PubMed Health⌕ Search

Biomedical subjects

G C Koo

Publications and source records attributed to G C Koo.

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

Activation of murine natural killer cells and macrophages by 8-bromoguanosine.

It has been shown that 8-bromoguanosine (8-BrGuo) activates T and B cells, but the underlying mechanism of this effect is not clear. We found that it also activates NK cells and macrophages by induction of IFN production. Culturing spleen cells with 8-BrGuo for 16 to 18 h induced cytotoxic activity to YAC cells. The cytotoxic cells expressed Qa-5, asialo-Gm-1, and NK-1.1 Ag. Similarly, preincubation of peptone-elicited peritoneal macrophages with 8-BrGuo induced macrophage cytolytic activity to P815 cells in an 18-h assay. Anti-IFN antibodies to IFN-alpha -beta and -gamma abolished these inductive events. Furthermore, elimination of asialo-Gm-1+ cells reduced the responses of NK and macrophages to 8-BrGuo, indicating that these cells possibly produce the IFN. We conclude from these observations that one biologic effect of 8-BrGuo is due to IFN production.

Animals↗
PubMed1988

In vivo function of natural killer cells as regulators of myeloid precursor cells in the spleen.

In order to study the in vivo effect that natural killer (NK) cells may have on hematopoietic precursor cells in the autologous host, NK-depleted mice were constructed by injection of an anti-NK-1.1 monoclonal antibody. Only the spleen, and not the bone marrow, of such NK-depleted mice shows an increase in the number of myeloid precursur cells able to form colonies in soft agar as compared to control mice with normal levels of NK activity. The increase in number of hematopoietic immature cells due to lack of a regulatory cell (i.e. NK cell) is selective for the committed myeloid precursur cells, and not evident for erythroid or pluripotent progenitor cells. This is direct evidence in support of the hypothesis that NK cells in the autologous host serve as a regulator of extramedullary myelopoiesis.

Animals↗
PubMed1988

Absence of a facilitory role for NK 1.1-positive donor cells in engraftment across a major histocompatibility barrier in mice.

Ex vivo T cell depletion of donor marrow grafts in humans and mice has virtually eliminated severe graft-versus-host disease (GVHD). However, as a consequence of T cell depletion, sustained donor cell engraftment is likely compromised. Since the majority of T cell depletion techniques also deplete natural killer (NK) cells, we investigated the role of donor NK cells in engraftment and GVHD in a murine model. Using a monoclonal antibody directed against an NK-specific epitope, we have selectively depleted NK cells while preserving donor marrow T cells. In an established model of engraftment, selective NK depletion demonstrated that removal of donor NK cells did not impair the engraftment process under conditions in which donors and recipients are major histocompatibility complex-disparate. In contrast, recipients of anti-Thy 1.2 plus complement (C')-treated marrow grafts had a significantly higher incidence of either partial engraftment or graft rejection as compared with recipients of selective NK-depleted donor grafts or control grafts. In addition, we have observed that NK-specific depletion of donor marrow/splenocyte inocula does not alter the incidence of GVHD. Recipients of NK-depleted donor grafts developed lethal acute GVHD, whereas recipients of anti-Thy 1.2-depleted donor grafts did not (P less than 0.0001). Interestingly, NK 1.1-depleted donor graft recipients had a significantly increased mortality in comparison with control groups receiving C'-treated grafts (P = 0.04) or anti-Thy 1.2 plus C'-treated grafts (P less than 0.05). Thus, NK depletion may reduce immunosurveillance, thereby increasing the risk of posttransplant infection. We conclude from these results that donor NK cells play an insignificant role in engraftment as well as in the afferent phase of GVHD, but may be important in immunosurveillance when murine bone marrow is transplanted across the major histocompatibility barrier.

Animals↗
PubMed1987

Depletion of natural killer cells in mice by monoclonal antibody to NK-1.1. Reduction in host defense against malignancy without loss of cellular or humoral immunity.

Weekly injections of a monoclonal antibody (MAb) to the antigen NK-1.1 were used to sustain depletion of NK cells from the spleens of adult C57BL/6 mice for up to 8 wk. Mice depleted of NK cells in this manner had no lasting alteration in the distribution of other lymphocyte subsets in the spleen and did not demonstrate reduced cellular or humoral immunity. Depletion of NK cells, however, markedly increased the localization and growth of B16 melanoma cells or CT 38 colon carcinoma cells in the lung after i.v. administration of tumor cells. Moreover, mice given B16 tumors and treated with anti-NK-1.1 had reduced survival. NK cells were important in host resistance to sublines of B16 that had been passaged either in vivo or in vitro, which express, respectively, high and low levels of class I major histocompatibility antigens. These findings support a role for NK cells in host defense against malignancy. The ability to selectively remove NK cells in vivo by MAb will permit a better understanding of their physiologic role.

Adenocarcinoma↗
PubMed1987

Morphological development of the mouse gonad in tda-1 XY sex reversal.

tda-1 XY sex reversal occurs when the Y chromosome of at least some populations of wild Mus musculus domesticus is placed on the C57BL/6J genomic background. Gross anatomical observations have previously revealed morphological similarities among fetal ovotestes of tda-1 and Tas-inherited XY sex reversals and BALB/cWt mosaic hermaphrodites. We studied the histology of tda-1 XY sex-reversed gonads, ranging in age from day 14 of gestation to adult. The obtained data revealed additional similarities with ovotestes of BALB/cWt mosaic hermaphrodites as well as with ovotestes of hermaphrodites found in XXSxr and XX/XY chimeras. It is proposed that ovotestes occurring in these various hermaphroditic conditions may be formed through a common pathway.

Aging↗
PubMed1987

Studies on the genetics of tda-1 XY sex reversal in the mouse.

When the Y chromosome of at least some populations of the house mouse of Western Europe and the Mediterranean, Mus musculus domesticus, is placed into the C57BL/6J (B6) inbred mouse genome, XY fetuses develop into hermaphrodites or females. It has been hypothesized that the testis-determining gene on the Y chromosome of M. m. domesticus (TdyDOM) interacts improperly with a putative B6/J recessive, testis-determining, autosomal gene (tda-1). The present study extended these earlier findings. The mating of B6 mice possessing the Y chromosome of M. m. domesticus (B6.YDom/Na; N6-N9) to females of the AKR, BALB/c, C3H/An, and C3H/He, but not SJL, strains resulted in aberrant testicular differentiation in day-14/15 F1 fetuses. The aberrant testes were characterized by a delay in testicular differentiation at the cranial and caudal poles of the gonad, i.e., the presence of a thin (or no) tunica albuginea and the presence of disorganized (or no) seminiferous tubules. Crossing B6.YDom male phenotypes with SJL females did not result in aberrant testicular differentiation, suggesting that the SJL strain possesses the dominant testis-determining, autosomal-1 allele, Tda-1. Studies using recombinant DNA probes specific for the murine Y chromosome have suggested that the SJL and AKR strains possess the M. m. domesticus Y chromosome. When Y chromosomes of the SJL and AKR strains were placed on the B6 background, aberrant testicular differentiation similar to tda-1 XY sex reversal occurred in only 1 out of 87 (1%) N4 day-14/15 fetuses possessing YSJL, but in 25 out of 45 (56%) N4 day-14/15 fetuses possessing YAKR.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

The NK-1.1(-) mouse: a model to study differentiation of murine NK cells.

The NK-1.1(-) mouse was constructed by weekly injections of monoclonal anti-NK-1.1 antibody from birth through adulthood. Spleen cells from these mice have decreased NK-1.1+ cells and null (Thy-1- and B220-) cells. Their splenic NK activity to YAC targets was low and was not enhanced by IFN-alpha or IFN-beta. Bone marrow (BM) of these NK-1.1(-) mice have normal precursors to NK cells: 1) NK activity could be generated from NK-1.1(-) BM cells cultured in rIL 2 for 5 to 6 days. These cultured BM cells expressed Qa-5, Thy-1, AsGm-1, and NK-1.1 antigens. The precursor cells of these BM cytotoxic cells are NK-1.1-; 2) transfer of BM cells from the NK-1.1(-) mice reconstituted the NK activity of irradiated, NK-depleted recipients. Lymphokine-activated killer cells could also be generated from spleens of these NK-1.1(-) mice. Therefore, the NK-1.1(-) mice were specifically depleted of mature cytotoxic NK cells, but not the NK-1.1- precursors of NK cells. This mouse model is valuable to study ontogeny and physiologic relevance of NK cells.

Animals↗
PubMed1986

Generation of cytotoxic cells from murine bone marrow by human recombinant IL 2.

Murine bone marrow (BM) cells were cultured in recombinant IL 2 (rIL 2) and interferon-alpha, -beta, and -gamma, and cytotoxic activity against YAC cells was determined in a 4-hr 51Cr-release assay. rIL 2 at 20 U/ml was the only lymphokine that consistently induced significant cytotoxic activity within 3 days of culture, peaking around 5 to 7 days. The cytotoxic cells generated are heterogeneous, consisting of at least two populations of cells: a) NK-1+, Qa-5+, AsGm-1+ Thy-1+/-, Lyt-2- cells, similar to natural killer (NK) cells, and b) NK-1-, Qa-5+, AsGm-1+ Thy-1+, Lyt-2+ cells, similar to cytotoxic T lymphocytes. The precursor/accessory cells of these BM cytolytic cells maintained in 20 U/ml of rIL 2 were Qa-2+, Qa-5+, Thy-1+/-, AsGM-1+/-, and NK-1+/- but Lyt-2-. They also lysed NK-resistant targets, P815 and BW5147, and the antigenic phenotypes of these cells were similar to those that lysed YAC cells. These studies indicate that IL 2 alone is adequate to generate cytotoxic activity from BM and that these cytotoxic cells were similar to splenic NK cells.

Animals↗
PubMed1986

Characterization of cytotoxic cells generated from bone marrow culture.

Bone marrow (BM) harbors precursors (Pre-NK) to NK cells. Recently, we devised an in vitro culture system that induces differentiation of the presumptive BM Pre-NK cells into cytotoxic cells to YAC in the presence of rat concanavalin A (Con A) conditioned medium. We have now analyzed the antigenic phenotype of the effector cells, precursor cells, and the target specificity of these cytotoxic cells. The cytotoxic cells had antigenic profiles similar to endogenous NK cells with the exception of Lyt-2 antigen. They are strongly positive for Qa-5, Thy-1, and partially positive for NK-1, Ly-5, Ly-6, Ly-10, and AsGm-1 and Lyt-2 antigens. The Pre-NK or accessory cells are positive for Qa-5, Ly-10, and Ly-20 and partially positive for NK-1, Thy-1, and AsGm-1 antigens. These Qa-5+ NK cells do not exhibit cytotoxic activity to WEHI or P815. They could also be generated from BM of nude mice as well as beige mice. We concluded from these studies that rat Con A-conditioned medium contained factors that could differentiate Pre-NK cells to mature NK cells and that these cells are heterogeneous. This in vitro culture system is useful in delineating the ontogeny of NK cells.

Animals↗
PubMed1985

Effect of tamoxifen on H-Y antigen expression and gonadal development in chicken embryos.

Avian species follow the ZW/ZZ system of sex determination, which the female is heterogametic and expresses H-Y (or, more appropriately, 'H-W') antigen. We present the results of an investigation into the effects of the antiestrogen, tamoxifen, on gonadal differentiation and H-Y antigen expression in chickens. When given at doses of 0.25-2 mg per egg immediately before incubation, tamoxifen blocked regression of the right gonad in a significant number of 14-day-old female embryos. The nonregressed right gonad had a testis-like external appearance and, in some cases, contained what appeared to be spermatogenic tubules. Tamoxifen had no histologically detectable effect on the differentiation of the left ovary or the testes. In spite of tamoxifen's histological effects on right female gonads, it did not masculinize the steroidogenic capabilities of these gonads. Whether obtained from drug- or vehicle-treated embryos, the left and right female gonads always contained appreciable amounts of estrogen. In contrast, testes obtained from either drug- or vehicle-treated embryos did not contain detectable amounts of estrogen. Tamoxifen reduced the H-Y antigen levels in female liver and gonads. In both left and right female gonads, the reduction was to male levels. In female livers, tamoxifen reduced H-Y antigen to levels intermediate between those of normal males and females. Thus, the expression of H-Y antigen in both gonadal and nongonadal tissue is estrogen dependent, but the dependency appears to be more stringent for gonadal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Inherited XX sex reversal in the cocker spaniel dog.

Nine XX true hermaphrodites and two XX males were discovered in a family of American cocker spaniels. The true hermaphrodites were partially-masculinized females with ovotestes; the XX males had malformed male external genitalia and cryptorchid aspermatogenic testes. Wolffian and Mullerian duct derivatives were present in both true hermaphrodites and XX males. All four sires of sex-reversed dogs were normal XY males; five of the dams were anatomically normal females and one was an XX true hermaphrodite. A second true hermaphrodite reproduced as a female, producing anatomically normal offspring. All matings that produced sex-reversed offspring were consanguineous. Matings of the parents of sex-reversed cocker spaniels to normal beagles with no family history of intersexuality produced only normal offspring. Examination of G-banded karyotypes of the affected animals, their parents, and siblings, revealed no structural anomalies of the chromosomes that were consistently associated with sex-reversal. In assays for serologically-detectable H-Y antigen, the group of XX true hermaphrodites and the group of XX males had mean levels of the antigen not significantly different from that in normal male controls. Female parents of sex-reversed dogs and some of their female siblings were typed H-Y antigen positive, but the mean level of the antigen in this group was less than that of normal male controls. It is proposed that XX sex reversal in cocker spaniels is due to a mutant gene which when homozygous in females, results in a level of H-Y antigen similar to that found in normal males and the gonads develop as ovotestes or testes. When the gene is heterozygous in females, the level of serologically-detectable H-Y antigen is lower than that found in normal males and the gonads develop as normal ovaries. The persistence of Mullerian structures in the presence of testicular tissue suggests that Mullerian inhibiting substance is deficient or ineffective in its action in this condition.

Animals↗
PubMed1984

Reacting mouse sperm with monoclonal H-Y antibodies does not influence sex ratio of eggs fertilized in vitro.

The fertility of Y-bearing mouse sperm was examined after reacting cauda epididymal sperm with monoclonal H-Y antibodies and protein A sensitized sheep red blood cells. Treated sperm were used for the in vitro fertilization of mouse oocytes which subsequently produced live offspring. There was no significant shift in the sex ratio in favor of females, suggesting that X- and Y-bearing sperm may share the surface antigen. Additional studies were directed toward ascertaining whether haploid expression, as measured by the presence of H-Y antigen, occurs in epididymal sperm or during their capacitation in vitro. Ligation of the corpus epididymus, preventing subsequent transport of sperm to the cauda region, resulted in a linear decrease in H-Y positive cauda sperm. By 17 days after ligation, no positively reacting sperm were observed. Incubation of cauda epididymal sperm for 3 h in capacitating medium eliminated positive reaction by the capacitated sperm to the H-Y antiserum. Furthermore, the percentage of H-Y-positive sperm from different regions of the male reproductive tract appeared to decrease during their transport from the testis to the epididymus and vas deferens. We suggest that H-Y antigen appears on the sperm surface during association with testicular constituents and is removed during epididymal transport and capacitation. No evidence of haploid expression by epididymal mouse sperm was found.

Animals↗
PubMed1984

H-Y antibodies recognize the H-Y transplantation antigen.

The question is raised whether the H-Y transplantation antigen, as defined by skin graft rejection, is the same as the "male-specific" antigen that is identified by H-Y antibodies. We have addressed that question by injecting female mice of the inbred C57BL/6 strain with serologically defined H-Y antigen, and measuring the response of those female mice to skin grafts from intrastrain male mice. The results of our study indicate that the "two" male antigens are crossreactive or identical.

Animals↗
PubMed1984

A radiobinding assay for human H-Y antigen using monoclonal antibodies.

Radiobinding assays using monoclonal H-Y antibodies were performed on human peripheral blood leukocytes, concanavalin-A-(conA)3 stimulated blast cells, and fibroblast primary cell cultures. For peripheral blood leukocytes, male-specific binding was demonstrated only when the cells were enriched for T cells and the H-Y antisera were partially purified for the IgG or IgM fractions. Similar results were obtained with con-A-stimulated blast cells. Fibroblast cells could be tested with unpurified H-Y antisera. With our monoclonal antibodies, best results were obtained using con A blast cells and fibroblasts.

Antibodies, Monoclonal↗