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L M Cobb

Publications and source records attributed to L M Cobb.

At least 19 recordsLinked to original sources
PubMed1992

Obstructive jaundice associated with polysplenia syndrome in an older child.

Polysplenia syndrome includes malrotation and various forms of heterotaxy. Associated with this and malrotation are extrahepatic biliary anomalies. Actual obstruction, other than in associated biliary atresia, is extremely rare, and rarer still in older children. An 11-year-old girl presented with obstructive jaundice, malrotation, and heterotaxy, which were found in association with common bile duct anomalies and intermittent common bile duct obstruction. This case illustrates that the differential diagnosis of obstructive jaundice, even in older children, should include congenital anomalies, and that biliary anomalies should be considered in cases of malrotation and heterotaxy.

Abnormalities, Multiple↗
PubMed1992

Retention of misonidazole in normal and malignant tissues: interplay of hypoxia and reductases.

Tritiated misonidazole (MISO) was injected intravenously (iv) into mice bearing five different tumors. At 24 hr the tumors were removed for analysis of bound MISO, and at the same time three normal tissues were removed (liver, labial gland, and esophagus). The labial gland and esophagus were selected as representatives of sebaceous and stratified squamous tissues, respectively, tissues that in many parts of the body retain high levels of MISO. The tumors used were early transplant generations of spontaneous mouse tumors of mammary gland, lung, and liver. The levels (mean +/- SEM) of MISO at 24 hr for the five tumors and three normal tissues, expressed as percentage of the injected dose per gram of tissue were: A110 (0.03 +/- 0.007), A114 (0.103 +/- 0.04), A150 (0.09 +/- 0.005), A167 (0.037 +/- 0.012), A168 (0.122 +/- 0.0016), esophagus (0.507 +/- 0.09), labial gland (0.125 +/- 0.013), liver (0.11 +/- 0.004). Histochemical examination of the normal tissues showed reductase activity in all three. In the esophagus and labial gland, inhibition of the reaction by dicumarol indicated the likely presence of the reductase DT-diaphorase which, by 2-electron transfer, can be expected to reduce MISO to a reactive, locally-binding metabolite, even in the presence of oxygen.

Animals↗
PubMed1991

Spinal anesthesia reduces the hazard of apnea in high-risk infants.

General anesthesia in premature babies is associated with a significant risk of life-threatening apnea. Spinal anesthesia in the high-risk infant is simple, safe, and effective, but the incidence of apnea with its use has not been previously determined. The total absence of apnea in 84 high-risk infants suggests that surgery below the umbilicus under spinal anesthesia can safely be performed on an outpatient basis in preterm infants or babies with a history of apnea. Ketamine as an adjunctive agent adds no apparent risk. The technique is relatively easy, surgery is not compromised, and parental acceptance is high.

Anesthesia, General↗
PubMed1990

Tissue distribution of 14C- and 3H-labelled misonidazole in the tumor-bearing mouse.

The retention of labelled misonidazole (MISO) was measured in a range of normal tissues in the mouse 24 hr after the intravenous injection of [14C]MISO (ring labelled) and [3H]-MISO (side-arm labelled). For [14C]MISO the 24 hr tissue retention, in order of the highest to the lowest levels (excluding pathways of excretion), was esophageal epithelium, liver, foot pad, eyelid, lung, subcutaneous lung tumor (A110), esophageal wall, uterus, eye ball, blood, salivary gland, spleen, voluntary muscle, pancreas, inguinal fat. It was assumed that the 14C represented MISO metabolite(s) bound to macromolecules. An approximately similar pattern was observed for [3H]MISO, but a higher percentage of the injected activity per gram of tissue was retained, probably due to the presence of tritiated water in the tissues. It has generally been assumed that significant levels of MISO binding are restricted to hypoxic tissues, for example tumors, but the present results show that significant levels of binding can also occur in apparently normoxic tissues. The explanation is put forward that this binding may be due to local high levels of nitroreductase capacity.

Adenocarcinoma↗
PubMed1990

NAD(P)H nitroblue tetrazolium reductase levels in apparently normoxic tissues: a histochemical study correlating enzyme activity with binding of radiolabelled misonidazole.

Hack and Helmy's method for the histochemical identification of NAD(P)H nitroblue tetrazolium reductase activity was employed to pinpoint reductase activity in certain cells in the mouse. High activity was observed in the following: lower airway epithelium, liver (centrilobular zone), eyelid (meibomian and sebaceous glands), vulval gland and parotid gland (striated cells of intralobular ducts). All of these cells had previously been identified as sites of binding of the reactive metabolites formed from the enzymic reduction of misonidazole (MISO) (Cobb et al., 1989). It had previously been thought that MISO binding would only take place in significant amounts in hypoxic tissues (tumour and possibly liver) since in normoxic tissues oxygen should reverse the initial one electron enzymic reduction, thus preventing progressive reduction to reactive species. We suggest that the very high levels of reductase in the above listed, probably normoxic, tissues contribute significantly to the accumulation of bound reactive MISO metabolite(s).

Animals↗
PubMed1990

Distribution of pimonidazole and RSU 1069 in tumour and normal tissues.

The tritium-labelled analogues of pimonidazole and RSU 1069 were injected into mice bearing the KHT murine sarcoma which has a hypoxic cell fraction of approximately 10%. The distribution of activity at 24 h was recorded using autoradiography and measurement of tissue activity. Autoradiographs with both drugs showed high activity in particular cells within tumour, eye (melanin-associated cells), eyelid (Meibomian gland), liver (centrilobular area), skin (sebaceous gland and melanin), stomach (squamous area), footpad, oesophagus, labial gland, Zymbal's gland, preputial gland, parotid gland (intralobular ducts) and airway epithelium. These tissues had previously been identified as sites of binding of misonidazole. The measurement of total tissue radioactivity showed significantly higher activity in liver, eyelid (Meibomian gland), oesophageal lining, kidney and labial gland than was found in the tumour.

Animals↗
PubMed1990

The effect of the alpha-particle emitter astatine-211 in the mouse at the minimum toxic dose.

The radioactive halogen astatine-211 was injected into mice in an amount producing minimal toxicity. Histopathological examination of tissues at intervals between 3 d and 16 weeks showed the following changes: 1. Radiation-induced necrosis and progressive fibrosis of the thyroid gland. The gland was reduced to 25% of its original mass with only a few relatively normal follicles persisting. 2. A small, temporary, reduction in peripheral blood lymphocytes, platelets and red cells and a significant persistant increase in polymorphs. 3. Severe reduction in reproductive cells in the testis with some signs of recovery at 16 weeks.

Animals↗
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↗