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Biomedical subjects

M A Martin

Publications and source records attributed to M A Martin.

At least 181 records · Page 10Linked to original sources
PubMed1985

Envelope and long terminal repeat sequences of a cloned infectious NZB xenotropic murine leukemia virus.

An infectious NZB xenotropic murine leukemia virus (MuLV) provirus (NZB was molecularly cloned from the Hirt supernatant of NZB-IU-6-infected mink cells, and the nucleotide sequence of its env gene and long terminal repeat (LTR) was determined. The partial nucleotide sequence previously reported for the env gene of NFS-Th-1 xenotropic proviral DNA (Repaske, et al., J. Virol. 46:204-211, 1983) is identical to that of the infectious NZB xenotropic MuLV DNA reported here. Alignment of nucleotide or deduced amino acid sequences, or both, of xenotropic, mink cell focus-forming, and ecotropic MuLV proviral DNAs in the env region identified sequence differences among the three host range classes of C-type MuLVs. Major differences were confined to the 5' half of env; a high degree of homology was found among the three classes of MuLVs in the 3' half of env. Alignment of the nucleotide sequence of the LTR of NZB xenotropic MuLV with those of the LTRs of NFS-Th-1 xenotropic, mink cell focus-forming, and ecotropic MuLVs revealed extensive homology between the LTRs of xenotropic and MCF247 MuLVs. An inserted 6-base-pair repeat 5' to the TATA box was a unique feature of both NZB and NFS-Th-1 xenotropic LTRs.

Animals↗
PubMed1985

Nucleotide sequence of a full-length human endogenous retroviral segment.

The nucleotide sequence of a full-length (8.8-kilobase) endogenous C-type human retroviral DNA (clone 4-1) is presented and compared with that of Moloney murine leukemia virus (MoMuLV) DNA. Colinearity of deduced amino acids of clone 4-1 with MoMuLV in the gag and pol regions was clearly evident, and overall amino acid homology in these regions was about 40%. Identification of the putative N terminus of gag and p30, the gag-pol junction, and the C terminus of pol could be established on the basis of sequence homology with MoMuLV. Unique characteristics of the endogenous human retroviral DNA included a tRNA Glu primer binding site separated from the 5' long terminal repeat by a pentanucleotide and a putative env sequence which does not appear to overlap the C terminus of pol and has virtually no homology with the env gene of known infectious retroviruses. Clone 4-1 represents a defective prototype of a human C-type retrovirus which integrated into the germ line some time in the distant past.

Base Sequence↗
PubMed1985

Characterization of a molecularly cloned retroviral sequence associated with Fv-4 resistance.

The murine leukemia virus (MuLV) sequence associated with the resistance allele of the Fv-4 gene (Fv-4r) was molecularly cloned from genomic DNA of uninfected mice carrying this allele. The 5.2-kilobase cloned EcoRI DNA fragment (pFv4) was shown by nucleotide sequencing to contain 3.4 kilobases of a colinear MuLV-related proviral sequence which began in the C-terminal end of the pol region and extended through the env region and the 3' long terminal repeat. Cellular sequences flanked the 3' as well as the 5' ends of the truncated MuLV sequence. Alignment of the N-terminal half of the pFv4 env sequence with ecotropic, mink cell focus-forming, and xenotropic MuLV env sequences established the relatedness of pFv4 and ecotropic MuLV env sequences. A subcloned 700-base pair segment (pFv4env) from the 5' env region of pFv4 was used as an Fv-4-specific probe; it hybridized specifically to the Fv-4r-associated proviral sequence but not to endogenous ecotropic MuLV proviral DNA under high stringency. All Fv-4-resistant mice contained the same retroviral segment associated with the same flanking cellular DNA. Expression of Fv-4r-specific mRNA was demonstrated in the spleens of Fv-4r mice but not Fv-4s mice, supporting the previously proposed resistance model based on interference.

Animals↗
PubMed1985

Characterization of human endogenous retroviral envelope RNA transcripts.

We characterized the structure of human endogenous retroviral env RNA transcripts by Northern blot hybridization and cDNA cloning. Polyadenylated 3.0- and 1.7-kilobase env RNAs can be identified in placenta, colon carcinoma, and breast carcinoma cells. We have obtained partial cDNA clones of both size classes of RNAs. Both env RNAs contained putative gp70 coding sequences; the 1.7-kilobase species, however, lacked sequences in the 3' env region which could specify a p15E analog. Both cDNA clones contained in-frame termination codons; thus, neither could encode full-length env proteins.

Amino Acid Sequence↗
PubMed1985

The effect of colonizing mice with laboratory and wild type strains of E. coli containing tumor virus genomes.

Conventional, antibiotic-compromised, and germ-free mice were either fed or subcutaneously inoculated with laboratory or wild type strains of E. coli containing monomeric or dimeric forms of polyoma (PY) virus DNA. Mice were bled at 3 and 6 weeks following administration of E. coli and their sera examined for the presence of PY hemagglutination inhibiting antibodies. None of the mice developed PY infection; despite colonization of the intestinal tract accompanied by prolonged excretion of high titers (10(9) colony-forming units/gram feces) of E. coli harboring potentially infectious PY virus DNA, no evidence of infection could be demonstrated.

Animals↗
PubMed1984

Distinctive termini characterize two families of human endogenous retroviral sequences.

Human DNA contains many copies of endogenous retroviral sequences. Characterization of molecular clones of these structures reveals the existence of two related families. One family consists of full-length (8.8 kilobases) proviral structures, with typical long terminal repeates (LTR's). The other family consists of structures, which contain only 4.1 kilobases of gag-pol sequences, bounded by a tandem array of imperfect repeats 72 to 76 base pairs in length. Typical LTR sequences that exist as solitary elements in the genome were cloned and characterized.

Base Sequence↗
PubMed1984

Prognosis of physicians treated for alcoholism and drug dependence.

Data on 73 physicians are compared with data on 185 middle-class patients similarly treated for alcoholism or drug dependence in a hospital-based inpatient program. General patients were contacted on year after treatment and physicians, one to five years later. The prognosis was more favorable for physicians than for general patients. When the groups were selected for study on the basis of completion of inpatient treatment, availability at time of contact, and not having died, 83% of physicians and 62% of the general group were noted to have favorable outcomes. Close monitoring may account, in part, for the better prognosis for physicians.

Alcoholism↗
PubMed1984

Relationship between a retroviral germ line reintegration and a new mutation at the ashen locus in B10.F mice. Retroviral integration and an ashen mutation.

In a litter of B10.F mice a single mouse was found with a "dilute-like" coat-color mutation. F2 matings were then carried out to establish sufficient numbers of mice carrying this mutation in a homozygous form. The coat-color mutation was found to be allelic to the ashen locus which is closely linked to the dilute locus on chromosome 9. Further analysis of the ashen mice showed they contained an additional ecotropic provirus integrated into their chromosomal DNA. This result initially suggested that retroviral integration was responsible for the mutation. However, backcross studies showed the mutation and provirus were genetically unlinked. The reintegrated provirus was molecularly cloned and transfection studies showed the virus was B tropic in host range. The restriction map of the cloned provirus was found to be similar to previously described B-tropic viruses. The results are discussed in view of the low probability of two rare and unlinked events occurring in a single mouse.

Alleles↗
PubMed1983

Characterization and partial nucleotide sequence of endogenous type C retrovirus segments in human chromosomal DNA.

Twenty-six different murine leukemia virus (MuLV)-related clones have been isolated from a human DNA library and characterized by restriction enzyme mapping and reciprocal nucleic acid hybridization reactions. The sequence of approximately 2,600 nucleotides, spanning more than 4.0 kilobases, of one of the MuLV-related cloned human DNAs was also determined. The deduced amino acid sequence permitted the alignment of this prototype cloned human DNA segment with the p12 gag, p30 gag, p10 gag, and pol regions of Moloney MuLV. A majority of the endogenous type C retrovirus-related segments present in human DNA are approximately 6.0 kilobases in size and appear to contain a deletion of env sequences.

Base Sequence↗
PubMed1983

Endogenous murine leukemia proviral long terminal repeats contain a unique 190-base-pair insert.

We have determined the nucleotide sequence in the U3-R regions of the long terminal repeat (LTR) associated with NFS-Th-1 xenotropic murine leukemia virus (MuLV) DNA and the LTR components of five endogenous proviruses cloned from BALB/c mouse chromosomal DNA. The five endogenous MuLV LTRs contained the regulatory signals thought to be important in viral transcription, such as "TATAA" and CCAAT-like boxes. A unique feature in four of the endogenous LTRs was the presence of a highly conserved 190-base-pair (bp) insert bounded by 6-bp direct repeats located 48 bp upstream from the C-C-A-A-T sequence. This segment was absent from LTRs associated with ecotropic, xenotropic, or mink cell focus-forming (MCF) MuLV proviruses. All five endogenous LTR segments also contained a 14-bp duplication of a sequence located near the 5' end of the first component of the long (greater than 72-bp) direct repeat of ecotropic and MCF MuLV LTRs. An evolutionary scheme relating LTRs associated with endogenous MuLV proviral DNAs to those found in ecotropic or xenotropic proviruses is presented. Nucleotide sequence analysis also suggested that the U3 region of the MCF247 MuLV LTR is derived from an NFS xenotropic related MuLV.

Animals↗
PubMed1983

Organization and stability of endogenous xenotropic murine leukemia virus proviral DNA in mouse genomes.

In a series of blot hybridization experiments, using a xenotropic envelope probe and restriction enzymes known to cut xenotropic proviral DNA a single time (EcoRI) or not at all (HindIII), we have studied the organization and relationship of endogenous xenotropic env-related sequences in various mouse strains. Multiple copies (18 to 28) of xenotropic env-reactive fragments were found in all mouse DNAs after digestion with either HindIII or EcoRI, and the majority of fragments were of sizes compatible with their origin from full-length proviral DNA. Five HindIII and five EcoRI restriction fragments were common to all inbred mouse DNAs tested. In addition, each strain exhibited unique characteristic xenotropic env-reactive bands; these bands were remarkably stable during many years of inbreeding. The cleavage patterns characteristic of each strain were also useful for showing genealogical relatedness among the various inbred mice.

Animals↗
PubMed1983

Nucleotide sequence of the env-specific segment of NFS-Th-1 xenotropic murine leukemia virus.

The sequence of 863 contiguous nucleotides encompassing portions of the pol and env genes of NFS-Th-1 xenotropic proviral DNA was determined. This region of the xenotropic murine leukemia virus genome contains and env-specific segment that hybridizes exclusively to xenotropic and mink cell focus-forming but not to ecotropic proviral DNAs (C. E. Buckler et al., J. Virol. 41:228-236, 1982). The unique xenotropic env segment contained several characteristic deletions and insertions relative to the analogous region in AKR and Moloney ecotropic murine leukemia viruses. Portions of an endogenous env segment cloned from a BALB/c mouse embryo gene library that had a restriction map and hybridization properties typical of xenotropic viruses (A. S. Khan et al., J. Virol. 44:625-636, 1982) were also sequenced. The sequence of the endogenous env gene was very similar to the comparable region of the NFS-Th-1 xenotropic virus containing the characteristic deletions and insertions previously observed and could represent a segment of an endogenous xenotropic provirus.

Base Sequence↗
PubMed1983

Effect of oral prednisolone on response to salbutamol and ipratropium bromide aerosols in patients with chronic airflow obstruction.

We examined the bronchodilator responses to inhalation of salbutamol (200 micrograms) and of ipratropium bromide (40 micrograms) in the morning and in the afternoon before and during a course of oral prednisolone (40 mg daily) in 15 patients with chronic, partly reversible airflow obstruction. Bronchodilatation was assessed by measuring serial peak expiratory flow rates (PEFR) for six hours after aerosol drug administration and calculating the area under the time-response curves. Eleven patients were found to be corticosteroid resistant in not attaining a baseline bronchodilatation of at least 25% during corticosteroid treatment. These patients also failed to show any enhancement of their bronchodilator responses to either salbutamol or ipratropium bromide during prednisolone administration. We therefore conclude that there is no rationale for giving or continuing corticosteroid treatment in known steroid-resistant patients in the hope of nevertheless potentiating their bronchodilator responses to salbutamol or ipratropium bromide.

Aerosols↗
PubMed1982

Evidence for the horizontal acquisition of murine AKR virogenes by recent horizontal infection of the germ line.

Several recent reports (8, 10, 11, 13) have established the biological and molecular genetic similarity between the endogenous AKV virus of strain AKR, and an N-ecotropic endogenous virus found in the genome of feral Japanese mice, Mus musculus molossinus. The similarities are so striking as to suggest a common origin of these viruses, which are present in some, but not all, inbred mouse strains. The virogenes of AKR mice may have been acquired by either: (a) common descent of AKR (and other AKV(+) strains) from a common ancestor of AKR and molossinus animals, or (b) horizontal germ line infection of the AKR strains by molossinus virus at 1;he strain's inception followed by fixation through inbreeding. The sexual descent model carries with it a prediction of relative consanguinity of the AKR strain and molossinus, whereas the horizontal infection model does not. We have examined the polymorphic allozyme (allelic isozyme) genotype of 51 nonvirus-related loci in 17 strains of mice including AKR, C58, BALB/c, Swiss, and molossinus. By comparing the composite allozyme genotype of different inbred and outbred mouse strains, the "genetic distance" statistic was derived. Genetic distance measures the degree of allelic substitution between populations and increases proportionately with the amount of time the populations have been reproductively isolated. The genetic distance computed between molossinus and AKR is large, nearly 5-10 times the distance between known related populations and strains (e.g., C57L vs. C57BL/6). Molossinus had a similarly large distance from AKV negative strains (Swiss, C57L) as it did from AKV- positive strains. Cellular DNA sequences that flank the integrated AKV provirus were analyzed by restriction enzyme digestion of liver DNA from molossinus, AKR, and additional inbred strains that express ecotropic murine leukemia virus. The integration flanks of three AKR provirus sequences, Akv-1, Akv-2, and a third uncharacterized sequence, were not evident in molossinus cell DNA, which contained at least six different proviral integration fragments. These data effectively exclude the interpretation of consanguinity of AKR and molossinus and support the notion of acquisition of the endogenous virus in AKR by horizontal infection of the molossinus virus.

AKR murine leukemia virus↗
PubMed1982

Cloning and characterization of an envelope-specific probe from xenotropic murine leukemia proviral DNA.

An 8.9-kilobase EcoRI restriction fragment was cloned from mink cells chronically infected with NFS-Th-1 xenotropic murine leukemia virus by using a lambda phage host vector system. After its transfer into pBR322, the EcoRI DNA insert was characterized and found to contain 6.7 kilobases of proviral DNA sequences and 2.2 kilobases of mink cellular DNA flanking the 5' end of the viral genome. A 500-base pair fragment which was located at the 3' terminus of the cloned DNA insert and which mapped to the env region of xenotropic proviral DNA was subcloned into pBR322. This xenotropic envelope proviral DNA segment did not hybridize to ecotropic murine leukemia proviruses but did anneal to representative alpha and beta xenotropic and seven different mink cell focus-inducing proviral DNAs. The cloned xenotropic envelope-specific probe was also used in blot hybridization experiments to analyze the arrangement of related sequences in preparations of different mouse liver DNAs.

Animals↗
PubMed1982

Characterization of proviruses cloned from mink cell focus-forming virus-infected cellular DNA.

Two proviruses were cloned from EcoRI-digested DNA extracted from mink cells chronically infected with AKR mink cell focus-forming (MCF) 247 murine leukemia virus (MuLV), using a lambda phage host vector system. One cloned MuLV DNA fragment (designated MCF 1) contained sequences extending 6.8 kilobases from an EcoRI restriction site in the 5' long terminal repeat (LTR) to an EcoRI site located in the envelope (env) region and was indistinguishable by restriction endonuclease mapping for 5.1 kilobases (except for the EcoRI site in the LTR) from the 5' end of AKR ecotropic proviral DNA. The DNA segment extending from 5.1 to 6.8 kilobases contained several restriction sites that were not present in the AKR ecotropic provirus. A 0.5-kilobase DNA segment located at the 3' end of MCF 1 DNA contained sequences which hybridized to a xenotropic env-specific DNA probe but not to labeled ecotropic env-specific DNA. This dual character of MCF 1 proviral DNA was also confirmed by analyzing heteroduplex molecules by electron microscopy. The second cloned proviral DNA (designated MCF 2) was a 6.9-kilobase EcoRI DNA fragment which contained LTR sequences at each end and a 2.0-kilobase deletion encompassing most of the env region. The MCF 2 proviral DNA proved to be a useful reagent for detecting LTRs electron microscopically due to the presence of nonoverlapping, terminally located LTR sequences which effected its circularization with DNAs containing homologous LTR sequences. Nucleotide sequence analysis demonstrated the presence of a 104-base-pair direct repeat in the LTR of MCF 2 DNA. In contrast, only a single copy of the reiterated component of the direct repeat was present in MCF 1 DNA.

AKR murine leukemia virus↗
PubMed1982

Internal organization of endogenous proviral DNAs of xenotropic murine leukemia viruses.

The internal organization of endogenous xenotropic murine leukemia virus proviruses was determined in a series of blot hybridization experiments in which DNA from several different inbred mouse strains, digested with restriction enzymes known to cleave xenotropic proviral DNAs at least twice, was annealed to generalized murine leukemia virus or xenotropic env-specific DNA probes. Comigrating bands of variable intensity which hybridized to the xenotropic env probe were identified in all inbred mouse DNA preparations. At least seven classes of endogenous xenotropic proviral DNA with respect to SacI cleavage maps were detected in mouse DNA. Two of the seven classes were indistinguishable from proviruses associated with known infectious xenotropic murine leukemia viruses. These results are consistent with the existence of related but organizationally distinct families of endogenous xenotropic proviral DNA that are present in different relative abundances in mouse genomic DNA.

Animals↗