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Biomedical subjects

R Guy

Publications and source records attributed to R Guy.

At least 55 records · Page 3Linked to original sources

A double-blind clinical study comparing the safety, tolerance and efficacy of ioversol and iohexol in intravenous urography.

A double-blind trial in 80 patients showed no significant difference in the efficacy, tolerance and safety for intravenous urography between the new contrast medium Ioversol (Optiray Mallinckrodt Inc.) and the well established medium Iohexol (Omnipaque, Nycomed [UK] Ltd). Minor transient rises in AST/ALT were noted in approximately 10% of each group which were regarded as clinically insignificant. Both media were well tolerated with no significant side-effects.

Adult↗

Site-directed mutations of human growth hormone that selectively modify its lactogenic activity and binding properties.

Two novel analogs of human (h) GH, 1) Des-7-hGH (Arg8Met, Asp11Ala) in which the Arg8 was substituted by Met and Asp11 by Ala, and 2) bovine (b) GH/hGH hybrid II (MetAla 1-13/14-191, Ala11Asp) composed of 13 N-terminal amino acid of bGH and elongated by two amino acids (Met-Ala-1-13) and 14-191 amino acids of hGH, were constructed and expressed in Escherichia coli. CD spectra indicated that the alpha-helix content of the purified proteins was similar to that of the native hormone. Both analogs retained their full ability to stimulate the proliferation of Nb2 lymphoma cells, and their binding to the lactogen receptors in homogenate of Nb2 cells and in microsomal fraction from bovine lactating mammary gland was only slightly reduced. However, their ability to bind to the somatogen receptors in intact IM-9 lymphocytes and bovine liver was reduced by 7- to 11-fold (bGH/hGH hybrid II) and 20- to 30-fold (Des-7-hGH). Both analogs were able to down-regulate the respective lactogen and somatogen receptors in intact Nb2 and IM-9 cells. The galactopoietic activity of both analogs in the lactating bovine mammary explants bioassay was almost completely abolished, and the bGH/hGH hybrid II exhibited a remarkable antagonistic activity. These results further indicate that the lactogen receptors in different species or organs are not identical. We have shown that the new recombinant analogs of hGH that recognize both somatogen and lactogen receptors but have modified postreceptor effects are helpful in elucidating these differences.

Base Sequence↗

Antigen-specific, MHC-restricted B cell activation by cell-free Th2 cell products. Synergy between antigen-specific helper factors and IL-4.

Ag-specific and MHC-restricted Th clones of different Ag specificities and MHC haplotypes were tested for their ability to produce soluble factors capable of providing the signals required for B cell activation and IgG antibody production. Each of five Th clones tested generated significant helper activity in supernatants derived from coculture of the T cell clone with specific Ag and syngeneic APC. The same helper activity was detected in supernatants of clones stimulated with immobilized anti-CD3 antibody in the absence of Ag or APC. The secreted helper activity resembled the activity of the intact Th cells in that it was Ag-specific, carrier-hapten-linked and MHC-restricted. These T cell products functioned to activate only those B cells expressing MHC products which corresponded to the specificity of each Th clone. Thus, the specificity of the cell-free T cell product mimicked precisely that expressed by the intact Th cell and presumably mediated by the cell surface TcR. In addition to the apparent presence of specific helper factor in Th clone supernatants, a role for nonspecific lymphokines was also identified in these preparations. Although recombinant or purified IL-4 alone was not sufficient to stimulate hapten-primed B cells to secrete hapten-specific IgG antibodies, mAb specific for IL-4 blocked the induction of antibody secretion by Th cell supernatant. These results indicate that stimulation of B cells to produce hapten-specific IgG antibody requires at least two distinct signals: an Ag-specific T cell signal which is restricted by MHC products expressed on the B cells, and a nonspecific signal mediated at least in part by the lymphokine IL-4.

Adjuvants, Immunologic↗

Antigen-specific helper function of cell-free T cell products bearing TCR V beta 8 determinants.

Although the T cell receptor (TCR) alpha beta heterodimer and its encoding genes have been characterized, a cell-free form of this receptor, which is needed for the study of functional or ligand-binding properties of the receptor, has not previously been isolated. When the cell-free supernatant products of activated cloned T helper (TH) cells were found to mediate helper activity with antigen specificity identical to that of intact T cells, experiments were carried out to determine whether this functional activity was mediated by a cell-free form of TCR-related material. A disulfide-linked dimer indistinguishable from the T cell surface alpha beta heterodimer was precipitated from cell-free supernatants of cloned TH cells with F23.1, a monoclonal antibody specific for a TCR V beta 8 determinant. Moreover, when cell-free TH products were bound to and eluted from immobilized F23.1, these affinity-purified materials had antigen-specific and major histocompatibility complex-restricted helper activity that synergized with recombinant lymphokines in the generation of B cell antibody responses. These findings suggest that the factor isolated from T cell supernatants is a cell-free form of the TCR alpha beta dimer.

Animals↗

Brawny cutaneous induration and granulomatous panniculitis in large cell non-Hodgkin's (T suppressor/cytotoxic cell) lymphoma.

A 56-year-old lady presented with striking peau d'orange-like, woody, diffuse infiltration of the skin of the upper, inner aspects of both arms and thighs. Initial biopsy specimens showed a granulomatous panniculitis with non-specific lymphohistiocytic infiltration. Clinical deterioration occurred with development of ascites and peripheral oedema; a single axillary node became palpable. Cytology of ascitic fluid, and histology and immunopathology of the axillary node, and of a further skin biopsy, now revealed diagnostic changes of a diffuse large cell lymphocytic lymphoma of T suppressor/cytotoxic type. Granulomatous panniculitis resulting in diffuse cutaneous infiltration may rarely be a presenting sign of malignant lymphoma.

Arm↗

Studies on the mechanism of benzene toxicity.

Using the 59Fe uptake method of Lee et al. it was shown that erythropoiesis in female mice was inhibited following IP administration of benzene, hydroquinone, p-benzoquinone, and muconaldehyde. Toluene protected against the effects of benzene. Coadministration of phenol plus either hydroquinone or catechol resulted in greatly increased toxicity. The combination of metabolites most effective in reducing iron uptake was hydroquinone plus muconaldehyde. We have also shown that treating animals with benzene leads to the formation of adducts of bone marrow DNA as measured by the 32P-postlabeling technique.

Aldehydes↗

Expression of T cell receptor V beta 8 determinants on antigen-specific T helper factor.

The ability of cell-free T helper cell products to provide helper activity in B cell antibody responses has been studied. The supernatants of activated T helper cells were sufficient to support hapten-specific IgG antibody responses by B cells in the absence of intact T cells. Moreover, this help was both antigen-specific and major histocompatibility complex (MHC)-restricted: T cell clone supernatant helped only when the hapten recognized by B cells was covalently linked to the carrier protein for which the corresponding T helper cell was specific; and this help was effective in supporting responses of only those B cells which express an MHC type corresponding to the MHC specificity of the cloned T cell. Active T helper supernatants consisted of at least two components, both of which are necessary for B cell responses. One is the lymphokine interleukin 4 (IL-4). The other is an antigen- and MHC-specific product which has been affinity purified by binding to a monoclonal antibody specific for T cell alpha beta receptor V beta 8 determinants. It therefore appears that a shed or secreted factor with serologic and functional similarities to the alpha beta T cell receptor (TCR) has been isolated and shown to be capable of direct signaling of B lymphocytes.

Animals↗

Antigen-specific helper factor production by immortalized clone of OVA-specific T cells. I. In vitro activity.

Immortalized clones of virally transformed OVA-specific T cells produce antigen-specific helper factor upon stimulation in vitro. The helper factor activate DNP-primed B cells to multiply and synthesize IgG anti-DNP antibodies. The trigger of the helper clone is antigen specific and the B cell-stimulating hapten must be coupled to the specific T cell carrier in order to transfer the help signal from the activated T clone to the B lymphocytes. Activation of the helper clone is performed by antigen-pulsed macrophages and cannot be achieved by the free soluble antigen. However, cell-free supernatant of the antigen-pulsed macrophages can stimulate the helper cells. Thus the antigenic determinant must be presented to the helper cell in the form of macrophage-processed antigen. These requirements for antigenic stimulation and the activity of the secreted helper factor demonstrate that the immortalized helper clone preserved the cellular components which control the antigen-specific immune function of the normal T lymphocyte.

Animals↗

Triazine herbicide resistance in the photosynthetic bacterium Rhodopseudomonas sphaeroides.

The photoaffinity herbicide azidoatrazine (2-azido-4-ethylamino-6-isopropylamino-s-triazine) selectively labels the L subunit of the reaction center of the photosynthetic bacterium Rhodopseudomonas sphaeroides. Herbicide-resistant mutants retain the L subunit and have altered binding properties for methylthio- and chloro-substituted triazines as well as altered equilibrium constants for electron transfer between primary and secondary electron acceptors. We suggest that a subtle alteration in the L subunit is responsible for herbicide resistance and that the L subunit is the functional analog of the 32-kDa Q(B) protein of chloroplast membranes.

Journal Article↗

Observations on natural and experimental infections with Giardia isolated from cats.

The course of infection with Giardia was studied in (a) naturally infected cats and (b) experimentally infected Mongolian gerbils using Giardia cysts isolated from cats. Natural infection was characterized by: (a) a latent period of 11 to 13 days, (b) the pattern of cyst release which was either continuous or intermittent during the acute phase of infection and (c) elimination of the infection in four to five weeks after exposure. Mongolian gerbils were found to be susceptible to infection with Giardia isolated from cats. The course of infection in gerbils was characterized by intermittent cyst release and elimination of the infection in about three weeks. The pattern of cyst release in gerbils infected with Giardia isolated from cats was similar to the previously reported pattern of cyst release in gerbils infected with Giardia isolated from humans. The possible role of pets in the zoonotic transmission of giardiasis is discussed.

Animals↗