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Biomedical subjects

A M Spence

Publications and source records attributed to A M Spence.

At least 73 records · Page 4Linked to original sources
PubMed1986

Synthesis, biodistribution, and autoradiography of radiolabeled S-2-(3-methylaminopropylamino)ethylphosphorothioic acid (WR-3689).

35S- and 3H-labeled S-2-(3-methylaminopropylamino)ethylphosphorothioic acid (WR-3689) have been synthesized in our laboratory and used to study organ and cellular level distribution in C3H/Km mice bearing RIF-1 tumors. Tissue biodistributions obtained with 35S-WR-3689 showed that blood levels peak at 15 min postinjection and decline gradually over 60 min. At 30 min after drug injection the highest uptake is in kidney and submandibular salivary gland, with lowest levels in brain and moderate to low levels in the RIF-1 tumor, comparable to levels in skin and muscle. High resolution diffusible substance autoradiography with 3H-WR-3689 reveals a homogenous distribution of label over cells in liver and lung and nonuniform distribution of silver grains over the cytoplasm of cells in the kidney cortex, parotid and submandibular salivary glands, and small intestine. There are no indications of preferential nuclear location of label from protective drug in any tissue. Correlations of biodistribution and autoradiography data with measures of radioprotection in different tissues will be useful in interpreting mechanisms of radioprotection with this phosphorothioate.

Amifostine↗
PubMed1986

Quantitative autoradiography using a personal computer.

A video digitizing system based on an Apple II personal computer has been developed for use in quantitative autoradiography. The selection process of an acceptable video camera, an illumination system, and the functions provided in the software are discussed. This system is in routine use and has been duplicated by several other laboratories.

Autoradiography↗
PubMed1985

Biodistribution of the radioprotective drug 35S-labeled 3-amino-2-hydroxypropyl phosphorothioate (WR77913).

3-Amino-2-hydroxypropyl phosphorothioate (WR77913), a less toxic phosphorothioate radioprotector than WR2721, has been labeled with 35S. The biodistribution of a radioprotective dose of 800 mg/kg was determined in C3H mice bearing RIF-1 tumors as a function of time after intraperitoneal injection and was expressed as percentage injected dose/gram (% ID/g). Levels of 35S in the blood peaked 10 min after injection, and radioactivity in most tissues was highest at 15 min. Label in most tissues declined markedly between 15 and 60 min, but in gut, salivary glands, tumor, and brain, the levels of radioactivity remained quite stable over 1 hr. At 30 min after injection the highest levels of labeled drug were found in submandibular salivary glands, gut, and kidney, with the lowest level in brain. Tumors had approximately the same amount of label as blood, muscle, skin, and esophagus. Two principal differences between the distribution of label from WR77913 and WR2721 were defined. Although blood levels of 35S-WR2721 also peaked 10 min after injection, the 10-min blood levels achieved for WR77913 were more than fourfold greater than those attained by WR2721. Maximum levels of WR2721 occurred in most tissues 30 to 60 min after administration of the drug, compared to 15 min for WR77913. The basis for these differences remains to be determined, but these results suggest that the optimum interval between administration of WR77913 and irradiation may be shorter than for WR2721.

Amifostine↗
PubMed1984

Analysis of S-35 labeled WR-2721 and its metabolites in biological fluids.

Studies with WR-2721 and related compounds have been hindered by the lack of a suitable assay for the drug and its major metabolites. We have developed a chromatographic method which requires no derivatization for the separation and detection of WR-2721, the free thiol, its symmetrical disulfide and other mixed disulfides. Our procedure involves ion-pairing for separation of ionizable compounds by causing polar molecules to become more lipophilic and hence separable using reverse phase HPLC. Detection is based upon liquid scintillation counting of S-35 incorporated during the synthesis of the parent compound. This method requires no pre-column preparation of samples and, by detecting the S-35 label, eliminates the chance that a coeluting species could interfere with detection, as might occur with post-column derivatization. Chromatography was done using a 10 micron C8RP column and 35% MeOH/65% 0.0113M NaH2PO4, 0.005 M hexanesulfonate, pH 5.9, flowing at 1 ml/min. Half-minute fractions were collected into scintillation vials for counting. Retention volumes for the various compounds were: column breakthrough (3.5 ml), WR-2721 (4.5 ml), WR-1065 (9 ml), and WR-33278 (24 ml). This analytical technique employing radiotracers can be used to study radioprotective mechanisms by time dependent measurements of the tissue distribution and chemical form of labeled drug. Such chemical information can then be correlated with biological measures of radiation protection.

Amifostine↗
PubMed1981

Scanning and transmission electron microscopy of cloned rat astrocytoma cells treated with dibutyryl cyclic AMP in vitro.

Two cloned rat astrocytoma cell lines, 36 B-10 and 40 A-2, maintained in vitro were treated with 1 mM dibutyryl cyclic AMP. This treatment induced arborization of cellular processes and rounding-up of cell bodies in both cell lines and was associated with increased microvillous development in 40 A-2. There were not detectable concomitant changes in either (a) the quantity or organization of microtubules or 80-100 nm microfilaments, or (b) the intensity of glial fibrillary acidic protein indirect immunofluorescence staining.

Animals↗
PubMed1981

Combined cyclotron fast-neutron and BCNU therapy in a rat brain-tumor model.

The combination of cyclotron fast-neutron radiotherapy with BCNU chemotherapy was compared to 137Cs gamma photon radiotherapy combined with BCNU in the 36B-10, F-344 rat-transplanted glioma model. Radiation and drug treatments were administered 7 to 8 days after intracerebral tumor implantation. Increase in animal survival time was used as the measure of the effectiveness of various treatment schedules. Single-dose neutron or gamma radiotherapy was tested on Day 7 over the ranges 0 to 900 rads and 0 to 2000 rads, respectively. This therapy produced increases in mean survival times up to 70% at the highest radiation doses. When BCNU (10 mg/kg body weight) was administered intravenously on Day 8, 1 day following radiotherapy, mean survival times were increased by an additional 35% to 50%, irrespective of the dose or type of irradiation. In contrast, by using the same radiation and drug doses but scheduling combined therapy trials so that BCNU was administered 1 hour before either neutron or gamma irradiation on Day 7, there was enhancement of the radiation effect by BCNU. Under these conditions, the maximum enhancement of the mean survival time was 70% to 75% in neutron-treated animals and 120% to 150% in gamma-treated animals. Treatment with BCNU 1 hour before or 1 day after neutron irradiation proved to be no more effective in proving the survival time of tumor-bearing animals than the drug similarly combined with conventional gamma irradiation.

Animals↗
PubMed1980

Cerebral embolism in Libman-Sacks endocarditis.

Left homonymous hemianopia, hemiparesis, left-body clonic seizures, and progressive deterioration of consciousness complicated the clinical course of a 57-year-old woman with systemic lupus erythematosus (SLE). Autopsy documented the presence of multiple brain infarcts and cerebral arterial emboli that originated from the verrucae of Libman-Sacks endocarditis. Clinicians and pathologists should consider this unusual vascular mechanism of cerebral injury in patients with SLE who develop strokes.

Brain↗
PubMed1979

Nitrogen digestion in sheep given poor-quality indigenous hill herbages.

1. In two experiments, the sites of digestion of non-ammonia nitrogen (NAN) and the amounts of urea N recycled to the rumen were measured in mature wether sheep given diets of indigenous hill herbage (Agrostis-Festuca and heather). 2. Duodenal and ileal flow values were obtained using 103Ru-phenanthroline and 51Cr-EDTA markers in animals prepared with simple (T-shaped) cannulas. Amounts of urea N recycled to the rumen were estimated from measurements of the transfer of plasma urea carbon into rumen bicarbonate and the production rate of rumen bicarbonate using 14C-labelled urea and bicarbonate respectively. 3. The flows of NAN at the duodenum and ileum were linearly related to the intake of herbage (P less than 0.001). There was a net gain of non-ammonia N anterior to the duodenum on both diets (at an intake of 460 g organic matter (OM)/d, 3.7 g NAN/d on Agrostis-Festuca and 3.3 g NAN/d on heather). 4. Net digestibility of NAN entering the small intestine was within a normal range on the Agrostis-Festuca (0.58 at 460 g OM intake) diet but low on the heather diet (0.43 at 460 g OM intake). 5. It was calculated that at 460 g OM intake only 0.9 and 1.1 g/d respectively of the duodenal NAN on the Agrostis-Festuca and heather diets could have been derived from urea-N recycled to the rumen. Thus 2.8 g and 2.2 g/d had to be accounted for as non-urea endogenous NAN.

Animal Feed↗
PubMed1979

Lactic dehydrogenase in ethylnitrosourea-induced rat gliomas. Total lactic dehydrogenase activity and isozymes in autochthonous gliomas and cloned transplantable astrocytomas.

Total lactic dehydrogenase (LDH) levels and LDH isozyme patterns were measured in homogenates of 12 autochthonous ethylnitrosourea-induced rat gliomas and 5 cloned rat astrocytoma cell lines maintained in culture and transplanted to brain or flank sites in syngeneic hosts. The total LDH values in the autochthonous gliomas did not differ appreciably from normal brain controls, but the proportions of the cathodal isozymes, LDH4 and LDH5, were increased to a degree similar to that reported by others in spontaneous human malignant astrocytic gliomas. The cloned astrocytoma lines, both in vitro and in transplants at intracerebral or subcutaneous sites, commonly demonstrated elevated total LDH values and, without exception, showed a preponderance of isozymes, LDH4 and LDH5, that was distinctly more marked than in autochthonous tumors. Especially in cultured and transplanted rat gliomas, these findings suggest that astrocytic tumor cells maintain energy supplies by utilizing anaerobic glycolysis in relatively hypoxic environments. These data further underscore the need to develop laboratory brain tumor models for use in therapy trials that not only retain the convenience and predictability of transplantable gliomas but also approximate closely the metabolic properties of human spontaneous gliomas.

Animals↗
PubMed1978

Scanning electron microscopy of cloned astrocytic lines derived from ethylnitrosourea-induced rat gliomas.

Six cloned astrocytoma cell lines derived from four ethylnitrosourea-induced F-344 rat gliomas were viewed by scanning electron microscopy in vitro, and two were examined in vivo after transplantation to the intracerebral site. All clones consisted of stellate cells that were reasonably homogeneous within individual glioma lines. Cell membrane features common to all tumor lines included microvilli, blebs, ruffles, and miniridges, mainly confined to perikarya, and filopodia emanating chiefly from cell processes. One cell line demonstrated a profuse, and another cell line a moderate, degree of microvillous development and cell surface roughening, which in one tumor correlated with rapid in vitro cell doubling time. Both cell lines maintained these topographical appearances when transplanted into brain. These results extend the SEM observations of astrocytomas, particularly in cloned ethylnitrosourea-induced tumors in rats. The confirm that distinct variations in cell membrane topography do occur among tumors of this type, probably irrespective of their origin in humans or rats, and irrespective of their mode of genesis as spontaneous, chemically-induced, or virally-induced tumors.

Animals↗
PubMed1978

The Ommaya reservoir: newly recognized complications and recommendations for insertion and use.

Two of 27 patients treated with intraventricular chemotherapy via an Ommaya reservoir developed unusual life-threatening complications attributable to the reservoir. In one patient treated for meningeal Burkitt's lymphoma, the cause of death was a large mass of tumor cells growing around the cannula. Also the tip of the cannula was found in the contralateral cerebral peduncle. In the other patient, the tip of the cannula apparently perforated the ventricular wall postoperatively and migrated into the contralateral thalamus. In both cases evidence for methotrexate-associated leukoencephalopathy was present at autopsy. Based on the experience with these two patients, we offer specific recommendations for reservoir insertion and use.

Adult↗
PubMed1978

A comparison of the voluntary intake and digestion of a range of forages at different times of the year by the sheep and the red deer (Cervus elaphus).

1. Comparisons were made between castrated male Scottish Blackface sheep and red deer (Cervus elaphus) of voluntary forage intake (VFI), digestibility and the mean retention time (MRT) of a particulate-phase marker (103Ru-phenanthroline) in the alimentary tract, when a range of forages: dried-grass pellets, chopped dried grass, fresh-frozen Agrostis-Festuca spp. and heather (Calluna vulgaris, L. Hull) were given at different times of the year. 2. On both the dried-grass-pellet and chopped dried-grass diets the red deer and sheep ate similar quantities. Both species had a higher VFI of dried-grass pellets in July than in November. The sheep digested the dried-grass-pellet diet better than the red deer and this was associated with a longer MRT of the particulate-phase marker in the alimentary tract. 3. The VFI of Agrostis-Festuca spp. and heather by the red deer was twice that of the sheep. The VFI of heather by the sheep increased by 32% between January and April, and the VFI of both the Agrostis--Festuca spp. and heather diets by the red deer increased by 65--70%. The sheep digested the Agrostis--Festuca spp. better than the red deer but the red deer digested the heather slightly better than the sheep. MRT of the particulate-phase marker was greater for the sheep than for the red deer on both the diets. The digestibility and MRT of both diets in the red deer did not decrease with the seasonal increase in VFI, suggesting a possible hypertrophy of the alimentary tract.

Animal Feed↗