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L M Cobb

Publications and source records attributed to L M Cobb.

At least 37 records · Page 2Linked to original sources
PubMed1990

Nonuniformity of tumor dose in radioimmunotherapy.

The conventional approach to calculating tumor radiation dose from internally administered radioisotopes is by the MIRD schema. The raw input data for such dose calculations is obtained by immunoscintigraphic methods, PLANAR or SPECT imaging. Limitations in the spatial resolution of these techniques can lead to a considerable underestimate of the gross variation in tumor dose. The use of radiolabeled monoclonal antibodies for therapy can result in large nonuniformities in tumor dose. This paper discusses how antibody distribution can influence the energy deposition in the nuclei of target cells. Heterogeneity of antibody binding will lead to an expected decrease in the effectiveness of the radiation delivered. However, enhanced cell killing is possible if the radiolabeled Ab binds to the cell surface membrane and may be further enhanced if the Ab is internalized. Calculations are presented for two cases: (a) a three-dimensional random packing arrangement of cells as a model of the astructural nondifferentiated form seen in some tumors, and (b) differentiated carcinoma of the colon with the cells in tubules. Results for the magnitude of the mean energy deposition to individual cell nuclei from: (a) cell membrane bound 211At, 199Au, 131I, and 90Y-labeled Abs, and (b) a uniform distribution of these sources, as a function of internuclear distance for the two histologies are presented. Energy deposition in tumor cell nuclei from membrane bound radiolabeled antibody may be several times greater than estimated with the assumption of a uniform source distribution.

Adenocarcinoma↗
PubMed1989

Intratumour factors influencing the access of antibody to tumour cells.

The histological structure and biochemical composition of human tumours is very varied, as is the structure of the microvascular network. It can be expected, therefore, that the extravasation, diffusion and convection of macromolecules will vary between tumours - and also between areas in the same tumour. The major factors influencing the intratumour distribution of injected antibody are reviewed and an attempt made to identify the tumour types in which therapeutic antibody, with or without a cytotoxin, will distribute most effectively.

Animals↗
PubMed1989

Distribution of injected monoclonal antibody in lymphoma-infiltrated spleen.

Specific and non-specific antibody was injected into mice with lymphoma-infiltrated spleens in order to assess the distribution with both time and with extent of tumour infiltration. The specific antibody (MRC OX7) bound to the Thy 1.1 antigen on the lymphoma cells (A120). There was evidence that the diffusion of MRC OX7 deeply into the tumour was hindered by competitive binding to the tumour cells immediately surrounding the supplying blood vessels. In some circumstances this situation persisted to 24 h, after which time the antibodies were being cleared from the host in significant amounts.

Animals↗
PubMed1989

Autoradiographic study of tritium-labeled misonidazole in the mouse.

The localization of tritiated misonidazole metabolites in a number of normal tissues in the mouse is reported from autoradiography. The labeled misonidazole was injected at 750 or 75 mg/kg body weight (Rel. Sp. Act. 74 and 740 MBq/mg respectively). The grain count ratio, parenchyma:stroma, for selected tissues was: liver (centrilobular zone) 13; meibomian gland (acini) 68, (duct) 116; esophagus (keratinized layer) 61; enamel organ 17. It is concluded that there are a number of tissues which will accumulate MISO metabolites although they may not all be hypoxic.

Animals↗
PubMed1989

Microscopic distribution of misonidazole in mouse tissues.

Mice were injected with tritiated misonidazole (750 mg/kg-1), killed after 24h and the excised tissues prepared for autoradiography (ARG) to identify sites of accumulation. The previously reported high grain count associated with bound misonidazole metabolite(s) was observed in the liver. The ratio of grain count in the emulsion above the centrilobular hepatocytes to the count over connective tissue (stroma) was 12. A higher count ratio for 'target' cells to stroma was observed in the following cells/tissues: meibomian gland (ducts 110, acini 65), oesophagus (keratinised layer 60), incisor (enamel organ 17), nasal septum (subepithelial glands 13). For some of these tissues the explanation might appear to lie with localised hypoxia, but for others which were probably normoxic there is as yet no obvious reason for these findings.

Animals↗
PubMed1988

Relative concentration of astatine-211 and iodine-125 by human fetal thyroid and carcinoma of the thyroid in nude mice.

The concentrations of 211At and 125I were measured in various tissues in nude mice bearing xenografts of human thyroid tissue (fetal and malignant). The relative concentration of the two halogens was obtained at 4 and 24 h after injection. Samples were taken of the host blood, muscle and thyroid gland and the grafted tissues. The mouse thyroid concentrated 125I more efficiently than 211At but the human grafts concentrated both halogens about equally.

Adenocarcinoma↗
PubMed1988

Toxicity of astatine-211 in the mouse.

The toxicity of the alpha particle emitting halogen astatine-211 was examined in male and female mice. Pathological changes were seen in mice killed at 14 days and/or at 56 days following a single injection of 61 kBq211 At per g body weight. The tissues affected, in order of severity were: spleen, lymph nodes, bone marrow, gonads, thyroid, salivary glands and stomach.

Animals↗
PubMed1987

Treatment of the murine lymphoma A31 with intravenous, sterilized, 114mIn-loaded A31 cells.

The effect on a mouse B-cell lymphoma (A31) of intravenously (i.v.) injected, sterilized, A31 lymphoma cells loaded with [114mIn]oxine was examined. The treatment of the B-cell lymphoma was started 14 days after the i.v. injection of 10(2) viable cells. The [114mIn]oxine-bearing gamma-ray sterilized A31 cells were injected at two dose levels either with 37 kBq on days 15, 22 and 27 (total dose 110 kBq) or 74 kBq on days 15, 16, 17, 22 and 27 (total dose 370 kBq). The smaller amount (110 kBq) of 114mIn activity did not extend the survival of mice when compared with non-treatment controls but the greater amount (370 kBq) produced a significant extension in survival. This survival time was longer than that produced by 370 kBq [114mIn]oxine without carrier cells, lethal total body irradiation (with bone marrow rescue), splenectomy at day 14 or a single injection on day 14 of a maximum tolerated dose of vincristine sulphate. The increase in survival time was thought to arise mainly from 114mIn held by spleen macrophages. The accumulated spleen dose by 7 days after the fifth of the five injections of 74 kBq was 167 Gy. At this dose level the spleen was hypoplastic and the red cells, white cells and platelets in the peripheral blood were severely, though not permanently, suppressed.

Animals↗
PubMed1987

The central venous anatomy in infants.

A study of 21 consecutive autopsy specimens of infants less than one year of age and weighing less than 6 kilograms was performed to determine the topographic anatomy and regional relationships of the central venous anatomy. This anatomy was compared with 14 additional autopsies performed upon older children. There was no significant difference in diameter between the internal jugular and subclavian venous system, on either the right or left side. In the infant, the right and left subclavian veins entered the central system at an acute angle. The left innominate vein joined the right innominate vein at a right angle. These angulations become less acute after one year of age. This adult configuration may account for the relative ease of central venous cannulation through the percutaneous subclavian approach in the older patient. In contrast, the external and internal jugular veins entered centrally in almost a straight line even in the infant. The findings of this study suggest that the internal and external jugular veins should be considered as safe and reliable portals for percutaneous entry into the central venous system in infants. In the infant less than one year of age, the difficult patient (for example, those with thrombocytopenia or severe pulmonary failure) or when the surgeon is less familiar with the infraclavicular approach, the veins of the neck may, in fact, be the site of choice. Additionally, we believe that a surgeon should not hesitate to switch to the internal or external jugular site after unsuccessful attempts at percutaneous entry into the subclavian vein.

Brachiocephalic Veins↗
PubMed1986

The influence of prior total body irradiation on the tissue distribution of mouse lymphoma/leukemia.

The effect of a single dose of 10 Gy X rays on the distribution of subsequently injected mouse lymphoma/leukemia cells was studied. The organ distribution of an acute myeloid leukemia (A46) was not affected by prior (90 days) administration of 10 Gy X rays. A T-cell lymphoblastic lymphoma/leukemia (A55) and a B-cell lymphoblastic lymphoma/leukemia (A31) produced enhanced infiltration of the lung when 10 Gy of total body irradiation (TBI) was given 90 days before the tumor cells. The infiltration was predominantly in the peribronchiolar and perivascular spaces. Enhancement was not seen in any tissues other than lung. The possibility is raised that in those acute lymphoblastic leukemia patients whose treatment includes TBI, residual circulating cells may be encouraged to infiltrate the lung.

Animals↗
PubMed1986

Characterisation of a new murine B cell lymphoma.

The characterisation of a new murine B cell lymphoma, A31, is described. Histopathological examination of passaged tumour indicates that initial infiltration occurs in the spleen, lymph nodes, Peyer's patches and liver, while in the terminal phase the bone marrow, gonads and occasionally the central nervous system become involved. The terminal spread is coincidental with the leukaemic phase in the tumour. The tumour cells show typical B cell characteristics in vitro. These include surface immunoglobulin (Ig) of mu, kappa isotype, surface Ia, Thy-1 negativity and an increased uptake of tritiated thymidine following incubation with lipopolysaccharide. A31 cells secrete low levels of IgM into the tissue culture fluid. Short-term culture produced only 100 ng IgM per 10(7) cells over 8 h and no tumour-associated monoclonal band could be detected in the serum of tumour-bearing mice. Chromosomal karyotypes of A31 cells gave model numbers 2n=40 normal, and 2n=41, with partial trisomy of chromosome 2, and trisomy of 17. There was loss of a chromosome 6 and the Y chromosome, together with the translocation of part of an 11 to one of the two unidentified marker chromosomes. The responses of lymphoma-bearing mice to therapeutic levels of cyclophosphamide and vincristine sulphate and also to whole body X-radiation are illustrated. This tumour may help in unravelling the complex biology of B cell lymphoma and because of its low level of Ig secretion, be of particular value in experimental immunotherapy.

Animals↗
PubMed1986

Radioimmunotherapy of malignancy using antibody targeted radionuclides.

Antibodies directed against tumour associated antigens provide a means for delivering preferentially cytotoxic radionuclides to the cells of primary and secondary tumours. The factors that influence the effectiveness of the radiation in the tumour compared with its effect on the radiosensitive normal tissues include the specificity of the antibody, the distribution of targeted energy within the tumour and the host's response to the injected foreign antibody. Recently some encouraging results from clinical trials of radioimmunotherapy have been reported in the literature. There is a continual search for more avid and specific antibodies, and the techniques of genetic engineering are being applied to the problem of reducing the antigenicity and mass of the carrier antibody. The improved efficiency of the labelled antibody needs to be supplemented by an identification of those tumours most likely to respond to this form of therapy.

Animals↗
PubMed1986

Intestinal perforation due to blunt trauma in children in an era of increased nonoperative treatment.

Over the past decade, nonoperative management of most pediatric blunt abdominal trauma has emerged as accepted practice. It is possible that treatment of associated hollow visceral disruption might be missed or delayed because of this nonoperative approach. In a review of all cases of intestinal perforation from blunt trauma seen over the past 6 years, we found 12 cases of intestinal disruption in more than 600 cases of significant blunt trauma. Child abuse caused eight cases and four were motor vehicle related (MVR). Seven of eight battered children had a delay of more than 48 hours from injury to hospital presentation. Three of four MVR patients had an 18-hour delay from injury to operation. Ten of 12 patients survived. The two children who succumbed were both battered and were moribund and unstable when first seen and failed to respond to aggressive stabilization and surgery. Serial physical examinations, contrast radiographic studies, and peritoneal lavage were the most helpful diagnostic modalities. There were no significant complications and no patient required more than one operation (except for ostomy closure). All surviving patients are well at followup and seven of ten have been followed for more than 3 years; two are not yet 1 year from surgery and one is lost to followup. Several principles have emerged from this review: 1) motor vehicle trauma and child abuse are the major etiologic factors in childhood blunt trauma; 2) accurate and rapid diagnosis of intestinal perforation in children is difficult; 3) recovery in the presence of stable vital signs can be expected, even with the long delays; and 4) abused children must be carefully evaluated for abdominal trauma.

Accidents, Traffic↗
PubMed1984

Long-term survival of adult human lung growing subcutaneously in congenitally athymic nude mice.

Small airways and alveoli from normal adult human lung were implanted subcutaneously in nude mice. When the tissue was removed at 16 months the airway had formed into fluid-filled epithelium-lined cysts. The epithelial lining was typical of small and terminal airways, except where intracystic pressure had apparently flattened the epithelium. Ultrastructural examination of the columnar ciliated cells revealed supranuclear accumulations of granules, some irregular in outline and others lamellated. The nonciliated secretory cells closely resembled serous cells. The alveoli survived less well. Although partly expanded by secretion, probably from the type II pneumonocytes, the walls were frequently thickened by an increase in connective tissue, and there were few capillaries. The cells for which there was positive identification, or good presumptive evidence, for being of human type were columnar ciliated cells, serous cells, smooth muscle, cartilage, mast cells, type II pneumonocytes, and basal epithelial cells; the latter two cell types were apparently proliferating. The results show that human airway can be maintained long term as a xenograft.

Aged↗