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Biomedical subjects

J E Coe

Publications and source records attributed to J E Coe.

At least 37 records · Page 2Linked to original sources

Estrogen induction of hepatocellular carcinomas in Armenian hamsters.

Liver tumors were found in most Armenian hamsters (Cricetulus migratorius) injected with on 15-mg pellet of diethylstilbestrol. The tumors were detectable as early as 1 1/2 mo after diethylstilbestrol administration and were usually present as multiple nodules that progressively increased in size. Histologically, the multicentric neoplasms were all hepatocellular carcinomas of varied degrees of differentiation and frequently (42.8%) contained Mallory bodies; preneoplastic lesions were not observed. This hepatocellular carcinoma hamster model is unique because estrogen alone without any other known mutagen is responsible for induction of hepatocellular carcinoma.

Animals↗

Armenian hamster female protein: a pentraxin under complex regulation.

The serum of Armenian hamster (Cricetulus migratorius) contains a protein homologous to female protein (FP) that has been characterized in the Syrian (golden) hamster. Of unknown function, FP belongs to a family of proteins (called pentraxins) that have a common ancestral gene and are widely expressed in nature. Whereas serum concentration of FP in Syrian hamsters (SFP) is many fold greater (200- to 300-fold) in females vs. males, Armenian hamster FP (AFP) is only moderately elevated (approximately 3-fold) in female vs. males and only for the fall-winter months of the year. In the Armenian hamster testosterone administration to females or castration of males has no effect on AFP serum levels, whereas in Syrian hamster these treatments change SFP serum concentration to that characteristic of the opposite sex. Some sex steroid control of hepatic AFP synthesis is evident, however, as serum levels decrease after exogenous estrogen treatment. In contrast to Syrian hamster FP, normal levels of AFP are dependent on an intact hypophysial-pituitary axis and also are influenced by the season of the year. As an acute-phase protein, AFP responds in a typical fashion, with increasing serum levels detected in both sexes in contrast to the divergent sex-limited response in Syrian hamsters. Although AFP and SFP are similar structurally, morphologically, and antigenetically and share common binding specificities, the regulation of FP synthesis in Armenian hamster is very different from that previously found in Syrian hamster.

Acute-Phase Reaction↗

Antibody response in white-footed mice (Peromyscus leucopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi).

White-footed mice (Peromyscus leucopus), the primary reservoir for Borrelia burgdorferi in the northern midwest and northeastern United States, were experimentally inoculated with an infectious strain or a noninfectious strain of the Lyme disease spirochete and examined for their specific antibody response with the enzyme-linked immunosorbent assay and Western blot (immunoblot) analysis. Immunoglobulin M (IgM) anti-B. burgdorferi antibodies were detected in mice 1 to 2 days after inoculation with either the infectious or noninfectious strain of spirochetes and peaked on days 4 and 5. Mice inoculated with the infectious strain of spirochete had a secondary increase in IgM 21 days after inoculation. Mice also produced both IgG1 and IgG2 antibodies beginning 5 to 7 days after inoculation and they increased in titer until 84 days after inoculation when the experiment was terminated. Western blot analysis of sequential plasma samples from mice inoculated with the infectious strain of spirochete demonstrated the development of IgM, IgG1, and IgG2 antibodies to numerous spirochetal antigens, whereas mice inoculated with the noninfectious strain had reduced blot patterns with antibodies reactive primarily to the 31,000-kilodalton outer surface protein A. Persistent spirochetal infection in some mice, in spite of a strong and diverse antibody response, deserves further investigation.

Animals↗

Tamoxifen inhibits estrogen-induced hepatic injury in hamsters.

Estrogens have an unusual toxic effect on the liver of two hamster species, the Armenian and the Chinese hamster. The hepatotoxicity was detectable clinically by hyperbilirubinemia and confirmed histologically by the presence of hepatic degenerative-regenerative changes. Administration of tamoxifen with estrogen [either ethynyl estradiol or diethylstilbestrol (DES)] completely abrogated the hepatotoxic effects, suggesting that estrogen receptor (ER) was necessary for estrogen to damage liver. In Armenian hamsters, estrogens decreased hepatic synthesis of female protein (FP); tamoxifen also abolished this DES effect and resulted in a net increase in serum FP levels. DES administration produced higher serum bilirubin levels and lower serum FP levels in females than in males. Paradoxically, tamoxifen blocked these DES effects more effectively and efficiently in females than in males. Estrogens did not injure uteri of Armenian and Chinese hamsters and were nontoxic to livers of other hamsters species, such as Syrian and Turkish. This model provides another perspective of the acute cellular derangement that can be effected by estrogen-ER complex and may indicate a yet unknown mode of ER action.

Animals↗

Hamster female protein, a pentameric oligomer capable of reassociation and hybrid formation.

Syrian hamster female protein (SFP), a serum oligomer composed of five identical subunits, was reassociated in vitro from monomer subunits. The reconstituted pentamer was genuine by morphologic, antigenic, and structural criteria. Another female protein (FP), a homologue from Armenian hamsters (AFP), also reassociated into a pentamer after dissociation with 5 M guanidine hydrochloride. These two FP's hybridized when a mixture of them was dissociated and then reassociated. Differences between the parent FP's were used to show that the recombinant pentamer contained monomer subunits from both SFP and AFP. Reassociation of both FP's was enhanced by increasing FP concentration and also by adding Ca2+ during reassembly. The two FP's differed in their reassociation profile in that SFP was especially efficient in reassembly, whereas AFP was more dependent upon Ca2+. Female protein is a homologue of C-reactive protein and amyloid P component, and all of these proteins (pentraxins) share a similar structure. The in vitro dissociation-reassociation of female protein described herein may reflect an in vivo dissociation-reassociation which is functionally important and a common metabolic feature within this family of proteins.

Alpha-Globulins↗

The role of the female Syrian hamster protein on the interaction between serum lipoproteins and heparin.

We have previously shown the effect of phosphorylcholine-binding proteins from rat (PCBP) and rabbit (CRP) on the precipitation of serum lipoproteins by heparin in presence of Ca2+. The present paper describes the effect of a phosphorylcholine-binding protein from the female Syrian hamster (FP) on the lipoprotein precipitation reaction. The precipitation of lipoproteins by heparin was lower in assays using female hamster serum in which FP is a prominent protein, compared with assays with male serum in which FP is present in very low concentration. Depletion of FP from female serum resulted in increased lipoprotein precipitation. The addition of purified FP to assays using human very low density lipoprotein (VLDL) inhibited the precipitation reaction. The precipitation of lipoproteins was also examined using serum from male hamsters treated with diethylstilbestrol and female hamsters treated with testosterone, treatments known to modulate the levels of FP. Results indicate an inverse relationship between serum FP levels from normal and hormone-treated hamsters and the precipitation of lipoproteins from their serum. The partially desialylated FP when added to precipitation assays using human VLDL resulted in reduced inhibition of VLDL precipitation.

Animals↗

Effect of immune serum and its immunoglobulin fractions on hamsters challenged with Treponema pallidum ssp. pertenue.

Passive transfer of frambesial immune serum is capable of conferring complete protection on hamsters against challenge with Treponema pallidum ssp. pertenue. Treponemicidal activity in the pooled immune serum is relatively high. Immune serum and its immunoglobulin fractions, especially IgG2, also killed T. pallidum ssp. pertenue in vitro. Treponemicidal activity was present only when immune serum was administered to hamsters within a short time (three days) of frambesial challenge. By contrast, administration of pooled immune serum to hamsters infected for more than one week failed to reduce the number and size of lesions and the weight and number of treponemes in the lymph nodes. These results suggest that hamsters can develop the humoral components necessary to protect them against frambesial challenge, but these components are unable to destroy treponemes at the primary foci of infection.

Animals↗

Complement activation by female protein, the hamster homologue of human C-reactive protein.

The capacity of Syrian hamster female protein (FP), a phosphorylcholine (PC)-binding pentraxin, to activate complement was tested in an in vitro system consisting of PC-coupled sheep red blood cells and guinea pig serum as the complement (C) source. FP was demonstrated to fix complement as reflected by hemolysis. Such hemolysis was eliminated by heat treatment (56 degrees C, 30 min) of guinea pig serum and inhibited by PC chloride but not dinitrophenyl lysine. The inability of C4-deficient guinea pig serum to provide lytic activity indicated that lysis proceeded through the classical hemolytic pathway.

Acute-Phase Proteins↗

Medroxyprogesterone acetate induces diabetes insipidus in Chinese hamsters.

Injection of a synthetic progesterone, medroxyprogesterone acetate (MPA or Depo-ProveraR), a widely used contraceptive, into Chinese hamsters (Cricetulus griseus) induced a profound polyuria with daily output of dilute urine equal to about 50% body weight of the hamster. However, relatively normal ability for renal urine concentration was demonstrated by administration of exogenous vasopressin. Body weight did not increase during onset of MPA-induced polyuria or during interval of vasopressin-induced oliguria, suggesting that primary polydipsia was not etiologic. Administration of this steroid to Chinese hamsters was nontoxic, although these polyuric animals were unusually sensitive to water deprivation. This polyuria was not observed when progesterone alone was injected into Chinese hamsters or when MPA was given to other related hamster species (Armenian, Syrian, Turkish or Djzungarian). The MPA-injected Chinese hamster represents a unique model of vasopressin sensitive diabetes insipidus induced by a steroid in a species-specific fashion.

Animals↗

Hamster female protein, a sex-limited pentraxin, is a constituent of Syrian hamster amyloid.

Female protein (FP) is a pentraxin of Syrian hamster which is a homologue of two human pentraxins, C-reaction protein (CRP) and amyloid P component (AP). Functionally, FP has been shown to be similar to CRP, although FP has more homology at the amino terminus with AP. The present work investigated amyloid in the Syrian hamster to determine whether FP was involved in a manner analogous to AP. FP was found to be a constituent of Syrian hamster amyloid. This conclusion was based on the following results: (a) FP was consistently detected in amyloid deposits by fluorescent microscopy with specific antisera; (b) The amount of FP extractable from hamster livers directly correlated with the presence of amyloid; and (c) 125I-FP injected intravenously into amyloidotic hamsters rapidly left the intravascular compartment and was found subsequently in amyloid deposits. This unusual alteration of plasma metabolism and amyloid localization of 125I-FP was a characteristic finding in amyloidotic hamsters and was specific for 125I-FP. Therefore, as an amyloid component, FP appears to be functionally similar to human AP. However, FP synthesis is under sex steroid control and the unique sex-limited expression of this pentraxin was associated with an equally novel propensity for deposition of amyloid in female hamsters under normal or experimental conditions. Thus, a high serum level of FP, as found in normal females or diethylstilbestrol-treated males, was associated with enhanced amyloidosis. Although speculative at present, a primary role for serum FP in hamster amyloid deposition may be experimentally approachable by hormonal manipulation of FP synthesis.

Age Factors↗

Hamster female protein. A divergent acute phase protein in male and female Syrian hamsters.

Normal adult male hamsters have low levels (10-20 micrograms) of female protein (FP) in serum which increase approximately fivefold during an acute phase response. In contrast, normal females have 50- to 100-fold higher serum levels and the acute phase reaction consists of a transient decrease in FP (approximately 50%), followed by a return to normal levels even under adverse conditions such as cortisone treatment (which by itself has a depressing effect on FP levels in normal females). The acute phase response was not inherently associated with gender, as the pattern of response could be changed to that of the opposite sex by appropriate hormonal manipulation. That is, castrated or diethylstilbestrol-treated males with high FP levels showed a female-type response whereas testosterone-treated females with low FP levels showed a male-type response. Studies on catabolism of 125I-FP showed a similar rapid half-life (T1/2, 9-16 h) in normal males and females and indicated that the sex difference in serum concentration was due to greater synthesis of FP in females. The divergent acute phase reaction of serum FP was related directly to changes in the FP synthetic rate (increased in males, decreased in females). As an indicator of serious pathology, a decrease of FP to very low levels in females was associated frequently with impending death.

Alpha-Globulins↗

Leukocyte subpopulations which amplify or suppress antigen-induced proliferation in Syrian hamsters.

The proliferative response of spleen cells, obtained from Syrian hamsters sensitized to hen egg albumin emulsified in complete Freund's adjuvant, is lower in magnitude than the response of draining lymph node cells. In this study, the cellular regulatory mechanisms which may lead to splenic hyporesponsiveness were examined. Although unfractionated spleen cells were not suppressive, the addition of nylon wool nonadherent normal spleen cells to sensitized draining lymph node (target) cells markedly suppressed antigen- but not mitogen-induced proliferation. Suppressor cell activity was not detected in normal lymph nodes. Suppression could be overcome by culturing splenic suppressor plus target cell mixtures in the presence of large quantities of antigen. Suppressor cell activity was radioresistant. In addition to nonadherent suppressor cells, the hamster spleen also contains an adherent cell population(s) which amplified antigen-induced proliferation. Adherent cells with amplifying activity were also present in lymph nodes. The addition of adherent cells abrogated splenic suppression of proliferation. Collectively, these data indicate that the hamster spleen contains both suppressive and amplifying leukocyte subpopulations which may be involved in the regulation of the immune response to certain antigenic stimuli.

Animals↗

Demonstration of Aleutian disease virus-specific lymphocyte response in mink with progressive Aleutian disease: comparison of sapphire and pastel mink infected with different virus strains.

Lymphocyte blastogenesis was used to study the antiviral lymphocyte response of sapphire (Aleutian) and pastel (nonAleutian) mink inoculated with Pullman or Utah 1 Aleutian disease virus (ADV). Both mink genotypes developed a virus-specific response when inoculated with Utah 1 ADV. In contrast, after inoculation of Pullman ADV, sapphire mink had a positive virus-specific response, whereas pastel mink did not. Response occurred late after infection (8 wk) and correlated with the development of progressive Aleutian disease (AD). The response to keyhole limpet hemocyanin (KLH) and concanavalin A (Con A) was also determined. Most mink of either genotype, inoculated with either virus strain, maintained an anti-KLH response during disease. Most mink also responded to Con A, although some exhibited suppressed Con A response late in the disease course. These results indicated that mink develop an anti-ADV lymphocyte response during progressive AD and are not immunosuppressed with regard to other antigens or mitogens.

Aleutian Mink Disease↗