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Biomedical subjects

J F Burman

Publications and source records attributed to J F Burman.

At least 37 records · Page 2Linked to original sources
PubMed1985

Lysis of type-I collagen by squamous carcinomas of the head and neck.

Lysis of type-I collagen by squamous carcinomas of the head and neck has been studied in freshly excised tissues, xenografts and established cell lines. Investigations with 35 freshly excised tumours showed only low levels of active and total collagenase in both carcinomas and controls. A difference became apparent when the tissues were set up in explant organ culture where a significant (p less than 0.05) increase in total collagenase was found in 13/19 tumours compared with paired control tissues over a 4-week culture period. Two xenografts showed little capacity to lyse collagen in vitro and there was only limited evidence of an increase in total collagenase after explantation and growth in organ culture. Twenty tumour cell lines showed low levels of active collagenase. Total collagenase levels were significantly increased (p less than 0.05) in 4 of the cell lines derived from cancers of the tongue; this activity was sustained in subsequent passages. Six control fibroblastoid cell lines also showed low levels of active collagenase. Levels of total collagenase were consistently high, but this activity was transient and declined in subsequent passages. Co-cultivation experiments with II tumour-cell lines and 5 fibroblastoid cell lines showed some enhanced, synergistic destruction of collagen. Parallel experiments with supernatant media from the carcinoma and fibroblastoid lines showed no enhancement, indicating that intact carcinoma cells and fibroblastoid cells are required for synergistic collagenolysis to take place.

Animals↗
PubMed1985

Immunohistochemical localization of basement membrane type IV collagen in invasive and metastatic squamous carcinomas of the head and neck.

The immunohistochemical localization of basement membrane type IV collagen was investigated with a mouse monoclonal antibody in major surgical resections from 25 patients with invasive squamous carcinomas of the head and neck. Irrespective of site, size or stage of the disease, the 16 primary invasive tumours were almost completely surrounded by a layer of type IV collagen. Focal abnormalities were regularly present, consisting of thickening and aggregation of type IV collagen together with attenuation and segmental loss. Similar changes were seen in metastatic squamous carcinomas in 36 cervical lymph nodes. It is suggested that the probable formation of a normal basement membrane protein by these squamous carcinomas indicates the preservation of a normal function of differentiating squamous epithelia. The results indicate that a major basement membrane component, type IV collagen, continues to co-exist with invasive and metastatic squamous carcinomas.

Adult↗
PubMed1985

Absent ileal uptake of IF-bound vitamin B12 in vivo in the Imerslund-Grasbeck syndrome (familial vitamin B12 malabsorption with proteinuria).

A Syrian family is described with three children who had inherited selective vitamin B12 malabsorption associated with proteinuria. (Imerslund-Grasbeck syndrome). Although inherited the defect was apparently not present at birth. A third child had less severe vitamin B12 malabsorption, was not vitamin B12 deficient and had no proteinuria. Studies on two of the affected children with subcellular fractionation of the uptake of radioactive vitamin B12 by ileal tissue in vivo indicate a defect in the ileal receptors for IF-bound vitamin B12. These findings are different from the single in vitro experiment on a patient with this condition that has been previously reported.

Adolescent↗
PubMed1984

Sequential development of platelet, neutrophil and red cell autoantibodies associated with measles infection.

This study describes the development of autoimmune thrombocytopenia followed by autoimmune haemolytic anaemia in a Negro woman with measles. An IgM platelet autoantibody was detected using a fluorescent labelled antiglobulin technique. The thrombocytopenia resolved spontaneously, although the platelet autoantibody persisted and platelet survival remained shortened, suggesting a compensated thrombocytolytic state. An IgG granulocyte autoantibody was present transiently although the patient was never neutropenic. The haemolytic anaemia was due to an IgM cold autoantibody (anti-I), which was active up to 30 degrees C, and an IgG warm autoantibody, which was detectable only when she was severely anaemic. After an initial blood transfusion, the anaemia resolved and the red cell autoantibodies disappeared. The platelet, granulocyte and red cell autoantibodies were cell-specific and not a single cross-reacting antibody.

Adult↗
PubMed1983

Patterns and mechanisms of bone invasion by squamous carcinomas of the head and neck.

Patterns and mechanisms of local bone invasion by squamous carcinomas of the head and neck have been investigated. Detailed surgical pathology has shown that these tumors invade contiguous skeletal or metaplastic bone principally through an indirect process; the normal bone resorbing cells of the host (osteoclasts) are activated and erode bone in front of the advancing tumor edge. Tumor cells take over the destructive process when the osteoclast response has waned. These morphologic patterns have been reproduced in an in vitro model where calcium-45-labelled mouse calvaria, cocultured with a tumor for 3 days, are resorbed by osteoclasts. Freshly excised tumors, established tumor cell lines, and tumor xenografts release osteolysins in vitro which act as osteoclastic stimulants. They include both prostaglandins E2 and F2 alpha, and nonprostaglandin factors, and are derived from tumor cells and from the associated host stroma. Virtually all the tumors examined released osteolysins and resorbed bone in vitro independent of their site, size, degree of differentiation, and the presence or absence of clinical bone invasion.

Bone Neoplasms↗
PubMed1983

Further observations on mechanisms of bone destruction by squamous carcinomas of the head and neck: the role of host stroma.

Mechanisms of bone invasion by squamous carcinomas of the head and neck have been investigated using fresh tumours and established tumour cell lines in an in vitro bone resorption assay with 45Ca-labelled mouse calvaria. Fresh tumours regularly resorb bone in vitro. Activity is consistently reduced by indomethacin. The tumours release E2 prostaglandins (PGE2) in amounts sufficient to account for approximately 50% of the bone resorption observed. Small amounts of non-prostaglandin (indomethacin-resistant) osteolytic factors are also produced. Control non-neoplastic tissues show a variable capacity to resorb bone in vitro; PGE2 levels in these tissues may be related to their content of inflammatory cells. Tumour cell lines also resorb bone in vitro but, for most lines, activity is not significantly blocked by indomethacin and PGE2 levels are generally insufficient to account for the osteolysis observed. Non-prostaglandin bone resorbing factors thus predominate. It is concluded that most squamous cancers of the head and neck are osteolytic in vitro and release a mixture of prostaglandin and non-prostaglandin factors which stimulate osteoclastic bone resorption. These factors are derived from both neoplastic and stromal elements, and are "tumour-associated" rather than "tumour-specific". In vitro bone resorption and prostaglandin release does not correlate with pathological features of the tumour or with post-operative survival.

Animals↗
PubMed1981

Some mechanisms of local bone destruction by squamous carcinomas of the head and neck.

An in vitro osteolysis assay with 45Ca-labelled mouse calvaria has been used to investigate mechanisms of direct bone invasion by squamous carcinomas of the head and neck. Short-term (3-day) organ cultures of 8 fresh squamous carcinomas showed varying degrees of in vitro bone-resorbing activity which was blocked by indomethacin, an inhibitor of prostaglandin synthesis. Supernatant media from 6 established cell lines also induced bone resorption in vitro and evoked an osteoclastic response in the cultured calvaria. Osteolysis by supernatant media was not blocked by indomethacin in all the tumour-cell lines, and the production of non-prostaglandin osteolysins by the indomethacin-resistant lines is postulated. The two principal findings that emerge are: (1) Stimulants for osteoclastic activity are derived from both squamous-carcinoma cells and from host cells in the tumour stroma. (2) These stimulants are diverse. Indomethacin-sensitive agents, presumed to be prostaglandins, are most convincingly demonstrated in the fresh tumours. Indomethacin-resistant agents, presumably not prostaglandins, are more characteristic of the carcinoma cell lines.

Adult↗
PubMed1981

Severe megaloblastic bone marrow change associated with unsuspected mild vitamin B12 deficiency.

Two patients are reported who developed peripheral blood abnormalities and marked megaloblastic bone marrow change within eleven days of cardiac bypass surgery. The patients were shown to have unsuspected mild vitamin B12 deficiency due to Addisonian pernicious anaemia. The megaloblastic changes were presumed to be precipitated by the increased demand for erythrocytes and platelets after surgery.

Anemia, Pernicious↗
PubMed1979

Inherited lack of transcobalamin II in serum and megaloblastic anaemia: a further patient.

We have studied a patient, unrelated to the patients previously described, with inherited lack of the vitamin B12 binding protein Transcobalamin II. Severe haematological abnormalities were found within a few weeks of birth and responded to treatment with both vitamin B12 and folic acid. He was maintained in partial remission with such treatment until adolescence, except for a time in early childhood when folic acid alone was given and he suffered severe neurological deterioration. A the age of 18 years he was admitted to hospital because of convulsions; the deoxyuridine suppression test showed intracellular deficiency of B12 despite a normal serum B12 and normal haemoglobin concentration. His serum failed to promote the uptake of radioactive B12 by bone marrow cells, and analysis of serum B12 binding proteins demonstrated the lack of Transcobalamin II. Treatment with injections of 1000 micrograms of B12 three times weekly corrected the abnormality shown in the deoxyuridine suppression test; following this treatment, together with changes in anticonvulsive therapy, he remains healthy without occurrence of further convulsions, and is haematologically normal.

Adult↗
PubMed1978

Megaloblastic haemopoiesis in patients receiving nitrous oxide.

In a prospective study the incidence of megaloblastic change after ventilation with nitrous oxide for periods of up to 24 h has been determined and the cause of the altered D.N.A. synthesis studied with the deoxyuridine (dU) suppression test in 22 patients undergoing cardiac bypass surgery. 8 patients who received nitrous oxide and oxygen for 24 h had megaloblastic bone-marrow aspirates and abnormal dU suppression tests at the end of ventilation. 5 patients who received no nitrous oxide had normoblastic aspirates and normal dU suppression test. Of the remaining 9 patients, who received nitrous oxide during the operation only, 3 had abnormal dU suppression tests at 24 h. The abnormality revealed by the dU suppression tests was identical with that found in vitamin-B12 deficiency, but the patients' serum-B12 concentrations were normal. These results suggest that nitrous oxide interferes with the function of vitamin B12. Nitrous oxide oxidises vitamin B12 in vitro, and probably also in vivo when premixed 50% nitrous oxide and 50% oxygen mixture ('Entonox') is given.

Acute Disease↗
PubMed1977

Reversible C3 hypocomplementaemia in megaloblastic anaemia due to vitamin B12 deficiency.

Serum C3 and C4 levels have been determined in patients with Addisonian pernicious anaemia (PA) and megaloblastic anaemia due to vitamin B12 deficiency from other causes, before and after treatment, in order to study the interaction between vitamin B12 deficiency and complement and the role of complement in the pathogenesis of the gastric lesion of PA. C3 levels are significantly reduced in vitamin B12 deficiency and return to normal on treatment; C3 levels correlate with the degree of anaemia but not with serum vitamin B12 levels at diagnosis. C4 levels are normal. These observations suggest that the observed C3 hypocomplementaemia is not a consequence of immune mechanisms, but may be due to altered synthesis of C3 complement component.

Anemia, Macrocytic↗
PubMed1976

The serum vitamin B12 level: its assay and significance.

1. Low serum B12 levels can be measured with considerable precision by microbiological assay with the Euglena gracilis assay and B12 deficiency can be recognised with a high level of consistency by either the Euglena or L. leichmannii assays. Either method is ideally suited for the assay of large numbers of specimens. The Lactobacillus leichmanii technique requires preliminary extraction of protein and it has been suggested that this may be a source of inaccuracy. 2. The radioisotope dilution assay should be the ideal method of measuring B12 levels in small or moderate numbers of specimens for it is a simple method that can be carried out in any laboratory with suitable counting equipment. After many false starts the conditions required for accurate assay are now understood. Each of 40 to 50 radioisotopic dilution techniques that have been introduced claims to be capable of differentiating B12 deficiency from control subjects but the reported correlations between the actual levels found in the two different assays are variable and the levels may be much higher with some radioisotopic methods. 3. The subnormal serum levels which are found in pernicious anaemia with all these techniques indicate severe reduction of the liver B12 level. A low serum B12 level in other conditions has, in the absence of associated folate or iron deficiency, the same significance. If the fall in the serum B12 level is associated with folate or iron deficiency, the tissue B12 levels are usually reduced but not to the low levels found in B12 deficiency states. 4. In practice, a subnormal B12 level is a valuable pointer not only to unsuspected pernicious anaemia but also to other gastrointestinal or nutritional disorders. The significance of a fall in the B12 level can only be understood if its cause is defined by a full clinical and gastroenterological investigation. 5. Falsely low serum B12 levels are found under certain iatrogenic conditions and B12 levels may be normal in spite of cellular deficiency of B12 under the rare circumstances of pernicious anaemia being associated with chronic myeloid leukaemia or when there is deficiency of TC 2.

Anemia, Megaloblastic↗