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Biomedical subjects

J R Head

Publications and source records attributed to J R Head.

At least 55 records · Page 3Linked to original sources
PubMed1984

Lymphatic vessels in the uterine endometrium of virgin rats.

Uteri from four diestrous rats fixed by perfusion were examined histologically for the presence of lymphatic vessels in the endometrium, using 1 micron epoxy sections stained with toluidine blue. For each animal, multiple random sections were prepared from 3 tissue samples. In all sections, lymphatics were readily apparent in the myometrium, being identified by their irregular shape and contents of stained lymph proteins, which contrasted with the clear, empty blood vessels. While similar lymphatics were not seen in the endometrium of most tissue samples, one sample from each of three females revealed a small lymphatic vessel near the bases of the uterine glands, clearly in the endometrium. One of these was followed in serial alternating light and electron microscopic sections. The vessel maintained its relative position to the endometrial glands for a considerable distance, and also joined with two separate branches that appeared along its course. Ultrastructural observations, including a thin endothelium without a continuous basal lamina, the presence of anchoring filaments, and only mononuclear cells and cellular debris in the lumen, confirmed the vessel's identification as a lymphatic. The vessel's size was normally large enough to be followed by light microscopy; however, at some places along its course, the lumen narrowed to such a degree that it was only identifiable ultramicroscopically . These observations refute claims that there are no lymphatic vessels in rodent uterine endometrium, but indicate that they are small and sparsely distributed.

Animals↗
PubMed1984

Spontaneous autoradiographic grain activation associated with mast cells in methacrylate plastic embedded tissue sections.

Autoradiographic tracing using tritium labeled compounds or cells is a common laboratory technique for light and electron microscopy. This report describes a chemographic effect associated with certain cells in sections from tissues embedded in the new methacrylate plastic embedding compounds. When tissue sections from rats and rhesus monkeys that received no radioisotope were coated with nuclear track emulsion and subsequently developed, cells with morphologic characteristics of mast cells showed significant grain formation over the entire cell. Three different types of methacrylate plastics were tested using rat and monkey tissues and all three were found to promote grain formation over mast cells; however, this phenomenon was not seen in similar tissue sections from paraffin or epoxy embedded material. The properties of methacrylate plastics which promote positive chemography by mast cells may reflect the greater permeability of this class of plastics. Due to their wide tissue distribution, the presence of such chemographically active cells could cause false estimates of the distribution of either exogenous radiolabeled cells or radioisotopes within many tissues.

Animals↗
PubMed1983

Autoradiographic analysis of lymphocyte migration into the mammary epithelium and milk of lactating female rats.

Adoptively transferred radiolabeled lymphoid cells migrating to the lactating mammary gland were shown to enter the alveolar epithelium and ultimately the milk. Lactating female rats were injected intravenously with [3H]uridine-labeled syngeneic mesenteric lymph node cells, and the distribution of the cells 24 and 48 h later within intestinal and mammary tissues and their presence in milk were assessed autoradiographically. At both time periods, numerous labeled cells were found in the Peyer's patches and mesenteric lymph nodes. The mammary tissue and intestinal mucosa (lamina propria and epithelium) contained fewer labeled cells per unit area than those sites. Labeled cells within the mammary tissue were distributed equally between the alveolar epithelium and the intralobular connective tissue, where they were seen in both blood vessels and in the loose connective tissue. Occasional labeled cells were observed among the mononuclear cells seen in the alveolar lumina, and an average of 4.8% of the cells harvested from milk samples were labeled. Labeled cells within the secretory epithelium and milk always had the morphologic characteristics of mononuclear leukocytes. Thus, at least a portion of the lymphoid cells which have been shown to migrate to the mammary tissue in increased numbers during lactation actually enter and traverse the epithelium and contribute to the lymphoid component of mammary secretions.

Animals↗
PubMed1983

Uterine lymphatics: passage of ink and lymphoid cells from the rat's uterine wall and lumen.

The fate of ink and viable lymphoid cells placed in the wall and the lumen of the cycling rat uterus was determined. India ink injected into the myometrium rapidly filled major lymphatic trunks, going to the ipsilateral renal and/or iliac lymph nodes, depending on the site of inoculation along the uterus' length. No other abdominal or thoracic nodes seem to be involved. However, ink injected into the uterine lumen penetrated the endometrial stroma very slowly and only scattered dye-containing phagocytic cells could be seen in draining nodes. Ink-laden macrophages were retained for at least several days in the endometrium. Lymphoid cells similarly injected were traced by several techniques: 1) scintillation counting of tissues for 51Cr-labeled cells; 2) autoradiography for [3H]uridine-labeled cells; 3) fluorescent microscopy for fluorescein-containing cells in frozen tissues; and 4) graft-versus-host reactivity in draining lymph nodes. All techniques gave the same results: cells injected into the myometrium appeared rapidly in draining nodes, inducing a graft-versus-host reaction, whereas cells placed in the uterine lumen were found in only small numbers in the regional nodes, even after several days, and graft-versus-host reactions were minimal or absent. The barrier(s) to cell movement from the uterine lumen remains to be defined, but is of considerable interest since cell traffic in the other direction is a well-documented normal process. The combined effect of restricted cell entrance to the stroma, long retention of macrophages at this site, and an apparent paucity of lymphatic vessels in the endometrium most likely is to slow antigen handling from this site, which may help regulate maternal immune responses during pregnancy.

Animals↗
PubMed1983

Reconsideration of the lymphatic drainage of the rat testis.

An extensive investigation of the lymphatic drainage from the rat testis was carried out in an effort to detect any characteristics which might be important in the immunological privilege the testis extends to allografts. Three different methods revealed a consistent and very efficient lymphatic drainage involving primarily the iliac and renal lymph nodes and to a lesser extent the external lumbar, para-aortic, and posterior gastric nodes. Within minutes, dye or labeled cells injected into the testis could be found within regional nodes. Node hypertrophy was induced by injecting the testes of F1 hybrids with parental strain lymphoid cells (a regional graft-versus-host reaction). Besides indicating that efficient filtration occurs in these nodes, this also established that they are a hospitable environment for cellular immune reactions. Similarly, the capacity of allogeneic cells injected into the testis to induce production of humoral alloantibodies by recipients confirms that exposure to antigens via this route does not in itself suppress immune responsiveness.

Animals↗
PubMed1983

Increased free plasma corticosterone and adrenal hyperactivity associated with graft-versus-host disease.

This study profiles adrenal function in 14-day-old neonatal and adult rats with graft-versus-host disease (GVHD). Measurements of adrenal function included total serum corticosterone, the relative percentage of free corticosterone (a measure of biologically active hormone), adrenal cholesterol content, adrenal weights, and adrenal histology. Diseased animals in both age groups displayed a shift from the protein-bound to the free corticosterone fraction, with, surprisingly, no change in total serum corticosterone titers. We discuss the possibility that such a shift toward the biologically active, free-hormone pool results in a physiologic hyperglucocorticoidism that might contribute to the progress of GVHD. Compared with littermate controls, diseased adults had enlarged adrenals. In neonates with GVHD, no adrenal hypertrophy was evident, yet decreased adrenal cholesterol content and associated depletion of adrenal lipid droplets--evidence of adrenal hyperactivity--were identified. The GVHD must be responsible for the observed alterations in adrenal function because treatment of affected animals with alloantiserum directed against donor cells halted the disease and elevated the cholesterol content toward control levels. The possible contribution of adrenal dysfunction to the pathogenesis of secondary manifestations of GVHD is discussed.

Adrenal Glands↗
PubMed1983

Immune privilege in the testis. I. Basic parameters of allograft survival.

The fate of solid tissue allografts--skin or parathyroid glands--implanted in the interstitial tissue of the testis was investigated using inbred rats. The results affirm that the testis is an immunologically privileged site despite its efficient lymphatic drainage. Skin allografts survived at least several days longer than orthotopic grafts of similar size, whether major histocompatibility complex (MHC)-compatible or MHC-incompatible, and failed to induce an alloantibody response in most recipients or to prime for secondary antibody responses on rechallenge. Further assessment employed parathyroid grafts that allowed appraisal of their function and its duration, by monitoring serum calcium levels. Most intratesticular MHC-incompatible parathyroids survived for at least twice as long as control grafts in nonprivileged sites, with a median survival time (MST) of 41 days--and one-third of the grafts functioned at 100 days. MHC-compatible grafts fared even better (MST of 60 days), some surviving more than 400 days. Most F1 hybrid grafts survived virtually indefinitely. Splenectomy 5-23 days prior to implantation had a beneficial rather than a detrimental effect on the privilege afforded intratesticular parathyroid allografts. Allograft rejection was accompanied by antibody production in only one-half the animals. Grafts that had undergone functional rejection at the time of recovery usually had an intense mononuclear cell infiltrate, and long-term surviving grafts displayed varying degrees of cellular infiltration among cords of healthy, functional chief cells. Accepted parathyroids were destroyed by active immunization of the host but were unaffected by passively administered alloantibodies. The possible mechanisms controlling graft rejection in this unique privileged site are discussed.

Animals↗
PubMed1982

Immunotherapy of graft versus host disease with specific alloantiserum: restoration of cerebellar development in infant rats.

Fischer (FI) rats were stimulated to produce high-titre alloantiserum against DA antigens for alleviation of the symptoms of graft versus host disease (g.v.h.d.) in FI neonates. G.v.h.d. was procured by intravenous injection of DA lymph node cells on the day of birth. Daily injections of alloantiserum on postnatal days 11-13 not only prevented the progress of the disease in the whole animal but reversed the altered neuronal histogenesis that was present in diseased animals at day 11. Specifically, by 3 days after onset of alloantiserum treatment, the severely depressed DNA synthesis had returned to near normal levels. The decreased numbers of newly formed cells in the cerebellar cortex matrix area seen at day 11 was also reversed. For example, there was a significant increase in the number of newly formed basket and stellate cells in 14 day old alloantiserum-treated animals. G.v.h.d. did not result in a lymphocytic infiltration or an inflammatory response in the cerebellum. Therefore, we postulate that the deleterious effects of g.v.h.d. and the restoration effects of alloantiserum treatment are not directly cell-mediated. Rather, some soluble factor(s) interfering with the cerebellar cell cycle may be released during the interaction of donor lymphocytes and host cells at sites distant from the cerebellum. In support of this, in vitro analysis of DNA synthesis revealed that removal of cerebellar cells from the internal milieu of g.v.h.d. permitted DNA synthesis to proceed at a rate similar to that in control tissue.

Animals↗
PubMed1982

Manipulation of brain DNA synthesis is achieved by using a systemic immunological disease.

Previously, we showed that as early as postnatal day 11 an immunological disease, graft-versus-host disease, induced by grafting allogeneic lymph node cells into an immunoincompetent neonatal rat significantly decreases cerebellar histogenesis--i.e., DNA synthesis and the number of newly formed neurons. Here, we report that, subsequent to successful immunotherapy, there was a reversal of the deleterious graft-versus-host disease-induced alterations in DNA synthesis in individual cerebellar germinal cells. Immunotherapy involved treating the diseased rats on postnatal days 11, 12, and 13 with alloantiserum specifically directed against the grafted lymph node cells injected on the day of birth. On postnatal day 14, diseased, serum-treated, and control littermates were injected with [3H]thymidine and, 15 min later, the cerebella were excised and autoradiographed. A 0.72-mm segment of the external granular layer in the cerebellar fissure between lobules VIB and C was searched for labeled cells. The control group had the greatest number of labeled cells, defined by the presence of six or more autoradiographic grains. (43 +/- 4, mean +/- SEM) and the greatest number of grains per cell (9.5 +/- 0.2). Rats with the disease had few labeled cells (4 +/- 2) and the number of grains per cell was low (6.6 +/- 0.6); however, serum treatment increased both the number of labeled cells (26 +/- 8) and the number of grains per cell (7.4 +/- 0.2). These results show that without mononuclear infiltrates or inflammation in the cerebellum, a systemic immunological disease can dramatically decrease DNA synthesis per germinal cell and, moreover, that halting the disease by alloantiserum therapy can reverse this effect. These findings emphasize the sensitive plastic nature of neuronal cell acquisition in the normally developing brain.

Animals↗
PubMed1982

Fibronectin and cell shape in vivo: studies on the endometrium during pregnancy.

The rat endometrium during pregnancy was used as a model system to study fibronectin in vivo. Fibronectin distribution on stromal fibroblasts, as determined by indirect immunofluorescence staining, was studied in relationship to cell shape during decidual transformation. Fibroblasts of the estrus endometrial stroma were elongated cells with a fibrillar pattern of fibronectin on their surfaces. During days 1-6 of pregnancy, as these elongated cells acquired a round morphology, fibronectin changed first to a patched distribution on the cells'a surfaces and then disappeared. The change in fibronectin was specific for the fibroblasts since over the same time period there was no decrease in fibronectin found associated with blood vessels or in the epithelial-stromal basement membrane. These results support the proposed relationship between cell surface fibronectin and cell shape that has been inferred from in vitro experiments. After implantation, fibronectin distribution was studied in relationship to the position of the conceptus. In the stroma proximal to the implanting conceptus, fibronectin was absent except around blood vessels, which may help explain how decidual tissue could act as a barrier to trophoblast invasion. Finally, fibronectin distribution was studied in the uterus after parturition. Debris in the uterine lumen was coated with fibronectin, which may be important in the rapid removal of this material by phagocytic cells. Also, fibronectin associated with the epithelial-stromal basement membrane was reorganized after reepithelialization had occurred.

Animals↗
PubMed1982

Pregnancy-induced hyporesponsiveness to paternal alloantigens. II. Factors affecting altered expressions of immunity in parous rats.

It was previously demonstrated that female Fischer rats, primiparous by allogeneic DA males, produced only low levels of agglutinating antibody to a challenge skin graft bearing paternal alloantigens, although graft rejection was unimpaired. In this report, the phenomenon of pregnancy-induced hyporesponsiveness was further investigated with regard to factors responsible for its induction and maintenance. Increasing parity by DA males resulted in increased suppression of the Fischer females' agglutinating antibody production postpartum to a challenge skin graft bearing paternal antigens. Moreover, multiparity also resulted in impaired graft rejection, with greater numbers of litters causing more prolonged survival. Either humoral or cellular hyporesponsiveness, or both, persisted for several weeks or even months in many females. Removal of the iliac lymph nodes prior to pregnancy resulted in less severe suppression which was not maintained through the observation period (21 days postgrafting), whereas splenectomy either before mating or on day 7 of pregnancy had no effect. Tubal-ligated females exposed to multiple DA ejaculates, without pregnancy, manifested weakened humoral immunity similar to that of primiparous females, whereas those exposed to (Fischer X DA)F1 hybrid trophoblast multiple times in ectopic sites had not only somewhat suppressed antibody responses but also significantly impaired capacity to reject the challenge allograft. The potential roles of various antigenic stimuli and the complexities of intrauterine antigen processing during gestation are discussed in relation to this naturally induced allosuppression phenomenon.

Animals↗
PubMed1981

Alterations in cerebellar germinal cell division induced by graft-versus-host disease.

A systemic immunological syndrome, graft-versus-host disease (GVHD), which does not cause inflammation or cell death in the cerebellum, is shown to retard granule cell production by decreasing the rate of DNA synthesis (S phase) and prolonging mitosis (M), at metaphase. The rate of cell production in diseased animals at postnatal day 14, quantitated by analysis of the rate of labeling of DNA with 3H-thymidine (3H-Tdr), revealed decreased ability to synthesize new DNA. The number of cells taking up 3H-Tdr label per mm2, as detected by autoradiography, was similar in 14-day-old GVHD and control tissue as was the area of the germinal matrix zone and the number of mitotically active germinal cells per mm2 in sagittal sections near the midline. However, because the total volume of the cerebellum was less, the total number of mitotically active cells in the whole cerebellum of 11-, 14-, and 17-day-old diseased animals was less than in littermate controls. Furthermore, DNA synthesis per mitotically active germinal cell was less in diseased animals at each age examined. The mitotic index was unaffected until late in the disease (day 17), suggesting that a prolongation of the cell cycle was responsible for this GVHD-induced decrease in DNA synthesis. Consistent with a prolongation of the cell cycle was the finding that the mitotic figures in 14-day-old GVHD cerebella were mostly metaphase figures, whereas those in control cerebella were, as predicted, mostly prophase. Prolongation of the cerebellar cell cycle in 11- and 14-day-old diseased animals may explain the dramatic decrease in the mitotic index, the thickness of the germinal matrix zone, and the number of germinal cells at postnatal day 17.

Animals↗
PubMed1981

Current trends in reproductive immunology: an overview.

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 is here 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 Rhesus disease and its prophylaxis, and the principle of immunological tolerance, from investigations on the peculiarities of dizygotic twins in cattle.

Antibodies↗