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Biomedical subjects

M W Shaw

Publications and source records attributed to M W Shaw.

At least 37 records · Page 2Linked to original sources
PubMed1988

Protection against virulent H5 avian influenza virus infection in chickens by an inactivated vaccine produced with recombinant vaccinia virus.

A cloned cDNA copy of the haemagglutinin (HA) gene of A/Chicken/Scotland/59 (H5N1) influenza virus has been expressed in vaccinia virus. This pox virus is poorly infectious or non-infectious for chickens. However, immunization of chickens with lysates of cell cultures infected with the recombinant vaccinia virus, that had been emulsified with adjuvant and which contained an estimated 0.5 microgram influenza HA, elicited a substantial neutralizing antibody response to influenza virus. Challenges of immunized and non-immunized adult chickens with virulent A/Chicken/Scotland/59 influenza virus showed that the immunized animals were highly protected while the non-immunized controls died. Immunized birds were also protected against infection with the recent virulent H5 avian influenza virus, A/Chicken/Pennsylvania/83 (H5N2).

Animals↗
PubMed1988

Effect of BCG upon functional and phenotypic immune markers in rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma.

Rats bearing (or not bearing) the Dunning R3327 MAT-LyLu prostatic adenocarcinoma were treated with Bacillus Calmette-Guérin (BCG) and evaluated for immune competence using functional and phenotypic markers. Tumor presence significantly depressed total T and helper T cell representation along with the helper/suppressor T cell ratio. Functional immunity, measured by phytohemmagglutinin (PHA) induced blastogenesis, was also significantly depressed. When BCG was administered to non-tumor bearing animals, it had no effect upon T cell subset distributions but significantly reduced PHA induced blastogenesis. BCG similarly administered to tumor bearing animals did not alter the depressed helper/suppressor T cell ratio found in tumor bearing rats, but did significantly elevate PHA induced blastogenesis. However, these elevated levels of functional immunity in BCG treated tumor-bearing rats remained significantly below normal. These data demonstrate a poor correlation between functional and phenotypic assessments of immune capability.

Adenocarcinoma↗
PubMed1987

Immunoregulatory markers in rats carrying Dunning R3327 H, G, or MAT-LyLu prostatic adenocarcinoma variants.

The Dunning R3327 tumor represents a system for studying prostate cancer in Copenhagen X Fischer rats. Animals bearing variant sublines (H, G, and MAT-LyLu) differing in growth rate, differentiation, hormone responsiveness, and metastatic ability were assayed for three immunological markers. Spleens were passed through a tissue sieve, and mononuclear cells were obtained by Ficoll-Hypaque centrifugation. These were assayed for leukocytic subsets using monoclonal antibodies. An adherent population was isolated and evaluated using thin-layer chromatography for conversion of radiolabeled arachidonic acid to E series prostaglandins. Finally, sera from these animals were assayed for levels of circulating immune complexes using polyethylene glycol precipitation. Data from 52 rats bearing the various tumors were obtained, correlated with subline aggressiveness, and compared to 15 controls. Each tumor group demonstrated significantly lower helper/suppressor T-cell ratios than controls, probably due to general tumor presence. In addition, the most aggressive R3327 MAT-LyLu variant had significantly increased prostaglandin E synthesis by adherent spleen cells compared to the H or G sublines and significantly increased levels of circulating immune complexes relative to the H subline. G subline values for both prostaglandin E and circulating immune complexes levels were intermediate, suggesting that these markers correlate better with tumor aggressiveness than helper/suppressor T-cell ratios.

Adenocarcinoma↗
PubMed1987

Combination therapy using polyamine synthesis inhibitor alpha-difluoromethylornithine and adriamycin in treatment of rats carrying the Dunning R3327 MAT-LyLu prostatic adenocarcinoma.

Prostate cells of human and rat origin produce polyamines in high content, whose apparent functions relate to cellular proliferation and secretory activities. Formation is dependent on the enzyme ornithine decarboxylase (ODC) which is irreversibly inhibited by alpha-difluoromethylornithine (DFMO). It has been postulated that pretreatment with DFMO may render cells more susceptible to subsequent chemotherapy. Copenhagen X Fischer F1 rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma were given DFMO or adriamycin (ADR), alone or in combination. Those receiving DFMO were continuously provided the drug ad libitum, in water (2.5%), for the duration of the experiment, beginning 2 days prior to ADR administration. At intervals, tumor sizes were measured, animal survivals noted and comparisons made to nontreated, tumor-bearing controls. The results indicate that ADR alone or in combination with DFMO significantly reduced tumor progression, but that only combination therapy significantly prolonged survivals. Decreased tumor progression produced by DFMO alone was not statistically significant. Differences produced with combined use were additive and suggest that DFMO may augment ADR chemotherapy.

Adenocarcinoma↗
PubMed1987

Effect of cyclophosphamide on leukocytic subset distributions in rats carrying the Dunning R3327-MAT-LyLu prostatic adenocarcinoma.

The Dunning R3327 adenocarcinoma represents a model for studying prostate cancer in rats; early studies have indicated its utility for studying relationships between tumor growth, immunologic markers, and chemotherapy. Normal animals and those bearing the metastatic Dunning R3327 MAT-LyLu tumor were treated with 10, 30, and 100 mg/kg doses of cyclophosphamide (CTX) and their spleens assayed for leukocytic subset distributions using monoclonal antibodies. Tumor-bearing animals had significant reductions in helper T cell content as well as reduced helper/suppressor T cell ratios, compared to controls. These effects occurred rapidly following implantation and were not reversed by chemotherapy. When administered to both tumor- and non-tumor-bearing animals, CTX also depleted T cell populations. Despite reductions produced in all subsets, two administrations of CTX (30 mg/kg) were capable of retaining (in non-tumor-bearing animals) or restoring (in tumor-bearing) normal helper/suppressor T cell ratios. Such studies aid in identifying therapeutically effective dosages of cytotoxic drugs that minimize their deleterious effects on the immune system.

Adenocarcinoma↗
PubMed1987

Comparison of the immune response to variant influenza type B hemagglutinins expressed in vaccinia virus.

To compare the immune response induced by influenza hemagglutinin (HA) variants differing by a single amino acid, the genes for each HA variant were cloned and expressed in vaccinia virus. These variant HA genes have been previously described as being present exclusively in either egg-derived or MDCK cell-derived subpopulations of influenza B/England/222/82 virus. By using this approach we were able to vaccinate animals with homogeneous preparations of these viral antigens and thus circumvent the problem of heterogeneity within RNA virus stocks. Immunization and challenge experiments in mice indicated that even though vaccination with the recombinant vaccinia viruses induced different levels of cross-reactive neutralizing antibodies, mice vaccinated with either recombinant vaccinia virus were protected from infection with either subpopulation of influenza virus. Results with this model system support the view that influenza vaccines prepared with egg-derived virus should be protective against microvariants of virus that grow preferentially in MDCK and possibly other mammalian cells.

Animals↗
PubMed1987

Segment-specific and common nucleotide sequences in the noncoding regions of influenza B virus genome RNAs.

The nucleotide sequences of the 3' noncoding regions of all eight segments of influenza B virus RNA and the sequences of the 5' noncoding regions of segments 4-8 were determined in virus strains isolated over a period of 40 years. Nearly complete conservation of the noncoding sequences was found. Nine nucleotides at the 3' termini and 11 nucleotides at the 5' termini were common to all segments examined. In the region immediately adjacent to the common 3' terminal region, the nucleotides were specific for each segment and these segment-specific sequences were conserved in all strains examined. In each of the five segments in which both termini were examined, the segment-specific 3' sequences exhibited perfect inverted complementarity to a segment-specific sequence adjacent to the common 5' terminus. In addition, in the 3' noncoding region of RNA segments 1-3, which encode proteins involved in RNA synthesis, a single nucleotide substitution at position 10 was found that distinguishes these segments from segments 4-8. Comparison of these data with published reports has revealed that some of the features found in the noncoding regions of influenza B virus are also present in influenza A and C virus RNAs. In the RNAs of all three virus types, there is a segment-specific sequence of nucleotides near the 3' terminus that shows inverted complementarity to a sequence near the 5' terminus. This segment-specific sequence may play a role in the transcription of individual segments or in sorting of segments during virion assembly.

Animals↗
PubMed1987

Administration of recombinant tumor necrosis factor to rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma.

Copenhagen X Fischer F1 rats bearing palpable Dunning R3327 MAT-LyLu prostatic adenocarcinomas were treated by intraperitoneal (i.p.) or intratumor (i.t.) injection with either human serum albumin alone or in combination with recombinant tumor necrosis factor (rTNF). At intervals tumors were measured and survivals noted. A maximum tolerable dose and least toxic route of administration was then determined. Those treated i.t. with rTNF survived significantly longer and ultimately developed significantly smaller tumors than untreated controls. Those administered rTNF by the i.p. route had less significant increases in survival with intermediate final tumor sizes.

Animals↗
PubMed1986

Leukocytic subset distributions of spleen cells obtained from rats bearing variants of the Dunning prostatic adenocarcinoma.

Employing monoclonal antibodies, the relative frequencies of mononuclear cell types found in spleen cell populations were compared between rats bearing variants of the Dunning prostate adenocarcinoma and a series of non-tumor bearing control animals. The identification and quantitation of such subsets greatly expands our knowledge of immune status and function. The results indicate that the spleen cell populations from animals bearing either the Dunning R3327-H, G or MAT-LyLu sublines have significant decreases in their helper T cell/suppressor T cell ratios when comparisons are made to cells obtained from non-tumor bearing animals. In addition decreases in total T cell content and increases in splenic monocytes were noted. It appears that most of these deviations are the result of general Dunning tumor presence, rather than due to any particular subline characteristic. These changes may be analogous to similar alterations reported in the peripheral blood of humans bearing Stage D prostatic cancer, suggesting that the Dunning tumor may provide an appropriate model for evaluating interactions between the immune response, the tumor and therapy.

Adenocarcinoma↗
PubMed1986

Adherent spleen cell production of E series prostaglandins in rats bearing variants of the R3327 Dunning prostatic adenocarcinoma: effect of cyclophosphamide.

Prostaglandins of the E series (PGE) have been implicated in many facets of immunoregulation, as well as having a possible role in metastatic dissemination. Variant sublines of the Dunning R3327 rat prostatic adenocarcinoma, differing in growth rate, hormonal responsiveness and in propensity for metastasis, were carried in Fisher X Copenhagen F1 animals. Adherent spleen cells were assayed in vitro for their ability to convert arachidonic acid to prostaglandins of the E series. These glass adherent cells presumably include the monocytic and T cell populations which have been implicated as being immunoregulatory. The results indicated that those spleen cells obtained from animals carrying the metastatic R3327-MAT-LyLu subline tumor converted more arachidonic acid to PGE's than cells derived from animals bearing non-metastatic sublines. Cyclophosphamide therapy did not alter such conversion. Multiple regulatory mechanisms for prostaglandin metabolism are suggested.

Adenocarcinoma↗
PubMed1985

The effect of low-dose cyclophosphamide and immunologic exposure upon growth of established Dunning R-3327-G subline rat prostate adenocarcinomas.

Utilizing the Dunning rat prostate adenocarcinoma, a low dose of cyclophosphamide (CY), 30 mg/kg, administered either alone or following diethylstilbestrol (DES) therapy, was as effective as higher levels of CY (100 mg/kg) in ability to initiate tumor regression. A lower dose (10 mg/kg) of CY was initially ineffective. Animals which had been injected with tumor an additional 10 days prior to initiation of CY treatment were apparently more responsive to this mode of chemotherapy. The effect of this additional 10 days of immunologic exposure supports the belief that the activity of CY is augmented by the presence of immunologic competence. All animals which responded favorably toward therapy utilizing CY, alone or in combination with DES, were similarly able to reject subsequent tumor challenges. It is thought that low-dose CY may reduce the immunosuppressive effects observed with higher levels and presumably preserve the helper T cell population necessary to mount secondary immune responses.

Adenocarcinoma↗
PubMed1985

The effect of hormone therapy on peripheral blood leukocytic subset distribution in stage D prostatic cancer patients.

The distribution of mononuclear cell types found in the peripheral blood of patients bearing carcinoma of the prostate were compared by stage and to a control group using monoclonal antibody techniques. Patients with lower stage disease (A, B) had no significant alteration in subset distribution when compared to a control group, while those with higher stage disease (D) had significant deviations. Stage D patients had a decreased representation of helper-inducer T cells and an increased representation of suppressor-cytotoxic T cells, with an overall reduction in the total T cell content. In addition elevated levels of monocytic, granulocytic and null cells were recognized by the polyspecific OKM1 antibody. These differences were in part reversible following hormonal therapy. Such alterations in the ratios between the various T cell populations could be useful in patient staging and treatment selection.

Adult↗
PubMed1985

Immunobiology of the Dunning R-3327 rat prostate adenocarcinoma sublines: plasma and tumor effusion prostaglandins.

Enhanced production of prostaglandins (PGs) by experimentally-induced and naturally occurring tumors and their effect on tumor growth and immunosurveillance have been noted. Directed toward further evaluation of the relationship between prostatic tumor growth and its milieu, i.e., microenvironment, we investigated the possible correlation between levels of PGs, tumor size, and metastatic potential. For this purpose, the levels of PGE2 and PGF2 alpha in plasma and tumor effusions of three tumor sublines of the Dunning R-3327 rat prostate adenocarcinoma were measured: R-3327H, well-differentiated, slow-growing, and poorly metastatic; R-3327G, poorly differentiated, fast-growing, and poorly metastatic; and R-3327 Mat LyLu, anaplastic, fast-growing, and highly metastatic. The level of PGF2 alpha was highly variable with no significant differences being noted between the tumor sublines. The mean values of PGF2 alpha were, however, higher, although not significantly so, in the smaller tumors within each of the sublines. The levels of PGE2 were significantly higher in Mat LyLu effusions than those from the nonmetastasizing R-3327G and H sublines. Evaluation and comparison of the relationship between tumor burden, i.e., size versus levels of PGE2 and PGF2 alpha showed no significant differences. A vasodilator and regulator of immunological responsiveness, PGE2, may function as a modulator of tumor metastases. In consonance with studies by others elevated levels of PGE2 may possibly serve as a prognostic marker for the high metastatic potential of neoplastic cells.

Adenocarcinoma↗
PubMed1985

Effect of transfer factor on tumor-associated immunity and tumor growth of the Dunning R-3327G rat prostate adenocarcinoma.

Of importance in the design and application of improved or new modalities of treatment are their evaluation on relevant animal models. In the case of prostate cancer (PCa) the Dunning R-3327 rat prostate adenocarcinoma (PCa), and its variant sublines, is one such experimental tumor model of its human counterpart. In a preliminary study, the effect of transfer factor (TF), one form of passive immunotherapy, on tumor-associated immunity (TAI) and tumour growth and histology of the G subline (a poorly differentiated, fast-growing, androgen sensitive, and poorly metastatic tumour of the Dunning R-3327 rat PCa) has been evaluated. TF prepared from the leukocytes of tumor-bearing animals and nontumor-bearing animals referred to as sensitized (STF) and unsensitized (UTF), respectively, had no significant effect on TAI or tumor size. The only noticeable effect of TF in this study was the presence of variable and moderate lymphocytic infiltrates, necrosis, and degenerative-type cells in tumors of animal recipients of STF. The failure to observe significant differences in TAI among tumor bearing and nontumor bearing animals raises doubt in part, of the immunogenicity of the G subline tumor and its appropriateness, at least for subsequent immunological studies. Further factors considered in this regard, are questions of tumor load, including the possible need for the use of adjuvant, and the parameters and sensitivity of immune responsiveness selected for evaluation and immunocompetency. Subsequent evaluation of the effect of TF on other more immunogenic variant sublines of the Dunning R-3327 rat tumor may yet provide further and more useful information.

Adenocarcinoma↗