on absolute number of helper T cells that was independent of the effect of HTLV-III antibody status. However, independent effects of a history of mononucleosis or hepatitis and of cigarette smoking were noted. The data support the hypothesis that no immune dysfunction beyond that due to the initial infection alone arises from repeated exposure to HTLV-III. Most risk factors appear to act as exposure factors, exerting their effect on the immune system merely by increasing the probability of contact with the agent. The independent effects of a history of mononucleosis or hepatitis suggest that viral agents may be cofactors in the production of immune dysfunction.