Severe illness associated with appearance of antibody to human immunodeficiency virus in an African.
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Biomedical subjects
Publications and source records attributed to S Alexander.
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Antisera raised against Rauscher leukemia virus (R-MuLV) contain a preponderance of antibodies against glycoprotein gp70 that are dependent on the presence of carbohydrate side chains for reactivity, as judged by immunoprecipitation or Western blotting. However, the majority of neutralizing antibodies were not dependent on the presence of carbohydrate, as indicated by (i) the ability of deglycosylated R-MuLV to adsorb neutralizing antibody from sera as efficiently as glycosylated R-MuLV and (ii) the ability of deglycosylated R-MuLV to induce neutralizing antibody responses when injected into rabbits. Moreover, a faster response was obtained with deglycosylated R-MuLV than with untreated control virus in the latter experiments. The results indicate that the neutralizing antibodies are a discrete subpopulation of the total antibody response. Furthermore, the carbohydrate moieties appear to afford protection to the virion during infection, rather than serve as a target for neutralization.
Mutant strains of Dictyostelium discoideum carrying dis mutations fail to transcribe specifically the family of developmentally regulated discoidin lectin genes during morphogenesis. The phenotypes of these mutants strongly suggested that the mutations reside in regulatory genes. Using these mutant strains, we showed that multiple regulatory genes are required for the expression of the lectin structural genes and that these regulatory genes (the dis+ alleles) act in trans to regulate this gene family. These regulatory genes fall into two complementation groups (disA and disB) and map to linkage groups II and III, respectively. A further regulatory locus was defined by the identification of an unlinked supressor gene, drsA (discoidin restoring), which is epistatic to disB, but not disA, and results in the restoration of lectin expression in cells carrying the disB mutation. Mutant cells carrying the drsA allele express the discoidin lectin gene family during growth and development, in contrast to wild-type cells which express it only during development. Therefore, the suppressor activity of the drsA allele appears to function by making the expression of the discoidin lectins constitutive and no longer strictly developmentally regulated. The data indicate that normal expression of the discoidin lectins is dependent on the sequential action of the disB+, drsA+, and disA+ gene products. Thus, we described an interacting network of regulatory genes which in turn controls the developmental expression of a family of genes during the morphogenesis of D. discoideum.
A delay of more than one month between the birth of twins is an unusual occurrence presenting the obstetrician and the neonatalogist with many questions regarding the management of the case. There is the risk of prematurity for the second twin as labor has already occurred in the pregnancy. There is also a risk of infection to both mother and fetus during the interval between the two deliveries, since the stump of the first twin's cord may precipitate ascending colonization from vagina and cervix. Germs frequently recovered from the vagina e.g. Ureaplasma urealyticum, are associated with prematurity. The latter has also been responsible for lethal interstitial pneumonia in the neonate. We present a case of a patient who though she delivered twice normally, had suffered 4 first trimester abortions and one late abortion, all spontaneous. Her eighth pregnancy was a twin pregnancy. She underwent a cerclage at 14 weeks, but went into labor at 17 weeks, when she delivered the first macerated twin. She was then treated with fenoterol and ampicillin; nevertheless she delivered twin the second at 26 weeks. This 750 g baby-girl presented with severe respiratory distress. Repeated chest X rays showed perihilar infiltrates which became nodular. All cultures were negative. At the end of the first week, when her condition was considered satisfactory, she deteriorated dramatically and died in respiratory failure and DIC. Tracheal aspirates were positive for Ureaplasma urealyticum.
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Western blot analysis was used to document the development and changes in human T lymphotropic virus III (HTLV-III) antibody among Danish homosexual men followed longitudinally over three years. Reactivity against p15, p24, and p55 appeared earliest. After seroconversion the antibody concentration fluctuated, but in one instance a steady decline in banding intensity was seen during the 18 months before onset of the acquired immune deficiency syndrome (AIDS) and throughout the remaining eight months of his life.
The prevalence of antibodies against HTLV-III and -I was studied among populations of 6 distinctly different regions of Kenya, an equatorial African country in which AIDS has rarely been observed. Overall, 21% of subjects had ELISA reactions suggesting the presence of antibody against HTLV-III. The frequency of HTLV-III antibodies was highest among the Turkana people (50%) and lowest among the Masai (8%). Prevalence increased with age but was not related to sex. The pattern of ELISA-detected antibody against HTLV-I was similar. The specificity of these antibodies was supported by Western blot analysis of a subset of sera with high and low ELISA ratios, in which 66% and 73% of those with ELISA ratios considered positive (= greater than 5.0 in this study) also had a profile of bands consistent with HTLV-III and HTLV-I respectively. The antibodies detected were not cross-reactive between HTLV-III and HTLV-I on Western blot analysis. In a series of subjects with various parasitic and infectious diseases, patients with idiopathic splenomegaly and with schistosomiasis had a high proportion of antibodies against both HTLV-III and HTLV-I. This survey shows that reactivity in the ELISA HTLV-III and HTLV-I assays are common among Kenyans but vary considerably by region.
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Mitral valve prolapse (MVP), often the result of myxomatous degeneration of the mitral valve, is the most commonly known pathologic entity leading to pure mitral regurgitation (MR). Reconstruction of the mitral valve rather than replacement is particularly applicable to this pathologic defect, but is not often used in the U.S. Experience with reconstruction of the mitral valve for MR secondary to MVP during the period January 1970 to January 1984 was reviewed. A total of 479 patients with mitral valve disease underwent operation during this period, 82 (17%) of whom had MR secondary to MVP. Thirty-one patients (6%) had valve reconstruction by a technique of leaflet plication and posteromedial anuloplasty. Eleven of these patients had associated cardiac disease requiring correction: 2 requiring aortic valve replacement and 9 requiring coronary artery bypass grafting procedures. One hospital death (3%) and 6 late deaths (19%) occurred, of which only 3 were related to cardiac factors. Major complications included recurrent MR in 5 patients and cerebral embolus in 1 patient. The adjusted 5-year survival rate was 89 +/- 6 (mean +/- standard error of the mean), and the overall survival rate of patients free of cardiac-related complications was 73 +/- 9%. Thus, reconstruction of the mitral valve is a highly effective surgical approach to the management of symptomatic patients with MR secondary to MVP, and its use is favored over replacement in the management of these patients.
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The specific activities of the enzymes alpha-mannosidase and N-acetylglucosaminidase increase immediately after the initiation of the development of bacterially grown cell cultures of Dictyostelium discoideum. The regulation of these two enzymes was found to be dissociable in the developmental timer mutant, FM-1, which aggregates 4.5 h earlier than wild-type cells due to the absence of the first rate-limiting component of the preaggregative period. The increase in alpha-mannosidase activity occurs in the absence of the first rate-limiting component, but the increase in N-acetylglucosaminidase activity does not. These results indicate the following: (1) the increase in the specific activity of alpha-mannosidase is not related to the timing of subsequent developmental stages; (2) the increase in the specific activity of N-acetylglucosaminidase is not necessary for the subsequent developmental program; and (3) either the increase in the specific activity of N-acetylglucosaminidase is dependent upon progress through the first rate-limiting component, or the increase in this enzyme activity and the first rate-limiting component are both dependent upon an early event for which FM-1 is defective. In addition to early development, we monitored the two enzyme activities during dedifferentiation. The results demonstrate that there is no difference between dedifferentiating wild-type cells and dedifferentiation-defective mutant HI-4 cells. Changes in enzyme specific activity accompanying dedifferentiation are dependent upon the composition of the dedifferentiation-inducing media and are consistent with the levels of these enzymes observed in cells growing in the different nutrient media.
Dictyostelium discoideum strains that carry the dis mutations fail to express the family of developmentally regulated discoidin lectin genes during morphogenesis. We show here that this absence of discoidin lectin expression is due to the failure to transcribe the discoidin genes. Furthermore, the dis mutations appear to affect only discoidin expression and not the expression of other proteins during development, as assessed by a two-dimensional gel analysis of pulse-labeled proteins and by the accumulation of developmentally regulated enzymes. The dis mutations appear to define trans-acting regulatory loci, the products of which act at the transcriptional level to control specifically the developmental expression of the discoidin gene family.