Spontaneously occurring A-strain mouse mammary carcinomata were individually passaged, at equal intervals into separate groups of isogenic hosts. The tumours showed evidence of increasing autonomy as judged either by the decreasing host lymphoid hyperplasia they evoked, or their decreased killing time, as passaging continued. However, in general, no reduction was found in the ability of spleen cells from hosts bearing succeeding passages of the same tumour to induce a graft-versus-host reaction in (A × CBA)F(1) hybrid mice. It is therefore suggested that the increasing malignancy of the tumours studied was associated with a change in the tumour rather than increasing immunodepression in successive hosts.

Animals↗

PubMed1971

Further observations on whether host immunodepression is associated with tumour growth in mice.

In order to investigate whether the presence of a tumour was associated with immunodepression in the host, spleen cells from parent line animals with tumours were injected intravenously into F(1) hybrids, half of which carried the same tumour. Further groups of F(1) hybrid with and without the tumour received spleen cells from non-tumour bearing parent line animals. The G.V.H. reactions induced in the four groups of F(1) hybrid were compared and no significant differences were found. This was true in separate experiments, involving two mammary carcinomata and a 3-methylcholanthrene induced sarcoma, wherein the period of tumour growth in the parent line donor and F(1) hybrid recipient was varied.

Animals↗

PubMed1971

Simple and choice reaction time in spastic hemiplegics.

Explore the source record for details and available documents.

Adolescent↗

PubMed1971

Observations on whether immunodepression is associated with the presence of a tumour in mice.

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

Mesenteric arteriopathy in the rat induced by phosphodiesterase III inhibitors: an investigation of morphological, ultrastructural, and hemodynamic changes.

A reproducible model of a phosphodiesterase III (PDE III) inhibitor-induced arteriopathy has been developed in the rat after subcutaneous administration of SK&F 95654. Administration of this potent PDE III inhibitor induced an arteriopathy of mesenteric arteries within 24 hr that was dose-related in intensity and incidence over the range 0.174, 0.348, 0.523, and 0.697 mmol/kg. The arteriopathy was restricted to muscular arteries of external diameter of 100-800 microns and was shown microscopically to be focal or segmental medial necrosis and hemorrhage. A time-course experiment, conducted from 3 to 24 hr postdosing, showed that the first changes observed 6 hr postdosing were on the endothelium followed by focal hemorrhages into the media at 12 hr postdosing, causing compression, degeneration, and necrosis of myocytes. From 16 hr postdosing, there was focal endothelial cell necrosis and loss of confluence. Leukocytes and activated platelets were found adhering to exposed basement lamina and seen to pass through endothelial gaps into the subintima. By 24 hr postdosing, medial necrosis was extensive with large areas of media replaced by erythrocytes, cell debris, and a few leukocytes and platelets. The effect of 3 structurally dissimilar PDE III inhibitors administered subcutaneously at a dose of 0.697 mmol/kg was compared with that of SK&F 95654. The arteriopathy induced by these compounds were identical to that produced by SK&F 95654 with the incidence and severity of lesions ranked in the following order: SK&F 95654 > WIN 62582 > SK&F 94836, with no macroscopic lesions observed for SK&F 94120. Systolic blood pressure was measured for these 4 PDE III inhibitors at regular intervals over the 24-hr period postadministration by a plesthymographic method. The severity of the arterial lesions correlated with the magnitude of hypotension induced by these agents. It is postulated that the arterial damage is a consequence of profound vasodilation resulting in abnormal endothelial permeability and increased wall tension, resulting in progressive medial necrosis and hemorrhage.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMedDate not supplied

An ultrastructural histochemistry and light microscopy study of the early development of renal proximal tubular vacuolation after a single administration of the contrast enhancement medium "Iotrolan".

The time course of contrast media (CM)-induced renal proximal tubular vacuolation was investigated in rats by light microscopy, transmission electron microscopy (TEM), and ultrastructural histochemistry for acid phosphate activity. Young adult male rats were treated with a single dose of 3.0 g I/kg Iotrolan (Isovist 300 mg I/ml) and sacrificed at 0 min, 5-min, 15-min, 15-min, 2-hr, and 24-hr intervals. Light microscopy of vibratome sections of freshly excised tissue of cryostat and paraffin sections was also performed to allow comparison of the appearance of the vacuoles in the fresh state with light and electron microscopy. The sequence of events seen to occur can be summarized as follows. CM-induced vacuolation occurred at a low level a soon as 5 min after compound administration. The vacuolation was observed by TEM but could not be detected by light microscopy. This was followed by an increase in size and numbers of vacuoles up to the 24-hr timepoint with a sequential increase in the staining for acid phosphatase activity of the vacuoles, most marked at the 24-hr timepoint. At timepoints less than 24 hr there appeared to be no marked increased in the normal complement by lysosomes or in the components of the Golgi-endoplasmic reticulum-lysosome pathway. At 24 hr, the vast majority, but not all, of the CM-induced vacuoles were positive for acid phosphatase activity. The intensity of staining varied, and there was evidence of infusion of small lysosomes with CM-induced vacuoles. These results suggest that formation of CM-induced vacuoles is a 2-stage process, following a normal pathway for the handling of endogenous and exogenous substances.

Animals↗

PubMedDate not supplied

Cholesterol lowering trials: advice for the British physician.

In summary, there is considerable agreement as to the appropriate management of hyperlipidaemia in patients at high risk of CHD. As in all branches of medicine, there are contentious areas particularly with respect to the 'middle risk range', where a strong case can be made for further appropriate clinical trials to be performed. Several of the hitherto published guidelines for the treatment of hyperlipidaemia have been inconsistent and have overestimated the proportion of the population who would benefit from the therapeutic intervention. Nevertheless, the reality of the situation in contemporary British clinical practice is that a large proportion of high-risk patients are not adequately treated, and that the perfectly reasonable clinical aphorism of 'first do no harm' is erroneously extrapolated and used as a therapeutic nihilist's charter. As always, British clinicians will use their discretion in the treatment of individual patients, but where consensus clearly does exist, it would be an appropriate subject of clinical audit to review not only those patients who may be inappropriately receiving lipid lowering drugs but, equally if not more importantly, also to justify why large numbers of patients who would clearly benefit from such drug intervention are not currently receiving it. The cholesterol debate should no longer be the justification for therapeutic nihilism.

Aged↗