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Biomedical subjects

L S Lin

Publications and source records attributed to L S Lin.

103 records · Page 6Linked to original sources
PubMed1981

Isolation of a Biologically active fragment of human alpha interferon.

When treated with pepsin under limited digestion conditions, human leukocyte-derived alpha interferon (HulFN-alpha) is partially inactivated. While the initial HulFN-alpha preparation is about equally active on human and on bovine cells, the residual antiviral activity of HulFN-alpha after pepsin treatment is significantly more active on bovine cells than on human cells. Furthermore, pepsin-treated HulFN-alpha, when assayed on bovine cells, yields an active production which is smaller and antigenically distinguishable from the native forms of HulFN-alpha.

Animals↗
PubMed1979

Production, purification and characterization of rat interferon.

Priming with heterologous mouse interferon, increased production of an antiviral substance induced in rat diploid fibroblasts by Newcastle disease virus. This substance was characterized as an acid stable interferon. This rat interferon exhibited marked cross-species antiviral activity when tested in mouse L929B cells, guinea pig embryo fibroblasts, human fibroblasts and bovine cells but was not active on chick embryo cells.

Animals↗
PubMed1978

Characterization of the size and charge heterogeneities of human leukocyte interferon populations.

Human leukocyte interferons are separable into two size components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and are separable into two charge-components by DEAE-BiGel A chromatography. However, each of the charge-components resolved by ion-exchange chromatography contained both size-components, when analysed by SDS-PAGE. Thus, there are more than two distinct molecular populations of human leukocyte interferons.

Cells, Cultured↗
PubMed1978

Interferoids: in vitro and in vivo conversion of native interferons to lower molecular weight forms.

Mouse interferons appear as two distinct molecular forms, one migrating at 38,000 daltons in sodium dodecyl sulfate/polyacrylamide gels and one migrating at 22,000 daltons; these interferons comprise about 80% and 20% of total activities, respectively. When such interferon preparations are briefly exposed to acidic periodate buffer, the larger interferon species is apparently converted to the smaller form since the activity at 38,000 daltons is completely eliminated while the activity at 22,000 daltons increases significantly; upon further oxidative cleavage, antiviral activity becomes detectable migrating at 15,000 daltons. Because no native mouse interferon has been reported as such small molecules, this antiviral activity is designated mouse "interferoid" to distinguish it from the native, naturally occurring interferon forms. Prolonged acidperiodate treatment fails to quantitatively convert the 22,000-dalton interferon to the 15,000-dalton interferoid since both are inactivated. When L cells are induced to make interferon in the presence of glycosylation inhibitors, either D-glucosamine or 2-deoxy-D-glucose, they produce approximately normal levels of antiviral activity. However, when such preparations are analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, little activity (<10%) migrates as either the 38,000-dalton or 22,000-dalton native interferons. The interferons and interferoid are antigenically and hydrophobically indistinguishable. These data suggest that induced mouse cells normally synthesize the interferoid as a precursor polypeptide that is either partially or extensively modified by carbohydrate additions to produce, respectively, the 22,000- and 38,000-dalton mouse interferons. Because interferoid is apparently fully biologically active without these moieties, chemical synthesis of such unmodified polypeptides or active fragments from them appears feasible.

Cells, Cultured↗
PubMed1977

Elimination of size and charge heterogeneities of human leukocyte interferons by chemical cleavage.

Human leukocyte interferon (HuLeIF) preparations contain distinct molecular forms of interferon exhibiting significant heterogeneties in sizes when analyzed by electrophoresis in sodium dodecyl sulfate (NaDodSO(4))/polyacrylamide gels, migrating in two broad bands of activity with peaks at about 21,000 and 15,000 daltons. HuLeIFs exhibit extensive charge heterogeneities when analyzed by isoelectric focusing, resolving into several major peaks of approximately equal activity distributed from pH 5.7 to 7.0. When HuLeIF preparations are treated with 0.01 M sodium periodate buffer, pH 4.5, at 4 degrees , both the size and charge heterogeneities rapidly disappear: periodate-treated HuLeIF migrates as a single, narrow band at 15,000 daltons in NaDodSO(4)/polyacrylamide gels and focuses as a single, narrow band at pH 5.7. Quantitative considerations suggest that either the larger, heterogeneously charged HuLeIFs are converted to the smaller, size- and charge-homogeneous interferon by extensive chemical deglycosylation, or, alternatively, the smaller, 15,000 dalton, pH 5.7 interferon is much more stable to periodate treatment than are the other interferon forms. However, the activity of each of the variously charged forms of HuLeIF isolated from focusing gels exhibited the same stability as the pH 5.7 component; similarly, the activity of each of the size-forms of HuLeIF isolated from NaDodSO(4)/polyacrylamide gels exhibited the same stability as the 15,000-dalton interferon.

Chemical Phenomena↗
PubMedDate not supplied

Sequence-specific DNA cleavage by dipeptides disubstituted with chlorambucil and 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid.

Two dipeptides, each containing a lysyl residue, were disubstituted with chlorambucil (CLB) and 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA): DMQ-MA-Lys(CLB)-Gly-NH2 (DM-KCG) and DMQ-MA-beta-Ala-Lys(CLB)-NH2 (DM-BKC). These peptide-drug conjugates were designed to investigate sequence-specificity of DNA cleavage directed by the proximity effect of the DNA cleavage chromophore (DMQ-MA) situated close to the alkylating agent (CLB) inside a dipeptide moiety. Agarose electrophoresis studies showed that DM-KCG and DM-BKC possess significant DNA nicking activity toward supercoiled DNA whereas CLB and its dipeptide conjugate Boc-Lys(CLB)-Gly-NH2 display little DNA nicking activity. ESR studies of DMQ-MA and DM-KCG both showed five hyperfine signals centered at g = 2.0052 and are assigned to four radical forms at equilibrium, which may give rise to a semiquinone radical responsible for DNA cleavage. Thermal cleavage studies at 90 degrees C on a 265-mer test DNA fragment showed that besides alkylation and cleavage at G residues, reactions with DM-KCG and DM-BKC show a preference for A residues with the sequence pattern: 5'-G-(A)n-Pur-3' > 5'-Pyr-(A)n-Pyr-3' (where n = 2-4). By contrast, DNA alkylation and cleavage by CLB occurs at most G and A residues with less sequence selectivity than seen with DM-KCG and DM-BKC. Thermal cleavage studies using N7-deazaG and N7-deazaA-substituted DNA showed that strong alkylation and cleavage at A residues by DM-KCG and DM-BKC is usually flanked on the 3' side by a G residue whereas strong cleavage at G residues is flanked by at least one purine residue on either the 5' or 3' side. At 65 degrees C, it is notable that the preferred DNA cleavage by DM-KCG and DM-BKC at A residues is significantly more marked than for G residues in the 265-mer DNA; the strongest sites of A-specific reaction occur within the sequences 5'-Pyr-(A)n-Pyr-3'; 5'-Pur-(A)n-G-3' and 5'-Pyr-(A)n-G-3'. In pG4 DNA, cleavage by DM-KCG and DM-BKC is much greater than that by CLB at room temperature and at 65 degrees C. It was also observed that DM-KCG and DM-BKC cleaved at certain pyrimidine residues: C40, T66, C32, T34, and C36. These cleavages were also sequence selective since the susceptible pyrimidine residues were flanked by two purine residues on both the 5' and 3' sides or by a guanine residue on the 5' side. These findings strongly support the proposal that once the drug molecule is positioned so as to permit alkylation by the CLB moiety, the DMQ-MA moiety is held close to the alkylation site, resulting in markedly enhanced sequence-specific cleavage.

Antineoplastic Agents↗
PubMedDate not supplied

Maintaining study validity in a changing clinical environment.

BACKGROUND: Nurse scientists who conduct intervention research in a variety of clinical settings find themselves facing numerous challenges posed by today's changing and sometimes complex health care environment. Maintaining study validity thus becomes a major focus of interventional research, but existing literature does not fully address challenges to study validity nor offer potential solutions. OBJECTIVES: The purposes of this paper are to 1) discuss methodologic challenges to maintaining study validity of intervention research that is conducted in a changing clinical environment, and 2) share strategies for maximizing study validity. METHODS: A recently completed intervention study is used as an example to discuss two specific areas that affected study validity, provide examples of selected threats to validity, and outline strategies used to minimize these threats. RESULTS: Careful definition of goals, thoughtful decision making, and implementation of specific strategies to maintain study validity helped increased the rigor of the research. CONCLUSIONS: Investigators conducting intervention research in changing clinical settings can reduce threats to study validity and increase design rigor by considering clinical realities (e.g., clinician-researcher role conflict) when making methodologic decisions, becoming familiar with the setting, and involving clinicians in the research.

Decision Making↗