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J R Head

Publications and source records attributed to J R Head.

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Changes in RNA synthesis and messenger RNA content in the cerebellum of rats with graft versus host disease.

Cerebellar RNA accumulation, synthesis, and functional capacity was studied in 14-day-old F1 hybrid rats subjected to neonatally induced graft versus host disease (GVHD). There was a decrease in RNA synthetic rate as measured by the uptake of labeled precursors into RNA. The decrease in total cerebellar RNA synthesis was reflected both in a reduced amount of Nissl substance, visible in cresyl violet-stained 10-micron-thick sections of cerebella, and in the total amount of cytoplasmic RNA isolated from individual cerebella from diseased animals compared with control littermates. Analysis of the RNA translational capacity in wheat germ protein synthesizing systems showed that RNA from experimental animals was also biologically less active. Qualitative differences between protein populations in control and diseased animals were analyzed by two-dimensional gel electrophoresis. There were few alterations in the steady state levels of cerebellar protein. However, two-dimensional gel electrophoresis of the peptides synthesized in vitro by RNA from control and diseased animals showed that there were several changes in the relative abundance of some mRNAs between the two RNA populations. These data show that the cerebellar RNA from rats with GVHD differs both qualitatively and quantitatively from that of controls.

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Malformation of Purkinje cell dendrites induced by graft-versus-host disease.

Impairment of cerebral Purkinje cell growth was assessed in Golgi-Cox stained tissue in 14 day old (Fischer X DA)F1 hybrid rats subjected to graft versus host disease (GVHD). GVHD was induced by grafting parental strain lymph node cells (PSLNC) into the anterior facial vein on the day of birth. We have previously described GVHD induced changes in nucleotide and protein content [12] and RNA function [14] as well as alterations in cell numbers and areas of the external granular and molecular layers in diseased animals [13]. In this report some effects of GVHD on the gross morphology of Purkinje cells in 14 day old animals are enumerated. Most Purkinje cells (62%) from GVHD animals had a height to width ratio greater than 1, whereas most from control animals (71%) had ratios of less than 1. The majority of Purkinje cells (67%) from diseased animals had elongated main dendrites which were devoid of branches and often (13%) these elongated main dendrites were S-shaped. In addition, comparison of Purkinje cells from GVHD and control animals revealed a greater tendency (15%) toward retention of extrasomal process in GVHD animals. These findings suggest that GVHD affects nondividing, differentiating cell populations as well as those which are proliferating and migrating. Our evidence that, as a result of GVHD, the protein synthesizing capacity of the cerebellum is altered [14] and that Purkinje cells are more closely spaced at day 11 suggests that both intrinsic and extrinsic factors are involved in producing the changes in dendritic shape reported here.

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Transferrin receptor expression in early postimplantation mouse trophoblast and associated tissues.

The expression of the transferrin receptor (TR) was examined on murine trophoblast cells on days 6, 8 and 10 of gestation, using a monoclonal antibody visualized by indirect immunofluorescence on cryostat sections of the implant site. In the day 6 tissues, TR were observed on both the ectoplacental cone (EPC) and mural giant cell trophoblast populations, as well as on the embryonic ectoderm, anti-mesometrial decidual cells, uterine glandular epithelium and myometrium. By the 8th day of gestation, TR expression was weak, or undetectable on trophoblast giant cells (TGC), but remained strong on the proliferating cells of the EPC and embryo. In the definitive placenta (day 10), TR are expressed primarily on the differentiated labyrinthine trophoblast cells involved in the maternal-fetal transfer of iron.

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Isolation and characterization of trophoblast from murine placenta.

A discontinuous density gradient centrifugation method, devised to isolate enriched populations of trophoblast from murine definitive placentae, is described. It is concluded that the isolated adherent cells are trophoblast on the basis of the following characteristics: they are fetally derived, as determined by their donor glucose phosphate isomerase phenotype in embryo transfer experiments; epithelial cells, as shown by the presence of cytokeratin filaments and the absence of vimentin; negative for the stage-specific embryonic antigen-I (SSEA-I); and capable of progesterone secretion. Initially, they grew as individual polygonal cells, tending to form tight confluent monolayers with poorly defined intercellular boundaries. They were mono- or binucleate and increased their nuclear size with time. After two days, giant cells appeared to be formed from binucleated cells by nuclear fusion, and multinucleated cells appeared forming syncytia. Some of these cells also seemed to form giant cells. A low percentage (1 to 10 per cent) of contaminating cells, mainly macrophage-like cells, was observed. The isolated cells were a mixture of alkaline phosphatase- (AP-)positive and AP-negative cells, with some of the latter having phagocytic capacity. All were Fc receptor-negative. The possible identity of these cells in relation to trophoblast in the intact placenta is discussed. This method of isolating and characterizing trophoblast cells from the definitive mouse placenta will be a useful tool for studying the biology and immunology of trophoblast.

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Immunology of reproduction: present trends.

Over the past decade has come general recognition that, directly or indirectly, immunology intrudes into nearly every aspect of mammalian reproduction. Charles Darwin's notion that the profligacy of women led to reduced fertility gained plausibility with the subsequent discovery of the auto- and alloantigenicity of spermatozoa and of testicular material. From this observation arose the reasonable expectation that immunological control of fertility may be feasible. Discovery of the importance of natural transfer of immunity from mother to offspring, the ontogeny of the immune response and recognition that pregnancy is an almost consistently successful violation of the "laws of transplantation" are only a few highlights or components of the burgeoning, multifaceted field we have come to recognize as the immunology of reproduction. An overview of this subject will be presented with regard to its evolutionary origins, its accomplishments, its current trends and some of its potentialities. The immunology of reproduction has not developed in isolation; in recent years it has benefited enormously from developments in other fields, and in its turn it has exerted its own impact on other disciplines, especially on transplantation. The present preoccupation of many immunologists with immunoregulation stems largely from independent discoveries in the realm of reproductive immunobiology: the etiology of Rh disease and its prophylaxis, and the principle of immunological tolerance, from investigations on the peculiarities of dizygotic twins in cattle.

Allergy and Immunology↗

Uterine natural killer cells during pregnancy in rodents.

Large mononuclear cells with abundant prominent granules were described decades ago by morphologists studying implantation sites in pregnant rodents. These striking cells accumulated by midgestation in large numbers in a structure unique to rodent pregnancy that develops in the mesometrial region of the uterine musculature and was given the unfortunate name of metrial gland. Thus, the cells were originally termed granulated metrial gland (GMG) cells. Evidence provided over the last few years, especially in situ phenotyping and studies in mutant and transgenic mice, has reliably identified these cells as members of the natural killer (NK) cell lineage, and they are referred to here as granulated uterine NK (uNK) cells. Much of the evidence is reviewed here, along with a description of the spatial and temporal aspects of the differentiation of these cells. Especially highlighted are their life history and their likely importance early in pregnancy before development of the metrial gland proper. Their relation to other NK cell populations, especially activated cells, as well as their possible functions during pregnancy, are discussed. Because these cells develop in the unique microenvironment of the pregnant uterus and appear to differentiate along a specific pathway, hypotheses are proposed regarding the regulation of granulated uNK cell differentiation in this site.

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