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Biomedical subjects

W Ross

Publications and source records attributed to W Ross.

At least 91 records · Page 5Linked to original sources
PubMed1984

Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage.

Epipodophyllotoxins are an important new class of anticancer agents which include the compounds VM-26 (teniposide) and VP-16 (etoposide). The mechanism of action of these drugs appears to involve production of DNA single- and double-strand breaks by virtue of a temperature-sensitive interaction between drug and a heat-labile intranuclear component. We now report evidence indicating that type II topoisomerase is the likely intracellular target for the DNA strand-breaking effects of the epipodophyllotoxins. Both VM-26 and VP-16 stimulate site-specific DNA cleavage by a highly purified calf thymus type II topoisomerase. VM-26 is 5- to 10-fold more potent than VP-16 in this assay, a difference that is also seen when DNA strand breaks are assayed in isolated nuclei of mouse leukemia cells following drug exposure. Furthermore, a similar potency difference exists with respect to cytotoxicity. Equilibrium dialysis experiments using [3H]VP-16 indicate that the drug does not bind to DNA. Thus, we suggest that the epipodophyllotoxins exert their anti-cancer effects by "poisoning" type II topoisomerase without binding to DNA. In this regard, their actions may be analogous to those of nalidixic acid in bacteria.

Animals↗
PubMed1983

Low-dose streptokinase in the treatment of celiac and superior mesenteric artery occlusion.

Selective delivery of low-dose streptokinase was effective in the treatment of embolic occlusion of the celiac and superior mesenteric arteries. The two-catheter technique resulted in complete lysis of clot in the celiac artery and improvement in patency of the superior mesenteric artery. The procedure restored effective mesenteric blood flow and provided an alternative to surgery in a very ill patient.

Aged↗
PubMed1983

Patterns of lambda Int recognition in the regions of strand exchange.

Int protein has two classes of binding sites within the phage att site: the arm-type recognition sequences are found in three specific sites that are distant from the region of strand exchange; the junction-type recognition sequences occur as inverted pairs around the crossover region in both attP and attB. During recombination between attP and attB each of the four DNA strands is cut at a homologous position within each of the junction-type Int binding sites. In all four junction-type sites Int protein interacts primarily with the same face of the DNA helix, as determined by those purine nitrogens that are protected against methylation by dimethylsulfate. Efficient secondary attachment sites for lambda contain sequences with partial homology to the junction-type binding sites. In addition, the sequence between, but not part of, the two junction-type sites (the overlap region) is strongly conserved in secondary att sites. Thus, in the vicinity of strand exchange, attP and a recombining partner, such as attB, are very similar; each comprises two junction-type Int recognition sites and an overlap (crossover) region.

Bacteriophage lambda↗
PubMed1983

[Late mucous membrane changes following exclusive radiotherapy of malignant epipharynx tumors].

Long-term modifications of the mucous membrane after exclusive radiotherapy of malignant tumors are of great interest. Sixteen patients with malignant tumors of the epipharynx could be checked up after exclusive radiotherapy. The treatment had been passed for more than five years. The examinations showed that the essential troubles, i.e. the general xerostomia was due to long-term modifications of the mucous membrane in the nose and epipharynx. The endoscopic findings and the results of histological examination of tissue specimens are reported, compared to the indications of literature, and discussed.

Humans↗
PubMed1982

Bacteriophage lambda int protein recognizes two classes of sequence in the phage att site: characterization of arm-type sites.

Purified int protein from bacteriophage lambda binds to specific sites in DNA that are not part of the functional attachment sites (non-att DNA) as well as to specific sites in att DNA. Analysis of non-att sites protected from nucleases by int has permitted definition of two distinctly different consensus recognition sequences, one of which, the arm-type sequence, is characterized in this report. Both types of recognition sequence occur in attP; five copies of the arm-type consensus sequence are located distant from the crossover region in the P1, P2, and P' arm protected regions. The second type of recognition sequence occurs at the crossover region. Modification of int with N-ethylmaleimide selectively alters its interaction with arm-type sequences.

Bacteriophage lambda↗
PubMed1980

The lambda phage att site: functional limits and interaction with Int protein.

Site specific integrative recombination of bacteriophage lambda involves unequal partners. The minimal phage att site is composed of approximately 240-base pairs and four distinct binding sites for Int protein, at least three of which are crucial for function. This 'donor site' recombines efficiently with a smaller 'recipient site' that lacks the extensive interactions with Int protein.

Attachment Sites, Microbiological↗
PubMed1980

Site-specific recombination in bacteriophage lambda: structural analyses of reactive DNA sequences.

Site-specific integrative recombination in bacteriophage lambda involves unequal partners. The minimal phage att site is composed of approximately 240 base pairs and has four distinct Int binding sites that differ in size and response to heparin challenge. There appear to be two size classes of Int binding sites, approximately 30-35 base pairs and 15 base pairs. The sites at the common core and in the P' arm are of the former class. Two sites in the P arm are of the latter class. Thus far, three of the four sites have been shown to be necessary for att site function. In contrast, the minimal sequence required for a phage att site partner (such as the bacterial att site) may not be much larger than the 15 base pair common core. We have suggested a model in which integrative recombination involves two unequal partners; accordingly the phage att site is referred to as the "donor" and the bacterial att site, or its analogue, is referred to as the "recipient."

Bacteriophages↗
PubMed1980

[Influence of monodehydroascorbate on the acyl-CoA-desaturase system of rat liver microsomes (author's transl)].

The microsomal NADH- as well as the ascorbate-dependent fatty acid desaturation are diminished by monodehydroascorbate. This effect can be neutralized by borate. Borate forms an adduct with didehydroascorbate and thus prevents the formation of monodehydroascorbate. The ascorbate-dependent oleate formation is increased significantly by the same reaction (p less than 0.01). The NADH-dependent reaction is diminished by parallel reactions of the desaturase system and L-ascorbate: ferricytochrome b5 oxidoreductase at ferrocytochrome b5. In the case of the ascorbate-dependent reaction the diminished oleate formation is caused by the more positive oxidation state of cytochrome b5 in presence of monodehydroascorbate.

Animals↗
PubMed1979

Collection, storage and transfusion of blood stem cells for the treatment of hemopoietic failure.

Migration of hemopoietic stem cells via the blood to sites of stem cell need is a principle that becomes established during the embryonic development of hemopoiesis and can be observed in the adult whenever bone marrow transplantations are being performed. The regular presence of stem cells in the peripheral blood lends itself to the study of their collection, storage, and use for transfusion purposes in cases of bone marrow failure. Both in dog and in man, granulocyte-macrophage progenitor cells (CFU-C) can be collected by leukapheresis from the blood in large quantities, particularly if the yield is increased by the administration of mobilizing agents such as dextran sulfate, and appear to be an indicator for the presence of stem cells. For collection and storage, a closed plastic bag system has been developed that allows the safe handling of the cells. The loss of CFU-C from freezing and thawing with DMSO as a cryoprotective agent is only 10%-20%. If frozen and thawed mononuclear leukocytes are transfused into 1200 rad whole-body X-irradiated autologous or allogeneic recipient dogs, a hemopoietic take is observed when 0.2 X 10(5) CFU-C are present among the mononuclear leukocytes (MNC). Graft-versus-host disease can be avoided in the allogeneic situation when a purified CFU-C rich cell fraction is being transfused. In man collection and storage of MNC including CFU-C is feasible and may eventually become a therapeutic tool.

Animals↗
PubMed1979

Interaction of int protein with specific sites on lambda att DNA.

We have studied the interaction of highly purified Int protein with DNA restriction fragments from the lambda phage attachment site (attP) region. Two different DNA sequences are protected by bound Int protein against partial digestion by either pancreatic DNAase or neocarzinostatin. One Int binding site includes the 15 bp common core sequence (the crossover region for site-specific recombination) plus several bases of sequence adjoining the core in both the P and P' arms. The second Int-protected site occurs 70 bp to the right of the common core in the P' arm, just at the distal end of the sequence encoding Int protein. The two Int binding sites are of comparable size, 30-35 bp, but do not share any extensive sequence homology. The interaction of Int with the two sites is distinctly different, as defined by the observation that only the site in the P' arm and not the site at the common core region is protected by Int in the face of challenge by the polyanion heparin. Restriction fragments containing DNA from the bacterial attachment site (attB) region exhibit a different pattern of interaction with Int. In the absence of heparin, a smaller (15 bp) sequence, which includes the left half of the common core region and the common core-B arm juncture, is protected against nuclease digestion by Int protein. No sequences from this region are protected by Int in the presence of heparin.

Bacteriophage lambda↗