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Biomedical subjects

T J Chambers

Publications and source records attributed to T J Chambers.

At least 217 records · Page 12Linked to original sources
PubMed1981

Rate and pattern of epithelial cell proliferation in ulcerative colitis.

We investigated the pattern of proliferation of epithelial cells in rectal mucosa taken from normal individuals and patients with ulcerative colitis by incubating mucosa with tritiated thymidine in vitro and processing for autoradiography. We found that patients with ulcerative colitis in remission showed a proliferative pattern similar to that seen in both regenerating and "precancerous' mucosa. Patients with a short history were as likely to show this pattern as those with a long history, and this shows that the abnormal pattern does not signify impending malignant change. We also found that mucosa from patients with ulcerative colitis in remission showed an increased proportion of cells synthesising DNA, a proportion surprisingly close to that seen in an active phase; this suggests that the abnormal pattern seen in remission is the pattern of a regenerating mucosa. We feel that this high rate of mucosal turnover, sustained not just during clinically active disease but throughout remission, leads to the increased incidence of carcinoma and to the development of carcinoma in flat mucosa.

Adult↗
PubMed1981

A controlled trial of alternate day prednisolone as a maintenance treatment for ulcerative colitis in remission.

A double-blind crossover trial compared prednisolone, 40 mg given orally on alternate days, with placebo as a maintenance treatment for ulcerative colitis in remission. In each patient, the study was over two periods of 3 months. Of 24 patients who completed both periods, 11 relapsed while taking placebo but not while taking prednisolone, and 1 relapsed on prednisolone but did not on placebo (p less than 0.01). 1 patient had to stop prednisolone because of hyperglycaemia; other side effects noted were mild. Prednisolone, cautiously used in this way, could be justified for the few patients who relapse frequently despite sulphasalazine.

Administration, Oral↗
PubMed1980

Diphosphonates inhibit bone resorption by macrophages in vitro.

The diphosphonates are a group of synthetic compounds which are adsorbed onto hydroxyapatite crystal surfaces and inhibit both the growth and dissolution of these crystals. They also inhibit mineralisation and resorption of bone in vivo. The effects of diphosphonates were tested on the attachment of macrophages to bone and on the dissolution of bone mineral by macrophages. Attachment was unaffected but resorption was inhibited. Diphosphonates were found to be cytotoxic at much lower concentrations when bone mineral was present, and the most likely explanation for the effects of diphosphonate on bone resorption is that the drug is adsorbed onto the mineral surface where it reaches cytotoxic concentrations.

Animals↗
PubMed1980

The cellular basis of bone resorption.

The osteoclast is the major agent of bone resorption. Durang the last few years persuasive evidence has emerged from several sources which shows that the osteoclast is derived from the fusion of cells of the mononuclear phagocyte system. This fact makes a reevaluation of the pathophysiology of bone resorption necessary. The most plausible mechanism for osteoclast formation is that bone-lining alter bone locally in such a way as to lead to its phagocytic recognition by mononuclear phagocytes. These cells then accumulate on the altered bone surface, commence digestion, and fuse in a similar way to that shown for other macrophage polykaryons. Once formed, osteoclast function may be influenced in two ways: some agents, such as osteoclast-activating factor and lipopolysaccharide, may directly stimulate osteoclast resorptive activity, in the same way as they influence the activity of other cells of the mononuclear phagocyte system; other agents, such as parathormone and prostaglandins, because they also cause in increase in the number of osteoclasts, seem more likely to have a primary effect on bone-lining cells, which in turn regulate osteoclast activity by unknown mechanisms.

Animals↗
PubMed1979

Phagocytosis and trypsin-resistant glass adhesion by osteoclasts in culture.

Osteoclasts were cultured in vitro and tested for the functions normally associated with cells of the mononuclear phagocyte system. They were found to ingest glutaraldehyde-fixed red cells and latex, but not opsonised or complement-coated sheep red cells. Osteoclasts are glass-adherent and resist removal by trypsin. The implications of these findings for the identity of the osteoclast precursor cell and its mechanism of fusion are discussed.

Animals↗
PubMed1979

A functional assessment of macrophages from osteopetrotic mice.

Macrophages from osteopetrotic mice caused less bone resorption than normal sib macrophages in culture. The bone-resorbing activity lay in the culture supernatant, and reduced activity in cultures of macrophages from osteopetrotic mice correlated with reduced glass spreading and reduced latex phagocytosis. We suggest that macrophages from osteopetrotic mice show defective phagocytic recognition of glass, latex, and bone and that this defective recognition may reflect the cause of the failure of resorption which results in osteopetrosis.

Acid Phosphatase↗
PubMed1979

The increasing isolation of Serratia species from clinical specimens.

A 14-month survey was undertaken in a diagnostic bacteriology laboratory to determine the incidence of Serratia spp. in routine clinical specimens. Gram-negative organisms with enterobacteria-like colonies were tested by a simple screening procedure. Fifty-eight strains of S. marcescens and two strains of S. liquefaciens were isolated from 59 patients. The strains were usually non-pigmented and exhibited multiple antibiotic resistance. Serotyping and determination of bacteriocine sensitivity patterns revealed that the majority of infections were sporadic, although episodes of cross-infection did occur. S. marcescens was considered to contribute significantly to morbidity and mortality in 53% of patients and appears to be of increasing importance in hospital-acquired infections.

Adult↗
PubMed1979

Colonic adenomas--a colonoscopy survey.

A colonoscopy survey of 620 patients with 1049 colon adenomas showed a predominantly left-sided distribution (77%). Of these lesions 97% were amenable to endoscopic removal or ablation. Sixty per cent of patients presented with rectal bleeding as their major symptom. There was agreement between radiology and colonoscopy in only 62% of patients, as many of the studies were single contrast barium enemas, performed before referral. Forty-eight per cent of adenomas in our series were less than 1.0 cm in diameter. Of the larger adenomas (greater than 2.0 cm in diameter) 66% were situated in the sigmoid colon, and of those containing invasive carcinoma (4.8% of the total) an even higher percentage (94%) were in the sigmoid and low descending colon. With increasing polyp size, there was a greater predominance of villous elements and this was associated with a higher risk of malignant change than the more frequent and generally smaller tubular adenoma. Local colonoscopic excision alone is sufficient treatment for adenomas with malignant change unless they are poorly differentiated histologically and providing adequate resection is demonstrated. Twenty-eight patients treated in this way are alive without recurrence at periods from six to 62 months. Although 65% of patients had only one adenoma, and 90% three or less, there is a risk of developing other benign and malignant colon neoplasms and careful follow-up is required.

Adenoma↗
PubMed1979

The granuloma in Crohn's disease.

The number of granulomas in sections of bowel involved by Crohn's disease has been counted and related to length of previous history, treatment with steroids, site of involvement, and the subsequent course of the disease. It was found that a high content of granulomas predicted a good prognosis in the large bowel and anus, but was of no prognostic significance in the small bowel. A large regional variation in granuloma counts was observed from an average of 1 per section in the small bowel to 6 in the colon, 18 in the rectum, and 36 in the anus. Those patients with a long clinical history showed a low granuloma content. The findings are consistent with the view that the granuloma represents an adaptive mechanism for the removal or localisation of the causative agent of Crohn's disease.

Anus Diseases↗
PubMed1977

Fusion of macrophages following simultaneous attempted phagocytosis of glutaraldehyde-fixed red cells.

A model for the fusion of macrophages in areas of chronic inflammation in vivo has been presented which is derived from the associations of macrophage fusion in vivo and in vitro. It is suggested that in granulomata, where macrophages are closely packed in the presence of endocytogenic material, this material may on occasion attach simultaneously to more than one macrophage. Ensuing endosome margin formation may then lead to the endosome margins of one macrophage fusing with those of the other. By causing macrophages to phagocytose glutaraldehyde-fixed red blood cells in vitro under circumstances which more closely reflect in-vivo phagocytosis than the phagocytosis of the red cells by macrophages in a glass adherent monolayer, it has been shown that simultaneous attachment leads to macrophage fusion. It is suggested that giant cell formation in vivo in granulomata results from the process of simultaneous attempted endocytosis.

Animals↗
PubMed1977

The mechanism of fusion of hamster macrophages induced by antimacrophage serum.

The mechanism of antihamster macrophage serum (AHMS)-induced fusion of hamster macrophages has been investigated using the serum alone or conjugated to ferritin or Sepharose beads. It has been shown that AHMS attaches to and is interiorised by hamster macrophages. When macrophages are brought into contact before AHMS bound to their surface is interiorised, fusion results. The results strongly support the hypothesis that macrophage fusion is the consequence os simultaneous endocytosis of particles or colloids. It is suggested that a similar mechanism underlies the formation of macrophage giant cells in granulomata where closely packed macrophages attach to and interiorise the denatured materials produced in the chronically inflamed environment.

Animals↗
PubMed1977

Failure of altered macrophage surface to lead to the formation of polykaryons.

Experiments have been performed which were designed to test the hypothesis of Mariano and Spector (1974), that the granulomatous environment leads to changes on the macrophage surface which result in fusion with normal incoming macrophages. Macrophages of different species were cultured together and it was observed that there was no apparent interaction between the xenogeneic cells, and no fusion resulted. Macrophages were cultured both in vivo and in vitro for varying periods of time before exposing them to a population of fresh macrophages. Again, no fusion was noted. Finally, an alternative hypothesis, which would account for the findings of Mariano and Spector was tested. Macrophages were cultured in inflammatory exudates, both in vitro and in diffusion chambers already containing exudate, in vivo. Inflammatory exudates were found to have no effect on macrophage fusion, either in vivo or in vitro. On the basis of previous work it is suggested that macrophage fusion depends on simultaneous endocytosis and that this in turn depends upon a supply of fresh macrophages.

Animals↗
PubMed1977

Fusion of hamster macrophages induced by lectins.

The fusion of hamster peritoneal macrophages by lectins is described. The conditions under which this occurs are very similar to those previously reported using glutaraldehyde-fixed red cells and anti-hamster macrophage serum. Under conditions in which macrophages are brought into contact before interiorisation of surface-bound lectin, fusion results. It is suggested again that in granulomas, binding of endocytosable material to more than one macrophage results in giant cell formation by a mechanism of simultaneous interiorisation.

Animals↗
PubMed1977

Studies on the phagocytic capacity of macrophage polykaryons.

Following the demonstration by Chambers (1977a,b and c) that simultaneous attachment of macrophages to endocytogenic material in vitro leads to fusion, as analysis of the phagocytic potential of giant cells has provided evidence that the same mechanism is operating in macrophage polykaryon formation in vovo. Unlike previously proposed models for macrophage fusion, fusion by simultaneous attempted endocytosis is associated with the interiorisation of surface membrane during fusion. This has been shown to have occurred during glass coverslip-induced fusion in vivo. Evidence has also been presented that it is the endocytogenic material produced in the granulomatous environment which leads to fusion, not necessarily the simulaneous attempted endocytosis of the implanted foreign material.

Animals↗
PubMed1976

A case of primary lymphoma of the liver.

A case of primary malignant lymphoma of the liver is described. Presenting with epistaxis, he died in hepatic encephalopathy with an intractable bleeding post-bulbar duodenal ulcer.

Hepatic Encephalopathy↗