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Biomedical subjects

D J Cameron

Publications and source records attributed to D J Cameron.

At least 73 records · Page 4Linked to original sources

In vivo macrophage-mediated tumor cytotoxicity in the mouse.

Tumor-bearing animals injected with either LPS-activated or control macrophages were capable of suppressing tumor growth in vivo. Tumor growth rate and survival times were assessed for each group of animals. At day 12 after injection of the P815 tumor cells, no difference in tumor size could be demonstrated in any of the groups. However, by day 17 the tumors in the animals treated with 2.5 X 10(6) or 5 X 10(6) control as well as LPS-activated macrophages did not continue to increase in size as was seen in the case of the control animals. When examining survival times, it appeared that the animals treated with control or activated macrophages generally survived approximately 10 days longer than did the animals receiving no treatment (30-day vs 20 day survival). Thus, it appears that tumor cell growth can be slowed down in vivo when control or activated macrophages are injected into the site of the tumor mass.

Animals↗

Relationship of the suppression of macrophage mediated tumor cytotoxicity in conjunction with secretion of prostaglandin from the macrophages of breast cancer patients.

Peripheral blood monocyte derived macrophages obtained from breast cancer patients are non-cytotoxic towards human tumor cells. However, when indomethacin, a prostaglandin synthetase inhibitor, was added to the macrophage tumor cell incubation mixture, the breast cancer patient's macrophages became capable of killing the tumor cells. Furthermore, the macrophage preparations obtained from breast cancer patients demonstrated a 64% increase in the secretion of PGE2, when compared with macrophages obtained from normal donors. It is already known that prostaglandin can inhibit both natural lymphocyte cytotoxicity and antibody dependent cell-mediated cytotoxicity against human tumor cells in vitro. These results indicate that increased synthesis of prostaglandin can also inhibit macrophage mediated cytotoxicity. Therefore, it is possible that manipulation of this mechanism might enhance the effectiveness of the macrophage response and should be a consideration in assessing macrophage-tumor cell interaction in vitro and in vivo.

Breast Neoplasms↗

The effect of cimetidine on meal-stimulated gastric function and exogenous pancreatic enzymes in cystic fibrosis.

Some patients with cystic fibrosis (CF) have malabsorption of fat and protein in spite of large amounts of supplemental pancreatic enzymes. This is partly due to acid inactivation of exogenous pancreatic enzymes in the stomach. The effect of cimetidine on gastric function and exogenous pancreatic enzymes was assessed by a marker perfusion technique in 4 CF children in a double-blind controlled fashion. Gastric acid secretion was higher in CF patients than in controls (P less than 0.005) and was reduced significantly by oral cimetidine (P less than 0.02). Rapid inactivation of exogenous trypsin and lipase occurred when gastric pH fell to less than 4.5. There was no loss of enzyme activity during treatment with cimetidine when gastric pH remained above 5.5. Activity of lipase and trypsin in the jejunum improved in all subjects. Fat and nitrogen absorption assessed by a balance technique during the study period showed a small improvement in fat absorption while on cimetidine. We conclude that some CF patients have a high meal-stimulated gastric acid output which causes inactivation of trypsin and lipase. Cimetidine was effective in reducing acid secretion in such patients and led to small improvements in fat absorption.

Adolescent↗

Specificity of macrophage mediated cytotoxicity: role of target cell sialic acid.

Five paired human cell lines consisting of either skin fibroblasts or tumor obtained from patients with osteogenic sarcoma were studied for their susceptibility to macrophage mediated cytotoxicity. In two of the matched pairs, the malignant cell lines were susceptible to the effects of cytotoxic macrophages, whereas normal targets were not. In two other pairs, both malignant and normal targets were resistant to the effects of cytotoxic macrophages. In the fifth pair, both targets were sensitive to the effects of the macrophages. Cell surface sialic acid content of the five matched pairs and several previously studied targets was determined. It was found to correlate with susceptibility to macrophage mediated cytotoxicity. The resistant normal cell lines contained approximately 50% less sialic acid than did the sensitive tumor cell lines. Furthermore, the three resistant tumor lines also had cell surface sialic acid content in the range of the normal resistant targets. Sensitive tumor cells with high cell surface sialic acid, after neuraminidase treatment, became resistant to the effects of cytotoxic macrophages and the effect of the neuraminidase treatment was blocked by addition of sialic acid to the incubation mixture. Thus, it appears that susceptibility to macrophage mediated cytotoxicity is associated with increased levels of sialic acid on the cell surface membranes.

Cell Line↗

In vitro killing of tumor cells by macrophage factors obtained from cancer patients and normal donors.

Macrophages obtained from cancer patients as well as normal volunteers secrete products that are cytotoxic to malignant but not normal cells. The susceptibility of the target cells varies considerably. These macrophage products have the following characteristics: 1) They are strongly absorbable to cellulose nitrate membrane filter materials. 2) They are quantitatively elutable with dilute hydrochloric acid. 3) They are relatively stable over a wide range of temperatures. 4) They are nondialyzable. When these macrophage products were subjected to polyacrylamide gel electrophoresis, it was found that the tumoricidal products secreted by the macrophages obtained from normal donors and cancer patients could be resolved into 8-10 protein bands, which were qualitatively identical. However, the products obtained from the macrophages of cancer patients differed quantitatively from the products obtained from the normal donor's macrophages. Utilizing column chromatography, the products secreted by the macrophages of cancer patients and normal donors were further purified. Eleven protein fractions with tumoricidal properties were recovered. In 7 of the 11 fractions, the cytotoxic capacity of the products secreted by the cancer patients' macrophages was equivalent to that of the normal donors. One fraction (MW 25,000) isolated from the cancer patients' macrophage supernatants was more cytotoxic than the macrophage product obtained from normal donors. In contrast, a second fraction (MW 45,000) isolated from the cancer patients' macrophage supernatants was less cytotoxic than the normal donors' macrophage products.

Breast Neoplasms↗

Cytotoxicity of human macrophages for tumor cells: enhancement by bacterial lipopolysaccharides (LPS).

Bacterial lipopolysaccharide (LPS) stimulates human macrophages derived from peripheral blood monocytes to kill tumor cells in vitro. Maximum cytotoxicity was observed after 8 to 24 hr of incubation with LPS. However, if the macrophages are activated with LPS for 8 hr and then maintained in medium for an additional 16 hr before assay, their cytotoxic capacity is lost. In comparison to normal macrophages, LPS-activated macrophages were cytotoxic to the three malignant cell lines tested but had no effect on the three nonmalignant cell lines. Human macrophages can be made tumoricidal by the addition of greater than or equal to 10 microgram/ml LPS, and the effect is abolished in the presence of polymyxin B.

Adenocarcinoma↗

The spectrum of cow's milk allergy in childhood. Clinical, gastroenterological and immunological studies.

Seventeen of 52 children suspected of having cow's milk allergy had this diagnosis confirmed after milk challenge in hospital. A broad spectrum of reactions was obsserved including skin eruptions, respiratory symptoms and gastrointestinal disturbance. Not all patients with gastrointestinal symptoms showed small bowel mucosal damage. Only patients with skin reactions had positive skin tests. IgA deficiency and IgE elevation were common. Four patients had symptoms within 3 days of birth. Twelve children tolerated cow's milk by three years of age. Cow's milk allergy can cause a variety of symptoms. Challenge with milk for several days may be required before allergic manifestations can be demonstrated.

Animals↗

Diarrhea and rotavirus infection associated with differing regimens for postnatal care of newborn babies.

Surveillance of 2,041 babies born during 4 winter months in one obstetric hospital in Melbourne, Australia, showed that 215 developed acute diarrhea during the first 2 weeks of life. Babies requiring special care from birth had a high incidence of sporadic diarrhea (36%). The incidence of diarrhea among healthy full-term babies was low if they were "rooming-in" with their mothers (2 to 3%) but high if they were housed in communal nurseries (29%). The most important factor influencing incidence of diarrhea was proximity to other newborn babies and frequency of handling by related adults. Breast feeding did not always protect babies from diarrhea. Excretion of rotaviruses was temporally retlated to diarrhea in 61 to 76% of healthy full-term babies and in 44% of babies requiring special care. Other eneteric pathogens, including enerotoxigenic Escherichia coli, were occasionally isolated. Calculation of the ratios of symptomatic to asymptomatic infection suggests that babies requiring special care are much more likely to develop symptomatic illness after rotavious infection than are full-term babies.

Australia↗

Cytotoxicity of human macrophages for tumor cells. Enhancement by human lymphocyte mediators.

Human macrophages, derived from peripheral blood monocytes, acquire enhanced cytotoxicity for human target cells after incubation in mediator-rich supernates from antigen-stimulated lymphocytes. Maximum cytotoxicity was observed after 24-h incubation in mediators. In comparison to normal macrophages, mediator-activated macrophages were cytotoxic to five of the six malignant cell lines tested but had no effect on five nonmalignant cell lines. In 20 experiments with one target (SK-BR-3), mean cytotoxicity was 23 +/- 2.7% and with another target (MA-160), was 29 +/- 3.4%. Macrophages became cytotoxic after 8-h incubation with mediators and the enhanced cytotoxicity persisted for at least 40 h after the lymphocyte mediators were removed. These findings are consistent with the hypothesis that macrophages, activated by antigen-induced lymphocyte mediators, can contribute to the host resistance to tumor growth in man.

Cell Division↗

Pattern of shedding of two noncultivable viruses in stools of newborn babies.

Noncultivable viruses have been associated with diarrhea affecting newborn babies in obstetric hospital nurseries. Persisting infection in a special care nursery in Melbourne, Australia, permitted a study of the pattern of excretion of these viruses. Ten babies admitted to the nursery within 2 hr of birth were randomly selected for prospective study. Feces were collected daily for 14 days and were examined by electron microscopy. All ten babies excreted detectable amounts of duovirus (rotavirus, HRVL agent, IGV) for at least 1 day. Age at onset of excretion varied from 2 to 13 days. Eight of the ten babies developed diarrhea. Excretion of duovirus preceded the onset of diarrhea by 12--72 hr and persisted for at least 3 days. Seven of the ten babies also excreted detectable amounts of 28-nm virus-like particle for 3--8 days. The identity of this particle is unknown. Morphologically it resembles Norwalk agent and "astrovirus." Excretion of this 28-nm particle coincided with symptoms of diarrhea in four babies, all of whom were also excreting duovirus. It is concluded that most newborn babies admitted to a nursery where duovirus infection is endemic will excrete this virus at least once during the first 2 weeks of life. Excretion of virus particles will either precede development of diarrhea or be asymptomatic. Selective isolation of babies with diarrhea is thus unlikely to control spread of duovirus infection within a hospital nursery.

Australia↗

Noncultivable viruses and neonatal diarrhea: fifteen-month survey in a newborn special care nursery.

During a 15-month period of surveillance, diarrhea developed in 257 of 913 babies (28%) admitted within 2 hours of birth to a special care nursery in Melbourne, Australia. Diarrhea was seasonal, affecting a maximum of 43% of babies admitted during one winter month (July) and a minimum of 13% of babies admitted during one summer month (December). Diarrhea was no more frequent nor more severe in babies of very low birth weight or of very early gestational age. Two noncultivable viruses were located by electron microscopy in feces from babies with or without diarrhea. Excretion of a reovirus-like particle (rotavirus, duovirus, human reovirus-like agent, infantile gastroenteritis virus) was temporally related to diarrheal symptoms. Asymptomatic infection with this virus also occurred. A 28-nm virus-like particle was excreted by some babies, but it could not be implicated on epidemiological grounds in the etiology of the diarrhea. Rotavirus infection may be an important cause of endemic diarrhea in nurseries for the newborn. Infection may be difficult to control or eradicate, since it is often asymptomatic and may be influenced by infection in the community at large.

Australia↗

New virus associated with diarrhoea in neonates.

Since December, 1974, there has been an increase in the incidence of acute diarrhoea in the neonatal nurseries of five Melbourne metropolitan hospitals. Four of these have had epidemics, and the incidence of endemic diarrhoeal disease has increased. Extracts of faeces from 148 patients from the five hospitals were examined by electron microscopy. "Duovirus" particles were detected in 82 of these extracts, including at least one from each hospital. No bacterial pathogens were isolated. It seems likely that "duovirus" is an important cause of sporadic and epidemic acute diarrhoeal disease in neonates. It is important to note that the absence of a recognized bacterial pathogen does not exclude an infective cause, especially when sugar intolerance is present. Appropriate measures to minimize the spread of infection must be employed.

Acute Disease↗