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Biomedical subjects

W D Smith

Publications and source records attributed to W D Smith.

At least 91 records · Page 5Linked to original sources

Development of immunity to incoming radiolabelled larvae in lambs continuously infected with Ostertagia circumcincta.

Infective larvae of Ostertagia circumcincta were radiolabelled with 75selenium by a method which did not affect their viability. Three groups of five-month-old lambs were infected daily with 1000 unlabelled infective larvae for four, eight and 12 weeks, respectively. After each period one of these groups and a group of worm-free controls were challenged with three consecutive daily doses of 1000 radiolabelled third stage larvae. The lambs were killed 13 days after the first dose of challenge larvae and their worm burdens examined. The first indication of immunity was retardation of developing worms observed at four weeks. Resistance to the establishment of incoming worms developed between four and eight weeks and a brief period of population turnover probably took place at this time. Simultaneously a greater inhibition of worm development occurred resulting in an increase in the number of parasites recovered as early fourth stage larvae. By 12 weeks the animals were almost completely immune to incoming worms. The development of resistance to incoming worms correlated with a rise in serum antibody titre and an increase in the number of intraepithelial globule leucocytes in the gastric mucosa.

Animals↗

Development of immunity to incoming radiolabelled larvae in lambs continuously infected with Trichostrongylus vitrinus.

Infective third stage larvae (L3) of Trichostrongylus vitrinus were radiolabelled with 75 selenium by a method which did not affect their viability. Three groups of six-month-old lambs were infected daily with 1000 L3 for four, eight and 12 weeks, respectively. After each period, one of those groups (n = 5) and a group (n = 4) of worm-free controls were challenged with three consecutive daily doses of 1000 radiolabelled L3, killed 10 days after the first dose, and their worm burdens examined. After four weeks of continuous infection partial immunity to the establishment of challenge L3 was apparent, and by eight and 12 weeks, with the exception of one sheep, there was almost total resistance to incoming worms. Immunity was also expressed as an inhibition of the development of established worms.

Animals↗

The generation of ovine bone marrow-derived mast cells in culture.

Ovine mast cells generated in vitro are morphologically and biochemically similar to mast cells localized to the gastrointestinal tract in vivo. Bone marrow (BM)-derived haemopoietic precursor cells were cultured in the presence of conditioned medium (CM) prepared from in vitro-activated lymphocytes from nematode-infected sheep. Mast cells developed rapidly after 2 weeks of culture and could persist for 2-3 months. The presence of sheep mast cell proteinase (SMCP) in the cultured cells correlated with the number of morphologically recognizable mast cells by Leishman-Giemsa staining and is definitive as, in vivo, this enzyme is unique to mast cells. The content of SMCP per cell increased as the cultures developed. In vivo, increased serum concentrations of SMCP are associated with mast cell function at the site of nematode infection. The availability of the cultured cells should now facilitate mast cell biochemical and functional studies.

Animals↗

Phenytoin infusion in severe pre-eclampsia.

Intravenous phenytoin sodium was given as a high-dose infusion (10 X 8-18 mg/kg) for anticonvulsive prophylaxis to 2 eclamptic patients and to 24 patients with moderate to severe pre-eclampsia. There were no major maternal or neonatal side-effects. Plasma phenytoin levels were within the therapeutic range (7-20 mg/l) at 30 min and 6 h after the infusion in all patients, and remained at a therapeutic level in 21 patients after 12 h. After a second dose of phenytoin in 19 patients, drug levels were within the therapeutic range at 24 h.

Female↗

Phagocytosis of yeast by human oocytes: fine structural observations.

Fine-structure observations have been made on the interaction between invasive yeast cells and human oocytes. The yeast appear to make their way through the zona pellucida and once in the perivitelline space are incorporated into phagocytic vacuoles by surface activity of the oocyte. The yeast attach to the vitelline membrane via fuzzy surface material on the cell wall, and incorporation appears to be aided by oocyte microvillar activity. Coated pits in the oocyte plasma membrane are incorporated into the phagosomes, but no lysosomal activity is seen, and neither oocytes nor yeast cells appear to undergo degeneration in the time frame investigated.

Cells, Cultured↗

Systemic release of a mast cell proteinase following nematode infections in sheep.

An enzyme-linked immunosorbent assay (ELISA) for sheep mast cell proteinase (SMCP) has been developed. Concentrations of SMCP in homogenates of abomasal tissue from parasite-immune sheep (341 micrograms SMCP/g tissues) were raised when compared to those in normal (non-infected) abomasa (0.145 micrograms SMCP/g tissue). SMCP was not detected in sera from normal animals challenged with Haemonchus contortus but was present (less than 1.0 ng SMCP/ml) in sera from 8/11 immune sheep 2 h after intra-abomasal challenge with 1 x 10(6) exsheathed Haemonchus larvae. In two further experiments, the SMCP response in gastric lymph was monitored after homologous larval challenge in sheep immune to Ostertagia circumcincta and in normal controls. SMCP (less than 1.4 ng SMCP/ml) was detected in lymph from 2/3 and 4/5 immune animals between 1 and 4 days post-challenge with 50,000 larvae, but not from normal animals. SMCP was not detected in lymph from immune animals following challenge with 1000 Ostertagia larvae. The relatively low concentrations of SMCP in blood and lymph reflect the presence of proteinase inhibitor(s) which interfered with the ELISA.

Abomasum↗

Mucosal IgA production and lymph cell traffic following prolonged low level infections of Ostertagia circumcincta in sheep.

Some aspects of the local immune response to daily challenge with 2000 Ostertagia circumcincta larvae were studied by monitoring changes in the composition of gastric lymph of naive and previously infected sheep. The main changes in the naive group were increases in lymphoblast output and concentrations of pepsinogen whereas lymph albumin values decreased markedly and IgA concentrations were usually unchanged. In contrast, in the previously infected sheep, the continuous challenge stimulated only transient increases in lymphoblast and IgA containing cell traffic whereas lymph IgA and pepsinogen concentrations remained elevated throughout the experiment. By temporarily interrupting the challenge in a second group of previously infected sheep it was shown that elevated IgA and pepsinogen values were maintained only if larval intake was continuous.

Abomasum↗

Surgery without pain--Part 1: Background.

This paper was commissioned to cover the beginnings of anaesthesia: the transition from surgical operations with pain to those without. It reviews some previous pre-anaesthetic histories (Part I): it focuses upon attitudes to pain; and it seeks evidence from the one hundred years before the discovery of anaesthesia. Finally (Part II) it outlines the introduction of nitrous oxide and of ether anaesthesia.

Anesthesia↗

Surgery without pain--Part II: 1800-1847.

This paper was commissioned to cover the beginning of anaesthesia: the transition from surgical operations with pain to those without. It reviews some previous pre-anaesthetic histories (Part I): it focuses upon attitudes to pain; and it seeks evidence from the one hundred years before the discovery of anaesthesia. Finally (Part II) it outlines the introduction of nitrous oxide and of ether anaesthesia.

Anesthesia↗

Transfer of immunity to Ostertagia circumcincta and IgA memory between identical sheep by lymphocytes collected from gastric lymph.

Sheep rendered immune to Ostertagia circumcincta were challenged with 50,000 larvae and lymphocytes were collected from the gastric lymph up to eight days after challenge. The cells were transferred intravenously to genetically identical worm-free sheep which, together with controls, were challenged with 50,000 larvae and killed nine days later. Cells obtained during the donors lymphoblast response to challenge transferred partial immunity, measured either as stunting or loss of worms. Significantly less immunity was transferred by cells collected either before or after this response. Thus the responding cells can mediate protective immunity to O circumcincta. On the other hand the donor sheep remained immune to their challenge infection despite being depleted of these functional cells, showing that their presence was not essential for immunity to be maintained. Comparison of the immunoglobulin A (IgA) concentrations in the gastric lymph of recipient and control sheep showed that a local IgA response had also been transferred. Enumeration of mucosal mast cells suggested that a mastocytosis had been transferred to the two recipients which were most immune to challenge.

Animals↗

Ca2 and Ca3. New monoclonal antibodies evaluated as tumor markers in serous effusions.

Ca2 and Ca3 are new monoclonal antibodies of IgG1 class, directed against the Ca antigen, a mucus-type glycoprotein expressed on the surface of a wide range of malignant human cells and certain specialized normal epithelia. These antibodies were produced by immunization with purified preparations of the Ca antigen. They were tested to assess their value in the diagnosis of malignant effusions. Immuno-alkaline-phosphatase staining was used. Smears of pleural and peritoneal effusions were chosen to show: undoubted malignant cells of various types; and mesothelial cells in effusions from cases in which cancer was not in question. The Ca2 antibody, at 1 in 20 dilution of the culture supernatant, was the most specific, giving no reactions with benign mesothelial cells from any of the 35 cases tested. Malignant cells were clearly stained in 35 of 40 cases of carcinoma or mesothelioma. The staining was negative in two cases of oat cell bronchial carcinoma, and in three of four cases of carcinoma of the colon. Ca3 gave similar, but somewhat stronger, reactions with carcinoma cells, but was less specific, reacting weakly with mesothelial cells in 8 of 35 benign effusions. Because the false-negative reactions given by the Ca series of antibodies are to some extent complementary to those given by monoclonal antibodies directed against the carcinoembryonic antigen (CEA), a combination of Ca2 and anti-CEA is recommended as a most useful addition to the normal cytologic examination of effusions.

Antibodies, Monoclonal↗

Age immunity to Ostertagia circumcincta: comparison of the local immune responses of 4 1/2- and 10-month-old lambs.

In 2 experiments, the local immune response to infection with 50,000 O. circumcincta was monitored in 4 1/2-month-old previously infected lambs by following changes in the composition of gastric lymph. The previously infected lambs were partially resistant to the challenge in that they harboured a greater proportion of early fourth stage parasites and that the developing larvae recovered from them were distinctly shorter than those present in controls. They also exhibited a secondary local immune response in the gastric lymph consisting of increases in the output of lymphoblasts and IgA cells which peaked 3 to 5 days after challenge, followed by increases in lymph IgA and IgA anti-larval antibody on days 6 and 7. The size of the total IgA response in a sheep was highly correlated with the degree of stunting of its larvae, suggesting that IgA antibody can reduce the growth of developing Ostertagia. When compared with the results of 2 identically designed experiments carried out previously in 10-month-old sheep, the younger lambs were measurably less resistant to challenge and most aspects of the magnitude of the local immune response were significantly depressed, although the timing of the response was similar. It is suggested that this poorly developed ability to mount a secondary mucosal immune response may explain the relative failure of the younger lamb to develop resistance to gastro-intestinal nematodes.

Aging↗

Air rifle ammunition and its influence on wounding potential.

Two new types of air rifle pellet have been introduced; Prometheus, made from steel and nylon, and 'Sabo', made from lead alloy and plastic. Both have radio-opaque and radio-lucent components and their manufacturers claim better penetration. To establish their capabilities and the clinical implications a comparison of penetration was made between diablo, Prometheus and 'Sabo' pellets using gelatin 20% as a tissue simulant. Prometheus penetrated no further than diablo pellets but fragmented in up to 70% of cases. 'Sabo' penetrated 46% further than diablo (p = 0.001) and its plastic component did not penetrate at ranges greater than 0.5 m. Prometheus penetrated steel, unlike the other pellets, and is therefore potentially more dangerous in head injury. Because of fragmentation after impact it should be remembered that the radio-lucent sleeve is likely to be lying in the wound track. 'Sabo' would appear to be the most dangerous in soft and medium density materials.

Forensic Medicine↗