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G R Clarke

Publications and source records attributed to G R Clarke.

At least 19 recordsLinked to original sources
PubMed1998

Children as income-producing assets: the case of teen illegitimacy and government transfers.

This paper develops a classical model of the teen fertility decision in the presence of public income transfers. The theoretical model predicts that welfare payments will encourage fertility, holding constant other economic opportunities, and that better economic opportunities will discourage fertility. Considering the possible simultaneity of illegitimacy rates and benefit levels, due to the collective choice process, the authors confirm the theoretical model's predictions with state-level data from 1980 through 1990. The authors find that including fixed effects in the regression to control for unobserved differences between states does not sufficiently control for endogeneity. After controlling for endogeneity, real welfare benefits are strongly and robustly related to teen illegitimacy. The point estimates of the elasticity with respect to changes in the illegitimacy rate are around +1.3 for White teens and +2.1 for Black teens. Real wages for women with a high school education or less are negatively related to teen illegitimacy for White teens, with an elasticity of around -0.4. Finally, male wages appear to have little effect on the illegitimacy rate for White teens but appear negatively correlated with the illegitimacy rate for Black teens in some model specifications.

Adolescent↗
PubMed1997

Phosphorylation of the NC-1.1 receptor and regulation of natural cytotoxicity by protein kinase C and cyclic GMP-dependent protein kinase.

Natural cytotoxicity (NC) against cancer involves receptor-ligand interactions between lymphohemopoietic cells that mediate NC against tumor cells. The only candidate for a receptor on cells mediating NC is NC-1.1, identified using mAb 1C4. In this study we showed that mAb 1C4 blocked NC-1.1+ cell conjugation to WEHI-164 tumor cells, indicating that NC-1.1 is a surface protein required for cell-cell interaction. Affinity-purified NC-1.1 was a 45-kDa monomeric protein. It was a good in vitro substrate for cyclic GMP (cGMP)-dependent protein kinase (PKG) and protein kinase C (PKC) and a relatively poor substrate for cAMP-dependent protein kinase (PKA). Phosphopeptide mapping revealed one phosphopeptide phosphorylated by PKG and PKA, and two additional peptides phosphorylated by PKC. Phosphorylation by PKG or PKA abolished phosphorylation at the PKC sites, while coincubation of NC-1.1 with both PKG and PKC reduced phosphorylation of all sites. NC-1.1 was also a phosphoprotein after immunoprecipitation from intact spleen cells and its phosphorylation was increased after cell stimulation with PKC or PKG activators (phorbol esters or 8-bromo-cGMP). The possible consequences of intracellular signaling were tested in functional assays for NC. Phorbol ester activation of spleen cells increased NC, while 8-bromo-cGMP and 8-bromo-cAMP had little effect. However, coincubation with both phorbol ester and either 8-bromo-cGMP or 8-bromo-cAMP virtually abolished NC without affecting cell conjugation. These results suggest that NC-1.1 is a receptor for a ligand on certain tumor cells and reveal that key intracellular signaling pathways involving PKC, PKG, and PKA interact to effect a coordinated control of NC.

Animals↗
PubMed1997

TNF-alpha is not the sole mediator of WEHI-164 tumour cell killing in natural cytotoxicity.

Using a mAb to NC-1.1, a receptor involved in recognition of tumour targets, the authors have examined the dogma that murine natural cytotoxicity (NC) is exclusively mediated by TNF-alpha. Three different NC-1.1+ spleen cells, WEHI-3BR1 myelomonocytic cells and an uncloned mast cell line-MCL) were reacted with NC-sensitive WEHI-164 targets in vitro, and the induction of TNF-alpha mRNA, surface expression of TNF-alpha, and the appearance of apoptotic bodies in the culture were simultaneously measured. NC-1.1+ spleen cells and WEHI-3BR1 cells showed marked induction of TNF-alpha mRNA within 30 min and this was maintained for up to 18 h. Only transient TNF-alpha mRNA induction was observed in MCL cells at 30 min. Surface TNF-alpha was detected on WEHI-3BR1 cells by 4 h, but was not detected on MCL cells. All three effector cell types mediated NC against WEHI-164 targets within 18 h, but they responded differently to the addition of anti-TNF-alpha mAb: anti-TNF-alpha completely blocked WEHI-3BR1 NC, blocked NC-1.1+ spleen cell NC by approximately 70%, and did not block NC by MCL cells. This indicates that TNF-alpha is induced during NC by WEHI-3BR1 effectors and NC-1.1+ spleen cells, is the sole mediator of NC by WEHI-3BR1, and appears to play no role in NC by MCL cells.

Animals↗
PubMed1997

The antitumor effects of levamisole in mice are mediated by NC-1.1+ cells.

Murine natural cytotoxicity, which is a major component of the innate immune response in cancer, is mediated by leukocytes that express the NC-1.1 receptor. Mice depleted of natural cytotoxicity by treatment with an anti-NC-1.1 mAb show enhanced growth of certain transplantable tumors, so agents that enhance natural cytotoxicity by NC-1.1+ cells have the potential to be effective anticancer therapeutic agents. We have examined the immunomodulatory effect of levamisole on natural cytotoxicity mediated by NC-1.1+ cells against the BALB/c WEHI-164 murine fibrosarcoma. Administration of levamisole to BALB/c mice significantly enhanced in vitro splenic natural cytotoxicity against 51Cr-labeled WEHI-164 tumor cells. The effect was most marked 48 h after levamisole treatment, at a dose of 10 mg/kg body weight. This enhancement of natural cytotoxicity by levamisole could be completely abrogated by pretreatment of mice with an anti-NC-1.1 mAb. Treatment of BALB/c mice with 10 mg/kg levamisole significantly reduced the growth of WEHI-164 and this effect was abrogated by pretreatment of mice with anti-NC-1.1, indicating that the antitumor effect of levamisole was mediated, at least in part, via NC-1.1+ cells.

Adjuvants, Immunologic↗
PubMed1997

Experimental vesicular stomatitis in swine: effects of route of inoculation and steroid treatment.

An enzootic focus of vesicular stomatitis virus New Jersey serotype (VSV-NJ) exists on Ossabaw Island, Georgia. Many questions regarding the epizootiology of this virus at this focus still exist, but evidence suggests that the vector for this virus is a phlebotomine sand fly (Lutzomyia shannoni), with feral swine serving as a potential source of virus for the sand fly and for other swine via contact transmission. We conducted 2 experimental trials in domestic swine using VSV-NJ isolated from a sand fly from Ossabaw Island to determine if route of inoculation or immunosuppression via steroid administration affected the development of disease, viremia, viral shedding, or the neutralizing antibody response. In a third trial, we studied the potential for contact transmission among swine using this isolate. Virus isolations were made from nasal cavity or palatine tonsil of the soft palate, and VSV-NJ neutralizing antibodies developed when pigs were inoculated intradermally in the apex of the snout, ear, or coronary band, intravenously, intranasally, or via scarification of the apex of the snout or coronary band. Vesicles developed only in pigs inoculated in the apex of the snout or coronary band, and these vesicles were at the site of inoculation. Steroid treatment did not potentiate the development of secondary vesicles and did not prolong the period of virus shedding from VSV-NJ-infected swine. Contact transmission, as determined by shedding of virus from the tonsil of the soft palate and the development of VSV-NJ neutralizing antibodies, occurred in pigs in contact with animals inoculated in the apex of the snout but not in contact animals exposed to pigs inoculated intradermally in the coronary band or intranasally. These trials show that contact transmission can occur and VSV-NJ can be shed without the development of clinical disease (i.e., vesicle formation). Viremia was never detected in any of the experimental pigs, suggesting that swine may not be a good amplifying host for VSV-NJ.

Animals↗
PubMed1996

An IL-3-induced splenic NC-1.1+ mast cell line mediates natural cytotoxicity independent of TNF-alpha.

Long-term culture of mouse spleen cells in IL-3-conditioned medium induced a stable mast cell line. This mast cell line (MCL) which could not be cloned expressed NC-1.1, a receptor on cells which mediate natural cytotoxicity (NC), and CD32/CD16 but no markers of T cells, B cells, macrophages, or NK cells. The MCL cells were large and granular, with abundant cytoplasm and >90% stained with Alcian blue, a mast cell-specific stain. Probing total RNA with cDNA encoding a mast cell-specific proteinase mMCP-5 identified the approximately 1-kb mMCP-5 transcript which was confirmed at the protein level. MCL cells mediated very high NC against WEHI-164 which increased with time in culture and which was blocked by anti-NC-1.1 but not by anti-TNF-alpha. When incubated with WEHI-164 tumor cells, MCL cells showed transient induction of TNF-alpha mRNA, but no detectable surface protein. Thus long-term culture of murine spleen cells in IL-3 induces mast cells which express the NC-1.1 receptor of cells which mediate NC, and utilize a cytotoxic effector mechanism which is not TNF-alpha.

Animals↗
PubMed1994

Bimodal distribution of V beta 2+CD4+ T cells in human peripheral blood.

The distribution of T cells using the V beta 2 gene was studied in a group of 99 humans. The distribution of V beta 2+CD4+ levels was bimodal. Twelve individuals had levels of V beta 2+CD4+ less than 2% and 86 others had values greater than 5%. Only one individual had a value between 2% and 5%. The V beta 2 low (mean 1.3 +/- 0.49) and V beta 2 high (mean 8.2 +/- 1.65) phenotypes were stable. The V beta 2 low phenotype is inherited and not limited to HLA or T cell receptor V beta gene complexes. The CD8V beta 2 levels of CD4V beta 2 low individuals are also low. The residual V beta 2+ T cells in V beta 2 low individuals were not anergic to V beta 2-specific stimulation. These data are compatible with the effects of an endogenous superantigen.

Adult↗
PubMed1994

Natural killer and natural cytotoxic cells are present at the maternal-fetal interface during murine pregnancy.

NK cell activity has been detected in the early murine decidua, and hypothesized to be mediated by granulated metrial gland (GMG) cells. The possibility that natural cytotoxic (NC) cells are also present in the decidua has not been investigated. In this study mAb to NK cells (anti-NK-1.1) and NC cells (anti-NC-1.1) were used to characterize the decidual cells of days 8-14 pregnant (CBA x C57BL/6) F1 mice. Flow cytometric and immunohistological analyses showed predominantly NK-1.1+ and NC-1.1+ large and granular single nucleated decidual cells with abundant cytoplasm. A 'bright' and a 'dim' subset were identified for both NK-1.1+ and NC-1.1+ cells. The NC-1.1dim and NK-1.1dim cells increased in number and size as pregnancy progressed. When tested in 51Cr-release assays, the decidual cells showed significant levels of both NK and NC activities which increased with progression of pregnancy. The NK and NC activities were partially inhibited (47 and 34%) by preincubation of the decidual cells with anti-NC-1.1 and complement (C'), or anti-NC-1.1 alone. Results indicate that natural cell-mediated cytotoxicity in the decidua is in part, at least, mediated by NK-1.1+ and NC-1.1+ cells, and that the NK-1.1dim and NC-1.1dim cells are very likely to be GMG cells. This is the first report of NC cells in the mouse uterus.

Animals↗
PubMed1994

The human T cell antigen receptor repertoire: skewed use of V beta gene families by CD8+ T cells.

The TCR repertoire of human CD8+ peripheral blood lymphocytes has been determined using MoAbs to the V beta 2, 3, 5.1, 5.2/5.3, 6.7, 8, 12 and 19(17)V beta gene families. The CD8T cell repertoire for V beta 2 and V beta 3 is shown to be skewed, with an excess of individuals having higher values than are consistent with a normal distribution. A significant majority of these individuals are over the age of 40. High values of V beta CD8+ cells were found for each V beta family studied except for 6.7a. Individual high values are stable for at least 12 months. In addition, the total percentage of CD4 and CD8 cells reacting with this panel of reagents was determined. There is a significant excess of V beta + CD4+ cells (33%) over CD8+V beta + cells (21.9%). Thus the human CD8 V beta repertoire differs from the human CD4 repertoire in a number of important ways.

Adult↗
PubMed1975

Preliminary studies in measuring range of motion in normal and painful stiff shoulders.

This study has been prompted by the need to provide basic data for prospective studies in the management of the painful stiff shoulder. We have used a hydrogoniometric technique of proven accuracy to measure passive movement at the gleno-humeral joint in a normal population, patients currently attending with a painful stiff shoulder, and a retrospective group. We have shown that there are significant age and sex differences in the range of motion of normal and affected groups. A significant number (42 per cent) of patients had persisting limitation of range of the gleno-humeral joint six years after the onset of the disability. The study indicates the importance of matching patients for age and sex, and the need for long-term follow-up for meaningful results.

Adult↗