PubMed Health⌕ Search

Biomedical subjects

S Hartman

Publications and source records attributed to S Hartman.

32 records · Page 2Linked to original sources
PubMed1993

Greater diversity of the HIV-1 V3 neutralization domain in Tanzania compared with The Netherlands: serological and genetic analysis.

OBJECTIVE: To compare variation in the HIV-1 V3 neutralization domain in Tanzania and The Netherlands. METHODS: For serologic analysis, the specificity of anti-V3 antibodies (immunoglobulin G) for a panel of V3 peptides was determined in sera from 55 symptomatic HIV-1-infected Tanzanians and 51 Dutch AIDS patients. For genetic analysis, viral RNA was isolated from 15 of the Tanzanian sera and six of the Dutch sera. The V3 encoding region was reverse-transcribed, polymerase chain reaction-amplified and bacterially cloned, and sequences were determined over a stretch of at least 207 nucleotides. RESULTS: Thirty-five per cent of the Tanzanian sera, versus 2% of the Dutch sera, showed the highest reactivity to a V3 sequence of Zairian origin (RKSIHVGPGQAFYATG). Twenty-nine per cent of the Tanzanian sera, versus 82% of the Dutch sera, showed the highest reactivity to V3 sequences of US/European origin (RKSIXIGPGRAFYTTG; X = H, P or N). The Tanzanian RNA sequences showed greater diversity (mean distance, 19%) than the Dutch RNA sequences (10%). The measured anti-V3 specificities of the Tanzanian sera did not match accurately with the V3 sequences recovered from these sera. However, reactivity to the Zairian V3 peptide was associated with the sequence GPGQ, found in the centre of the V3 in 50% of the Tanzanian sequences. Sera from both countries that showed similar reactivities to the peptide panel contained RNA sequences that were relatively distant. CONCLUSIONS: The diversity of the HIV-1 population in Tanzania is much greater than that in The Netherlands. An indication of the HIV-1 V3 variation in a particular geographic region can be obtained by serological methods, but sequence analysis should not be omitted.

Adolescent↗
PubMed1993

Large DNA restriction fragment polymorphism in the Mycobacterium avium-M. intracellulare complex: a potential epidemiologic tool.

Mycobacterium avium-M. intracellulare complex (MAI) isolates were studied by comparing the large restriction fragment (LRF) patterns produced by digesting their DNAs with infrequently cutting restriction endonucleases and separating the resultant large fragments by pulsed-field gel electrophoresis. Four reference strains and 35 randomly selected clinical MAI isolates gave highly diverse LRF patterns when their DNAs were digested with XbaI or AsnI. The LRF patterns of random isolates identified to be the same species by DNA probe analysis were not similar. The LRF patterns of random isolates of the same serotype were also different. In contrast, all isolates recovered from the same patient gave identical patterns. This included 28 isolates from nine patients. One isolate from sputum, one isolate from bone marrow, and two isolates from blood recovered over a 27-month period from a patient with AIDS were identical. Seven isolates recovered from the sputum of a second patient over 37 months also had identical patterns. The LRF patterns of unrelated MAI strains are highly polymorphic, appear to be strain specific, are relatively stable, and offer exciting promise as epidemiologic markers for the study of MAI infections.

DNA, Bacterial↗
PubMed1991

Construction of a human shuttle vector containing a single nitrogen mustard interstrand, DNA-DNA cross-link at a unique plasmid location.

DNA cross-linking reagents are frequently unusually cytotoxic, and many, including the nitrogen mustards, are potent chemotherapeutic agents, presumably because DNA cross-links effectively block DNA replication. Most of these reagents form both inter- and intrastrand DNA cross-links, but it is unknown which is more effective at blocking replication and why. To evaluate the role of interstrand cross-links, a human shuttle vector was constructed that contains a single, nitrogen mustard interstrand cross-link at a unique site. In previous work (J.O. Ojwang, D. A. Grueneberg, and E. L. Loechler, Cancer Res., 49: 6529-6537, 1989) a duplex oligonucleotide was synthesized that had an interstrand cross-link derived from a nitrogen mustard moiety bound at the N(7)- position of the guanines in the opposing strands of a 5'-GAC-3' 3'-CTG-5' sequence. Herein, a procedure is described to incorporate this oligonucleotide into an SV40-based human shuttle vector, which was designed for these experiments. The purified cross-linked vector was characterized and shown: (a) to have a chemical (i.e., a nitrogen mustard) modification at the anticipated genome location; (b) to have a modification that covalently joins the two duplex strands of the vector together; and (c) to contain a single interstrand cross-link per genome. The methodologies described to construct this vector are expected to be generally applicable and, thus, site-specific incorporation of an interstrand cross-link derived from any appropriate chemical should be possible. These procedures complement existing methodologies that permit the incorporation of monoadducts and intrastrand cross-links into vectors in a site-specific manner.

Base Sequence↗
PubMed1991

HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies.

DNA coding for the principal neutralization epitope of HIV-1 (the V3 domain of the envelope glycoprotein gp120) was amplified by polymerase chain reaction from postmortem brain and spleen tissue of three perinatally infected children who died of AIDS with progressive encephalopathy. Sequences obtained directly (without cloning) from this DNA were compared with sequences of 52 molecular clones made from this DNA. Cluster analysis showed that V3 domain sequences from two of the three children were similar to sequences from the American MN/SC isolates, while those from one child were more closely similar to the Caribbean RF isolate. Comparison of sequences obtained directly with consensus sequences derived from cloned DNA showed that V3 sequences are characteristic for an individual host. In one child, the V3 sequence determined directly from brain DNA was very distant from the consensus brain clone sequence and from the spleen sequences, suggesting a diverging quasispecies distribution. Site-directed hybridization demonstrated that brain-specific sequences present in 33% of brain-derived clones were absent from clones derived from spleen. The evidence suggests that brain- and spleen-specific variants evolve independently within each host-delimited quasispecies.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Differential sensitivity of two functions of the insulin receptor to the associated proteolysis: kinase action and hormone binding.

Since we observed that after purification the receptor kinase activity is rapidly lost under conditions where insulin binding function seems to be preserved, we have studied the cause(s) of receptor kinase inactivation. Highly purified placental insulin receptor preparations were analyzed by NaDodSO4/PAGE followed by silver staining or immunostaining using domain-specific antibodies raised against synthetic peptides corresponding to the amino acid sequences of the beta subunit. These studies revealed the intact 90-kDa beta subunit is degraded first to an 88-kDa form and then to a 50-kDa beta 1-subunit form by proteolysis even after purification when stored at 4 degrees C. The 88-kDa beta subunit, which lacks the carboxyl-terminal approximately equal to 2-kDa portion exhibits almost no autophosphorylation activity, nor does insulin stimulate autophosphorylation. The loss of kinase activity as measured by phosphorylation of the src-related peptide is correlated with the loss of the intact 90-kDa beta subunit. Degradation of the beta subunit to the 50-kDa form seems to be facilitated by the removal of the approximately equal to 2-kDa peptide. Present studies thus suggest that only the intact form of the beta subunit has full kinase activity in an insulin-dependent manner and that other forms, such as the 88-kDa beta subunit show little kinase activity. The inactivation appears to arise from a conformational change of the 90-kDa form, which makes it susceptible to proteolysis at the carboxyl-terminal end. These results imply that the carboxyl-terminal of the beta subunit is important for the manifestation of the tyrosine kinase activity of the insulin receptor.

Amino Acid Sequence↗
PubMed1986

Long-term survival following bony metastases from basal cell carcinoma. Report of a case.

A patient with recurrent basal cell carcinoma developed cervical-vertebral and epidural metastases. He received palliative irradiation and had a durable remission for three years. With relapse, he underwent a laminectomy and chemotherapy and remained asymptomatic at 54 months following the diagnosis of bony metastases. To our knowledge, he is the longest reported survivor with bony metastases and is illustrative of the potential survival advantage from palliative therapy.

Basal Cell Carcinoma↗
PubMed1982

Comparison of five assays for immune complexes in the rheumatic diseases. An assessment of their validity for rheumatoid arthritis.

Clinical assessment (disease activity, severity, and extraarticular manifestations) of 101 rheumatoid arthritis patients was correlated with several laboratory tests, including 5 immune complex assays: the bovine conglutinin, 125I-Clq binding, monoclonal rheumatoid factor inhibition, Raji cell, and staphylococci binding assays. Elevated disease activity indices were most closely associated with the presence of immune complexes detected by the 125I-Clq and staphylococci binding assays. There were significant but weak correlations between the level of disease activity and the level of immune complexes as measured by the bovine conglutinin, 125I-Clq binding, Raji cell, and staphylococci binding assays. Articular disease severity, as measured by anatomic stage, was discriminated by the bovine conglutinin, monoclonal rheumatoid factor inhibition, and staphylococci binding assays. Extraarticular manifestations were best discriminated by the Raji cell and staphylococci binding assays. We concluded that the sensitivity, specificity, predictive value, and overlap of the associations were not sufficient to warrant their wide use for the diagnosis and management of rheumatoid arthritis in individual patients. Conversely, the 125I-Clq and staphylococci binding assays were as good as the erythrocyte sedimentation rate and the IgG rheumatoid factor test (the 2 best of many examined) in assessing disease activity. Further prospective studies with these assays will determine their usefulness in following rheumatoid arthritis for a prolonged period.

Antigen-Antibody Complex↗
PubMedDate not supplied

The efficacy and safety of auranofin compared to placebo in rheumatoid arthritis.

This double-blind multicenter study compares the effect of adding auranofin (AF) 3 mg bid or placebo to patients already taking nonsteroidal antiinflammatory drugs for rheumatoid arthritis. The 242 patients who completed 3 months of therapy demonstrated that the group receiving AF responded better than those receiving placebo. Of the 144 patients who completed 6 months coded medication, the efficacy in the AF group was superior to the placebo group in several parameters including a reduction in the number of painful or swollen joints, grip strength, dropout rate, and global efficacy as judged by the evaluating physician. A significant lowering of the Westergren erythrocyte sedimentation rate and immunoglobulin levels was noted in the AF treated patients. This study includes data summarizing the difference between both groups with respect to on-therapy conditions and toxicity.

Arthritis, Rheumatoid↗