DNA restriction-site polymorphisms associated with the alpha 1-antitrypsin gene.

Restriction-site variation in and around the alpha 1-antitrypsin gene has been studied using two genomic probes. With use of restriction enzymes SstI, MspI, and AvaII, three polymorphic sites have been described with a 4.6-kb probe in the 5' portion of the gene. With use of a 6.5-kb probe, polymorphisms in the coding and 3' regions of the gene have been detected with AvaII, MaeIII, and TaqI. All of these polymorphisms are of sufficiently high frequency to be useful in genetic mapping studies. The polymorphisms with AvaII and MaeIII (6.5-kb probe) are particularly useful for prenatal diagnosis. PI types and M subtypes tend to be associated with specific DNA haplotypes; there are two different types of DNA haplotypes associated with PI M1. The extent of linkage disequilibrium differs throughout the region of the alpha 1-antitrypsin gene.     

Facilitating care of patients with HIV infection by hospital and primary care teams.

To complement the role of primary care teams working with patients with HIV disease and AIDS within greater London and to ease the load on the special hospital units a home support team was developed. It comprises six specialist nurses, a general practitioner trained medical officer, and a receptionist and is funded from regional and district sources and charities. A nurse is available for out of hours and emergency weekend calls, with support from the patient''s general practitioner or the attached medical officer. During the first 18 months 249 patients were seen; the mean duration of care was five months. Nearly a third (18/50, 30%) of patients who were terminally ill died at home. The team''s activities included practical nursing care, emotional support for carers and patients, and advice and guidance to primary care teams. Problems in providing care in patients'' homes included issues relating to confidentiality and 24 hour cover. With the increasing incidence of HIV infection the home support team may be a useful model for care of large numbers of patients with symptomatic HIV disease, especially in large urban areas.     

Two abnormalities of hexosaminidase A in clinically normal individuals

Two abnormalities of beta-hexosaminidase A (HEX A) activity are described. One, found in two unrelated Jewish children, was characterized by the complete absence of HEX A activity in serum, but low levels of activity in leukocytes and fibroblasts using artificial substrate. The other, found in a non-Jewish man, was characterized by uniformly low levels of HEX A activity in leukocytes, fibroblasts, and serum against artificial substrate. In all cases, the pH optimum of HEX A was normal, there was no increased lability at 37 degrees C, and no inhibitor was detected to account for the deficiency of activity. Cultured fibroblasts of these individuals were capable of synthesizing and processing alpha- and beta-subunits of HEX A and capable of cleaving GM2 ganglioside. The patients, ranging in age from 6 to 30 years, are clinically normal. They are probably genetic compounds carrying the classical Tay-Sachs gene and a differently mutated allele that imparts the anomalous phenotypic features observed.     

Optical difference spectrum of the electron acceptor Ao in photosystem I

Optical measurements were made during low temperature photoreduction of photosystem I acceptors, A₁ and A₀. In the presence of a significant amount ofA₁ (detected by EPR), no absorbance changes occurred between 750-350 nm, indicating that this species is not a chlorophyll or pheophytin molecule. Spectral changes in this region that may be correlated with the appearance of A⁻₀, suggest that this component is a chlorophyll a anion monomer. The species is present in reaction centres in a ratio of 0.94 A_o/P700.

Photosystem I Primary acceptor Optical difference spectrum Chlorophyll a monomer     

MAJOR CLADES OF THE ANGIOSPERMS

Abstract— Our knowledge of fundamental angiosperm interrelationships is still very incomplete. The absence of a narrowly circumscribed gymnosperm outgroup, ideally the sister group, makes character evaluation, necessary for a cladistic analysis, difficult. According to current views the superorder Magnoliiflorae with a number of other groups, for example the monocotyledons, may represent a complex of families near the base of the angiosperms. Interrelationships of groups within the monocotyledons are much better understood than those between groups within the dicotyledons. A cladogram of monocotyledon orders based on earlier work by R. Dahlgren, H. T. Clifford, and F. N. Rasmussen is presented. A data matrix for a sample of the angiosperms with 61 characters for 49 taxa, mostly magnoliifloran and related families, is presented. The characters are polarized mainly according to the current view that the primitive angiosperm morphotype is a woody dicotyledon with strobiloid flowers. As an alternative the matrix is adjusted following W. C. Burger's conjecture that the primitive angiosperm was a herbaceous monocotyledon with trimerous flowers. Both matrices were run in a computerized parsimony analysis, resulting in numerous equally parsimonious solutions. This result is illustrative of the great homoplasy in the available character information, and also of how little actually is known about fundamental angiosperm interrelationships or phylogeny.     

Lymphocyte function in experimental African trypanosomiasis. VII. Loss of antigen-nonspecific suppressor-T-cell activity

The extent of immunosuppression occurring in mice infected with the pathogenic African trypanosomes was studied. Spleen cells from Trypanosoma rhodesiense-infected C57BL/6J mice were tested for antigen-nonspecific suppressor-T-cell (Ts) activity after concanavalin A (Con A) treatment in vitro. After exposure to Con A, control and infected mouse spleen cells were added to responder spleen cell cultures stimulated with sheep erythrocytes (SRBC). Assays for the resultant plaque-forming cell responses to SRBC revealed that antigen-nonspecific Ts activity was lost during the first week of infection. Changes in infected mouse T-cell subpopulations, including a terminal loss of Lyt 2.2+ cells, accompanied but did not precede the demonstrable loss of Ts function. Splenic suppressor macrophages which arise during infections with T. rhodesiense also did not seem to be associated with the loss of antigen-nonspecific Ts activity. It is concluded that the generalized immunosuppression associated with experimental African trypanosomiasis extends to the mitogen-induced Ts population.     

Assignment of orthologous relationships among mammalian alpha-globin genes by examining flanking regions reveals a rapid rate of evolution

In order to study the relationships among mammalian alpha-globin genes, we have determined the sequence of the 3' flanking region of the human alpha 1 globin gene and have made pairwise comparisons between sequenced alpha-globin genes. The flanking regions were examined in detail because sequence matches in these regions could be interpreted with the least complication from the gene duplications and conversions that have occurred frequently in mammalian alpha-like globin gene clusters. We found good matches between the flanking regions of human alpha 1 and rabbit alpha 1, human psi alpha 1 and goat I alpha, human alpha 2 and goat II alpha, and horse alpha 1 and goat II alpha. These matches were used to align the alpha-globin genes in gene clusters from different mammals. This alignment shows that genes at equivalent positions in the gene clusters of different mammals can be functional or nonfunctional, depending on whether they corrected against a functional alpha-globin gene in recent evolutionary history. The number of alpha-globin genes (including pseudogenes) appears to differ among species, although highly divergent pseudogenes may not have been detected in all species examined. Although matching sequences could be found in interspecies comparisons of the flanking regions of alpha- globin genes, these matches are not as extensive as those found in the flanking regions of mammalian beta-like globin genes. This observation suggests that the noncoding sequences in the mammalian alpha-globin gene clusters are evolving at a faster rate than those in the beta-like globin gene clusters. The proposed faster rate of evolution fits with the poor conservation of the genetic linkage map around alpha-globin gene clusters when compared to that of the beta-like globin gene clusters. Analysis of the 3' flanking regions of alpha-globin genes has revealed a conserved sequence approximately 100-150 bp 3' to the polyadenylation site; this sequence may be involved in the expression or regulation of alpha-globin genes.      

Evolutionary analysis of the multigene pregnancy-specific β1-Glycoprotein family: Separation of historical and nonhistorical signals

The pregnancy-specific ₁-glycoproteins (PSG) form a large family of closely related proteins. Using newly developed methods of sequence analysis, in combination with protein modeling, we provide a framework for investigating the evolution and biological function of genes like the PSG. Evolutionary trees, based on C-terminal sequence, group PSG genes in a manner consistent with their genomic organization. Trees constructed using the N-terminal domain sequences are unreliable as an indicator of phylogeny because of non-neutral processes of sequence change. During duplication of the PSG genes, evolutionary pressures have resulted in a gradient of constrained change across each gene. The N-terminal domains show a nonrandom pattern of amino acid substitutions clustered in the immunoglobulin complementarity-determining region (CDR)-like regions, which appear to be important in the function of the protein.