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Biomedical subjects

F L Brown

Publications and source records attributed to F L Brown.

At least 37 records · Page 2Linked to original sources
PubMed1981

Toward a molecular paleontology of primate genomes. II. The KpnI families of alphoid DNAs.

KpnI restriction of anthropoid primate DNAs, from a New World monkey to man, releases a series of segments that are remarkable among all of the alphoid DNAs in the constancy of their relative amounts in the various primate genomes, in their long-range organization, and in their internal sequence structure. These segments are labeled the KpnI A, B, C and D segments. Cross-hybridization analysis by Southern filter-transfer hybridization indicates that the KpnI segments represent separate and distinct families of alphoid DNAs. These families are termed the KpnI A, B, C and D families of alphoid sequences, of which only the KpnI A and B families were studied in detail here. - Evidence is presented suggesting that the KpnI segments do not exist as long, tandemly repeated sequences in the primate genome: rather, they may occur interspersed among other, perhaps nonalphoid sequences. From the stained gel patterns and from Southern filter-transfer hybridization experiments, the KpnI families appear to be absent from the genomes of the two prosimians studied - the galago and the black lemur. The KpnI A and B families are found among all of the anthropoid primates, including the New World capuchin monkey. The KpnI C family was detected in the genomes of the Old World anthropoid primates whereas the KpnI D family was detected only among the great apes and man. - The results are in accord with the observation (Musich et al., 1980) that with the continued evolutionary development of the primate Order, there has been a parallel trend toward an increased number and variety of alphoid DNA sequences. The properties of the KpnI families suggest that these sequences, unique among the alphoid DNAs, have been conservatively maintained throughout primate phylogeny and that they are among the most ancient of all primate DNAs.

Animals↗
PubMed1980

Highly repetitive component alpha and related alphoid DNAs in man and monkeys.

The genomes of Old-World, New-World, and prosimian primates contain members of a large class of highly repetitive DNAs that are related to one another and to component alpha DNA of the African green monkey by their sequence homologies and restriction site periodicities. The members of this class of highly repetitive DNAs are termed the alphoid DNAs, after the prototypical member, component alpha of the African green monkey which was the first such DNA to be identified (Maio, 1971) and sequenced (Rosenberg et al., 1978). The alphoid DNAs appear to be uniquely primate sequences.--From the restriction enzyme cleavage patterns and Southern blot hybridizations under different stringency conditions, the alphoid DNAs comprise multiple sequence families exhibiting varying degrees of homology to component alpha DNA. They also share common elements in their restriction site periodicities (172 . n base-pairs), in the long-range organization of their repeating units, and in their banding behavior in CsCl and Cs2SO4 bouyant density gradients, in which they band within the bulk DNA as cryptic repetitive components.--In the three species from the Family Cercopithecidae examined, the alphoid DNAs represent the most abundant, tandemly repetitive sequence components, comprising about 24% of the African green monkey genome and 8 to 10% of the Rhesus monkey and baboon genomes. In restriction digests, the bulk of the alphoid DNAs among the Cercopithecidae appeared quantitatively reduced to a simple series of arithmetic segments based on a 172 base-pair (bp) repeat. In contrast with these simple restriction patterns, complex patterns were observed when human alphoid DNAs were cleaved with restriction enzymes. Detailed analysis revealed that the human genome contains multiple alphoid sequence families which differ from one another both in their repeat sequence organization and in their degree of homology to the African green monkey component alpha DNA.--The finding of alphoid sequences in other Old-World primate families, in a New-World monkey, and in a prosimian primate attests to the antiquity of these sequences in primate evolution and to the sequence conservatism of a large class of mammalian highly repetitive DNA. In addition, the relative conservatism exhibited by these sequences may distinguish the alphoid DNAs from more recently evolved highly repetitive components and satellite DNAs which have a more restricted taxonomical distribution.

Animals↗
PubMed1980

Delayed hemolytic transfusion reaction presenting as sickle-cell crisis.

Eighteen patients with sickle-cell disease underwent partial exchange transfusion. Three developed delayed hemolytic reactions, with selective disappearance of transfused cells. All reactions occurred within 6 days of transfusion, and patients presented with the clinical features of painful crises. The two most severe reactions were associated with antibodies to Jka. These patients developed fever, arthritis, and a clinical course suggesting serum sickness. In both patients, other alloantibodies had previously been seen. A fourth patient developed multiple alloantibodies, accelerated destruction of tranfused cells, but milder illness. Such reactions may be commoner than in appreciated and should be suspected when patients have recurrent or severe sickle crises after transfusion. Blood that is nonimmunogenic in antigen systems frequently associated with delayed hemolytic reactions (Rh, Kell, Duffy, and Kidd) is preferred for sickle-cell patients who lack these antigens, especially if these patients have previously demonstrated capability to form erythrocyte alloantibodies.

Adolescent↗
PubMed1980

Improved exercise performance after exchange transfusion in subjects with sickle cell anemia.

Ten patients with sickle cell anemia underwent partial exchange transfusion with hemoglobin-A-containing cells using a technique that allowed hemoglobin concentration and blood volume to remain constant. The mean fraction of hemoglobin-A in these patients increased from 9% to 55%, but the mean hemoglobin concentration increased by only 1.44 g/dl. The exchange resulted in a large improvement in submaximal exercise capacity: the mean of the anaerobic threshold (the work at which lactic acid begins to accumulate in the blood) increased from 68 to 114 W. The mean work performed at a heart rate of 170/min, an estimation of maximal work capacity, increased from 128 to 187 W. Improved exercise performance after partial exchange transfusion may result from the superior flow properties of hemoglobin-A-containing red cells. Furthermore, we believe that exercise testing in sickle cell anemia has great potential utility as a means to monitor therapy and to evaluate the benefits of exchange transfusion.

Adult↗
PubMed1978

Cae I: an endonuclease isolated from the African green monkey with properties indicating site-specific cleavage of homologous and heterologous mammalian DNA.

Component alpha DNA is a highly repetitive sequence that comprises nearly a quarter of the African green monkey (Cercopithecus aethiops) genome. A previous microbial restriction enzyme analysis showed that the repeat structure of component alpha DNA is based upon a monomeric unit of 176 +/- 4 base-pairs. An endonuclease, provisionally termed Case I, has been isolated from African green monkey testes that cleaves component alpha DNA into multimeric segments based upon the same repeat periodicity as that revealed by microbial restriction enzymes. The primary sites of Cae I cleavage in the component alpha sequence appear to be 120 +/- 6 base-pairs distant from the Hind III sites and 73 +/- 6 base-pairs distant from the Eco RI* sites. Cae I has been partially characterized with special reference to the effects of ATP and S-adenosylmethionine on the cleavage of component alpha DNA. Cae I may be a member of a class of similar site-specific nucleases present in mammalian cells. Cae I also cleaves mouse satellite DNA into a multimeric series of discrete segments: the periodicity of this series is shorter than that revealed by Eco RII retriction analysis of mouse satellite DNA.

Adenosine Triphosphate↗
PubMed1977

Subunit structure of chromatin and the organization of eukaryotic highly repetitive DNA: nucleosomal proteins associated with a highly repetitive mammalian DNA.

Component alpha DNA is a homogeneous, highly repetitive fraction that comprises nearly a quarter of the African green monkey (Cercopithecus aethiops) genome. By restriction enzyme analysis, it has a repeat periodicity of 176 +/- 4 nucleotide base pairs, corresponding closely with the length of DNA contained within a nucleosome. The sequence is organized into large blocks of constitutive heterochromatin. A method is described here for the isolation of intact polynucleosomal arrays containing only component alpha sequences. Isolated monkey nuclei are treated with EcoRI, which releases only component alpha nucleosomal arrays; the arrays are then fractionated and purified by sedimentation in sucrose gradients. The method permits a compositional analysis of the proteins associated with a constitutively repressed, heterochromatic sequence. The major differences in the proteins associated with component alpha nucleosomes that distinguish them from the bulk DNA nucleosomes are a decrease in the content of the H1 histones in the component alpha nucleosomes and a concomitant increase in the amount of certain nonhistone proteins. The specific observations are: (i) In the component alpha nucleosomes, 65-70% of the proteins were nonhistone proteins; this contrasts with the value, 40%, for nonhistone proteins associated with nucleosomes containing bulk DNA. (ii) The amount of H1 histone in chromatin containing predominantly bulk DNA was about 13.7%. However, the H1 histone was depleted and possibly absent in component alpha oligonucleosomes. (iii) Coincident with the decrease in the H1 histones and in the same molecular weight range (24,000-43,000), there appeared five minor nonhistone proteins. The minor, low-molecular-weight, nonhistone proteins were not detected in chromatin containing bulk DNA but they represented nearly 12% of the protein in component alpha nucleosomes. The resistance to salt extraction (0.6-2.0 M NaCl) indicates that the low-molecular-weight nonhistone proteins are tenaciously bound to the component alpha nucleosomes. In addition, a class of high-molecular-weight (>100,000) nonhistone proteins was enriched 5- or 6-fold in component alpha oligonucleosomes. The relative amounts of the nucleosome core histones were not changed.

Cell Line↗
PubMed1976

Sex guilt and preferences for illegal drugs among drug abusers.

This study investigated the relationship between sex guilt and drug preferences. Seventy polydrug users completed a drug preference inventory and the Mosher Forced-Choice Sex Guilt Subscale. Results indicated that individuals who prefer sedatives are higher in sex guilt than either individuals who prefer stimulants or individuals with no definite preference.

Adolescent↗
PubMedDate not supplied

Transcription of the KpnI families of long interspersed DNAs in human cells.

The mammalian genome contains a variety of interspersed repetitive sequences of unknown function. It has, however, been suggested that interspersed repetitive sequences and their RNA transcripts are involved in the coordinate regulation of gene expression. Two major families of interspersed sequences in primates are the so-called Alu and KpnI families. Members of the KpnI families range in length from 1.2 to over 6 kilobases (kb). They exist in generally clustered arrangements, in 6 X 10(4) to 10(5) copies per diploid genome. Something is known of the arrangements of KpnI family sequences near human structural genes, but there has been no information on transcription of the sequences. We report here that the KpnI sequences are transcribed in HeLa cells by RNA polymerase II into abundant and heterogeneous species of RNA. The transcripts range in length from about 200 bases to over 5 kb, and are found predominantly in the non-polyadenylated fraction of the nuclear RNA. Transcripts homologous to both of the complementary strands of the KpnI sequences are present, but with a strong bias towards one strand.

Base Sequence↗