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Biomedical subjects

M W Simpson-Morgan

Publications and source records attributed to M W Simpson-Morgan.

At least 19 recordsLinked to original sources
PubMed1997

The proliferative responses of lymphocytes from foetal calves and adult cattle.

This paper describes the proliferative responses of prescapular lymph lymphocytes and peripheral blood lymphocytes of foetal calves compared with cells of similar origin from adult cattle. Lymph lymphocytes were collected continuously by means of cannulation of efferent lymphatic ducts of the prescapular lymph node of foetal calves and adult cattle. Peripheral blood lymphocytes were collected from the foetus by means of cannulation of superficial veins of the foetus or of the umbilical vessels and from the jugular vein of adults. Foetal lymphocytes in one-way mixed lymphocyte culture stimulated and responded as well as adult lymphocytes. Foetal cells stimulated and responded more to cells from unrelated animals than to cells from their dam. Lymph lymphocytes from foetal calves between 188 and 253 days of gestation proliferated as well as adult lymphocytes and at a high level after stimulation with concanavalin A, phytohaemagglutinin and pokeweed mitogen. Response to stimulation with lipopolysaccharide, soybean agglutinin and wheat-germ agglutinin was variable but generally low and within the same range recorded by adult cells. Proliferation by foetal and adult whole-blood cultures was on occasions as high as that recorded by separated lymphocytes, even though fewer lymphocytes were initially present in the whole-blood cultures. Foetal lymph lymphocytes exhibited lower proliferative responses in autologous lymph plasma than in foetal calf serum or pooled foetal lymph plasma. There was no consistent depression of proliferation by culture medium supplements from pregnant animals. Rabbit serum consistently abrogated responses. Fetuin at final concentrations of greater than 2.5 mg/ml significantly depressed proliferation in foetal and adult lymphocytes from efferent lymph and peripheral blood.

Animals↗
PubMed1997

The immune response of foetal calves.

The immunological response of foetal calves to tetanus toxoid was investigated. Emphasis was placed on foetal immunocompetence and how this related to responses seen in adult cattle. The establishment of indwelling cannulas in the efferent prescapular lymphatic ducts and superficial veins of foetal calves allowed continual monitoring of cellular and humoral changes in efferent lymph and peripheral blood. Foetal calves from 195 to 253 days gestational age had the capacity to mount cell-mediated and humoral immune responses of similar character and magnitude as adult cattle to tetanus toxoid. Intravenous and subcutaneous routes of challenge with tetanus toxoid resulted in specific antibody production which peaked 26 to 31 days after vaccination. Significant tetanus toxoid-stimulated lymphocyte proliferation was present 4 to 6 weeks after vaccination with tetanus toxoid in both a foetus and an adult. After antigenic challenge lymphocytes remained the predominant cell type in efferent prescapular lymph of foetuses and cows while at the same time a marked shift to the left, characterised by band neutrophils and neutrophilic metamyelocytes occurred in peripheral blood. Lymph flow rate increased and cell concentration decreased after antigenic challenge.

Aging↗
PubMed1997

The cellular response of lambs to Brucella ovis before and after birth.

The immunological response of lambs to Brucella ovis before and after birth was investigated. The establishment of indwelling cannulas in the efferent prescapular lymphatic ducts of foetal lambs allowed continual monitoring of the immune response of a single lymph node. Foetal lambs in the last trimester of pregnancy were shown to mount a strong cell-mediated immune response to B. ovis. Lymphocytes from the challenged lymph node stimulated with B. ovis in vitro usually first reacted significantly and had highest [3H]-thymidine incorporation between 4 and 6 days after primary and secondary challenge, whereas, lymphocytes from the unchallenged node did not exhibit significant [3H]-thymidine incorporation until some 24 h later. Lymphocytes from these lambs challenged as foetuses still exhibited significant [3H]-thymidine incorporation in response to B. ovis for 4 to 5 months after birth. The proportion of surface immunoglobulin-positive cells in efferent prescapular lymph of unchallenged lambs ranged from 0.5 to 2.0% but after B. ovis challenge this proportion ranged from 2.7 to 8.7% between 4 to 6 days after challenge. By 9 to 12 days after challenge, the proportion had declined to pre-challenge values.

Animals↗
PubMed1996

Fetal lambs are depleted of IgM+ cells following a single injection of an anti-IgM antibody early in gestation.

B-cell depleted fetal sheep were created following a single injection of an anti-IgM monoclonal antibody early in gestation. Six sheep fetuses were given a single intraperitoneal injection of a monoclonal antibody directed against IgM at 63 days of gestation (gestation in sheep = 150 days). The fetuses were killed at 138-142 days of gestation and lymphoid tissues were collected for subsequent light microscopy and immunohistochemical examination. The ileal and jejunal Peyer's patch (PP) follicles in four of the six injected fetuses were markedly reduced in size. Cells in the rudimentary follicles of the ileal PP of these animals showed no reactivity for IgM and most were negative for CD45. The dome regions contained many T cells, which were predominantly CD8+ cells and included gamma delta T cells. The interfollicular areas of the PP of the markedly affected fetuses contained large populations of T cells. The spleen and lymph nodes were also markedly depleted of IgM+ cells and these tissues contained only a small, scattered population of weakly IgM+ cells. Follicular accumulations of IgM+ cells were absent. Large populations of T cells were present in the white pulp of the spleen and cortex of the lymph nodes. The liver did not contain IgM+ cells and the medulla of the thymus was depleted of IgM+ cells. The results of this study suggest that a surface IgM+ B-cell population is present in the sheep fetus at 63 days of gestation, which is essential for the colonization of the ileal PP and subsequent B-cell development.

Animals↗
PubMed1994

Retarded and excessive development of skin appendages in fetal lambs in response to thyroidectomy before wool follicle appearance.

The impact on wool follicles of development in an athyroid environment was studied in a series of twin fetal lambs by surgically thyroidectomizing one of each pair before the appearance of follicle buds and comparing development of epidermal appendages in it with their development in the normal co-twin. Thyroidectomy was undertaken at 51 to 54 days' gestation, i.e. after approximately one-third of the gestation period. Each treated fetus was then replaced in the uterus, allowing pregnancy to continue. Eight pairs of twins were removed at intervals from 67 to 122 days' gestation and skin samples from the thyroidectomized and the intact twins were compared. Micromorphometric examination of the samples was used to assess quantitatively the effects of thyroid deprivation on wool follicle development. In thyroidectomized fetuses there was a failure of keratinization in primary wool follicles, an absence of secondary follicles, a tendency to excessive follicular branching and sweat gland development, and a paucity of sebaceous gland formation. The density of wool follicles was substantially increased, but the mean cross-sectional area of these follicles was reduced. The effects of very early thyroidectomy imply that the thyroid plays a role in the stimulation and regulation of wool follicle differentiation. To test the reversibility of the effects observed in the skin of thyroidectomized fetuses, grafts from these animals were transplanted to normal, young fetal lambs. Subsequent examination of grafted skin revealed that complete keratinization had occurred but that none of the other abnormal features had been reversed.

Animals↗
PubMed1994

Ontogeny of milky spots in the fetal lamb omentum.

Milky spots in the fetal lamb omentum were observed by light and electron microscopy under normal conditions and after intraperitoneal carbon injection in utero. Rudimentary milky spots first appeared as small aggregations of cells along capillaries of the omental branch of the right ruminal artery at 72 days of gestation. At 116 days of gestation, macrophages were detected immunohistochemically in the milky spots. At 125 days of gestation, T cells were detected in the milky spots, but B cells were absent. Under the conditions induced by intraperitoneal injection of carbon suspension, openings were observed between the omental mesothelial cells, and macrophage aggregations appeared on the surface of the omentum through the openings. At 148 days of gestation (newborn), the milky spots were noted as black spots because of aggregation of carbon laden macrophages. The present study demonstrates that milky spots are present at fixed sites in the fetal lamb omentum by the middle of the term, and that at birth the macrophages on the spots already possess phagocytotic ability. The fetus develops the ability to protect the peritoneal cavity by producing peritoneal macrophages from the milky spots in the greater omentum even in utero.

Animals↗
PubMed1993

Technique for in situ excision of distended samples of greater omentum from small laboratory animals.

A simple and reliable technique is described for in situ excision of distended samples of greater omentum from small laboratory animals. The omental bursa is distended by injecting whipped hen egg white. Filter paper frames then are applied to the selected areas of distended omentum and samples of omental membrane are excised together with the filter paper frames. This sampling technique yields undamaged materials suitable for various research purposes.

Animals↗
PubMed1993

Morpho-physiological function and role of omental milky spots as omentum-associated lymphoid tissue (OALT) in the peritoneal cavity.

The morpho-physiological function and role of milky spots in the greater omentum are reviewed. These milky spots are composed of cellular aggregations of mesenchymal cells, mainly macrophages and lymphocytes, surrounding capillary convolutions termed omental glomeruli. Initial lymphatics of the omentum begin at the milky spots and drain into lymph collectors. The lymphatic capillaries in the omental milky spots take part in the absorption of various substances from the peritoneal cavity. Omental milky spots probably act as the first line of defense in the peritoneal cavity and therefore are immunologically important. In human infants, most of the cells in these milky spots are macrophages (49%); less common are B lymphocytes (29%) and T lymphocytes (12%). Whereas macrophages form clusters near the peritoneal surface of the milky spots and are oriented toward the peritoneal cavity for migration, clusters of B and T lymphocytes are typically found in periarteriolar locations within the milky spots. This cell zonation facilitates phagocytosis and processing of circulating antigens and foreign bodies which emanate from the peritoneal cavity. During inflammation, the number and size of omental milky spots dramatically increase, and some develop germinal centers within the lymphatic follicles and produce antibodies. During intraperitoneal immunotherapy, the omental milky spots and their cellular elements may be activated by intraperitoneal administration of biological response modifiers, and thereby represent an important immunoregulatory system for the peritoneal cavity. Omental milky spots are also closely linked to the dissemination of cancer cells. Thus, intraperitoneally inoculated experimental tumor cells selectively invade the milky spots and proliferate there to form tumor nodules. This occurrence is relevant to clinical practice where nodular metastases to the omentum are common. Omental milky spots are analogous to regional lymph nodes and as such are the omentum-associated lymphoid tissues and participate in intraperitoneal immune reactions.

Animals↗
PubMed1992

Activation of omental milky spots and milky spot macrophages by intraperitoneal administration of a streptococcal preparation, OK-432.

Omental milky spots are omentum-associated lymphoid tissues that cede peritoneal macrophages and participate in the immunity of the peritoneal cavity. We studied the changing surface features of milky spots and milky spot macrophages of Wistar rats, following the i.p. administration of OK-432, a killed streptococcal preparation (1 Klinische Einheit (unit) in 5 ml of phosphate-buffered saline) by the use of scanning electron microscopy. OK-432-activated macrophages demonstrated marked surface membrane activity and migrated through the stomata of the milky spot into the peritoneal cavity. The characteristic features of activated milky spots and milky spot macrophages were noted as early as 3 h following the administration of OK-432, and continued to be observed until 7 days after the injection. By 14 days after the injection, the structural integrity of the milky spot was partially lost. The activation of milky spots and milky spot macrophages by OK-432 provides a convenient in vivo system for the monitoring and study of i.p. cellular events.

Animals↗
PubMed1990

Major lymph nodes of the head of the fallow deer (Dama dama) and lymphatic drainage of antlers.

Heads from 10 fallow deer bucks were examined to provide a description of the major lymph nodes in this region. The distribution and size of these nodes were similar to those of sheep and goats. To determine whether there was drainage of lymph from the skin of antlers, and to follow the route of this drainage, a solution containing Evans blue was injected intradermally into the antlers of 2 bucks whilst the animals were anaesthetised. Dye appeared in tracheal lymph ducts 14 to 30 min after injection. The spread of blue colouration in lymphatic ducts and nodes, seen at post-mortem examination, indicated that lymph flowed from antlers laterally into the ipsilateral parotid lymph nodes and from these via medial and lateral retropharyngeal lymph nodes to the tracheal ducts.

Animals↗
PubMed1988

Flow and composition of lymph from the ovary and uterus of cows during pregnancy.

Ovarian or uterine lymph was collected continuously for periods of up to 25 days from 16 cows cannulated at stages of pregnancy ranging from 96 to 278 days post coitum. Blood samples were taken acutely from the ovarian and uterine veins during surgery and periodically from the jugular vein during the course of lymph collection. The flow rate and cell content of lymph was measured and blood and lymph plasma samples were analysed for progesterone, pregnenolone, pregnenolone sulphate, androstenedione, testosterone, oestrone, oestrone sulphate, oestradiol-17 beta, prostaglandin (PG) F-2 alpha, total protein and albumin. There was a high flow rate of protein-rich lymph from luteal ovaries with rates up to 101.7 ml/h occurring in individual lymphatics over short periods. Peripheral ovarian and uterine lymph contained a low concentration of cells (mean less than 10(5) cells/ml) comprising about 82-87% lymphocytes, 11-14% macrophages and monocytes and 2-4% other cells. At all stages of pregnancy, the concentration of progestagens and androgens was higher in ovarian lymph than in uterine lymph or blood plasma. The differences were greatest for progesterone and androstenedione which occurred at 200-fold and 60-fold greater concentration respectively in ovarian lymph than in jugular plasma. When serial 10 min samples were collected over a 12-h period, the concentration and output of progesterone in ovarian lymph varied in a phasic manner, ranging from 3.5 to 7.6 microM and from 31.7 to 293.1 nmol/h respectively. There was a positive correlation between the output of progesterone in lymph and the progesterone concentration in jugular blood samples taken every 20 min. During most of pregnancy there was little difference between the concentration of oestrogens in ovarian lymph, ovarian venous plasma and jugular plasma but, during the 3-5 days before calving, these hormones occurred at slightly higher concentration in ovarian lymph. Apart from pregnenolone and androstenedione, all steroids occurred at lower concentrations in uterine lymph than in jugular plasma. Shortly before parturition there was an abrupt increase in the concentration of PGF-2 alpha in uterine lymph. Lymph reflects more accurately the milieu of tissue cells than efferent blood and further analysis of differences in the concentration of substances in lymph relative to the output in the ovarian and uterine arterial and venous blood may lead to the identification of factors important in local regulatory mechanisms in the reproductive tract.

Androgens↗
PubMed1988

Traffic and proliferative responses of recirculating lymphocytes in fetal calves.

The thoracic duct or efferent prescapular duct was cannulated in four fetal calves aged 121-259 days post-conception. The duration of lymph flow ranged from 2 to 20 days and the mean flow rates sustained over these collection periods varied from 5.4 to 48.8 ml/hr. Lymphocyte output ranged from 4.4 x 10(6) cells/hr in thoracic duct lymph from a 121-day fetus to 3.9 x 10(8) cells/hr in efferent prescapular lymph from a 259-day fetus. The circulating lymphocyte pool in fetal calves of about 120 and 190 days gestational age was calculated to contain, respectively, 4 x 10(8) cells and 2 x 10(10) cells. The proportion of lymphocytes bearing surface immunoglobulin detected in fetal lymph ranged from 2.1% to 8.7%. Recirculating lymphocytes from fetal calves produced strong proliferative responses when stimulated by T-cell mitogens but responded poorly to B-cell mitogens. Fetal lymphocytes also responded to stimulation by allogeneic cells and stimulated other cells to proliferate during mixed lymphocyte culture. When stimulated with Con A, fetal lymphocytes secreted IL-2 to a degree that was indistinguishable from the secretory behaviour of lymphocytes from adult animals. The results presented in this paper show that chronic lymphatic fistulae can be established successfully in fetal calves to give access to recirculating lymphocytes. This provides a new experimental approach for studying the development of the bovine immune system.

Animals↗
PubMed1986

The cause of the shorter gestation length for twin calves: A computer simulation.

The possibility that the shorter length of gestation for twin calves is because pregnancy is determined by the earlier maturing twin has been investigated by computer simulation. The simulation indicated that this explanation alone could account for only about half the shortening of gestation for natural twin calves, and it is suggested that the combined actions of both twins is superimposed on the stimulus of the earlier maturing twin to initiate parturition. With mixed-species twins produced by embryo transfer, the immaturity of the more slowly maturing Bos indicus is such that it cannot cooperate with the earlier maturing Bos taurus cotwin to shorten gestation to appreciably less than is normal for single Bos taurus pregancies.

Journal Article↗
PubMed1985

The lymph-borne response of foetal lamb lymph nodes to challenge with Brucella abortus in utero.

The cannulated prescapular lymph node of the foetal lamb was challenged with killed Brucella abortus. Usually, both efferent prescapular ducts were cannulated and one node left as a control. Nodes were given primary or secondary challenges with doses of 10(9) - 2 X 10(10) brucella organisms and the lymph-borne response of the nodes followed. The foetal lymph node produced a vigorous cellular response to the injected brucella, restricted to the challenged side. The total cell output and, more strikingly, large cell output increased to reach a peak value 4-5 days after challenge. This cellular response was seemingly dose-dependent. The output of antibody after a primary challenge was delayed considerably and could not be detected in the lymph until well after the cellular response had subsided. The concentrations of antibody produced were quite low and almost all mercaptoethanol-sensitive. With secondary challenges the output of antibody occurred much more quickly, in phase with the cellular response, and appreciable amounts of mercaptoethanol-resistant antibody were produced. Under exceptional circumstances, high titre, highly specific anti-brucella antibody has been produced in foetal lymph. The foetal lymph node provides a powerful tool for further studies of the ontogeny of the immune response, and might help elucidate the failure of newborn animals to respond to some important bacterial antigens.

Animals↗
PubMed1985

The long-term collection of lymph from single lymph nodes of foetal lambs in utero.

Surgical techniques are described for the long-term collection of lymph from both prescapular efferent lymph ducts of foetal lambs in utero. Lymph ducts in foetal lambs 95 to 136 days post-conception were cannulated with a high rate of success. Lymph flow from the cannulas was not compromised by deliberate primary or secondary challenge of the lymph nodes with a wide variety of antigens, and often continued for long periods after the lambs were born naturally. The techniques allow cellular and humoral lymph-borne immune responses of foetal lambs to authentic primary antigenic challenge to be studied in utero, uncomplicated by any previous experience of antigens. Loss of lymphocytes from the cannulated ducts depleted the numbers of cells in the lymph, but lymph protein concentrations were unaffected by lymph drainage.

Animals↗
PubMed1985

Epithelial cell renewal and antibody transfer in the intestine of the foetal and neonatal lamb.

The intestine of the foetal lamb was exposed to large quantities of alpha-globulin (IgG) by prolonged intra-duodenal infusion, and absorption of intact IgG, with transfer to the lymph, continued undiminished, i.e., there was no evidence of closure. The rate of proliferation of the intestinal epithelium of the foetal and newborn lamb was measured using mitotic indices and localised labelling with (3H)-thymidine (TdR). In the foetus, cell division in the crypts occurs at a lower rate than the newborn (p less than 0.001) and there is very slow replacement of the intestinal epithelium. In the newborn lamb, a portion of the small intestine was incubated in vivo with TdR and the progress of labelled cells from the crypts upwards along the villi estimated, using autoradiography of serial biopsies from the same animal. A front of mature, digestive epithelium could be seen advancing up the villi, displacing the immature foetal type of cell which was capable of transfer of intact IgG to the lymphatics of the intestine. The evidence presented supports the hypothesis that immediately after birth the intestinal epithelium of the lamb begins to be replaced by a digestive type of cell, and the layer of cells responsible for absorption of colostral antibodies progressively disappears from the villi, resulting in closure.

Animals↗
PubMed1976

Lymphopoiesis and lymphocyte recirculation in the sheep fetus.

The production and the circulation of lymphocytes has been examined in the sheep fetus where neither foreign antigen nor immunoglobulins occur. It was found that as the lymphoid organs increased in size during fetal life, the numbers and the output of lymphocytes in the thoracic duct lymph increased. The recirculating pool of lymphocytes was estimated to be 5.5 +/- 1.5 X 10(8) cells in fetal lambs 95-100 days of age, 5.7 +/- 1.2 X 10(9) cells in fetuses 130-135 days of age, and 1.2 +/0 9.3 X 10(10) cells in fetuses near to term. The rate of addition of lymphocytes to the recirculating pool was 3.2 +/- 1.9 X 10(6) cells/h in fetuses of 100 days and 3.4 +/- 0.9 X 10(7) cells/h in fetuses of 130 days of age. Lymphocytes recirculated from blood to lymph in fetuses; labeled cells injected into the blood stream reappeared in the thoracic duct lymph promptly and reached maximum levels around 12-18 h after they were injected. Labeled lymphocytes were detected subsequently in greatest numbers in the lymph nodes, particularly in the mesenteric lymph nodes and in the interfollicular areas of the Peyer's patches. Chronic drainage of thoracic duct lymph from fetuses in utero for periods of up to 36 days had no obvious effects on the growth or development of the fetus and only minimal effects on the content of lymphocytes in the various lymphoid tissues even though the number of cells in the blood and lymph were reduced to between 20-30% of normal levels. Thymectomy done in fetuses about 2 mo befor cannulation of the thoracic duct reduced the output of cells in the thoracic duct to about 25% of normal levels and caused a significant reduction in the content of lymphocytes in the various lymphoid tissues. Thymectomized fetal lambs subjected to thoracic duct drainage for periods up to 2 wk in utero had a similar complement of lymphocytes in their lymphoid tissues to intact thymectomized fetal lambs. Lymphocytes obtained from the thoracic duct lymph of lambs thymectomized 2 mo previously recirculated from blood to lymph when they were injected intravenously, although they did this at a significantly slower rate than did lymphocytes from normal lambs.

Animals↗