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J E Price

Publications and source records attributed to J E Price.

At least 91 records · Page 5Linked to original sources

Experimental analysis of factors affecting metastatic spread using naturally occurring tumours.

This paper describes the applications and latest results of recently developed techniques in metastasis research using naturally occurring animal and human tumours. Intravenous inoculation of cells from murine mammary tumours into syngeneic recipients has shown that some are consistently capable of heavy pulmonary colonisation (HCP) while others have low colonisation potential (LCP). These distinct characteristics are stable over wide cell-dose ranges. Autopsies on a sample of 100 consecutive tumour-bearing C3H/Avy mice revealed that the incidence of spontaneous metastasis is 26%. When inoculated intravenously, cells from some of the spontaneously metastatic primary tumours had HCP and others LCP. We now report that, knowing the degree of pulmonary colonisation of a particular tumour after intravenous inoculation, the degree of its spontaneous metastasis in the original host, and the dose-response relationships mentioned above, it is possible to back-titrate the degree of cell shedding from the tumour into the blood stream. Other experiments reported here demonstrate that separate mammary tumours on the same animal have independent colonisation potentials and growth rates, that tumours appearing later on an animal are not necessarily more capable of metastatic spread than the earlier ones, and that tumour weight and length of presence on the host do not show any strong correlation with spontaneous metastatic spread. A moderately significant association between pulmonary colonisation potential and tumour growth rate is reported and evidence corroborating our earlier observations that ability to colonise the lungs is possessed only by neoplastic mammary cells is also presented. Similar investigation are, of course, much more difficult to organise on tumour spread in man because of ethical and logistic considerations but it is possible to circumvent some of these difficulties and we refer to some of our ongoing studies.

Adipose Tissue↗

Macrophage content and colony-forming potential in mouse mammary carcinomas.

The macrophage content of cell suspensions from naturally occurring mouse tumours has been assessed by the Fc-mediated phagocytosis assay, and the results compared with the individual tumour's capacity for spontaneous metastasis and with its pulmonary colonization potential after i.v. inoculation. It was found that these tumours differ in their properties from the transplantable fibrosarcomas studied previously by other investigators, in that the macrophage content of all the tumours was uniformly low, ranging from 2 to 9% (mean 4.2 +/- 1.8%) and there was no inverse correlation with frequency of spontaneous metastasis, which was low. When the tumours were inoculated i.v. there was also no correlation with colony-forming capability, which varied greatly between tumours. Lung secondary deposits contained 1.7-6% macrophages (mean 4.4 +/- 0.6%) with a lower phagocytic activity for antibody-coated red cells than in the primary tumour.

Animals↗

Lectin agglutinability of mammary tumours with differing metastatic colonisation potentials.

A new fully quantitative method for assessment of lectin agglutinability has been used in this investigation to compare the surface composition of cells from tumours with high and low pulmonary colonisation potential. As in our previous work, we have used only primary (i.e., naturally-occurring) mammary tumours in mice. It was found that agglutinability with the lectins Concanavalin-A and Wheatgerm agglutinin bore no relationship to the pulmonary colonisation potential of the primary mammary tumour. However, cells from disaggregated secondary deposits of tumours which manifested high colonisation potential were consistently less agglutinable than the cells of the primary tumours from which they were derived.

Agglutination↗

Influence of microenvironment and vascular anatomy on "metastatic" colonization potential of mammary tumors.

This communication reports experiments demonstrating that some sites in which tumor cells lodge reproducibly fail to support secondary colony formation by a particular tumor, even though cells from the same tumor are already proven to have high colonization potential in other organs. The effect is not an expression of nonspecific hostility to tumor growth, since cells from certain other tumors readily colonize the same site. Cell suspensions obtained by disaggregation of a series of naturally occurring murine mammary tumors were each inoculated by four different routes into separate batches of syngeneic animals, and the resulting degree and distribution of colonization were studied 90 days later at autopsy. Standard doses of 1 million viable tumor cells were injected either i.p. or s.c. into the tail vein or the hepatic portal vein. It was found that some tumors could reproducibly colonize by all routes, whereas others could colonize only by a few, and the combination of sites colonized varied from tumor to tumor; still others were unable to grow in any site. Cells from nonneoplastic lactating mammary glands did not establish any colonies. We have demonstrated previously that individual naturally occurring mammary tumors differ in their pulmonary colonization potentials after i.v. inoculation and that the potential of a given tumor is an intrinsic property of its constituent cells. The current findings are evidence that the microenvironment of an organ can inhibit or permit expression of this intrinsic potential and that the degree and sites of colonization are thus the results of interaction between tumor and organ-specific factors. It was also found that circulatory anatomy partially influenced the distribution of colonies and that colonization of distant organs after blood-borne dissemination is distinct from general tumor transplantability.

Animals↗

A comparison of the efficacy of imidocarb dipropionate and tetracycline hydrochloride in the treatment of canine ehrlichiosis.

A comparison of the efficacy of imidocarb dipropionate solution and tetracycline hydrochloride in the treatment of naturally occurring ehrlichiosis of dogs presented at the University of Nairobi small animal clinic was carried out. Five to 7 mg per kg imidocarb dipropionate given intramuscularly twice at an interval of 14 days was as effective as 14 daily, oral doses of 66 mg per kg tetracycline hydrochloride in alleviating the clinical signs of disease. Imidocarb eliminated the infection in 81 per cent of the cases whereas tetracyclines cleared only 25 per cent as judged by cell culture isolation. Imidocarb had the further advantage of controlling concurrent babesiosis. The majority of dogs showed some transient side-effects after administration of imidocarb, while a small proportion of dogs dosed with tetracycline reacted adversely and dosage had to be reduced or stopped.

Administration, Oral↗

Free-living jackals (Canis mesomelas)-potential reservoir hosts for Ehrlichia canis in Kenya.

Using a modified cell culture test, Ehrlichia canis was found in eight of 15 free-living jackals (Canis mesomelas) and 14 of 31 dogs owned by pastoral communities in the same areas of Kenya. Two cross-bred puppies inoculated with blood from infected jackals developed mild, transient clinical disease, and E. canis was recovered from the puppies. Tick species found on the jackals were similar to those found on the infected dogs. Ehrlichia canis was not found in eight spotted hyaenas (Crocuta crocuta) from these areas.

Animals↗

Metastatic colonization potential of primary tumour cells in mice.

A model has been developed for studying the capability of cells from primary murine mammary tumours to establish colonies in distant organs. The model involves the i.v. inoculation of disaggregated tumour cells into autologous and syngeneic recipients. The results show that the metastatic colonization potential of cells from a given tumour is consistent within the animals of an inoculated batch. Also, the findings are uniform in the autologous host and the syngeneic recipients. Tumours vary in their colonization potential and can be classified in 2 main groups designated high and low. These findings indicate that: (i) cells from 37% of mammary tumours can heavily colonize the lungs when inoculated i.v., even though the incidence of metastatic spread of these tumours in the undisturbed animal is almost zero. Thus, the relative infrequency of spontaneous metastasis from murine mammary tumours is not due to inability of the tumour cells to survive and colonize once free in the blood stream; and (ii) the colonization potential of the tumours is an intrinsic property of the tumour cells rather than of the host, whose prior acquaintance with the cells does not seem to confer resistance to colonization. The model presents opportunities for identification of possible differences between tumours of high and low colonization potential, and is being used to study cellular properties which favour colonization of distant organs by comparison of observations in vitro with the behaviour of cells from the same tumour in vivo.

Animals↗

Improved longevity due to reduction of sudden death by aortocoronary bypass in coronary atherosclerosis.

To evaluate the efficacy of coronary bypass surgery in reduction of sudden death, the prognosis of 286 similar patients with multivessel coronary stenosis was studied prospectively and the results of medical therapy (Group I, 114 patients) were compared with those of surgical therapy (Group II, 172 patients) after cardiac catheterization and coronary arteriography. During 39 months' evaluation of both groups, mortality from congestive heart failure and noncardiac causes did not differ (Group I, 14 percent; Group II, 8 percent) (P greater than 0.05). Sudden was evaluated in the remaining 217 patients (Group I, 96; Group II, 121 patients) who were matched for age (Group I, 52 years; Group II, 51 years); duration of overt coronary disease (Group I, 3.8 years; Group II, 4.0 years); angina pectoris (Group I, 83 percent; Group II, 95 percent); prior myocardial infarction (Group I, 77 percent; Group II, 74 percent); and congestive heart failure (Group I, 30 percent; Group II, 23 percent) (all P greater than 0.05). In addition, the prevalence of coronary risk factors was the same (P greater than 0.05) in both groups (hypertension, cigarette smoking, diabetes mellitus, lipid abnormalities and family history of coronary disease). Importantly, arteriography and catheterization established a similar extent and location of major coronary arterial stenoses and of ventricular dysfunction; two vessel disease (Group I, 32 percent; Group II, 33 percent) and three vessel disease (Group I, 68 percent; Group II, 67 percent); left ventricular end-diastolic pressure (Group I, 13; Group II, 14 mm Hg);cardiac index (Group I, 2.85; Group II, 2.91 liters/min per m2); and coronary collateral vessels (Group I, 58 percent; Group II, 61 percent) (all P greater than 0.05). Fifty-six percent of patients in Group II had multiple bypass grafts and a late patency rate (average 21 months) of 87 percent of one or more grafts. During subsequent prospective evaluation of over 3 years, bypass surgery provided greater symptomatic benefit of improved functional capacity (Group I, 12 percent; Group II, 69 percent) (P less than 0.05) and complete anginal relief (Group I, 30 percent; Group II, 60 percent) (P less than 0.05). Moreover, bypass surgery was associated with marked reduction in sudden death (Group I, 24 percent; Group II, 6 percent) (P less than 0.05). Thus, in patients with multivessel coronary disease carefully matched for clinical factors, hemodynamics, atherogenic precursors and coronary pathoanatomy, effective aortocoronary bypass surgery appeared to prolong survival by decreasing the incidence of sudden death, possibly by a decrease of unexpected fatal arrhythmias.

Cardiac Catheterization↗

Fruit pit obstruction. "The propitious pit.".

Ingestion of fruit pit must be a frequent and innocuous phenomenon, judging from the expected frequency of such occurrences and the relative dearth of medical reports to the contrary. Reported here are four cases in which fruit pits of varied nature completed an otherwise incomplete intestinal obstruction. On of these was in the terminal ileum, with incomplete obstruction due to regional ileitis, in which the offending pit was seen radiologically but was not recognized as such. The other three were in the transverse colon, at the site of annular carcinomatous lesions. The completion of the obstruction by the fruit pits eventuated in earlier symptoms, diagnosis, and treatment. In one case, the fruit pits were multiple; in the remainder, they were single.

Aged↗