Subcutaneous implantation of double velour Dacron into the mouse: infiltration and angiogenesis

An experimental system has been devised for the study of tissue reaction to the subcutaneous implantation of double velour Dacron into the mouse. Animals were given Dacron implants for 3 months, 2 months, 1 month, 3 weeks, 2 weeks and 1 week and the infiltration of the material was assessed using light-microscopy, autoradiography, electron-microscopy and angiography. It was found that the implants became extensively infiltrated with host cells, the response being at a peak in the second and third weeks post-implantation. Macrophages were seen from an early stage, fibroblasts were numerous, and new capillaries penetrated the material. The observations, especially the angiogenic response, are discussed with reference to published information on the actions of the cell types that were seen, in particular the macrophage.     

INVOLVEMENT OF PHOSPHOPROTEIN PHOSPHATASE 1 IN COLLAGEN-PLATELET INTERACTION

The binding of type I collagen to its receptor initiates platelet aggregation, but the relationship of the receptor to other signal transduction components is not yet established. Correlation of platelet aggregation and anti-type I collagen receptor antibody immunoprecipitation of type I collagen treated [³²PO4]-labeled platelets showed that there are two phosphoproteins (M_r 53 kDa and 21 kDa) that coprecipitated with the 65 kDa platelet type I collagen receptor. In the present investigation, we have identified one of the phosphoproteins. A soluble component the 100,000×g supernatant fraction of 53 kDa protein is recognized by polyclonal anti-PP1 antibody. The activity of the precipitated phosphatase is inhibited by okadaic acid and inhibitor 1, suggesting that it is protein phosphatase 1 (PP 1). Phosphorylation decreases PP 1 activity as was found with [³²PO4]-phosphorylase b as the substrate. The immunocoprecipitation of the type-1 collagen receptor and PP 1 inot the result of cross reactivity of the anti-type I collagen receptor antibody with the PP I protein. These results indicate that the platelet type I collagen receptor, PP 1, and unidentified 21 kDa protein are in close association with the platelet type I collagen receptor upon the binding of type I collagen by the receptor. Copyright © 1996 Elsevier Science Ltd     

Developing community occupational therapy services in Canada.

International trends in health care point to increasing development of community services. However, the majority of occupational therapists work in institutional settings. A study, between 1985 and 1987, defined and created a profile of existing community occupational therapy services across Canada, and identified the processes and strategies which led to the development of these services. One hundred and eighty nine (189) services, including home care, other salaried services, and private or consulting services were identified. A national sample of community occupational therapy program developers described processes and strategies from which the author suggests a general "ripple effect" strategy to enhance the occupational therapy contribution to the community.     

Factors affecting serotonin uptake into human platelets

Because of complexities in platelet serotonin uptake dynamics, we studied the influence of the time of day and year as well as the subject's age on uptake parameters. While the assay itself was quite reproducible, and the kinetic parameters of 5 HT uptake were stable over a few days, at a given time, within an individual, the variance was quite large when samples from different times of the day or year or from different individuals were compared. An inverse relationship between V _max (moles/cell number/time) and platelet number was found in data from a group of individuals, suggesting regulation of V _max not at the level of uptake capacity per cell, but in a manner that somehow takes into consideration the number of platelets in the subject's plasma. Indeed, expressing V _max in a new way (called total V _max), not based on V _max per cell or per 10⁷ cells but for the total number of platelets in the volume of PRP used, greatly reduced the scatter in the between-individuals and across-time data. While V _max (moles/cell number/time) exhibited only a trend toward reduction with age, for example, the decline in total V _max with subject age was statistically significant. It is suggested that total V _max (moles/time) may be a more physiologically relevant expression for an uptake function than V _max (moles/time/cell number).     

Interaction of 2-halogenated dATP analogs (F, Cl, and Br) with human DNA polymerases, DNA primase, and ribonucleotide reductase

Recently, 2-halogenated deoxyadenosine analogs (F, Cl, and Br) have been shown to have antitumor activity. These analogs are phosphorylated by cells and are believed to exert their cytotoxic action at the nucleoside triphosphate level. In this work the interaction of these nucleoside triphosphate analogs with potential targets, such as DNA polymerase alpha, beta, and gamma, DNA primase, and ribonucleotide reductase was examined in detail. All of these compounds competitively inhibited the incorporation of dAMP into DNA by DNA polymerase alpha, beta, or gamma. F-dATP was able to completely substitute for dATP using DNA polymerase alpha and gamma, but not with DNA polymerase beta. Cl-dATP and Br-dATP substituted poorly for dATP using DNA polymerase alpha and beta. Extension of a 32P-labeled primer by DNA polymerase alpha, beta, or gamma on a single-stranded M13 template showed that these compounds were incorporated into the 3' end of the growing DNA chain and that elongation beyond the incorporated analogs was significantly retarded for Cl-dATP and Br-dATP using either DNA polymerase alpha or beta. DNA primase using poly(dC) as template was inhibited by these compounds at a concentration 4 to 5 times greater than that required for 2-F-araATP. The 2-halogenated dATP analogs were potent inhibitors of ADP reduction by ribonucleotide reductase. In conclusion, the cytotoxic action of 2-Cl-deoxyadenosine and 2-Br-deoxyadenosine may partially be mediated through the mechanism of "self-potentiation," by depression of the deoxynucleoside triphosphate pools due to inhibition of ribonucleotide reductase, which would facilitate their incorporation into DNA and result in the inhibition of DNA synthesis.     

Aspects of three dimensional reconstruction for a multi ring positron tomography

An important feature of multi ring positron tomographs is the inter plane septa, the purpose of which is to reduce random and scattered coincidences. In general, such septa also eliminate the coincidence lines of response between pairs of detectors more than one ring apart. The operation of a camera without septa must result in an increase not only in the true coincidence rate, but also in the singles, and therefore in the dead time and randoms rate, and in the scattered coincidences. A configuration option in the coincidence hardware of the 8 ring, 15 slice ECAT 931/08-12 enables a full set of 64 sinograms to be acquired when the septa are removed. The detector normalisation and transmission data for studies with the septa out can be obtained using a rotating pin source. To take maximum advantage of the additional signal, the emission data must be reconstructed using a fully three dimensional reconstruction algorithm. This paper presents an analysis of some phantom studies acquired without septa and reconstructed in three dimensions. The results are compared with data acquired with septa for the same phantoms imaged under similar conditions. It is found that, with the septa removed, the signal to noise for a uniform, 20 cm diameter cylinder improves by a factor of 2.8 in the centre of the field of view, whereas in regions distant from the centre in the axial direction, the signal to noise decreases due to the increase in scatter and randoms. An improvement in signal to noise is observed in 6 cm of the 10 cm axial length of the tomograph.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)     

2-deoxy-D-glucose inhibits the antitumor effects of α-difluoromethylornithine on the growth of colon cancer in vivo

Summary The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to inhibit the growth of certain cancers. -Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the ratelimiting enzyme in polyamine biosynthesis. DFMO has been shown to inhibit cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on MC-26 mouse colon adenocarcinoma tumors growing in vivo. Twenty-eight male Balb/c mice were inoculated with 250,000 MC-26 cells, and then randomized into four groups of 7 each: group I served as control; group II received DFMO (3% in drinking water); group III received 2-DG (500 mg/kg/d IP); group IV received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation. MC-26 tumor area was reduced 73% by DFMO compared to a 24% reduction caused by 2-DG. The tumor weight was reduced 80% by DFMO and 52% by 2-DG. The tumor contents of DNA, RNA, and protein were significantly reduced by DFMO but not 2-DG. The tumor concentration of the polyamines putrescine and spermidine were reduced by DFMO alone or combined with 2-DG while spermine levels remained unchanged. 2-DG alone did not alter polyamine levels. These results indicate that both 2-DG and DFMO, when added as single agents, inhibit tumor growth. However, the addition of 2-DG to the DFMO regimen inhibited the antitumor effects of DFMO. Survival studies performed on MC-26 cells in vitro corroborated the antagonisms between DFMO and 2-DG that were shown in vivo.Dr. Upp was awarded a fellowship grant from the American Cancer Society Texas Division.     

Dual effects of spinally delivered 8-bromo-cyclic guanosine mono-phosphate (8-bromo-cGMP) in formalin-induced nociception in rats

Interactions are known to occur in the brain between serotonin (5-HT) and substance P (SP). To investigate whether SP can directly influence serotonergic neurons, double immunohistochemical labelings were performed on rat brain sections with NK1 or NK3 affinity-purified antibodies and a 5-HT monoclonal antibody. It was found that the vast majority of serotonergic cell bodies do not colocalize NK1 or NK3 labeling. Only in the central linear nucleus and ventral part of the dorsal raphe nucleus were a few serotonergic neurons double-labeled for NK1 receptors (15 and 0.8% of serotonergic neurons, respectively). It is suggested that serotonergic neurons are not major direct targets for SP in the rat brain.